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Each experiment was independently replicated at least three times, with error bars showing standard deviation. Statistical analysis was performed using appropriate tests in GraphPad Prism, and P values were denoted as follows: ns ( P ≥ .05), * (0.01 < P < .05), ** (0.001 < P ≤ .01), *** , and **** . P values were listed in Supplementary Table 2 .
|
39530356_p16
|
39530356
|
Statistical analysis
| 3.063329 |
biomedical
|
Study
|
[
0.9985448122024536,
0.00021321410895325243,
0.0012420068960636854
] |
[
0.9704748392105103,
0.02765127830207348,
0.0015828029718250036,
0.0002910823095589876
] |
en
| 0.999997 |
P. rettgeri is a Gram-negative bacteria that can be found in B. dorsalis and other Tephritidae fruit flies gut microbiota in both lab and wild populations [ 28–33 ]. Our results and others have shown that P. rettgeri may benefit host fitness under certain circumstances . However, P. rettgeri is also a pathogenic bacteria to many insects, suggesting that P. rettgeri could be a pathobiont of B. dorsalis [ 30 , 35–37 ]. Our previous research has shown P. rettgeri promotes B. dorsalis larval growth but is also a potent inducer for host immune response . We confirmed that oral infection with our lab strain P. rettgeri led to host death, suggesting that P. rettgeri is a pathobiont in B. dorsalis adults .
|
39530356_p17
|
39530356
|
Pathobiont Providencia rettgeri triggers a countercurrent flow in Bactrocera dorsalis
| 4.127731 |
biomedical
|
Study
|
[
0.9992538094520569,
0.00018862509750761092,
0.0005575648974627256
] |
[
0.9994661211967468,
0.0002475908841006458,
0.0002456709335092455,
0.00004066209294251166
] |
en
| 0.999998 |
We have recently shown that pathogenic bacteria oral infection activates a renal–gut countercurrent flow in D. melanogaster that plays an important role in gut epithelial renewal . To test if pathobiont can induce countercurrent flow, we set up an ex vivo assay to test the existence of countercurrent flow in B. dorsalis . Briefly, flies were subjected to either oral infection for 2 h with P. rettgeri, or a control sucrose solution, then switched to fresh fly food . The experiments were performed as previously described . The results suggested that P. rettgeri infection induced the rapid Malpighian tubules absorption of Brilliant blue dye 2 h post infection. We observed the dye moved forward to the midgut and accumulated along the gut, including the anterior midgut and posterior midgut . We noticed an increase in the percentage of the gut displaying dye from 33.3%–65.6% upon oral infection. Almost half of the gut has a strong dye signal in the anterior part, suggesting a more robust flow than the unchallenged condition . Moreover, we also saw the countercurrent flow positive gut in the unchallenged condition, suggesting this flow might have a role with gut resident bacteria . We also performed an in vivo countercurrent flow measurement experiment. The results also suggested a stronger countercurrent flow following P. rettgeri infection . We also examined whether the intensity of countercurrent flow was determined by different dye absorption by Malpighian tubules. The results showed that the Malpighian tubules had similar dye accumulation suggesting a similar Malpighian tubules excretion ability . Altogether, these data revealed the existence of a Malpighian tubules–gut countercurrent flow after pathobiont oral infection in B. dorsalis .
|
39530356_p18
|
39530356
|
Pathobiont Providencia rettgeri triggers a countercurrent flow in Bactrocera dorsalis
| 4.354567 |
biomedical
|
Study
|
[
0.999421238899231,
0.00035673961974680424,
0.00022211665054783225
] |
[
0.9991725087165833,
0.00027133343974128366,
0.00044916110346093774,
0.00010692233627196401
] |
en
| 0.999997 |
Aquaporins are a family of membrane water channels, some of which are also capable of transporting glycerol . In D. melanogaster , aquaporin Drip is required in Malpighian tubules stellate cells, which are responsible for regulating ion balance and fluid secretion, for countercurrent flow formation . We then explored the role of aquaporins in controlling Malpighian tubules–gut countercurrent flow in B. dorsalis . We first confirmed the aquaporin Prip and Drip are expressed in the Malpighian tubules . We knocked down Prip and Drip using RNAi by injecting dsRNAs . The results showed that Prip RNAi flies failed to generate a strong countercurrent flow after P. rettgeri infection as indicated by the absence of the dye in the anterior midgut, suggesting that Malpighian tubules–gut countercurrent flow formation requires Prip . However, we saw no difference in dye accumulation between the Drip RNAi and the control groups, indicated by the accumulation of the dye in the anterior midgut, suggesting Drip may not be necessary for countercurrent flow formation . Above results suggested a role of Prip but not Drip in countercurrent flow formation in B. dorsalis .
|
39530356_p19
|
39530356
|
Countercurrent flow in Bactrocera dorsalis requires the aquaporin Prip and promotes early stage bacteria clearance
| 4.240134 |
biomedical
|
Study
|
[
0.9993748068809509,
0.000252545956755057,
0.0003726696886587888
] |
[
0.999489426612854,
0.0002461905241943896,
0.0002056826197076589,
0.00005873044938198291
] |
en
| 0.999999 |
The observation that counterflow is induced upon pathobiont infection points to its possible role in host defense. Next, we investigated whether this Malpighian tubules–gut retro flow is required for early stage bacteria clearance. Both Prip and Drip RNAi flies and control egfp RNAi flies were fed with P. rettgeri for 2 h and then switched to fresh food. We monitored bacteria persistence in the gut for the next 9 h. Importantly, we found that Prip RNAi flies lost their ability to clear invading bacteria . However, Drip RNAi flies, which have normal retro-flow, have successfully cleared invading bacteria 6 h after P. rettgeri infection, showing no difference compared to the control group . As Prip but not Drip is involved in the countercurrent flow formation, our results points to an important role of Malpighian tubules–gut retro-flow in bacterial clearance. In conclusion, the above results suggested that the aquaporin Malpighian tubules–gut countercurrent flow which involved Prip is required for efficient bacteria clearance after oral infection in B. dorsalis .
|
39530356_p20
|
39530356
|
Countercurrent flow in Bactrocera dorsalis requires the aquaporin Prip and promotes early stage bacteria clearance
| 4.289238 |
biomedical
|
Study
|
[
0.999508261680603,
0.00033325934782624245,
0.00015847859322093427
] |
[
0.9990480542182922,
0.00026504206471145153,
0.0005808799178339541,
0.00010606875002849847
] |
en
| 0.999995 |
The biogenic amine tyramine regulates many aspects of animal physiology. Tyramine also controls Malpighian tubules function in insects . We hypothesized that tyramine might be the signaling molecule inducing the countercurrent flow from the Malpighian tubules to the gut. To test this hypothesis, we first knocked down TyrR in B. dorsalis . TyrR is the tyramine receptor regulating Malpighian tubules stellate cell activity . We monitored Malpighian tubules–gut countercurrent flow using in vitro countercurrent experiments. TyrR knockdown strongly decreased the intensity of this retro-flow, as the dye could not reach the anterior midgut in TyrR RNAi flies after infection . More importantly, TyrR RNAi flies also had a weaker ability to clear invading bacteria . These data indicated that tyramine contributes to the Malpighian tubules–gut countercurrent flow. To further strengthen our conclusions, we directly fed B. dorsalis with tyramine and detected countercurrent flow. The results showed that feeding flies with a diet supplemented with tyramine enhanced gut countercurrent flow, promoting dye accumulation in the anterior midgut, similar to the oral infection . Furthermore, feeding tyramine significantly increased flies’ ability to eliminate invading bacteria. Tyramine-fed flies eliminated invading bacteria within 1 h after infection compared with 2 h in the control flies . We further tested whether TyrR signaling could regulate Prip’s transcriptional activity. The results showed that knocking down TyrR had no significant impact on Prip expression, suggesting that TyrR signaling may not directly regulate aquaporin Prip activity . Moreover, tyramine feeding did not rescue the countercurrent flow phenotype in Prip RNAi flies, indicating that aquaporin might act downstream of TyrR signaling .
|
39530356_p21
|
39530356
|
Exogenous tyramine is a signaling molecule that triggers Malpighian tubules–gut countercurrent flow
| 4.363091 |
biomedical
|
Study
|
[
0.9992964267730713,
0.0004532900347840041,
0.00025030141114257276
] |
[
0.999229907989502,
0.00027456542011350393,
0.00036215633735992014,
0.0001334419212071225
] |
en
| 0.999995 |
It is well characterized that bacteria, for example, Providencia bacteria, can produce large amounts of tyramine regulating host physiology . We wondered if the tyramine was produced by the flies or if the bacteria secret it. We first examined the tyramine quantity in ingested P. rettgeri and B. dorsalis . The results showed that both ingested P. rettgeri and B. dorsalis could produce tyramine . Ingested P. rettgeri produces higher amount of tyramine than the flies, suggesting a possible role of bacteria-derived tyramine in regulating Malpighian tubules functions. To validate our assumption, we knocked down the tyrosine decarboxylase 1 ( Tdc1 ) in B. dorsalis . Tdc1 is the enzyme that catalyzes the decarboxylation of tyrosine to tyramine and is necessary for renal function regulation in D. melanogaster . The results showed that Tdc1 RNAi flies had a similar Malpighian tubules–gut countercurrent flow as egfp RNAi flies, and bright blue dye could reach the gut R2 region after P. rettgeri infection , suggesting that intrinsic tyramine synthesis pathway is not required for countercurrent flow formation. Consistent with this finding, we also found that the bacteria clearance ability remained unchanged in Tdc1 RNAi flies . To further strengthen the conclusion, we detected tyramine levels in the gut and hemolymph in Tdc1 RNAi flies after P. rettgeri infection. The results showed that Tdc1 RNAi did not affect tyramine levels in the gut and hemolymph compared with the control group . In both tissues, we still observed an increase in tyramine content in both gut and hemolymph, suggesting that these tyramines are exogenous. Another tyrosine decarboxylase gene, Tdc2, has been identified in B. dorsalis . We attempted to knock down Tdc2 and evaluated its role in countercurrent formation and bacterial elimination. However, our results indicated that Tdc2 RNAi did not significantly affect either retro-flow formation or bacterial clearance . Taken together, these data suggested that tyramine secreted by pathogenic bacteria activates the countercurrent flow.
|
39530356_p22
|
39530356
|
Exogenous tyramine is a signaling molecule that triggers Malpighian tubules–gut countercurrent flow
| 4.282471 |
biomedical
|
Study
|
[
0.9994111061096191,
0.00035802708589471877,
0.00023089263413567096
] |
[
0.9994018077850342,
0.0002302416251040995,
0.0002648033550940454,
0.00010308330820407718
] |
en
| 0.999997 |
Gut pathobiontic bacteria can activate host Duox–ROS production to maintain gut homeostasis in D. melanogaster . We explored the role of the Duox–ROS production system in P. rettgeri clearance. We first checked ROS production in the gut after P. rettgeri infection 2 h post infection in B. dorsalis . The primary Duox ROS product is HOCl, while superoxide (O 2 − ) and H 2 O 2 are intermediate products . We monitored each of these ROS in the gut using appropriate assays: DHE for superoxide, hydrogen peroxide assay kit for H 2 O 2 and the R6G HOCI sensor for HOCl. We did not detect any increase in superoxide production , nor did we see an increased amount of H 2 O 2 . However, we saw a strong HOCl burst in the gut region corresponding to region R2 at 2 h post-infection . To check whether ROS is necessary for bacteria clearance, we monitored bacteria persistence in Duox RNAi flies . We found that Duox RNAi flies had a weaker ability to clear invading bacteria as these flies cannot remove the bacteria until 9 h after infection, suggesting that Duox-mediated ROS production mechanism is crucial for early B. dorsalis gut immune response . To further support our conclusion, we co-fed the flies with bacteria and vitamin C, a potent antioxidant. We found that B. dorsalis cannot clear P. rettgeri even at 9 h after infection when we remove the ROS using vitamin C . Altogether, our data showed that B. dorsalis relied on Duox–ROS to remove excessive P. rettgeri at the early stage of infection.
|
39530356_p23
|
39530356
|
Duox is required for early stage Providencia rettgeri clearance
| 4.330764 |
biomedical
|
Study
|
[
0.9993898868560791,
0.00041322348988614976,
0.0001969658478628844
] |
[
0.9992121458053589,
0.00026506511494517326,
0.0004086580593138933,
0.00011408801947254688
] |
en
| 0.999995 |
Recent studies have highlighted a possible key role of Duox in bacterial clearance by promoting muscle contraction . We therefore investigated whether peristalsis also contribute to B. dorsalis ability to eliminate bacteria. We fed flies with FITC-labeled dextran and monitored gut peristalsis upon oral infection with the Gram-negative bacteria P. rettgeri infection. We observed that oral infection increased gut peristalsis by 32% . This effect was absent in Duox RNAi flies indicating that gut peristalsis requires by Duox in B. dorsalis . Consistent with this finding, co-fed the flies P. rettgeri with vitamin C also inhibited increased gut peristalsis .
|
39530356_p24
|
39530356
|
Countercurrent flow ensures Providencia rettgeri clearance by promoting reactive oxygen species accumulation and gut peristalsis
| 4.119201 |
biomedical
|
Study
|
[
0.9995328187942505,
0.0002462810662109405,
0.00022085187083575875
] |
[
0.999495267868042,
0.0001965566916624084,
0.0002480535476934165,
0.00006013089296175167
] |
en
| 0.999996 |
We wondered whether blocking Malpighian tubules–gut countercurrent flow would affect the ROS amount and gut peristalsis. We quantified the HOCl amount in Prip RNAi flies. The results showed that Prip RNAi strongly decreased the number of HOCl-positive flies after oral infection, as indicated by the R6G HOCl sensor . This result suggested that countercurrent flow may promote gut bacteria clearance through HOCl distribution along the gut. To further support our conclusion, we also quantified HOCl amount in Drip RNAi flies. Drip RNAi did not have a strong impact on the number of HOCl-positive flies . To exclude the possibility that Prip RNAi would directly affect AMPs and ROS production, we examined Diptericin and Duox expression in Prip RNAi flies. The RT-qPCR analysis showed that Prip RNAi did not affect the Diptericin and Duox expression . Because Duox played an important role in gut muscle contraction and food defecation, we checked gut peristalsis in Prip RNAi flies. Prip RNAi inhibited the gut peristalsis increase after infection . Taken together, these observations suggested that the Malpighian tubules–gut countercurrent flow ensures gut pathobiont bacteria clearance by promoting ROS-mediated gut peristalsis.
|
39530356_p25
|
39530356
|
Countercurrent flow ensures Providencia rettgeri clearance by promoting reactive oxygen species accumulation and gut peristalsis
| 4.260788 |
biomedical
|
Study
|
[
0.999441921710968,
0.00033354878542013466,
0.00022449000971391797
] |
[
0.9993281364440918,
0.0002413096954114735,
0.0003436384431552142,
0.00008689154492458329
] |
en
| 0.999998 |
We wondered whether gut symbionts can also release tyramine and promote the formation of countercurrent flow. C. koseri and E. hormaechei are dominant microbiota species in B. dorsalis . We found these two bacteria also produce a considerable amount of tyramine . We expect these bacteria can also induce countercurrent flow. By in vitro assay, we found that C. koseri and E. hormaechei can induce a stronger countercurrent flow . This result suggests that symbionts also contribute to Malpighian tubules–gut countercurrent flow formation. We have shown earlier that countercurrent flow ensures bacteria clearance by promoting pathobionts-induced ROS-mediated gut peristalsis. So we tested whether symbiont also contribute to this process. We monitored HOCl production in the flies infected with C. koseri and E. hormaechei . The results showed that neither C. koseri nor E. hormaechei induce a strong HOCl burst at the early stage of infection .
|
39530356_p26
|
39530356
|
Gut symbiont promotes countercurrent flow but not reactive oxygen species production
| 4.119205 |
biomedical
|
Study
|
[
0.9992615580558777,
0.00025812897365540266,
0.0004803396877832711
] |
[
0.9995986819267273,
0.0001894966553663835,
0.00016746320761740208,
0.0000443982207798399
] |
en
| 0.999998 |
We next examined whether countercurrent flow is also required for microbiota control. We performed 16S rRNA sequencing in Prip RNAi flies to validate this assumption. Regarding relative abundance, the high-throughput sequencing revealed that Enterobacteriaceae , Morganellaceae , Orbaceae , and Streptococcaceae dominated the gut regions of egfp RNAi control flies. However, Enterobacteriaceae , the most abundant bacteria species, decreased to 22.5% in Prip RNAi flies compared to the control group. The less dominant species Streptococcaceae reduced to very low levels, becoming a minor microbiota species in the flies’ gut. On the contrary, we found an increase in Morganellaceae , which accounts for around 35.4% of the total microbiota in Prip RNAi flies. One minor species in control flies, Desuifovobrionaceae , also became a dominant microbiota species in Prip RNAi flies . These results suggested that inhibiting Malpighian tubules–gut countercurrent flow by Prip knockdown caused microbiota dysplasia in the gut. Furthermore, gut microbiota species richness and evenness were reduced in the Prip RNAi flies, as indicated by Simpson diversity indices .
|
39530356_p27
|
39530356
|
Gut symbiont promotes countercurrent flow but not reactive oxygen species production
| 4.241305 |
biomedical
|
Study
|
[
0.9994706511497498,
0.0003022875462193042,
0.00022705350420437753
] |
[
0.9994096755981445,
0.00019666098523885012,
0.0003189810086041689,
0.00007478453335352242
] |
en
| 0.999997 |
In this study, we identified a physiological mechanism essential for microbiota homeostasis contributed by pathobiont and symbiotic bacteria. We demonstrated that the host generates a Malpighian tubules–gut countercurrent flow in response to the presence of pathobiont and symbiotic bacteria-derived tyramine. This flow facilitates the accumulation of ROS upon recognition of pathobiont, and in turn, ROS ensures proper gut peristalsis. We also provided evidence that this flow is involved in maintaining microbiota homeostasis. This work suggested a mechanism involving both pathobiont and symbiotic bacteria that promotes the accumulation of ROS. Furthermore, our work also proved the involvement of Malpighian tubules in gut microbiota homeostasis, in addition to their well-known functions in regulating excretion physiology.
|
39530356_p28
|
39530356
|
Discussion
| 4.229605 |
biomedical
|
Study
|
[
0.9995135068893433,
0.0003100578032899648,
0.0001765064662322402
] |
[
0.9992091059684753,
0.00022843388433102518,
0.00046665663830935955,
0.00009581672202330083
] |
en
| 0.999997 |
Our results suggested that both pathobionts and symbionts contribute to the formation of Malpighian tubules–gut countercurrent flow, while ROS is produced by pathobionts in the early stage of infection. By interaction with both pathobionts and symbionts, host developed a successful gut immune response which is crucial for microbiota control. Growing evidence has shown the complexity of pathobionts and symbionts interactions. For example, it is common for pathobionts to adopt various mechanisms to promote their fitness. In cotton leafworm Spodoptera littoralis , extracellular symbiont Enterococcus mundtii produces potent antimicrobials selectively limiting pathobiont expansion, providing protection against infection . This phenomenon is also observed in many other insects . These examples highlight the possibility that interactions between microbes could be a key factor in maintaining microbe-host homeostasis. Here, we provided a new model that both pathobiont and gut symbiont shape the host gut immune response. Similar to previous findings, we found that pathobionts but not symbionts can induce host ROS production and gut peristalsis, implying host can retain most of the beneficial symbionts. It is well known that pathogenic bacteria, such as Pectobacterium carotovorum subsp. Carotovorum ( Ecc15 ) and others, release significant amounts of uracil, which is detected by an as-yet unidentified host receptor . Host then activated Duox activity upon recognition of these uracil . However, data indicate that gut-beneficial symbionts, such as Commensalibacter intestini A911T, Acetobacter pomorum , and Lactobacillus plantarum , do not release uracil, and therefore, do not activate Duox or trigger a HOCl burst . Gluconobacter morbifer G707T, a minor member of the natural gut-dwelling pathobiont community, can activate Duox through uracil release . Although untested, we hypothesize that C. koseri and E. hormaechei , which we isolated from B. dorsalis , are beneficial microbes that do not produce uracil, whereas P. rettgeri might do so. We used a short feeding scheme to investigate the host immune response in the early stage of infection. It is possible that under continuous infection or long-term colonization, a different mechanism could exist in insects. An open question remains as to whether pathobionts and symbionts might encounter a similar challenge in relation to gut peristalsis. The central question here is how gut microbes successfully establish a stable association with the host’s digestive tract. This process involves multiple mechanisms, including gut peristalsis, biofilm formation, and inter/intra-species competition. Future works are required to understand how pathobionts and symbionts might respond to host immunity distinctly.
|
39530356_p29
|
39530356
|
Discussion
| 4.591756 |
biomedical
|
Study
|
[
0.9989826083183289,
0.0006803005817346275,
0.0003370257618371397
] |
[
0.9985654950141907,
0.000391240231692791,
0.0008355185855180025,
0.00020771953859366477
] |
en
| 0.999997 |
The fact that ROS is well preserved by the Malpighian tubules–gut countercurrent flow proved that insects own a delicate system to prevent the loss of valuable resources. The countercurrent flow from Malpighian tubules to the anterior gut in B. dorsalis appears to be conserved in other insects. Recently, we found that countercurrent flow induced by Ecc15 infection was crucial for gut epithelial renewal in D. melanogaster . Early reports in locusts showed that a counter-current flow from Malpighian tubules occurred when the locusts were starved . By using dye feeding and observation of its distribution in the gut, Terra and colleagues proposed the existence of countercurrent flow in other insects, including Lepidoptera , Coleoptera , and Orthoptera . Our results suggested aquaporins’ critical role in forming the countercurrent flow in B. dorsalis . Aquaporins are also enriched in the anterior midgut in D. melanogaster , implying that the anterior midgut might be a major region for water absorption, thus forming a complete water flow cycle consisting of Malpighian tubules, hemolymph, and the gut . In the absence of tissue-specific knockdown tools, our results do not identify the specific tissue in which Prip or TyrR is required. It remains possible that these key genes are essential in tissues other than the Malpighian tubules. Moreover, although Prip RNAi does not have a strong impact on Duox and IMD target genes expression, it may exert its effects through other pathways.
|
39530356_p30
|
39530356
|
Discussion
| 4.297422 |
biomedical
|
Study
|
[
0.99935382604599,
0.00027718080673366785,
0.0003689852019306272
] |
[
0.9993804693222046,
0.00022753114171791822,
0.0003244923136662692,
0.00006745463906554505
] |
en
| 0.999998 |
The originally proposed function of countercurrent flow is the recycling of enzymes to increase digestion efficiency. The most solid evidence is that the enzyme concentration is higher within the ectoperitrophic space than in the endoperitrophic space . Our previous results suggested that this countercurrent flow could bring renal-derived Upd3 to regulate gut renewal upon oral infection . Here, we found that the retro-flow also participated in the immune response by promoting ROS accumulation and gut peristalsis. It is reasonable to expect that this mechanism could also promote the accumulation of other antimicrobial agents, such as AMPs, or regulate the immune-metabolism relationship. Our results suggest that this process may also play a role in regulating microbiota homeostasis. Prip RNAi flies exhibited a clear trend of microbiota dysplasia. However, no significant differences in countercurrent flow were observed between Prip RNAi flies and control flies without additional infection. This may be due to the need for more precise methods to monitor fluid flow within the ectoperitrophic space, rather than relying solely on dye as an indicator.
|
39530356_p31
|
39530356
|
Discussion
| 4.206168 |
biomedical
|
Study
|
[
0.9995235204696655,
0.0002500046684872359,
0.00022652416373603046
] |
[
0.9994027614593506,
0.0002091904025292024,
0.00031700398540124297,
0.00007104535325197503
] |
en
| 0.999997 |
The generation of ROS is a highly conserved physiological response to microbial presence across all organisms . It is well-established that Duox plays a key role in microbiota regulation. Evidence from mosquitoes, B. dorsalis , and other insects underscores the importance of Duox in maintaining proper gut microbial balance. This direct role of Duox in gut microbiota control has been demonstrated in studies involving mosquitoes and various other insects . More recently, research has shown that Duox also plays an indirect role in regulating gut symbionts in the bean bug, Riptortus pedestris . In this species, Duox expression is specific to the trachea and is essential for maintaining tracheal integrity, which is crucial for supporting mutualistic symbionts.
|
39530356_p32
|
39530356
|
Discussion
| 4.215062 |
biomedical
|
Study
|
[
0.9995149374008179,
0.00019834551494568586,
0.00028665253194049
] |
[
0.9804161190986633,
0.0006151847192086279,
0.018821869045495987,
0.00014686926442664117
] |
en
| 0.999998 |
Duox-derived ROS has been proposed to have a direct bacteria-killing effect in gut immunity and microbiota maintenance . In vitro biochemical evidence supports the role of Duox-derived HOCl but not H 2 O 2 as the major microbicidal molecule in insect gut immunity . However, Duox has also been suggested to be indirectly involved in gut immunity, possibly as a signaling molecule. For example, Duox-dependent ROS is involved in epithelial cell renewal during gut infection and indispensable for gut muscle contraction and food defecation in D. melanogaster during gut infection . These data together suggested a dedicated and controversial role of Duox in insect gut immunity.
|
39530356_p33
|
39530356
|
Discussion
| 4.319221 |
biomedical
|
Study
|
[
0.9995582699775696,
0.00019897041784133762,
0.00024267997650895268
] |
[
0.9742074608802795,
0.0008187734638340771,
0.024775154888629913,
0.00019868330855388194
] |
en
| 0.999997 |
The previous conclusion was drawn from a continuous bacterial oral infection, which might be a mixed outcome of both disease resistance and tolerance . Our experiments were done using a short-time oral infection and only focused on the bacteria elimination in the early stage of infection. We found that ROS depletion inhibits bacteria elimination may due to Duox’s role in regulating gut peristalsis, similar to previous findings . More importantly, we found that Duox RNAi only slowed down the clearance of bacteria but did not completely inhibit the process. Unlike our observation, it has been reported a prolonged Ecc15-GFP persistence in the Duox RNAi fly gut at 60 h post-infection, which could be explained by continuous bacteria feeding and long-lasting inhibition of gut peristalsis, as we discussed earlier. Other factors, such as differences in bacterial strains or host species, could also explain the discrepancy. Thus, we propose that early induction of ROS played a major role in supporting gut peristalsis to accelerate food-borne bacteria elimination. However, we cannot exclude the possibility that ROS accumulated in the gut plays a direct bactericidal function, especially under continuous infection. If this is the case, a key question arises: could symbionts, rather than pathobionts, be selectively protected from ROS molecules? Indeed, insect hosts have mechanisms to shield symbionts from damage caused by ROS and reactive nitrogen species. For example, a study in beewolves demonstrated that host-derived hydrocarbons could protect symbionts during transmission from a nitric oxide (NO) burst . Moreover, microorganisms themselves possess redox systems to counteract the effects of ROS . For instance, in bees, the intracellular parasite Nosema ceranae utilizes antioxidant systems to adapt to and reproduce within the midgut epithelium .
|
39530356_p34
|
39530356
|
Discussion
| 4.457266 |
biomedical
|
Study
|
[
0.9993506073951721,
0.0004411263216752559,
0.00020825827959924936
] |
[
0.9985257983207703,
0.0003338006208650768,
0.000990802189335227,
0.000149641782627441
] |
en
| 0.999997 |
In conclusion, our study highlighted the different roles of pathobionts and symbionts in gut microbiota homeostasis. Importantly, we have characterized Malpighian tubules as a key organ regulating gut immunity through recognizing bacteria-derived tyramine, providing an example of inter-organ communication in gut immunity. Recently, two papers have shown that gut tumors and Malpighian tubules have complex interactions promoting tumor-induced renal dysfunction . Because Malpighian tubules plays a key role in detoxification and excretion, we expect more of the role of the renal system in host physiology will be revealed in the future.
|
39530356_p35
|
39530356
|
Discussion
| 4.126793 |
biomedical
|
Study
|
[
0.999600350856781,
0.000231528450967744,
0.0001680999994277954
] |
[
0.9987180233001709,
0.0002705045626498759,
0.0009333454072475433,
0.00007814387936377898
] |
en
| 0.999997 |
Visual working memory (VWM) enables humans to temporarily store and process visual information, which requires accurate binding of items to their unique context. Accumulating studies posited that the posterior parietal cortex (PPC) is closely related to this binding process, the current study further examined their causal relationship. Through three strictly within-subject well–designed noninvasive neural stimulation experiments, we found that PPC stimulation selectively increased response time and binding error during VWM. Moreover, we found these changes were modulated by individual metacognition and only occurred during memory recall instead of recognition. Together, our results provided strong evidence that PPC is causally involved in the binding process during VWM retrieval.
|
39500573_p0
|
39500573
|
Significance Statement
| 4.16739 |
biomedical
|
Study
|
[
0.9987862706184387,
0.00036446659942157567,
0.0008493317873217165
] |
[
0.9995367527008057,
0.00016865821089595556,
0.0002377910859650001,
0.000056821729231160134
] |
en
| 0.999996 |
Visual working memory (VWM), a process of storing and processing visual information temporarily, is an essential basis of higher-level cognitive processes . Precise content–context binding is critical for multi-item VWM. An interference model indicates that VWM capacity is mainly limited by the binding interference between the content of multiple items and their context information . Moreover, impaired binding ability is a typical symptom in varying neurodegenerative disorders . Thus, understanding the mechanism underlying content–context binding in VWM is always an important theoretical question.
|
39500573_p1
|
39500573
|
Introduction
| 3.960011 |
biomedical
|
Study
|
[
0.9858977794647217,
0.0004887279937975109,
0.013613533228635788
] |
[
0.7987644076347351,
0.06037920340895653,
0.14040879905223846,
0.0004475837922655046
] |
en
| 0.999997 |
Increasing studies have demonstrated the relationship between posterior parietal cortex (PPC) activity and feature binding during VWM. In early studies, patients with right PPC lesions exhibited a decreased accuracy in tasks requiring multi-item bindings and reported illusory feature conjunctions during recall .Although earlier functional magnetic resonance imaging (fMRI) and electroencephalograph (EEG) studies have revealed that PPC activity was tightly correlated with the number of items kept during VWM , recent fMRI studies showed that holding the memorized items constant, PPC activity was higher when binding demands increased, suggesting that PPC played a closer role in the binding process .
|
39500573_p2
|
39500573
|
Introduction
| 4.141755 |
biomedical
|
Study
|
[
0.9989421963691711,
0.00027613414567895234,
0.0007816995494067669
] |
[
0.9844824075698853,
0.00041939070797525346,
0.01498388685286045,
0.00011441418610047549
] |
en
| 0.999998 |
Besides, modeling studies have advanced the relationship between PPC and feature binding to the individual and trial level. Bays et al. proposed a multiple-component mixture model to estimate individuals’ probability of nontarget responses, which reflected the failure of binding in a delayed estimation recall task. Accordingly, Cai et al. found that the neural decoding strength of the context information (i.e., location) in PPC predicted nontarget response rates. Moreover, Schneegans and Bays proposed a novel model to estimate the probability of nontarget recalls at the trial level. Combining this model and metacognitive reports, researchers further identified two types of nontarget responses that reflect different cognitive processes . In the misbinding condition, individuals are unconscious of recalling a nontarget item and report a high recall confidence (i.e., “remember trials”). In the informed guessing condition, in contrast, they know they may wrongly report a nontarget item and thus report low recall confidence (i.e., “forgotten trials”). Recently, Mallett et al. observed that participants responded with high confidence in about three-quarters of nontarget trials in a delayed estimation task. More importantly, they found that nontarget items could be decoded in PPC since early maintenance. Unfortunately, this study did not compare the differences between these two types of nontarget responses; thus the involvement of PPC in different nontarget responses was still unclear.
|
39500573_p3
|
39500573
|
Introduction
| 4.159763 |
biomedical
|
Study
|
[
0.9969465136528015,
0.00039998936699703336,
0.002653423696756363
] |
[
0.9839270710945129,
0.0003825121093541384,
0.015586317516863346,
0.00010412280971650034
] |
en
| 0.999997 |
Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique to explore the causal relationship between neural activities and cognitive processes. Typically, tDCS involves a two-electrode setup on the scalp to deliver weak direct current, with the anodal stimulation increasing cortical excitability while the cathodal stimulation inhibiting the excitability . Currently, tDCS research testing the relationship between PPC and VWM has focused on memory capacity, while the results were quite controversial . For these inconsistencies, researchers have proposed some important individual differences modulating tDCS effects, such as the VWM baseline , remember-subset strategy , and biorhythms . In sum, few tDCS studies have examined the causal relationship between PPC and feature binding, and to answer this question, it is critical to control irrelevant variables and consider potential individual differences that affected tDCS effects.
|
39500573_p4
|
39500573
|
Introduction
| 3.984428 |
biomedical
|
Study
|
[
0.9984992742538452,
0.00031536896131001413,
0.0011854751501232386
] |
[
0.840339720249176,
0.00150059605948627,
0.15794283151626587,
0.00021686835680156946
] |
en
| 0.999997 |
In this study, we systematically investigated the causal relationship between PPC and feature binding in VWM through three tDCS experiments. In Experiment 1, combined with the three-factor mixture model, we examined the effect of tDCS over PPC on binding process in a delayed estimation task and explored whether individual differences in capacity and recall strategies affected tDCS effect. In Experiment 2, we tried to replicate the results of Experiment 1 and further investigated the involvement of PPC in two types of nontarget responses (i.e., misbinding and informed guessing), by integrating remembered-forgotten self-reports. In Experiment 3, we examined whether the tDCS effects specifically during memory retrieval by using a change detection task (e.g., recognition) instead of a delayed estimation task (e.g., recall). If tDCS changed VSTM maintenance, similar effects should be observed in both tasks; otherwise, no such effect would be detected in the recognition task.
|
39500573_p5
|
39500573
|
Introduction
| 4.149482 |
biomedical
|
Study
|
[
0.9985027313232422,
0.00043161152279935777,
0.0010656495578587055
] |
[
0.9993307590484619,
0.00013466045493260026,
0.0004807001387234777,
0.00005396462438511662
] |
en
| 0.999999 |
Fifty-eight university students participated in Experiment 1 [34 females; mean (M), 20.10 years; SD, 1.40]. All participants were right-handed, had normal or corrected-to-normal vision, and reported no history of neurological or psychiatric disorders. Before the experiment, participants signed a written informed consent required by the institutional review board of the Department of Psychology and Behavioral Sciences, Zhejiang University. Participants received monetary compensation for participation (¥30 per hour).
|
39500573_p6
|
39500573
|
Participants
| 2.197295 |
biomedical
|
Study
|
[
0.967564046382904,
0.0017740712501108646,
0.0306619293987751
] |
[
0.9870516061782837,
0.012181557714939117,
0.00037386707845143974,
0.00039307281258516014
] |
en
| 0.999996 |
We modified a delayed estimation task for orientations from previous studies to estimate the tDCS effects on the feature binding process in VWM, and only high memory loads were included given researchers have reported higher chances of tDCS effects in the super-capacity condition . In each trial, after a 500 ms white central fixation (0.75 × 0.15°), an array of six or eight white, randomly oriented bars (2 × 0.3°) were presented for 200 ms. All bars were uniformly presented on an invisible circle (centered on the screen, radius of 6°), and orientations of these stimuli were randomly selected from 10 to 170° with at least 10° apart. After a 1 s delay, participants were instructed to recall the orientation of the bars at the probed position as precisely and fast as possible, by moving the mouse and clicking the left bottom on the white circular probe (radius of 2°). The maximum response time (RT) was 8 s. Participants completed the task before and after each tDCS session for ∼20 min. Each session consisted of 240 trials which were divided into four blocks, with two memory loads randomly mixed. Participants completed 24 practice trials in each memory load condition before the formal experiment to become familiar with the task.
|
39500573_p7
|
39500573
|
Experimental procedure
| 4.098701 |
biomedical
|
Study
|
[
0.9987982511520386,
0.0004184087738394737,
0.0007832784904167056
] |
[
0.9995679259300232,
0.00021183121134527028,
0.0001727902126731351,
0.000047468354750890285
] |
en
| 0.999996 |
Experimental stimuli were displayed on a 17 in color screen running MATLAB 2019a (MathWorks) and the Psychophysics Toolbox 3.0.12 . Participants were seated 60 cm away from the monitor (resolution, 1,920 × 1,080; refresh rate, 60 Hz) in a quiet room and were instructed to keep their eyes fixed on the center of the screen throughout the experiment. At the end of the experiment, participants completed a five-point scale to evaluate how often they use remember-all strategy or remember-subset strategy under different memory loads (1, always “remember-all”; 5, always “remember-subset”).
|
39500573_p8
|
39500573
|
Experimental procedure
| 3.4508 |
biomedical
|
Study
|
[
0.9705204367637634,
0.000826329633127898,
0.028653297573328018
] |
[
0.9969712495803833,
0.0027228202670812607,
0.00021241210924927145,
0.00009347705781692639
] |
en
| 0.999995 |
Participants underwent three tDCS sessions, including PPC stimulation, occipital cortex (OCC) stimulation, and sham stimulation. The order of stimulations was counterbalanced across participants, and three stimulations were performed separately with an exactly 48 h interval to minimize potential carryover effects and influences of circadian rhythms . tDCS was delivered by the DC-STIMULATOR MC device (neuroConn) using a pair of plastic electrodes (5 × 7 cm 2 ) in a saline-soaked synthetic sponge. In PPC stimulation, the anodal electrode was placed over P4 according to the international 10–20 EEG electrode system , the reference electrode was placed over the left cheek. Then a 20 min, 2 mA current was applied, with a linear fade in and fade out of 30 s which could minimize the uncomfortable feelings of sudden current changes. The choice of stimulation parameters referred to previous studies and guaranteed long-lasting stimulation effects during the poststimulation task . In OCC stimulation, the only difference is the anodal electrode was placed over Oz . For the sham condition, the anodal electrode was randomly placed over P4 or Oz, and the stimulation was only delivered within the first and last 30 s to simulate the itching feelings during active stimulation. During all stimulations, participants sat and took a rest. The current density distributions for tDCS settings were presented using COMETS, an open-source toolbox based on MATLAB .
|
39500573_p9
|
39500573
|
tDCS setup
| 4.133667 |
biomedical
|
Study
|
[
0.9991625547409058,
0.0005617569549940526,
0.00027576813590712845
] |
[
0.9993342757225037,
0.0003214803582523018,
0.0002678578603081405,
0.00007635440852027386
] |
en
| 0.999997 |
We calculated the RT and the recall error under different memory loads. RT was defined as the duration between the cue onset and response confirmation, and the recall error was obtained as the angular distance between the reported orientation and the targeted orientation. Then, we adopted the three-factor mixture model and fit the distribution of raw errors to obtain the precision of target responses (κ), the probability of target responses ( p T), the probability of nontarget responses ( p NT), and the probability of guess responses ( p U). Among these measures, a higher p NT indicated a higher probability of content–context binding errors. Memory capacity was calculated as p T × memory load according to previous research . One participant was excluded due to poor working memory performance (capacity <1). Then, 57 participants were included for further analysis.
|
39500573_p10
|
39500573
|
Estimations of behavioral performance
| 4.081314 |
biomedical
|
Study
|
[
0.9976921081542969,
0.000365199928637594,
0.0019427270162850618
] |
[
0.9996623992919922,
0.0001614551292732358,
0.0001395907165715471,
0.000036571967939380556
] |
en
| 0.999998 |
To examine tDCS effects, we first compared the behavioral parameters between active stimulation (PPC or OCC stimulation) and sham stimulation separately. For each behavioral parameter, we conducted a three-way repeated–measure analysis of variance (ANOVA) of stimulation condition (active vs sham), test time (pretest vs posttest), and memory load (Set Size 6 vs Set Size 8). If interaction effects were significant, we then performed two-way repeated–measure ANOVAs investigating the tDCS effects under each load. Furthermore, if any tDCS effect was significant in active stimulation, we tested whether this effect was region-specific by comparing tDCS effects over PPC and OCC with repeated–measure ANOVAs as well as calculating Pearson’s correlation between PPC and OCC tDCS effects (i.e., the behavioral changes before and after stimulation). We reported p values, effect size, and Bayesian factor (BF) for all statistical analyses.
|
39500573_p11
|
39500573
|
Estimations of tDCS effects
| 4.077276 |
biomedical
|
Study
|
[
0.9993728995323181,
0.0003484842018224299,
0.0002786281402222812
] |
[
0.9993962049484253,
0.00019641409744508564,
0.0003431406803429127,
0.00006423360900953412
] |
en
| 0.999997 |
For significant tDCS effects at the group level, we examined the potential influences of individual working memory capacity and recall strategy scores on tDCS effects via Pearson's correlation analyses. Because the capacity measures (i.e., p T × each memory load) were highly correlated in three prestimulation sessions and two memory loads ( r s > 0.379; p s < 0.01; BF 10s > 10.263), we averaged them as the individual capacity performance. The recall strategy scores were obtained in each memory load, and as expected, there was a higher chance of using the remember-subset strategy in higher memory load conditions [SS6, M (SD), 4.158 (0.841); SS8, M (SD), 3.368 (1.063); difference, t (56) = 6.926; p < 0.001; BF > 1,000]. Similarly, the recall strategy scores across set sizes were highly correlated ( r = 0.613; p < 0.001; BF 10 > 1,000), we then averaged them as the individual memory strategy if the tDCS effects were significant in both set sizes, while only using the recall strategy score in the specific memory load (i.e., Set Size 8) if the tDCS effect was load-specific.
|
39500573_p12
|
39500573
|
Examination of influence factors of tDCS effects
| 4.095545 |
biomedical
|
Study
|
[
0.9986068606376648,
0.00033521896693855524,
0.0010579410009086132
] |
[
0.9995711445808411,
0.00014739630569238216,
0.00024007909814827144,
0.0000412957051594276
] |
en
| 0.999997 |
The sample size was determined using G*Power 3.1 based on the effect size of increased p NT after PPC stimulation in Experiment 1 ( η p 2 = 0.119). A minimum sample of 28 participants was required to achieve a power of 90%, with a significance level of 0.05. We recruited 33 healthy university students (14 females; M, 23.10 years; SD, 2.70), and four participants were excluded due to poor task performance, resulting in a final sample of 29 in this experiment. Recruitment and payment criteria were consistent with Experiment 1.
|
39500573_p13
|
39500573
|
Participants
| 3.924531 |
biomedical
|
Study
|
[
0.9988258481025696,
0.0003449080395512283,
0.000829208642244339
] |
[
0.9994358420372009,
0.0004072752199135721,
0.00010907771502388641,
0.000047748508222866803
] |
en
| 0.999997 |
The task procedure was similar to Experiment 1, except that participants were required to make metacognitive evaluations of their recall during the task. This design could help us to distinguish misbinding errors and informed guessing . More specifically, in each trial, after 1 s delay, a white circle cueing the location of the probed orientation appeared for 200 ms, and participants were asked to report whether they remembered or forgot the probed orientation by pressing the left or right button of the mouse. The left–right buttons were counterbalanced across participants. Subsequently, participants were instructed to recall the targeted orientation at the probed position within 4 s by moving the mouse and making a confirming click. Finally, participants rated their confidence in a seven-point scale (1, “lowest confidence”; 7, “highest confidence”), which was introduced as a validation of the remember–forget binary forced choice .
|
39500573_p14
|
39500573
|
Experimental procedure and tDCS setup
| 4.042026 |
biomedical
|
Study
|
[
0.9933788776397705,
0.0004530930600594729,
0.006168011575937271
] |
[
0.9991881251335144,
0.0006007026531733572,
0.00016500097990501672,
0.00004617451850208454
] |
en
| 0.999999 |
Participants completed six blocks of the delay estimation task before and after stimulation, each block included 60 trials, and each task lasted for ∼20 min. In this experiment, we only focused on the high set size condition (i.e., Set Size 8) and included two tDCS sessions (i.e., PPC and sham). All stimulation setups were similar to Experiment 1 .
|
39500573_p15
|
39500573
|
Experimental procedure and tDCS setup
| 2.769225 |
biomedical
|
Study
|
[
0.9800916314125061,
0.0010567165445536375,
0.018851758912205696
] |
[
0.9973465204238892,
0.002289288677275181,
0.00023065572895575315,
0.0001335657580057159
] |
en
| 0.999997 |
Across all trials, we first examined tDCS effects over PPC on prolonged RT and increased p NT observed in Experiment 1 by conducting a two-way repeated–measure ANOVA for stimulation condition (PPC vs sham) and test time (pretest vs posttest). For significant two-way interaction effects, we further conducted simple effect tests. Similar to Experiment 1, for significant tDCS effects, we explored the potential influences of capacity and strategy through correlation analysis. Here, we used an advanced model fitting method to obtain all three parameters ( p NT, p T, p U) for each trial .
|
39500573_p16
|
39500573
|
Replicate the overall tDCS effects on RT and nontarget response
| 4.079338 |
biomedical
|
Study
|
[
0.9989857077598572,
0.00030446847085841,
0.0007097382913343608
] |
[
0.9995942711830139,
0.00014241403550840914,
0.00021699587523471564,
0.00004635095683624968
] |
en
| 0.999995 |
Trials were divided into remembered trials (trial number, M, 220.974; SD, 12.872) and forgotten trials (M, 131.371; SD, 10.570) based on the binary forced choice. Paired t tests revealed that errors for remembered trials were significantly lower than those for forgotten trials [M (SD), 16.280 (5.743) versus 29.208 (7.630); t (28) = −16.174; p < 0.001; Cohen's d = −3.003; BF 10 > 1,000], and confidence ratings were also significantly higher for remembered trials than for forgotten trials [M (SD), 4.922 (0.960) versus 2.302(0.629); t (28) = 15.638; p < 0.001; Cohen's d = 2.904; BF 10 > 1,000], suggesting that our metacognition categorization was validated, and forced choice self-reports reflected objective memory. Then, behavioral parameters for each trial type were averaged for follow-up tDCS effect comparisons.
|
39500573_p17
|
39500573
|
Compare tDCS effects between remembered and forgotten trials
| 4.126876 |
biomedical
|
Study
|
[
0.9989805817604065,
0.0003200785431545228,
0.0006993182469159365
] |
[
0.9995543360710144,
0.00014744893996976316,
0.00025355457910336554,
0.00004464382436708547
] |
en
| 0.999997 |
For the tDCS effects on RT and p NT, we examined whether these effects differed across trial types through a three-way repeated–measure ANOVA of trial type (remembered vs forgotten), stimulation condition (PPC vs sham), and test time (pretest vs posttest). We further conducted two-way repeated–measure ANOVAs and simple effect tests for stimulation condition and test time in each trial type if the three-way interaction effects were significant. Other parameters were also tested in a similar way.
|
39500573_p18
|
39500573
|
Compare tDCS effects between remembered and forgotten trials
| 4.049395 |
biomedical
|
Study
|
[
0.9991586208343506,
0.0002523471775930375,
0.0005889357416890562
] |
[
0.9994966983795166,
0.00020348741963971406,
0.0002583079331088811,
0.000041512754251016304
] |
en
| 0.999996 |
Thirty-four healthy university students (18 females; M, 22.00 years; SD, 2.06) were recruited. Six participants were excluded due to poor performance, leaving 28 participants for the following analysis. The sample size choice, participant recruitment, and payment criteria were consistent with Experiment 2.
|
39500573_p19
|
39500573
|
Participants
| 2.100754 |
biomedical
|
Study
|
[
0.9816785454750061,
0.0020669775549322367,
0.016254456713795662
] |
[
0.9923708438873291,
0.006876692175865173,
0.0003845463797915727,
0.00036788152647204697
] |
en
| 0.999998 |
The change detection task for orientations was adapted from a previous study . By including a lure-trial condition , we can examine the tDCS effects on the feature binding in VWM recognition. The encoding and maintenance periods were the same with the delayed estimation task, as well as the chosen orientation values. During the probe, a probed orientation appeared on the screen, and participants were required to make a judgment about whether the probed orientation changed compared with the orientation presented in the same location during the sample period, by pressing either the “F” or “J” key. The response keys were counterbalanced across participants, and the maximum response window was 2 s. The probabilities of orientation change and no change were equal. In the change trials, half of the probed orientation was different from all the orientations during the sample display, and it was 40° away from the target item (clockwise or anticlockwise) to make sure the change was detectable (i.e., “change trials”); the other half of the probed orientation was the same as the orientation located next to the probed location (i.e., “lure trials”). The change detection task consisted of 240 trials for each memory load (i.e., Set Size 6 and Set Size 8). Before and after stimulation, participants completed four blocks of the task, and each block consisted of 60 trials with two memory loads randomly mixed. The tDCS setup was consistent with Experiment 2 .
|
39500573_p20
|
39500573
|
Experimental procedure
| 4.094133 |
biomedical
|
Study
|
[
0.9979923963546753,
0.0003826052707154304,
0.0016250592889264226
] |
[
0.9995954632759094,
0.00020764961664099246,
0.00015397119568660855,
0.00004300444197724573
] |
en
| 0.999996 |
For all three of experiments, data and code that support the findings are available on the Open Science Framework at https://osf.io/q84a2/ . The code is available as Extended Data [noted that modeling was referred to previous work, please see Bays et al., and Schneegans and Bays ].
|
39500573_p21
|
39500573
|
Code accessibility
| 0.847779 |
biomedical
|
Other
|
[
0.624208390712738,
0.002764675533398986,
0.37302693724632263
] |
[
0.06303265690803528,
0.9340240359306335,
0.0018385018920525908,
0.001104770228266716
] |
en
| 0.999994 |
Estimation of behavioral performance and tDCS effects . First, we calculated overall RT and accuracy under each memory load based on all trials. RT was defined as the duration between the onset of the probe and button-press response, and accuracy referred to the proportion of correctly response trials out of all trials. Then, we also obtain RT and accuracy in no change trials, lure trials, and change trials, respectively. In lure trials, higher accuracy indicated better feature binding ability and lower nontarget responses (e.g., lower p NT in Experiments 1 and 2). To examine the tDCS effects on each behavioral parameter, we performed a series of 2 (stimulated region, P4 vs sham) × 2 (test time, pre vs post) × 2 (memory load, Set Size 6 vs Set Size 8) ANOVAs. If their interactions were significant, we further analyzed tDCS effects on each memory load. Besides, memory strategy scores were also collected in each set size. We replicated the results that the higher remember-subset strategy scores in Set Size 8 than that in Set Size 6 [SS6, M (SD), 3.250 (1.110); SS8, M (SD), 2.536 (1.071); difference, t (27) = 3.487; p = 0.0017; BF = 21.319], as well as the correlation between them . If significant tDCS effect was found, similar correlation analysis would be conducted. Based on the findings of Experiments 1 and 2, the effects of tDCS over PPC on overall RT and accuracy in lure trials were of most interest.
|
39500573_p22
|
39500573
|
Data analysis
| 4.088129 |
biomedical
|
Study
|
[
0.9988020658493042,
0.0003725161368492991,
0.0008253848645836115
] |
[
0.9996390342712402,
0.00012158280151197687,
0.0001928326819324866,
0.0000465159973828122
] |
en
| 0.999998 |
For tDCS effects over PPC in RT, the interaction effect of stimulation condition, test time, and memory load was not significant ( F (1,56) = 0.595; p = 0.444; η p 2 = 0.011; BF 10 = 0.205), whereas the interaction between stimulation condition and test time was significant ( F (1,56) = 6.228; p = 0.016; η p 2 = 0.100; BF 10 = 3.366). For both memory loads, we observed significant interactions between stimulation condition and test time ( F s > 5.179; p s < 0.027; η p 2 s > 0.085; BF 10 s > 2.309). Simple effect tests revealed that, although both PPC stimulation and sham stimulation lead to significantly reduced RT ( t s > 5.406; p s < 0.001; Cohen's d s > 0.716; BFs 10 > 1,000), the decrease was smaller in tDCS over PPC compared with that in sham . Meanwhile, at the individual level, the tDCS effects on prolonged RTs between two memory loads were highly correlated ( r (55) = 0.864; p < 0.001; BF 10 > 1,000; Fig. 2 B , top). Thus, we averaged RT changes in two memory loads to index the tDCS effects on RT in the following analysis. For tDCS effect over OCC in RT, on the contrary, our results revealed no three-way nor two-way interactions between test time and stimulation conditions ( F s < 2.622; p s > 0.111; η p 2 s < 0.045; BF 10 s < 0.458).
|
39500573_p23
|
39500573
|
PPC stimulation prolonged recall RT
| 4.18231 |
biomedical
|
Study
|
[
0.9987770915031433,
0.0004087599227204919,
0.0008141823927871883
] |
[
0.9995716214179993,
0.00015726021956652403,
0.00022319679555948824,
0.00004795058703166433
] |
en
| 0.999995 |
More importantly, we also found significant interactions between two stimulation conditions (i.e., PPC and OCC) and test time for both memory loads ( F s < 5.969; p s < 0.038; η p 2 s < 0.096; BF 10 s < 4.908). Similarly, further analyses found that the RT reduction was significantly smaller after PPC stimulation (Set Size 6, t (56) = 6.071; p < 0.001; Cohen's d = 0.804; BF 10 > 1,000; Set Size 8, t (56) = 5.406; p < 0.001; Cohen's d = 0.716; BF 10 > 1,000) than that after OCC stimulation (Set Size 6, t (56) = 8.179; p < 0.001; Cohen's d = 1.083; BF 10 > 1,000; Set Size 8, t (56) = 7.810; p < 0.001; Cohen's d = 1.034; BF 10 > 1,000). However, our results revealed that effect sizes of tDCS over PPC and OCC were not correlated across subjects ( r (55) = 0.098; p = 0.467; BF 10 = 0.214; Fig. 2 B , bottom). Together, these results indicated that PPC stimulation selectively prolonged RT.
|
39500573_p24
|
39500573
|
PPC stimulation prolonged recall RT
| 4.098322 |
biomedical
|
Study
|
[
0.9991551637649536,
0.00028083877987228334,
0.0005639251321554184
] |
[
0.9996019005775452,
0.00013920645869802684,
0.0002153162204194814,
0.00004360378079582006
] |
en
| 0.999996 |
Meanwhile, we did not find any significant interaction between test time and stimulation condition for tDCS effects on recall errors , suggesting no overall VWM performance changes after PPC or OCC stimulation.
|
39500573_p25
|
39500573
|
PPC stimulation prolonged recall RT
| 2.616347 |
biomedical
|
Study
|
[
0.9848582744598389,
0.000843744957819581,
0.01429791934788227
] |
[
0.996480405330658,
0.002869990421459079,
0.0004777279100380838,
0.0001718785788398236
] |
en
| 0.999996 |
For tDCS effects over PPC on p NT, we found significant interaction among stimulation condition, stimulation time, and memory load ( F (1,56) = 10.226; p = 0.002; η p 2 = 0.154; BF 10 = 4.925). Follow-up two–way ANOVA showed that the interaction between the stimulated region and test time was only significant in Set Size 8 condition ( F (1,56) = 7.593; p = 0.008; η p 2 = 0.119; BF 10 = 3.159; in Set Size 6, F (1,56) = 2.157; p = 0.147; η p 2 = 0.037; BF 10 = 0.473; Fig. 3 A ). For Set Size 8, nontarget responses were comparable before and after PPC stimulation ( t (56) = 0.254; p = 0.801; Cohen's d = 0.034; BF 10 = 0.149) but became significantly lower after sham stimulation ( t (56) = 3.426; p = 0.001; Cohen's d = 0.454; BF 10 = 24.009). Unlike the tDCS effects on RTs, the effect sizes of tDCS over PPC across memory loads were not correlated ( r (55) = 0.062; p = 0.646; BF 10 = 0.183; Fig. 3 B , top).
|
39500573_p26
|
39500573
|
PPC stimulation increased nontarget responses
| 4.144592 |
biomedical
|
Study
|
[
0.9991530179977417,
0.0003418206179048866,
0.0005051077459938824
] |
[
0.999562680721283,
0.00015517832071054727,
0.00022820287267677486,
0.00005398641951614991
] |
en
| 0.999995 |
To further examine the specificity of the tDCS effects of PPC on p NT, we compared p NT changes before and after stimulation over PPC and OCC in Set Size 8. The interaction between the stimulated region and test time was significant ( F (1,56) = 4.455; p = 0.039; BF 10 = 2.319). Specifically, comparable p NTs were observed after PPC stimulation ( t (56) = 0.254; p = 0.801; Cohen's d = 0.034; BF 10 = 0.149), whereas decreased p NTs were found after OCC stimulation ( t (56) = 2.944; p = 0.005; Cohen's d = 0.390; BF 10 = 6.563). Similarly, there was no correlation between the tDCS effects over PPC and OCC on p NT ( r (55) = −0.037; p = 0.783; BF 10 = 0.172; Fig. 3 B , bottom). Besides, additional correlation analysis revealed that tDCS effects on RT and p NT were also independent ( r (55) = 0.073; p = 0.589; BF 10 = 0.191). Together, these results suggested that, compared with sham stimulation, PPC stimulation specifically increased nontarget responses in the high memory load.
|
39500573_p27
|
39500573
|
PPC stimulation increased nontarget responses
| 4.137014 |
biomedical
|
Study
|
[
0.9990350008010864,
0.0003384313313290477,
0.0006265095435082912
] |
[
0.999591052532196,
0.00013287032197695225,
0.00022467815142590553,
0.000051343507948331535
] |
en
| 0.999997 |
Besides, for tDCS effects over PPC on precisions, target probability, and guessing probability, we only found a marginal three-way interaction effect among the stimulated region, test time, and memory load in p U ( F (1,56) = 3.244; p = 0.077; η p 2 = 0.055; BF 10 = 1.542; others, F s < 2.732; p s > 0.104; η p 2 s < 0.047; BF 10 s < 0.159). Further analysis indicated that, in Set Size 8, PPC stimulation decreased the random guesses ( t (56) = 2.535; p = 0.014; Cohen's d = 0.336; BF 10 = 2.670) while no such difference in sham stimulation ( t (56) = 3.426; p = 0.001; Cohen's d = 0.454; BF 10 = 24.009). In contrast, neither three-way interactions nor two-way interactions were observed for OCC stimulation ( F s < 2.862; p s > 0.434; BF 10 s < 0.504), showing no tDCS effect over OCC on all fitting parameters. Together, our results suggested that tDCS over PPC specifically increased the nontarget response while decreasing the random guessing, without changing general VWM performance.
|
39500573_p28
|
39500573
|
PPC stimulation increased nontarget responses
| 4.16148 |
biomedical
|
Study
|
[
0.9991135001182556,
0.00031356021645478904,
0.000572898075915873
] |
[
0.9995108842849731,
0.00015874645032454282,
0.00027492010849528015,
0.00005553043956751935
] |
en
| 0.999998 |
Correlation results showed that individual capacity or the recall strategy index were not correlated with the PPC tDCS effects of prolonged RT or increased p NT .
|
39500573_p29
|
39500573
|
tDCS effects over PPC were not modulated by capacity or strategy
| 2.771767 |
biomedical
|
Study
|
[
0.9933411478996277,
0.0007282031583599746,
0.005930591374635696
] |
[
0.9978285431861877,
0.0016813981346786022,
0.00035179342376068234,
0.00013836388825438917
] |
en
| 0.999996 |
Experiment 1 revealed that PPC stimulation specifically prolonged RT and increased p NT in the delayed estimation task, supporting the view that the parietal lobe played a critical role in content–context binding during VWM . In contrast, although studies reported OCC played an important role in information representation during VWM , stimulation over the occipital lobe did not change VWM performance. The results suggested the higher brain areas may play a more causal role in VWM.
|
39500573_p30
|
39500573
|
Summary of Experiment 1
| 4.083967 |
biomedical
|
Study
|
[
0.9977570176124573,
0.00034534817677922547,
0.0018975938437506557
] |
[
0.9995054006576538,
0.0002639576268848032,
0.0001843874342739582,
0.000046138022298691794
] |
en
| 0.999995 |
By introducing additional metacognition estimates, Pratte has proposed two types of nontarget responses: the misbinding trials where individuals reported high recall confidence (i.e., “remember trials”), and the informed guessing trials where individuals reported low confidence (i.e., “forgotten trials”). Researchers claimed that these two types of nontarget responses reflected different cognitive and metacognitive processes . Thus, in Experiment 2, we further examined whether PPC stimulation equally affected these two types of nontarget responses.
|
39500573_p31
|
39500573
|
Summary of Experiment 1
| 3.21072 |
biomedical
|
Study
|
[
0.8416260480880737,
0.0007953469757921994,
0.15757863223552704
] |
[
0.9967215657234192,
0.0027170260436832905,
0.00046354217920452356,
0.00009794455399969593
] |
en
| 0.999998 |
Consistent with Experiment 1, we observed a significant interaction between stimulation condition and test time on RT ( F (1,28) = 5.894; p = 0.028; η p 2 = 0.174; BF 10 = 5.178). Post hoc tests revealed that the RT decrease after PPC stimulation ( t (28) = 4.563; p s < 0.001; Cohen's d = 0.847; BF 10 = 282.944) was significantly smaller than that after sham stimulation ( t (28) = 7.356; Cohen's d = 1.366; p s < 0.001; BF 10 > 1,000). For p NT, the interaction between stimulation condition and test time was also significant ( F (1,28) = 4.498; p = 0.045, η p 2 = 0.138; BF 10 = 2.691). Post hoc analyses revealed that there was no difference after PPC stimulation ( t (28) = 0.836; p = 0.410; Cohen's d = 0.155; BF 10 = 0.272) but a significant decrease in p NT after sham stimulation ( t (28) = 3.816; p < 0.001; Cohen's d = 0.709; BF 10 = 46.613). Meanwhile, tDCS effects over PPC on RT and p NT were independent across participants ( r (27) = −0.256; p = 0.180; BF 10 = 0.544), and neither tDCS effect was correlated with individual differences in capacity or strategy [ r s < −0.297; p s > 0.118; BF 10 s < 0.739; capacity, M (SD), 5.497 (1.477); strategy score, M (SD), 3.455 (1.121)]. Besides, similar with the findings in Experiment 1, we observed a similar numerical trend of two-way interaction between stimulated region and test time for p U ( F (1,28) = 2.780; p = 0.107; η p 2 = 0.090; BF 10 = 1.497), while there was no significant effects on recall error, confidence ratings, and other parameters ( F s < 0.978; p s > 0.331; η p 2 s < 0.034; BF 10 s < 0.403).
|
39500573_p32
|
39500573
|
PPC stimulation prolonged recall RT and increased nontarget responses
| 4.19156 |
biomedical
|
Study
|
[
0.998670220375061,
0.0004630309995263815,
0.0008667735382914543
] |
[
0.9994968175888062,
0.0001743650354910642,
0.000267229595920071,
0.00006160710472613573
] |
en
| 0.999998 |
We further examined the tDCS effects over PPC between forgotten and remembered trials. For RT, the interaction among trial type, stimulation condition, and test time were significant ( F (1,28) = 6.385; p = 0.017; η p 2 = 0.186; BF 10 = 2.372; Fig. 5 D , top). Further two-way repeated–measure ANOVAs for each trial type indicated that the effect size in forgotten trials ( F (1,28) = 11.506; p = 0.002; η p 2 = 0.291; BF 10 = 65.871) was larger than in remembered trials ( F (1,28) = 4.293; p = 0.048; η p 2 = 0.133; BF 10 = 2.244). For p NT, however, no significant interaction effect among trial type, stimulation condition, and test time were observed , indicating comparable tDCS effects in two types of nontarget trials.
|
39500573_p33
|
39500573
|
tDCS effects over PPC on RT were greater in forgotten trials than in remembered trials
| 4.125765 |
biomedical
|
Study
|
[
0.9991996884346008,
0.0003304512647446245,
0.0004698971170000732
] |
[
0.9995612502098083,
0.00015655558672733605,
0.00022852573601994663,
0.000053672523790737614
] |
en
| 0.999995 |
In Experiment 2, we replicated the main findings of Experiment 1 that PPC stimulation increased RT and p NT during VWM. More importantly, compared with remembered trials, tDCS effects on RT were greater in forgotten trials while were comparable on p NT. In sum, these results suggested that PPC was causally involved in two types of nontarget responses, while it may be through different mechanisms.
|
39500573_p34
|
39500573
|
Summary of Experiment 2
| 4.037834 |
biomedical
|
Study
|
[
0.9975634813308716,
0.0003460116859059781,
0.002090526046231389
] |
[
0.9995558857917786,
0.00020645470067393035,
0.00019187838188372552,
0.000045774086174787953
] |
en
| 0.999998 |
A recent computational modeling study indicated that VWM recall and recognition involved different cognitive processes . Since delayed estimation and change detection are two typical VWM tasks to estimate memory recall and recognition respectively, we further examined whether the tDCS over PPC mainly affected VWM retrieval processes and caused behavioral changes, by using a change detection task in Experiment 3.
|
39500573_p35
|
39500573
|
Summary of Experiment 2
| 3.709858 |
biomedical
|
Study
|
[
0.979099690914154,
0.0004540203954093158,
0.020446302369236946
] |
[
0.9989995360374451,
0.0007256956887431443,
0.00021444936282932758,
0.00006024194590281695
] |
en
| 0.999995 |
No interaction effect between stimulation and test time was significant for RT ( F s < 1.251; p s > 0.273; η p s 2 < 0.044; BF 10 s < 0.390) or for accuracy in lure trials ( F s < 0.832; p s > 0.370; BF 10 s < 0.391), indicating that PPC stimulation did not affect RT or binding processes in VWM recognition . Similarly, there was no significant interaction effect on other behavioral parameters ( F s < 1.235; p s > 0.246; η p s 2 < 0.042; BF 10 s < 0.586; except for a trend effect on accuracy in high memory load in no change trials, F (1,27) = 3.441; p = 0.075; BF 10 = 0.945).
|
39500573_p36
|
39500573
|
No tDCS effect over PPC on RT or misbinding processes in recognition
| 4.098325 |
biomedical
|
Study
|
[
0.9983841180801392,
0.0003344398573972285,
0.0012814677320420742
] |
[
0.9996230602264404,
0.00014973810175433755,
0.00018980079039465636,
0.00003736311919055879
] |
en
| 0.999997 |
The current study established the causal relationship between posterior parietal activity and feature binding during VWM retrieval through three tDCS experiments. First, we found that anodal tDCS over PPC selectively increased recall RT as well as nontarget responses in the delayed estimation task. Meanwhile, combined with metacognitive evaluations, we clarified these tDCS effects could be observed in both types of nontarget responses (i.e., misbinding and informed guessing). Besides, we further identified that the effects of tDCS over PPC were specific during memory retrieval by demonstrating that such effects were not observed during memory recognition. Together, our findings deepen our understanding of the involvement of PPC in the feature binding during VWM retrieval.
|
39500573_p37
|
39500573
|
Discussion
| 4.152861 |
biomedical
|
Study
|
[
0.9987050294876099,
0.0003757950325962156,
0.0009192620636895299
] |
[
0.999462902545929,
0.00014880680828355253,
0.0003334161883685738,
0.00005494495417224243
] |
en
| 0.999996 |
First of all, in two independent samples, we replicated that anodal tDCS over PPC increased nontarget responses in the delayed estimation task. These results supported recent fMRI studies that emphasized the close relationship between posterior parietal activity and the feature binding processes during VWM . Meanwhile, we noticed the increased nontarget responses along with a trend of decreased random guesses. That is, tDCS over PPC biased the recall process. Two possibilities could explain these findings. One possibility is that enhanced posterior parietal activity may facilitate the reinstatement of content information from multiple items during retrieval, leading to an increased probability of nontarget responses. Supporting this view, Baddeley proposed the posterior parietal lobe as a core area for the episodic buffer during WM, and Xie et al. further interpreted PPC as a hub of multisensory information integration, which claimed PPC's critical role in representing and combining different features. Moreover, our results emphasized that PPC was causally involved during memory retrieval instead of recognition. Comparing the delayed estimation and change detection tasks, previous studies have shown similar neural activity during WM maintenance. For instance, EEG studies have found similar contralateral delay activity , and fMRI studies showed similar frontoparietal activity during these two tasks . In contrast, during the response, a recent study suggested that the delayed estimation task is mainly based on detailed retrieval while the change detection task is based on familiarity judgment . Although few studies directly compared the PPC activity between recall and recognition during WM, considerable evidence has supported the critical role of PPC in episodic memory retrieval but not in recognition. For example, studies have revealed that both activation strength and the neural representations in PPC increased during memory retrieval but not during recognition . Currently, our findings confirmed the causal relationship between the PPC and retrieval during VWM, which was similar to those in episodic memory.
|
39500573_p38
|
39500573
|
Discussion
| 4.375066 |
biomedical
|
Study
|
[
0.9990596175193787,
0.0005343213560990989,
0.00040614791214466095
] |
[
0.9989804625511169,
0.00031971975113265216,
0.000575947982724756,
0.00012388566392473876
] |
en
| 0.999998 |
Another possibility proposed that enhanced posterior parietal activity may increase cognitive resources and lead to the adoption of a more proactive retrieval strategy, increasing nontarget responses. Our results revealed that tDCS over PPC comparably increased both types of nontarget responses (i.e., misbinding and informed guessing). Researchers have proposed that misbinding responses were generated when participants misorganized information across different items, while informed guessing reflected participants actively making choices from all the memorized information . Consistently, recent studies revealed that misbinding mainly resulted from less efficient information processing during early encoding or storage whereas informed guessing more likely reflected the different neural activity during late storage or memory retrieval . Consequently, both nontarget responses required more cognitive effort compared with random guesses. From the source-consumption perspective, the latest study revealed that parietal tDCS could reduce the cumulative fatigue effect during tasks . Therefore, we could not exclude the possibility that anodal PPC stimulation enabled individuals to generate both more proactive nontarget responses during VWM retrieval.
|
39500573_p39
|
39500573
|
Discussion
| 4.166958 |
biomedical
|
Study
|
[
0.9989602565765381,
0.00031032890547066927,
0.000729359220713377
] |
[
0.9994922876358032,
0.00016653032798785716,
0.0002872223558370024,
0.00005390766091295518
] |
en
| 0.999998 |
Besides, we also found that PPC stimulation prolonged recall RT, which was in line with both explanations about increased nontarget responses above. However, some evidence in the current study suggested that the tDCS over PPC affected recall RT and feature binding through different pathways. For example, we found that tDCS over PPC only increased nontarget responses under high memory load, whereas it changed RTs across memory loads, and the effects were highly correlated across loads at the individual level. Meanwhile, we observed greater tDCS effects on RTs in informed guessing trials than in misbinding trials, while comparable effects on nontarget responses between these two types of trials. Furthermore, tDCS effects on RTs and nontarget responses were always independent at the individual level. Supporting these findings, the latest meta-analysis demonstrated that different PPC stimulation patterns enhanced WM accuracy and RT separately . However, future studies are needed to further clarify how PPC is differently involved in the recall speed and accuracy of memory retrieval.
|
39500573_p40
|
39500573
|
Discussion
| 4.096521 |
biomedical
|
Study
|
[
0.9987560510635376,
0.0002851427416317165,
0.0009587617823854089
] |
[
0.9993906021118164,
0.00013655931979883462,
0.00042562634916976094,
0.00004718108175438829
] |
en
| 0.999996 |
To be noted, our findings were not consistent with some previous relevant studies. Regarding the tDCS effects on increasing the nontarget response during the delayed estimation task, for example, using a similar paradigm, another study found anodal PPC stimulation did not change the nontarget response rate but increased the recall precision. On the opposite, the PPC cathodal stimulation decreased the nontarget response rate and increased the target response rate and recall precision . In this study, the reversed tDCS effect of cathodal stimulation on the nontarget response rate could be well explained by the polarity effects of tDCS reported in accumulating studies and supported the causality between PPC activities and feature bindings observed in the current study. Meanwhile, we would attribute the inconsistent anodal stimulation effects across studies to differences in timings of stimulations as well as task difficulty. The tDCS in our study was conducted when participants took a rest between tasks while the stimulation in Heinen's study was conducted exactly during the tasks. According to the recent state-dependent theory, the neural modulation effects were largely dependent on the ongoing neural states . Besides, the tDCS effects in our study were observed in a supra-capacity condition (Set Size 8), while tDCS effects in Heinen's study were in a much lower, around-capacity condition (Set Size 4). According to previous studies, task difficulty could be a critical modulation factor influencing the tDCS effects . Given that participants were more likely to employ the remember-subset strategy in the high-load condition, it is plausible that tDCS may have specifically impacted cognitive processes underlying this memory strategy (e.g. suppression “distractors” beyond memory capacity). In addition, we did not find that tDCS over PPC improved the general VWM performance in either delayed estimation or change detection tasks, which was consistent with some recent studies but challenged some other earlier studies . Besides, we did not replicate the correlation between tDCS effects and individual capacity or the adoption of remember-subset strategy . Usually, as we mentioned above, researchers suggested that these differences could be generally explained by a series of detailed methodological settings. However, regarding our null tDCS effects in the change detection task, in particular, we also suggested to understand these differences from the different probed displays and stimulus type. For example, Tseng et al. used a change detection task with the whole-item comparison design while we used the single-item comparison. Previous studies have revealed that the change detection judgments on the whole-item display can depend on additional integrated information while single-item judgment cannot . Thus, the tDCS over PPC may only facilitate processes for more integrated information instead of single-item retrieval. Meanwhile, we cannot exclude the differences was caused by varying stimuli across studies given there are not a few studies have revealed dissociated cognitive and neural basis underlying VWMs for different stimulus types .
|
39500573_p41
|
39500573
|
Discussion
| 4.22949 |
biomedical
|
Study
|
[
0.9985516667366028,
0.0004110629379283637,
0.0010373129043728113
] |
[
0.9993558526039124,
0.00014284998178482056,
0.0004445125814527273,
0.000056812095863278955
] |
en
| 0.999998 |
Different from the PPC stimulation effects, it is noteworthy that we did not observe any tDCS effects over the occipital cortex on VWM. A set of recent studies found there was a location-specific neural representation in the occipital cortex which requires accurate item–context binding , and some other studies also reported these neural representations predicted nontarget responses at the individual level . We suggested two possible explanations for this inconsistency. First, unlike the sustained activation of PPC during maintenance, the neural representations of the item or its context information did not depend on sustained activation in the occipital cortex . Since tDCS is expected to increase the neural activity of specific areas instead of promoting the neural representation directly, tDCS over the occipital cortex could not significantly affect behavior. Second, previous studies have suggested that occipital neural activity is regulated by feedback signals from the frontal and posterior parietal regions . Therefore, even if the occipital neural representation is affected by tDCS, the occipital cortex could maintain the memory information efficiently by receiving feedback signals from other brain areas. Together, these results indicated that the occipital activity has no causal effect on VWM performance or feature binding process.
|
39500573_p42
|
39500573
|
Discussion
| 4.188265 |
biomedical
|
Study
|
[
0.9991902709007263,
0.00031731915078125894,
0.0004923611413687468
] |
[
0.9995293617248535,
0.0001636924280319363,
0.000253467500442639,
0.00005349130151444115
] |
en
| 0.999997 |
Finally, some limitations need to be paid attention in the current study. First, our results were not consistent with some relevant studies mentioned above, and we cannot identify whether these differences are attributed to some specific factors (i.e., task paradigm, difficulty, stimulus type, individual differences, timing of stimulation, etc.) or a more complex interaction effect between them. Although our findings may not end the existing controversies, our study strongly reminded that future studies should systematically explore the potential factors influencing tDCS effects, and combining the high-definition stimulations and neuroimaging methods could provide insightful views. Second, we found that single-session tDCS only changed the response bias for nontargets but failed to change overall working memory performance, which should be further explored in future studies. For example, recent studies have demonstrated that local brain oscillations and interarea synchronizations contributed to feature binding during VWM ; thus future studies using transcranial alternative current stimulation (tACS) to change these band-specific neural activities may better improve the binding efficiency and VWM performance. Meanwhile, recent studies have also demonstrated that high-frequency randomized noise stimulation reveals a stronger effect on changing the cortical activities, which could also be a potential way to improve the general VWM performance .
|
39500573_p43
|
39500573
|
Discussion
| 4.12113 |
biomedical
|
Study
|
[
0.9982746839523315,
0.00040816643740981817,
0.0013171150349080563
] |
[
0.9991888403892517,
0.00012709446309600025,
0.0006343270069919527,
0.00004973436807631515
] |
en
| 0.999996 |
In conclusion, the present study demonstrates that enhanced posterior parietal activity prolongs RT in VWM retrieval and increases the probability of binding errors, and these effects are observed in two types of binding errors (i.e., misbinding and informed guessing). Our findings provide direct evidence of the causal relationship between the PPC and feature binding, deepening our understanding of the neural basis of feature binding in VWM.
|
39500573_p44
|
39500573
|
Discussion
| 4.147113 |
biomedical
|
Study
|
[
0.9990757703781128,
0.0003131461562588811,
0.0006111488910391927
] |
[
0.9994279742240906,
0.000215811567613855,
0.00028972685686312616,
0.00006647017289651558
] |
en
| 0.999995 |
Data and code that support the findings of this study are available on the Open Science Framework at https://osf.io/q84a2/ .
|
39500573_p45
|
39500573
|
Data and code availability statement
| 0.984521 |
other
|
Other
|
[
0.31205564737319946,
0.002745814621448517,
0.6851986050605774
] |
[
0.020785383880138397,
0.9779098033905029,
0.0006539189489558339,
0.0006509966333396733
] |
en
| 0.999997 |
Suicide is a global health issue, with over 700,000 people dying by suicide each year ( 1 ). In Australia, approximately nine people are lost to suicide each day ( 2 ). Recent estimates suggest that for each death by suicide 135 people are exposed ( 3 ), indicating the wide-reaching impact of suicide and the potential for further distress for individuals, families and communities. In addition to suicide deaths, one in six Australians aged 16-85 years have experienced suicidal thoughts or behaviours in their lifetime ( 4 ).
|
PMC11697290_p0
|
PMC11697290
|
Introduction
| 1.900408 |
biomedical
|
Other
|
[
0.8666761517524719,
0.004310831893235445,
0.1290130317211151
] |
[
0.018077190965414047,
0.9716941118240356,
0.00955536961555481,
0.0006733148475177586
] |
en
| 0.999997 |
Suicide prevention interventions can reduce suicide deaths and behaviors ( 5 ), and numerous brief interventions exist to support people experiencing suicide-related distress ( 6 ). One intervention that has been gaining popularity in both clinical and community settings is the Safety Planning Intervention (SPI; 7). The SPI involves developing a personalised list of coping and personal support strategies for use during the onset or worsening of suicide-related distress, typically through six components: a) recognising individual warning signs for an impending suicidal crisis; b) identifying and employing internal coping strategies; c) using social supports to distract from suicidal thoughts; d) contacting trusted family or friends to help address the crisis; e) contacting specific mental health services; f) eliminating or mitigating use of lethal means ( 7 ). Although widely used with US military veterans, the flexibility of the SPI has been demonstrated through its application across diverse age groups ( 8 , 9 ), settings ( 10 ), and with varied populations including refugees ( 11 ), autistic people ( 12 ) and individuals recently incarcerated ( 13 ). The SPI has also been incorporated within or alongside wider therapeutic approaches, such as motivational interviewing ( 14 ). Traditionally completed in hard-copy format, the SPI has more recently been adapted to various digital versions (e.g., 15,16) which can be used in clinical settings or accessed by the public without clinical support.
|
PMC11697290_p1
|
PMC11697290
|
Introduction
| 4.045979 |
biomedical
|
Review
|
[
0.9667511582374573,
0.0034335856325924397,
0.029815269634127617
] |
[
0.038547582924366,
0.009067559614777565,
0.9520750045776367,
0.0003098172601312399
] |
en
| 0.999998 |
Two recent systematic reviews ( 17 , 18 ) and one meta-analysis ( 19 ) have explored the effectiveness of the SPI and safety planning type interventions. Through narrative synthesis of results, two of the reviews (n = 20 studies, 17; n = 22 studies, 18) concluded that this intervention contributes to reductions in suicidal ideation and behaviour, as well as suicide-related outcomes, such as depression and hopelessness, and improvements in service use and treatment outcomes. While the meta-analysis of six safety planning type studies ( 19 ) also found reduced suicidal behaviour among intervention participants compared to treatment as usual, this study found no evidence for effectiveness on suicidal ideation. Thus, despite the difference in findings related to ideation, current evidence generally supports the efficacy of the SPI in improving people’s coping capacities and safety, with benefits particularly pronounced for reductions in suicidal behavior. However, less emphasis has been dedicated to understanding the underlying processes by which people using the SPI derive benefits ( 20 ). While there is emerging evidence linking the quality and personalisation of safety plans to reduced suicidal behaviour and hospitalisations ( 16 , 21 ), these mechanisms have been quantitatively assessed, rather than qualitatively described from the perspective of those who have used a safety plan. Contemporary thinking recognizes the critical role that lived and living experience plays in suicide prevention research yet there has been limited integration of lived experience in the development of existing suicide prevention interventions ( 22 ). Incorporating lived and living experience understandings into all stages of suicide prevention research is essential for ensuring that suicide prevention strategies meet the needs of those they have been designed for. Moreover, a personalized understanding of peoples’ experiences of using the SPI is needed to inform clinical practice, policy, and future research to enhance the effectiveness of the SPI and ultimately reduce the incidence of suicide and suicide-related distress.
|
PMC11697290_p2
|
PMC11697290
|
Introduction
| 4.200828 |
biomedical
|
Review
|
[
0.9866499304771423,
0.004484384786337614,
0.008865713141858578
] |
[
0.02736019343137741,
0.0008299200562760234,
0.9714836478233337,
0.00032625935273244977
] |
en
| 0.999995 |
This review aims to complement quantitative reviews and meta-analysis ( 17 – 19 ) by synthesizing the existing qualitative, peer-reviewed evidence regarding the experiences of diverse stakeholders (consumers, support persons, and clinicians) involved in the SPI. These stakeholder experiences include but are not limited to: what is perceived as helpful and unhelpful about safety planning; what processes facilitate positive effects; the collaborative process regarding how the safety plan is developed, used, accessed, and revised; as well as the perceived impact of the safety plan on suicide-related outcomes and other well-being indicators.
|
PMC11697290_p3
|
PMC11697290
|
Aims
| 3.989952 |
biomedical
|
Review
|
[
0.9594589471817017,
0.010356016457080841,
0.030185088515281677
] |
[
0.006039803382009268,
0.0013160633388906717,
0.9923294186592102,
0.0003147798706777394
] |
en
| 0.999997 |
This systematic review followed the PRISMA 2020 guidelines ( 23 ) and was conducted according to the Joanna Briggs Institute (JBI) methodology for systematic reviews of qualitative evidence ( 24 ). The review protocol was pre-registered with PROSPERO .
|
PMC11697290_p4
|
PMC11697290
|
Method
| 3.721421 |
biomedical
|
Review
|
[
0.9842221140861511,
0.004248001147061586,
0.011529888957738876
] |
[
0.014915505424141884,
0.004523308016359806,
0.980144739151001,
0.00041642700671218336
] |
en
| 0.999998 |
The search strategy was developed by MF, based on a previous safety planning systematic review ( 17 ), and refined in consultation with an academic librarian. We conducted searches on 28 November 2023 in seven databases: Embase, Emcare, MEDLINE and PsycInfo, in the Ovid platform; as well as CINAHL, Scopus and Web of Science. The final search strategy was broad, including terms for safety planning and suicide. Additional terms were trialed (e.g., for participant groups and study designs), however these restricted results and were excluded from the final strategy. We limited results to English language and a publication date range of 2000 to present. See Supplementary Data Sheet 1 for the search strategies used in each database. Reference lists of included articles were pearled in duplicate (MF, EO, KR) for potentially relevant studies.
|
PMC11697290_p5
|
PMC11697290
|
Search strategy and information sources
| 3.660732 |
biomedical
|
Study
|
[
0.995788037776947,
0.00044958436046727,
0.0037624414544552565
] |
[
0.9979948997497559,
0.0012453189119696617,
0.0006968757952563465,
0.00006292761099757627
] |
en
| 0.999997 |
Search results were imported to EndNote 21 (Clarivate, Philadelphia, USA) to manually identify and remove duplicates (MF). We screened the remaining results using Covidence (Veritas Health Innovation, Melbourne, Australia) in two stages, in duplicate: 1) title and abstract screening (MF, KR); 2) full-text screening (MF, EO, KR). Reviewers discussed any disagreements until 100% consensus was reached.
|
PMC11697290_p6
|
PMC11697290
|
Study selection
| 2.695202 |
biomedical
|
Study
|
[
0.9937625527381897,
0.0012728804722428322,
0.004964594729244709
] |
[
0.9685869216918945,
0.02977842092514038,
0.0012767119333148003,
0.00035789780667982996
] |
en
| 0.999996 |
Eligibility criteria included: published in English language; qualitative in design (or mixed-methods, but where qualitative data were able to be extracted); participants of any age who had direct involvement in safety planning (including consumers, support persons, service providers, clinicians, etc.) in any setting (e.g. emergency department, inpatient, outpatient, community, online, school, etc.); and where it was clear that safety planning was based on the Stanley and Brown ( 7 ) version. Studies could include the SPI as a standalone intervention, or as part of a wider intervention approach. Studies were excluded if they: were not published in English; were not primary research; were not qualitative in design (either purely quantitative or where qualitative method and data could not be extracted); participants had no direct involvement in safety planning; or where the type of safety planning intervention was irrelevant or unclear (i.e., no reference to Stanley and Brown, and/or no definition or description of safety planning procedures).
|
PMC11697290_p7
|
PMC11697290
|
Eligibility criteria
| 3.823043 |
biomedical
|
Study
|
[
0.962074339389801,
0.0025440019089728594,
0.03538169339299202
] |
[
0.9956483244895935,
0.0021502517629414797,
0.002100574318319559,
0.00010085506073664874
] |
en
| 0.999996 |
We custom-built an electronic survey (LimeSurvey, Hamburg, Germany) to extract key information from the included studies, including: aim; study location and setting; study design; participant characteristics (sample size, population description, age, sex); SPI details (delivery modality, format, other intervention components if relevant); methods of data collection and analysis. Reviewers (MF, EO, KR) extracted data independently, in duplicate. Where necessary, we discussed and consulted the original papers until consensus was reached.
|
PMC11697290_p8
|
PMC11697290
|
Data extraction
| 3.701269 |
biomedical
|
Study
|
[
0.99812251329422,
0.00040441271266900003,
0.001473023439757526
] |
[
0.9979878664016724,
0.0007160755340009928,
0.0012330440804362297,
0.00006304647104116157
] |
en
| 0.999998 |
As part of the data extraction phase, and to facilitate the meta-aggregation process, we read and re-read included studies in duplicate (MF, EO, KR) to extract individual findings (i.e., authors’ analytic interpretative statements of qualitative data) and accompanying illustrations (i.e., verbatim participant quotation that exemplifies the finding). Any verbatim analytic statement was eligible to be extracted as a finding, provided an accompanying illustration was available. Where an accompanying illustration was not available, the finding was not included in this review. As per JBI guidelines ( 24 ), we (independently and in duplicate) assigned finding and illustration pairings a credibility rating: unequivocal (i.e., illustration supports the finding beyond reasonable doubt and therefore not open to challenge), credible (i.e., illustration lacks clear association with the finding and is therefore open to challenge) or not supported (i.e., illustration does not support the finding).
|
PMC11697290_p9
|
PMC11697290
|
Data extraction
| 4.025414 |
biomedical
|
Review
|
[
0.9893976449966431,
0.0018606531666591763,
0.008741692639887333
] |
[
0.1450238972902298,
0.0034591362345963717,
0.851078987121582,
0.00043796442332677543
] |
en
| 0.999996 |
Risk of bias assessment was conducted for each eligible study independently by three reviewers (MF, EO, KR) using the JBI Checklist for Qualitative Research ( 25 ). In this 10-item tool, each item is rated as: yes, no, unclear, or not applicable. We resolved discrepancies via discussion, re-checking the papers together, and discussion with a fourth author (NP) as required. As per recent guidelines for ensuring review results represent the best available evidence ( 26 ) eligible studies were included if they satisfied at least six criteria on the appraisal tool.
|
PMC11697290_p10
|
PMC11697290
|
Risk of bias assessment
| 3.971072 |
biomedical
|
Study
|
[
0.9988802075386047,
0.0004449589177966118,
0.0006747445440851152
] |
[
0.9894249439239502,
0.0008872559992596507,
0.009577793069183826,
0.00010999455844284967
] |
en
| 0.999998 |
Qualitative findings were pooled via meta-aggregation ( 24 ). Findings, illustrations, and credibility data were exported and printed for repeated reviewing in hard copy and for discussion in duplicate by two authors (EO, KR). Using butchers paper, we manually grouped the printed findings into categories based on our discussions. We first placed findings into categories based on similarity of meaning. Second, we combined similar categories into ‘synthesized findings’, referring to indicatory statements that convey the whole, inclusive meaning of a collection of categories, and which can be used to develop policy and practice recommendations. We then transferred these hard copy synthesized findings back to an Excel spreadsheet for discussion with the wider team. Following team discussion, we prioritized these synthesized findings into conceptual order for presentation in the manuscript.
|
PMC11697290_p11
|
PMC11697290
|
Synthesis of results
| 3.811857 |
biomedical
|
Study
|
[
0.9633687734603882,
0.0009104092605412006,
0.03572087734937668
] |
[
0.9961502552032471,
0.002193432068452239,
0.0015824355650693178,
0.00007386292418232188
] |
en
| 0.999998 |
As per JBI guidelines, we used the ConQual approach ( 27 ) to establish confidence in each synthesized finding. ConQual argues that confidence in a meta-synthesized finding is determined by the dependability and credibility of the studies and individual findings that comprise it. Confidence ratings range from high, moderate, low, to very low. By default, qualitative studies are initially given a ‘high’ confidence rating, which can be downgraded based on dependability and credibility. Dependability is determined based on performance of each study on items 2-4 and 6-7 of the JBI Checklist for Qualitative Research, with the overall confidence level unchanging if the majority of individual findings are from studies with 4-5 ‘yes’ responses, downgraded one level for majority 2-3 ‘yes’ responses, and downgraded two levels for majority 0-1 ‘yes’ responses. For credibility, where a synthesized finding contains only unequivocal individual findings, no downgrading penalty is applied; however, confidence is downgraded one level if the synthesized finding comprises a mix of unequivocal and credible individual findings.
|
PMC11697290_p12
|
PMC11697290
|
Assessing confidence in findings
| 4.069284 |
biomedical
|
Study
|
[
0.9975098371505737,
0.0004905993118882179,
0.0019995032344013453
] |
[
0.972247838973999,
0.01977827399969101,
0.007810118608176708,
0.0001637786190258339
] |
en
| 0.999997 |
The overarching qualitative methodology guiding this review was an interpretivist approach, which recognizes subjectivity and reflexivity ( 28 ). This approach makes the perspectives and positioning of the authors explicit, ensuring that the impact of researcher lenses on the synthesis and examination of results is transparent. While the components of the SPI should be universal, we acknowledge our positioning in the Australian context, which is associated with a unique set of cultural factors and policy frameworks that influence SPI practices and implementation. It is also important to acknowledge the authors’ backgrounds. Collectively, the research team brings expertise across lived experience, clinical practice, and research. EO is a postdoctoral researcher with expertise in behavioral science and mental health. KR is an experienced mental health nurse and doctoral level health psychologist working in research and education. NP is a professorial level mental health nurse expert and leader in suicide prevention research and education. ML is a Lived Experience academic. AP is a PhD researcher in health and medical sciences and Expert by Experience with the SPI. J-AR is a mental health nurse expert in clinical and senior management. SP is an experienced mental health nurse. MF is a senior suicide prevention researcher.
|
PMC11697290_p13
|
PMC11697290
|
Reflexivity statement
| 3.575046 |
biomedical
|
Review
|
[
0.9699011445045471,
0.0029235132969915867,
0.027175381779670715
] |
[
0.04173878952860832,
0.01738664135336876,
0.9403083920478821,
0.000566116941627115
] |
en
| 0.999995 |
Database searching yielded 1862 results, reduced to 588 after removal of duplicates. Results were screened at the title/abstract level, leaving 60 eligible for full-text screening. One additional article was identified via a correction that appeared in the search results. No further articles were identified through reference list pearling. Twelve eligible studies were critically appraised; two ( 15 , 29 ) were excluded by the minimum risk of bias threshold, leaving ten studies for inclusion. See
|
PMC11697290_p14
|
PMC11697290
|
Study inclusion
| 3.839355 |
biomedical
|
Study
|
[
0.998683750629425,
0.00045599465374834836,
0.0008603216265328228
] |
[
0.995036780834198,
0.0010576656786724925,
0.003798322519287467,
0.00010712491348385811
] |
en
| 0.999998 |
Figure 1 for the full screening process, and Supplementary Data Sheet 2 for a list of all ineligible full-text results.
|
PMC11697290_p15
|
PMC11697290
|
Study inclusion
| 1.799412 |
biomedical
|
Study
|
[
0.9837250113487244,
0.004350308328866959,
0.011924587190151215
] |
[
0.910834789276123,
0.08189228177070618,
0.005941623356193304,
0.0013313612435013056
] |
en
| 0.999995 |
Included studies were published between 2015 and 2023 and primarily conducted in the United States (n =7). Results for this review are based on data from n = 243 participants (note: this relates to the total number of participants from eligible phases of the included studies). The mean sample size was 24 (range, n=12-50). Across all studies, participants included n = 113 clinicians/staff (n=5 studies), n = 103 adults (including 95 veterans, n=4 studies; and 8 general population, n=1 study), n = 20 adolescents (n=2 studies), and n = 7 support persons (n=2 studies). Eight studies included both female and male participants, two did not report any gender data, and none reported data on other gender identities. Study settings included combined inpatient and outpatient (n=4), outpatient only (n=4), emergency department (n=1), and community services (n=1), with six studies relating to the context of veterans.
|
PMC11697290_p16
|
PMC11697290
|
Characteristics of included studies
| 4.001233 |
biomedical
|
Review
|
[
0.9829521775245667,
0.004307644907385111,
0.01274020690470934
] |
[
0.0236006211489439,
0.0014185140607878566,
0.9746102690696716,
0.00037057901499792933
] |
en
| 0.999996 |
Six studies were purely qualitative ( 10 , 30 – 34 ), one was mixed methods ( 35 ), and while a further three identified as qualitative they also included some minor quantitative aspects (e.g., quantitative measures to collect participant clinical information, 36, 37; or quantification of time spent creating safety plans, 38) but were not considered mixed methods. Most studies (n=8) collected qualitative data via semi-structured individual interviews but focus groups (n=1) and open-ended survey items (n=1) were also used. Studies analyzed qualitative data using thematic analysis (n=4), content analysis (n=2), interpretive phenomenological analysis (n=1), and matrix analysis (n=1). Two studies did not clearly report an analytic method.
|
PMC11697290_p17
|
PMC11697290
|
Characteristics of included studies
| 3.988826 |
biomedical
|
Study
|
[
0.9981887936592102,
0.0005758308107033372,
0.0012354477075859904
] |
[
0.9698963165283203,
0.0006607465911656618,
0.02927541546523571,
0.00016753829549998045
] |
en
| 0.999997 |
There was substantial variability across studies in SPI features, and its role in suicide prevention and mental health care. Studies discussed versions of the SPI including additional components such as text-message and/or telephone follow-up support ( 31 , 35 ), and the inclusion of support persons ( 36 ). Most studies (n=9) used or discussed the SPI as one component of care, alongside other psychological interventions (e.g., individualized, outpatient psychotherapy). The specific format of initial construction, ongoing access, or both, was often unclear. Only three studies described a specific SPI format, including a traditional hard-copy format ( 33 ), a mobile phone app-based version ( 30 ), and either hard copy or electronic versions ( 38 ). There was also a lack of detailed reporting regarding delivery modality, with four studies ( 30 , 31 , 33 , 38 ) clearly indicating in-person creation of the SPI, and one describing a group-based SPI delivered online via telehealth ( 37 ). Eight studies described who the SPI was co-created with – working with a clinician was the most frequent approach ( 10 , 30 , 31 , 33 , 34 , 38 ), with one study describing construction with a study counselor ( 35 ), and another describing a collaborative creation process with other SPI users in a group format ( 37 ). See Table 1 for full characteristics of included studies.
|
PMC11697290_p18
|
PMC11697290
|
Characteristics of included studies
| 4.004863 |
biomedical
|
Study
|
[
0.9975589513778687,
0.000991318142041564,
0.001449748408049345
] |
[
0.9360707998275757,
0.00056584452977404,
0.0631585568189621,
0.00020473096810746938
] |
en
| 0.999997 |
Included studies performed well on critical appraisal items related to congruity between research methodology and study methods, as well as ethical research conduct and appropriateness of study conclusions. However, guiding philosophical perspectives were largely unreported, with only one study mentioning this ( 32 ), and studies did not consistently meet criteria for reflexivity, with only one study ( 32 ) locating the researchers culturally or theoretically, and two studies ( 10 , 32 ) discussing the influence of the researcher on the research and vice-versa. See Table 2 for study-level critical appraisal results.
|
PMC11697290_p19
|
PMC11697290
|
Risk of bias within and across studies
| 3.732405 |
biomedical
|
Study
|
[
0.9374591708183289,
0.0009033671813085675,
0.06163733825087547
] |
[
0.9790177941322327,
0.002143875230103731,
0.018710633739829063,
0.00012774509377777576
] |
en
| 0.999996 |
Ninety findings (82 unequivocal; 8 credible) related to stakeholders’ experiences of the SPI were extracted and aggregated into 14 unique categories according to similarity of meaning. Four synthesized findings (one moderate confidence and three low confidence) were developed via meta-aggregation. See Table 3 for a summary of the findings and categories used to create each synthesized finding, and Supplementary Table 1 for full ConQual results. Complete details of individual findings and illustrations are presented in Supplementary Table 2 . We provide a narrative description of each synthesized finding and associated categories below.
|
PMC11697290_p20
|
PMC11697290
|
Review findings
| 2.836886 |
biomedical
|
Study
|
[
0.7776880860328674,
0.0012479063589125872,
0.22106397151947021
] |
[
0.9956069588661194,
0.003202721243724227,
0.0010776495328173041,
0.000112695517600514
] |
en
| 0.999997 |
This synthesized finding comprises 21 individual findings across two categories, revealing that engaging with the SPI is an acceptable intervention, associated with varied benefits to the consumer in the short- and longer-term.
|
PMC11697290_p21
|
PMC11697290
|
Synthesized finding 1: Acceptability and positive outcomes associated with the SPI
| 2.132133 |
biomedical
|
Study
|
[
0.805219292640686,
0.0021809085737913847,
0.19259978830814362
] |
[
0.8310204744338989,
0.0867721289396286,
0.08134272694587708,
0.0008646260830573738
] |
en
| 0.999997 |
Five findings were located from two studies ( 31 , 38 ) describing stakeholders’ perspectives on the utility of the SPI. The SPI is deemed an acceptable and even essential intervention by clinicians working with suicidal veterans ( 31 , 38 ). Clinicians view the SPI as a useful addition to their repertoire, noting that its structured nature can help to facilitate conversations regarding consumers’ emotional states, early warning signs and risk factors ( 38 ). Despite initial skepticism about the SPI ( 31 ), clinicians describe it as a tool they rely on in everyday practice. For example, one emergency department clinician shared that the SPI assists in engaging individuals with emerging suicidality prior to the onset of suicidal behaviors:
|
PMC11697290_p22
|
PMC11697290
|
Category 1.1 – Perceived acceptability/usability of the SPI
| 3.66573 |
biomedical
|
Study
|
[
0.9887696504592896,
0.007171590346843004,
0.004058786202222109
] |
[
0.9671154022216797,
0.01060439646244049,
0.021660642698407173,
0.0006195889436639845
] |
en
| 0.999997 |
Further, clinicians who use the SPI with structured telephone follow up stated that it provides a concrete tool to facilitate reduced risk during the transition between inpatient and outpatient settings. For example:
|
PMC11697290_p23
|
PMC11697290
|
Category 1.1 – Perceived acceptability/usability of the SPI
| 1.668103 |
clinical
|
Other
|
[
0.37999647855758667,
0.5447131991386414,
0.07529030740261078
] |
[
0.02227093279361725,
0.9673629999160767,
0.0021527388598769903,
0.008213317021727562
] |
en
| 0.999996 |
Sixteen findings from six studies ( 10 , 32 – 34 , 37 , 38 ) of adolescent and adult consumers, and clinicians, form this category describing perceived benefits related to consumers’ ongoing engagement with SPI practices. SPI conversations can broaden consumers’ motivations for keeping themselves safe. This can be achieved by harnessing and amplifying consumers’ awareness of existing reasons for living and generating hope for a more positive future ( 10 ), as well as through greater awareness of the emotional pain that would befall consumers’ loved ones in the event of their suicide ( 33 ).
|
PMC11697290_p24
|
PMC11697290
|
Category 1.2 – SPI practices improve consumers’ understanding of their own suicide-related experiences, and enhance the use of adaptive self-regulatory skills and strategies to manage distress
| 2.219801 |
other
|
Study
|
[
0.4811011552810669,
0.0021992288529872894,
0.5166996121406555
] |
[
0.7413014769554138,
0.2459125816822052,
0.011958341114223003,
0.0008276327862404287
] |
en
| 0.999999 |
SPI processes - supported by reflective, collaborative discussions between consumer and clinician regarding consumers’ lived experiences - helped consumers to develop greater awareness of the character and quality of their emotional states, as well as individual triggers that precipitate the onset and worsening of distress ( 10 , 32 , 33 , 38 ). For example, one clinician described how collaborative conversations occurring during the SPI process could help young people to make connections between current distress and earlier triggers:
|
PMC11697290_p25
|
PMC11697290
|
Category 1.2 – SPI practices improve consumers’ understanding of their own suicide-related experiences, and enhance the use of adaptive self-regulatory skills and strategies to manage distress
| 2.45007 |
biomedical
|
Other
|
[
0.7451341152191162,
0.024309465661644936,
0.23055650293827057
] |
[
0.40440258383750916,
0.5893886089324951,
0.004504593554884195,
0.0017041899263858795
] |
en
| 0.999996 |
Another clinician noted that developing greater recognition of their own triggers, warning signs, and effective strategies for emotional regulation allowed consumers to communicate their needs more clearly to supportive others:
|
PMC11697290_p26
|
PMC11697290
|
Category 1.2 – SPI practices improve consumers’ understanding of their own suicide-related experiences, and enhance the use of adaptive self-regulatory skills and strategies to manage distress
| 2.071626 |
biomedical
|
Other
|
[
0.5584145784378052,
0.40507665276527405,
0.036508720368146896
] |
[
0.0168917253613472,
0.9741727113723755,
0.0023911339230835438,
0.006544431205838919
] |
en
| 0.999996 |
Creating a non-judgmental therapeutic environment that normalizes the experience of ambient and acute depressive states may foster consumers’ openness to engage in these difficult and deeply personal conversations ( 10 ).
|
PMC11697290_p27
|
PMC11697290
|
Category 1.2 – SPI practices improve consumers’ understanding of their own suicide-related experiences, and enhance the use of adaptive self-regulatory skills and strategies to manage distress
| 1.808151 |
biomedical
|
Other
|
[
0.5688414573669434,
0.004360129591077566,
0.42679840326309204
] |
[
0.0209970586001873,
0.9767611026763916,
0.0018189589027315378,
0.00042286631651222706
] |
en
| 0.999996 |
Clinicians described how, over time, consumers learned to independently select and engage ‘lower-level’ self-soothing strategies to avoid deeper states of crisis ( 38 ). This perspective was also voiced by consumers in multiple studies:
|
PMC11697290_p28
|
PMC11697290
|
Category 1.2 – SPI practices improve consumers’ understanding of their own suicide-related experiences, and enhance the use of adaptive self-regulatory skills and strategies to manage distress
| 1.864581 |
biomedical
|
Other
|
[
0.6202326416969299,
0.01572636514902115,
0.36404097080230713
] |
[
0.3981097340583801,
0.5867544412612915,
0.01219604816287756,
0.002939792349934578
] |
en
| 0.999998 |
Taken together, both clinicians and consumers noted that the SPI supported consumers’ autonomy to identify and effectively manage distress.
|
PMC11697290_p29
|
PMC11697290
|
Category 1.2 – SPI practices improve consumers’ understanding of their own suicide-related experiences, and enhance the use of adaptive self-regulatory skills and strategies to manage distress
| 1.833383 |
biomedical
|
Other
|
[
0.602655827999115,
0.21738161146640778,
0.17996256053447723
] |
[
0.16376011073589325,
0.8231222033500671,
0.007849565707147121,
0.005268137436360121
] |
en
| 0.999997 |
The second synthesized finding, supported by 32 findings and aggregated into five unique categories, highlights the SPI is perceived to be most effective when it is conducted within a person-centered and collaborative relationship, appropriately involves supportive others, and is integrated in an authentic way within consumers’ ongoing care and personal agency. For both clinicians and consumers, digital technologies may support successful SPI experiences.
|
PMC11697290_p30
|
PMC11697290
|
Synthesized finding 2: Maximizing the effectiveness of the SPI
| 2.963235 |
biomedical
|
Study
|
[
0.9035369753837585,
0.009174364618957043,
0.08728864043951035
] |
[
0.7407720685005188,
0.19412271678447723,
0.06404656916856766,
0.0010586966527625918
] |
en
| 0.999997 |
Five findings from four studies ( 10 , 32 , 33 , 38 ) supported this category. Clinicians cautioned that the SPI should not be prescribed by the service provider nor seen as a risk mitigation strategy, but rather constructed collaboratively ( 10 , 32 , 38 ). As one clinician noted:
|
PMC11697290_p31
|
PMC11697290
|
Category 2.1 – Collaborative, person-centered approach to constructing the safety plan
| 1.956339 |
biomedical
|
Study
|
[
0.8192396759986877,
0.15775266289710999,
0.02300768531858921
] |
[
0.607466459274292,
0.35965901613235474,
0.018096331506967545,
0.014778239652514458
] |
en
| 0.999996 |
Clinicians reported taking approximately 30 minutes to co-construct the initial plan in a collaborative way with meaningful involvement ( 38 ). For consumers, the content of the initial plan was arguably less important than the quality of the collaborative therapeutic interaction ( 33 ).
|
PMC11697290_p32
|
PMC11697290
|
Category 2.1 – Collaborative, person-centered approach to constructing the safety plan
| 1.977109 |
biomedical
|
Study
|
[
0.8242446184158325,
0.06512370705604553,
0.11063172668218613
] |
[
0.6174594759941101,
0.36882492899894714,
0.0101382527500391,
0.0035773932468146086
] |
en
| 0.999998 |
This category featured three findings from two studies ( 10 , 34 ). Staff working with refugees and asylum seekers reported needing to be flexible and creative to ensure that the SPI is accessible and culturally appropriate ( 10 ). Clinicians argued that people using the SPI should feel empowered to explore alternative approaches to visualizing and documenting each step, according to the unique consumer needs and preferences ( 10 ). Action planning a range of specific steps to take during future crises can help consumers to feel a sense of control in these scenarios, rather than behaving impulsively:
|
PMC11697290_p33
|
PMC11697290
|
Category 2.2 – Clinical strategies to improve consumer engagement
| 2.144078 |
other
|
Other
|
[
0.4239831864833832,
0.02846253477036953,
0.5475542545318604
] |
[
0.20390444993972778,
0.7880147695541382,
0.006394700147211552,
0.0016861000331118703
] |
en
| 0.999997 |
Subsets and Splits
SQL Console for rntc/test-pp-aa
The query retrieves a sample of documents that are clinical cases with an educational score above 3, providing limited analytical value.
Clinical Cases Sample
Returns a sample of 100 clinical case documents, providing a basic overview of the document type's content.