The role of ventromedial prefrontal cortex in reward valuation and future thinking during intertemporal choice

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1. 

   Version published to 10.7554/elife.67387 on eLife

   Aug 3, 2021
2. 

   eLife

   Jul 15, 2021

   Author Response:

   Reviewer #1:

   This study focuses on how the vmPFC supports delay discounting. The authors tested patients with vmPFC lesions (N=12) and healthy controls (N=41) on a delay discounting (DD) task with two additional conditions: (1) reward magnitude and (2) cues that should evoke episodic future thinking (EFT).

   The authors replicate their previous finding that patients with vmPFC lesions show steeper DD, and report two novel findings: (1) DD in patients is insensitive to reward magnitude, suggesting that vmPFC is critical for reward magnitude to modulate DD; (2) vmPFC patients show normal effects of EFT cues on DD, such that all subjects discounted less in the presence of cues that promote episodic future thinking. These findings have important implications for how vmPFC contributes to delay discounting, as they suggest …

   Author Response:

   Reviewer #1:

   This study focuses on how the vmPFC supports delay discounting. The authors tested patients with vmPFC lesions (N=12) and healthy controls (N=41) on a delay discounting (DD) task with two additional conditions: (1) reward magnitude and (2) cues that should evoke episodic future thinking (EFT).

   The authors replicate their previous finding that patients with vmPFC lesions show steeper DD, and report two novel findings: (1) DD in patients is insensitive to reward magnitude, suggesting that vmPFC is critical for reward magnitude to modulate DD; (2) vmPFC patients show normal effects of EFT cues on DD, such that all subjects discounted less in the presence of cues that promote episodic future thinking. These findings have important implications for how vmPFC contributes to delay discounting, as they suggest that vmPFC is not necessary for prospective thinking to affect the evaluation of future rewards.

   1. A potential issue with the EFT finding is that it rests on accepting the null hypothesis of no group differences. However, there are reasons to assume this is not a trivial null result due to a lack of statistical power. Specifically, there is a significant effect of EFT within the vmPFC patient group and there is a significant group difference for the effect of reward magnitude. Assuming comparable power to detect effects of EFT and reward magnitude, it seems unlikely that the non-significant EFT effect is simply a lack of power. In any case, this caveat has to be considered when interpreting the effect.

   We have added a discussion of this caveat on p. 10, which reads: “Before discussing this finding further, we note that it rests on accepting the null hypothesis of no group differences in the EFT effect on DD between vmPFC patients and controls. It is unlikely, however, that this null finding simply reflects a lack of statistical power, for example due to a small sample size. First, the null effect on group differences indeed reflects a significant within-participant effect, with greater regard for future amounts in the EFT compared to the Standard condition in vmPFC patients. Second, together with the preservation of the EFT effect, we found a significant reduction of the magnitude effect in the same vmPFC patient sample. Bayesian analyses confirmed greater evidence in favour of the null compared to the alternative hypothesis regarding group differences in the EFT effect on DD.”

   1. It is somewhat surprising that the authors had such a strong prediction about the absence of group differences for the EFT effect. Based on previous work (Bertossi et al., 2016a, b), one could expect a smaller EFT effect in the VMPFC group. The authors appear to put much weight on the results by Ghosh et al. 2014, which suggest that vmPFC is critical for schema reinstatement. The rationale for this strong prediction is not very clear from the introduction.

   We have now reframed our hypotheses as suggested by the reviewers and the editors. In the Introduction, we now make only the hypothesis of a reduced EFT effect on DD in vmPFC patients, which is based on previous evidence of an EFT impairment in vmPFC patients. We present the hypothesis that vmPFC is critical for schema instantiation only in the Discussion, as an explanation of the null finding on group differences on the EFT effect.

   Thus, p. 5 now reads: “Concerning prospection, previous studies have observed an EFT effect on DD, such that people discount future rewards less steeply if cued to imagine personal future events during intertemporal choice (Peters and Büchel, 2010; Benoit et al., 2011). Considering that vmPFC is implicated in prospection (Schacter et al., 2012) and that vmPFC patients are impaired in EFT (Bertossi et al., 2016a,b; Bertossi et al., 2017), vmPFC patients' DD should remain steep even when EFT cues are provided, because patients may nevertheless fail to construct the vivid future events that might be needed to counteract DD. Thus, we predict a reduced EFT effect on DD in vmPFC patients compared to healthy controls.”

   Reviewer #2:

   Ciaramelli et al. address a timely and theoretically important issue with respect to the functional role of the vmPFC in decision-making more generally, and temporal discounting in particular. Strong points of the paper include 1) a theoretically important research question and 2) much-needed lesion data on two important behavioral effects in temporal discounting: the magnitude effect, and a modulation of discounting via episodic future thinking. Weaker points of the paper include 1) lack of clarity for a number of methodological issues (group comparisons & control group for the AI data, inconsistency analysis) and 2) many remaining open questions with respect to how vmPFC patients might have utilized the EFT cues, and whether different processes were at work compared to controls.

   We thank the reviewer for this positive evaluation of the paper and address the reviewer’s comments below.

   Major points:

   1. The authors note that their interpretation of the preserved EFT effects in the vmPFC patients in terms of e.g. semantic processing remains speculative, but is supported by the finding of intact external details production following vmPFC damage in earlier studies. But was this also the case in the present data set? This remains unclear, because for the AI data, only z-scores relative to some earlier control group (Kwan et al. 2015) are reported (Table 1 and Supplement p. 30). Was this control group matched to the patients? And since the referenced Kwan et al. (2015) paper reports only on six patients (presumably the patients from the Canada site?) - what about the patients from the Italian site, which control group were their AI data compared to?

   The Crovitz data of the Canadian patients are unpublished (the Kwan et al., 2015 paper is not about vmPFC patients, but about 6 MTL patients). We compared them to a sample of 18 age-matched healthy controls, a subset of those included in Kwan et al. (2015). The 4 Italian patients were part of the vmPFC sample tested on EFT (and episodic memory) in Bertossi et al. (2016). We compared their performance with that of the 11 healthy controls from the same study who were age-matched to the patients.

   This is clarified on p. 17, which reads: “The results of the Italian patients (a subset of those included in Bertossi et al. 2016b) were contrasted with those of the 11 healthy controls from the same study (all males; Bertossi et al., 2016b) who were age-matched to the patients (vmPFC patients: M = 47.75, SD = 5.25; healthy controls: M = 41.63, SD = 11.89, t13 = -0.97, p = 0.34). The results of the Canadian patients (unpublished) were contrasted with those of 18 healthy controls (10 males; a subset of those included in Kwan et al., 2015) age-matched to the patients (vmPFC patients: M = 61.00, SD = 9.83; healthy controls: M = 67.94, SD = 13.57, t22 = 1.15, p = 0.26).”

   1. Directly related to my previous point: The methods section states that external details were in the normal range in the vmPFC group (mean z-score for EFT = -.73) but from Table 1 we can see that 8/10 patients in fact exhibit a negative z-score. This suggests that a direct group comparison of the external details scores would very likely reveal a significant group difference. Generally, it would help to report to actual control data here, not just the z-scores, and report the respective group comparisons.

   We now report the Crovitz data in Table 2 and have run two ANOVAs on internal and external details separately in vmPFC patients and controls tested in Italy and in Canada. As the two ANOVAs show, we confirm that both patient groups produced fewer internal (episodic) details but a similar number of external details during EFT (as well as episodic remembering) than healthy controls. Therefore, the previously reported EFT problems for internal (but not external) details in vmPFC patients also apply to the patients tested here.

   P. 17 now reads: “As for the Italian sample, an ANOVA on the details produced with Group (vmPFC patients, healthy controls), Time (Past, Future), and Detail (internal, external) as factors showed a significant effect of Time (F1,13 = 14.66, p = 0.002, partial η2 = 0.53), such that all participants produced more details for past than future events (18.19 vs. 15.37). There were also significant effects of Group (F1,13 = 6.16, p = 0.02, partial η2 = 0.32) and Detail (F1,13 = 9.14, p = 0.009, partial η2 = 0.41), qualified by a Group x Detail interaction (F1,13 = 8.99, p = 0.01, partial η2 = 0.40). Post hoc Fisher tests showed that vmPFC patients produced fewer internal details (11.45 vs. 25.51; p = 0.004) but a similar number of external details than controls (11.39 vs. 11.96; p = 0.89). No other effect was significant (p > 0.31 in all cases). The same ANOVA on the Canadian sample revealed an effect of Group (F1,22 = 17.76, p = 0.0003, partial η2 =20.44), qualified by a significant Group x Detail interaction (F1,22 = 4.72, p = 0.04, partial η = 0.18), again indicating that vmPFC patients produced fewer internal details (10.63 vs. 31.78; p = 0.0003) but a similar number of external details than controls (16.79 vs. 25.65; p = 0.09). No other effect was significant (p > 0.32 in all cases).”

   1. The description of the inconsistency analysis was somewhat unclear. The authors use the procedure suggested by Johnson & Bickel (2008), which makes sense, given the overall analytical approach that focuses on the analysis of indifference points. However, this procedure is based on a comparison of adjacent indifference points. In contrast, the authors are referring to the number of inconsistent choices - this is either a typo, or a different procedure. I think the former, because the reported absolute numbers (e.g. means around 1) and the single subject plots in the supplement appear to reflect the number of inconsistent ID points rather than choices. If this is the case, I disagree with the statement that the "mean number of inconsistent choices was very low" (p. 10) - as this probably reflects the mean number of inconsistent indifference points and not choices, about 1 out of 6 ID points was inconsistent in the vmPFC group, which is a lot.

   We apologize for lack of clarity. Yes, we are referring to indifference points (as in our previous study; Sellitto et al., 2010), not single choices. Inconsistent preferences are defined as “data points in which the subjective value of a future outcome (amount = R) at a given delay (R2) was greater than that at the preceding delay (R1) by more than 10% of the amount of the future outcome (i.e., R2 > R1 + R/10, as in Sellitto et al., 2010).” To avoid confusion, we have now corrected the expression ‘inconsistent choice’ to ‘inconsistent preference’ throughout the paper, and have eliminated the claim about the low number of inconsistent choices in vmPFC patients.

   1. The EFT cues are suggested to help vmPFC patients to "circumvent their initiation problems" (p. 12) but I am not sure I follow this logic. First, the AI procedure typically entails external cues as well, and here vmPFC patients showed impairments (Table 1, but see my point 1 above). Second, some of the cited papers (e.g. Verfaellie et al., 2019) also used specific event cues, and still observed reduced internal details production in vmPFC patients.

   The AI (Crovitz) procedure uses external cues but typically these are words that are not particularly meaningful to the participants (indeed, they are the same for all participants). e.g., Imagine attending a Fourth of July cookout a few years from now; Verfaellie et al., 2019) but, again, these cues are the same for all participants. We used personalized cues, which were events that participants (1) had selected themselves, and (2) had already planned or found them plausible in their future, and therefore presumably were the most self-relevant and familiar to the participants, including patients. We think that these events may have been effective in activating self- and event- relevant schemata. We clarify this point on p. 11, which reads: “We propose, therefore, that subject-specific event cues, which were self-relevant and familiar to the participants because they had been selected by participants themselves, and were already planned or were plausible in their future, acted as external triggers of self- and situation-relevant schemata, helping to circumvent vmPFC patients’ EFT initiation problems. Their intact MTLs allowed them to construct episodic future events, which were then integrated into intertemporal choice, reducing DD.” As we note on p. 14, indeed, vmPFC patients are capable of imagining detailed experiences if they are guided to choose for themselves a specific moment from an extended future event to narrate in detail (Kurczek et al., 2015). Of course, we agree with the Reviewer’s point below that this interpretation is speculative at this point.

   1. One shortcoming with the paper is that no data are available that could inform how vmPFC patients might have utilized the EFT cues, and whether the processes at work might have differed from those in controls. Many points mentioned in the discussion (self-referential processing, semantic processing, activation of schemata, self-initiation vs. external cueing etc.) thus necessarily remain conjecture.

   We agree with the Reviewer, and we admit in several parts of the Discussion that this interpretation is speculative at this point. However, the interpretation that we offer seems the most plausible to us at this time, considering what we know about the role of the vmPFC (vs. the MTL) in event construction and the absence of the EFT effect on DD in MTL patients. We also propose an alternative interpretation, but the pattern of findings on the EFT effect on DD makes it less likely to us. On p. 12, we state, “An alternative interpretation of the DD modulation is that EFT cues simply shifted attention towards the future, or conferred a positive valence to it, as we encouraged positively valenced EFT. If so, however, one should consistently observe an EFT-induced benefit on DD also in patients with MTL lesions, but this is not the case (Kwan et al., 2015; Palombo et al., 2015).”

   Reviewer #3:

   In this manuscript, Ciaramelli et al. examined the decision-making behavior of 12 patients with vmPFC damage in a delay discounting task. The authors carried out two manipulations in this task: 1. They presented participants with small and large offers for both the immediate and delayed reward (magnitude manipulation), 2. They prefaced decisions with a cue prompting participants to vividly imagine an event in their future that was expected to occur at the same delay as the proposed larger offer (episodic future thinking (EFT) manipulation). Compared to age and education matched healthy controls, patients with vmPFC damage showed steeper discounting of delayed rewards, particularly when the amounts offered were large (reduced effect of magnitude). However, like controls, vmPFC damaged patients displayed shallower discounting of delayed rewards following the EFT manipulation.

   The manuscript is clear and concise in its presentation of the results, while still providing a detailed description of the behavior of these patients. This paper is also a good example of how pooling participants from multiple institutions can increase statistical power in a study of patients with focal brain damage targeting a fairly specific cognitive question. The positive results of the study mostly replicate previous findings. While the null result for the EFT manipulation is novel, the finding is hard to interpret. The authors state that they predicted that the EFT manipulation would not change discounting behavior in vmPFC damaged patients a priori despite the deficits of these patients in EFT in previous papers, which are also replicated here. However, I do not know why the authors would design their task in such a way to test for a null result. It is also not clear if this null result is observed for the reason proposed by the authors (that the EFT cues externally activate this process), or if this result is null for some other reason that is not accounted for here. As the authors do not provide a direct test for their hypothesized rationale for predicting this null result, the findings are hard to interpret.

   We agree with the reviewer’s and editor’s point that this paradigm does not allow testing whether subject-specific, personally relevant cues, such as those we used, are indeed effective in externally initiating EFT in vmPFC patients. Therefore, we concur that, for the sake of clarity, this is best presented only as speculative discussion of the preserved EFT effect on DD in vmPFC patients. In the Introduction, therefore, we now formulate only the hypothesis based on previous evidence of impaired EFT in vmPFC patients (e.g., Bertossi et al., 2016a,b, Verfaellie et al., 2019), which would lead to the prediction of a reduced EFT effect in vmPFC patients. We present the hypothesis that vmPFC is critical for schema instantiation only in the Discussion, as an explanation of the null finding on group differences on the EFT effect.

   P. 5 now reads: “Concerning prospection, previous studies have observed an EFT effect on DD, such that people discount future rewards less steeply if cued to imagine personal future events during intertemporal choice (Peters and Büchel, 2010; Benoit et al., 2011). Considering that vmPFC is implicated in prospection (Schacter et al., 2012) and that vmPFC patients are impaired in EFT (Bertossi et al., 2016a,b; Bertossi et al., 2017), vmPFC patients' DD should remain steep even when EFT cues are provided, because patients may nevertheless fail to construct the vivid future events that might be needed to counteract DD. Thus, we predict a reduced EFT effect on DD in vmPFC patients compared to healthy controls.”

   Overall, this manuscript makes a relatively modest contribution to our knowledge about the function of vmPFC during inter-temporal choice. It bolsters previous claims about how vmPFC damage impacts delay discounting and EFT, while not revealing new information about how vmPFC specifically contributes to the processes involved in these behaviors and why damage to this region impacts intertemporal choice in this way.

   We concur with the reviewer that our findings confirm previous evidence that vmPFC is necessary for balanced DD and for EFT. However, we think that our finding of a complete abolishment of the magnitude effect together with a complete preservation of the EFT effect on DD in vmPFC patients configures a remarkable theoretical advancement on the role of vmPFC in intertemporal choice. Indeed, it shows that during intertemporal choice vmPFC is more prominently implicated in reward valuation than in prospection. This finding is important for current theories of intertemporal choice, and is surprising considering previous demonstrations of impaired EFT in vmPFC patients (a finding that was replicated in the current study), and therefore has important implications also for theories relating to the role of vmPFC in EFT. Finally, we note that the paper focuses on one important facet of impulsivity following damage to the vmPFC in humans: steep DD. Our findings, therefore, may inform the clinical management of impulsivity in patients with vmPFC damage or dysfunction, delineating the contextual manipulations that are or are not expected to push the reach of patients' choice into the future.

   Read the original source
3. 

   eLife

   Jul 15, 2021

   Evaluation Summary:

   This paper provides important data on the contribution of the vmPFC to temporal discounting, by showing differential modulation of two well-known effects in inter-temporal choice (magnitude effect, episodic future thinking). VMPFC damage abolished the magnitude effect, but not a modulation of discounting via future thinking, a finding of interest to cognitive neuroscientists working on prospection, decision-making and executive control.

   (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

   Read the original source
4. 

   eLife

   Jul 15, 2021

   Reviewer #1 (Public Review):

   This study focuses on how the vmPFC supports delay discounting. The authors tested patients with vmPFC lesions (N=12) and healthy controls (N=41) on a delay discounting (DD) task with two additional conditions: (1) reward magnitude and (2) cues that should evoke episodic future thinking (EFT).

   The authors replicate their previous finding that patients with vmPFC lesions show steeper DD, and report two novel findings: (1) DD in patients is insensitive to reward magnitude, suggesting that vmPFC is critical for reward magnitude to modulate DD; (2) vmPFC patients show normal effects of EFT cues on DD, such that all subjects discounted less in the presence of cues that promote episodic future thinking. These findings have important implications for how vmPFC contributes to delay discounting, as they suggest that …

   Reviewer #1 (Public Review):

   This study focuses on how the vmPFC supports delay discounting. The authors tested patients with vmPFC lesions (N=12) and healthy controls (N=41) on a delay discounting (DD) task with two additional conditions: (1) reward magnitude and (2) cues that should evoke episodic future thinking (EFT).

   The authors replicate their previous finding that patients with vmPFC lesions show steeper DD, and report two novel findings: (1) DD in patients is insensitive to reward magnitude, suggesting that vmPFC is critical for reward magnitude to modulate DD; (2) vmPFC patients show normal effects of EFT cues on DD, such that all subjects discounted less in the presence of cues that promote episodic future thinking. These findings have important implications for how vmPFC contributes to delay discounting, as they suggest that vmPFC is not necessary for prospective thinking to affect the evaluation of future rewards.

   1. A potential issue with the EFT finding is that it rests on accepting the null hypothesis of no group differences. However, there are reasons to assume this is not a trivial null result due to a lack of statistical power. Specifically, there is a significant effect of EFT within the vmPFC patient group and there is a significant group difference for the effect of reward magnitude. Assuming comparable power to detect effects of EFT and reward magnitude, it seems unlikely that the non-significant EFT effect is simply a lack of power. In any case, this caveat has to be considered when interpreting the effect.

   2. It is somewhat surprising that the authors had such a strong prediction about the absence of group differences for the EFT effect. Based on previous work (Bertossi et al., 2016a, b), one could expect a smaller EFT effect in the VMPFC group. The authors appear to put much weight on the results by Ghosh et al. 2014, which suggest that vmPFC is critical for schema reinstatement. The rationale for this strong prediction is not very clear from the introduction.

   Read the original source
5. 

   eLife

   Jul 15, 2021

   Reviewer #2 (Public Review):

   Ciaramelli et al. address a timely and theoretically important issue with respect to the functional role of the vmPFC in decision-making more generally, and temporal discounting in particular. Strong points of the paper include 1) a theoretically important research question and 2) much-needed lesion data on two important behavioral effects in temporal discounting: the magnitude effect, and a modulation of discounting via episodic future thinking. Weaker points of the paper include 1) lack of clarity for a number of methodological issues (group comparisons & control group for the AI data, inconsistency analysis) and 2) many remaining open questions with respect to how vmPFC patients might have utilized the EFT cues, and whether different processes were at work compared to controls.

   Major points:

   1. The authors …

   Reviewer #2 (Public Review):

   Ciaramelli et al. address a timely and theoretically important issue with respect to the functional role of the vmPFC in decision-making more generally, and temporal discounting in particular. Strong points of the paper include 1) a theoretically important research question and 2) much-needed lesion data on two important behavioral effects in temporal discounting: the magnitude effect, and a modulation of discounting via episodic future thinking. Weaker points of the paper include 1) lack of clarity for a number of methodological issues (group comparisons & control group for the AI data, inconsistency analysis) and 2) many remaining open questions with respect to how vmPFC patients might have utilized the EFT cues, and whether different processes were at work compared to controls.

   Major points:

   1. The authors note that their interpretation of the preserved EFT effects in the vmPFC patients in terms of e.g. semantic processing remains speculative, but is supported by the finding of intact external details production following vmPFC damage in earlier studies. But was this also the case in the present data set? This remains unclear, because for the AI data, only z-scores relative to some earlier control group (Kwan et al. 2015) are reported (Table 1 and Supplement p. 30). Was this control group matched to the patients? And since the referenced Kwan et al. (2015) paper reports only on six patients (presumably the patients from the Canada site?) - what about the patients from the Italian site, which control group were their AI data compared to?

   2. Directly related to my previous point: The methods section states that external details were in the normal range in the vmPFC group (mean z-score for EFT = -.73) but from Table 1 we can see that 8/10 patients in fact exhibit a negative z-score. This suggests that a direct group comparison of the external details scores would very likely reveal a significant group difference. Generally, it would help to report to actual control data here, not just the z-scores, and report the respective group comparisons.

   3. The description of the inconsistency analysis was somewhat unclear. The authors use the procedure suggested by Johnson & Bickel (2008), which makes sense, given the overall analytical approach that focuses on the analysis of indifference points. However, this procedure is based on a comparison of adjacent indifference points. In contrast, the authors are referring to the number of inconsistent choices - this is either a typo, or a different procedure. I think the former, because the reported absolute numbers (e.g. means around 1) and the single subject plots in the supplement appear to reflect the number of inconsistent ID points rather than choices. If this is the case, I disagree with the statement that the "mean number of inconsistent choices was very low" (p. 10) - as this probably reflects the mean number of inconsistent indifference points and not choices, about 1 out of 6 ID points was inconsistent in the vmPFC group, which is a lot.

   4. The EFT cues are suggested to help vmPFC patients to "circumvent their initiation problems" (p. 12) but I am not sure I follow this logic. First, the AI procedure typically entails external cues as well, and here vmPFC patients showed impairments (Table 1, but see my point 1 above). Second, some of the cited papers (e.g. Verfaellie et al., 2019) also used specific event cues, and still observed reduced internal details production in vmPFC patients.

   5. One shortcoming with the paper is that no data are available that could inform *how* vmPFC patients might have utilized the EFT cues, and whether the processes at work might have differed from those in controls. Many points mentioned in the discussion (self-referential processing, semantic processing, activation of schemata, self-initiation vs. external cueing etc.) thus necessarily remain conjecture.

   Read the original source
6. 

   eLife

   Jul 15, 2021

   Reviewer #3 (Public Review):

   In this manuscript, Ciaramelli et al. examined the decision-making behavior of 12 patients with vmPFC damage in a delay discounting task. The authors carried out two manipulations in this task: 1. They presented participants with small and large offers for both the immediate and delayed reward (magnitude manipulation), 2. They prefaced decisions with a cue prompting participants to vividly imagine an event in their future that was expected to occur at the same delay as the proposed larger offer (episodic future thinking (EFT) manipulation). Compared to age and education matched healthy controls, patients with vmPFC damage showed steeper discounting of delayed rewards, particularly when the amounts offered were large (reduced effect of magnitude). However, like controls, vmPFC damaged patients displayed …

   Reviewer #3 (Public Review):

   In this manuscript, Ciaramelli et al. examined the decision-making behavior of 12 patients with vmPFC damage in a delay discounting task. The authors carried out two manipulations in this task: 1. They presented participants with small and large offers for both the immediate and delayed reward (magnitude manipulation), 2. They prefaced decisions with a cue prompting participants to vividly imagine an event in their future that was expected to occur at the same delay as the proposed larger offer (episodic future thinking (EFT) manipulation). Compared to age and education matched healthy controls, patients with vmPFC damage showed steeper discounting of delayed rewards, particularly when the amounts offered were large (reduced effect of magnitude). However, like controls, vmPFC damaged patients displayed shallower discounting of delayed rewards following the EFT manipulation.

   The manuscript is clear and concise in its presentation of the results, while still providing a detailed description of the behavior of these patients. This paper is also a good example of how pooling participants from multiple institutions can increase statistical power in a study of patients with focal brain damage targeting a fairly specific cognitive question. The positive results of the study mostly replicate previous findings. While the null result for the EFT manipulation is novel, the finding is hard to interpret. The authors state that they predicted that the EFT manipulation would not change discounting behavior in vmPFC damaged patients a priori despite the deficits of these patients in EFT in previous papers, which are also replicated here. However, I do not know why the authors would design their task in such a way to test for a null result. It is also not clear if this null result is observed for the reason proposed by the authors (that the EFT cues externally activate this process), or if this result is null for some other reason that is not accounted for here. As the authors do not provide a direct test for their hypothesized rationale for predicting this null result, the findings are hard to interpret.

   Overall, this manuscript makes a relatively modest contribution to our knowledge about the function of vmPFC during inter-temporal choice. It bolsters previous claims about how vmPFC damage impacts delay discounting and EFT, while not revealing new information about how vmPFC specifically contributes to the processes involved in these behaviors and why damage to this region impacts intertemporal choice in this way.

   Read the original source
7. 

   Version published to 10.1101/2021.03.15.435400v2 on bioRxiv

   Jul 5, 2021
8. 

   Version published to 10.1101/2021.03.15.435400v1 on bioRxiv

   Mar 16, 2021