Studying the social mind: An updated summary of findings from the Vietnam Head Injury Study.

Lesion mapping studies allow us to evaluate the potential causal contribution of specific brain areas to human cognition and complement other cognitive neuroscience methods, as several authors have recently pointed out. Here, we present an updated summary of the findings from the Vietnam Head Injury Study (VHIS) focusing on the studies conducted over the last decade, that examined the social mind and its intricate neural and cognitive underpinnings. The VHIS is a prospective, long-term follow-up study of Vietnam veterans with penetrating traumatic brain injury (pTBI) and healthy controls (HC). The scope of the work is to present the studies from the latest phases (3 and 4) of the VHIS, 70 studies since 2011, when the Raymont et al. paper was published (Raymont et al., 2011). These studies have contributed to our understanding of human social cognition, including political and religious beliefs, theory of mind, but also executive functions, intelligence, and personality. This work finally discusses the usefulness of lesion mapping as an approach to understanding the functions of the human brain from basic science and clinical perspectives.

Understanding altruistic behavior: The joint role of prefrontal damage and OXTR genotype.

Altruism is a type of prosocial behavior that is carried out in the absence of personal benefit or even at an expense to self. Trait altruism varies greatly across individuals, and the reasons for this variability are still not fully understood. Growing evidence suggests that altruism may be partly determined by the oxytocin receptor (OXTR) gene, which regulates the emotions underlying altruistic attitudes, such as empathy and trust. Neuroimaging and lesion studies have also implied several higher-order brain regions, including the prefrontal cortex, in altruistic behaviors. Yet the existing reports are contradictory and suggest that the top-down control exercised by the prefrontal cortex may promote both altruistic and self-interested behaviors and, thus, could obscure one's natural proclivity towards altruism encoded by OXTR. Here, we hypothesized that extensive prefrontal damage would result in an increased influence of the OXTR genotype on one's altruistic attitudes and actions. To test this hypothesis, we recruited 115 male combat veterans with penetrating traumatic brain injury to the prefrontal cortex and other brain regions, as well as 35 demographically matched control subjects without brain injury. Participants completed a self-report altruism questionnaire and were genotyped for four OXTR single nucleotide polymorphisms implicated in prosocial behavior, including rs53576, rs1042778, rs2254298 and rs7632287. Consistent with the previous studies, we found that individuals homozygotic for the G allele of rs53576 and rs7632287 were significantly more altruistic than carriers of at least one "vulnerable" A allele. Remarkably, in patients with prefrontal cortex damage, greater lesion extent was associated with significantly lower altruism scores in carriers of the A allele of rs7632287, but not in G-homozygotes, suggesting that significant disruption of the prefrontal cortex increased the influence of genetic polymorphisms on prosocial behavior. This study presents the first account of an interaction effect between the OXTR genotype and the location and extent of brain damage.

Evidence of the role of the cerebellum in cognitive theory of mind using voxel-based lesion mapping.

Theory of Mind (ToM) is a social-cognitive skill that allows the understanding of the intentions, beliefs, and desires of others. There is a distinction between affective and cognitive ToM, with evidence showing that these processes rely on partially distinct neural networks. The role of the cerebellum in social cognition has only been rarely explored. In this study, we tested whether the cerebellum is necessary for cognitive and affective ToM performance. We investigated adults with traumatic brain injury (n = 193) and healthy controls (n = 52) using voxel-based lesion-symptom mapping (VLSM) and by measuring the impact on functional connectivity. First, we observed that damage to the cerebellum affected pure Cognitive ToM processing. Further, we found a lateralization effect for the role of the cerebellum in cognitive ToM with participants with left cerebellar injury performing worse than those with right cerebellar injury. Both VLSM and standard statistical analysis provided evidence that left cerebellar Crus I and lobule VI contributed to ToM processing. Lastly, we found that disconnection of the left thalamic projection and the left fronto-striatal fasciculus was associated with poor cognitive ToM performance. Our study is the first to reveal direct causal neuropsychological evidence for a role of the cerebellum in some but not all types of ToM, processing. It reinforces the idea that social cognition relies on a complex network functionally connected through white matter pathways that include the cerebellum. It supports evidence that the neural networks underpinning the different types of ToM can be differentiated.

Brain networks involved in the influence of religion on empathy in male Vietnam War veterans.

Humans all over the world believe in spirits and deities, yet how the brain supports religious cognition remains unclear. Drawing on a unique sample of patients with penetrating traumatic brain injuries (pTBI) and matched healthy controls (HCs) we investigate dependencies of religious cognition on neural networks that represent (1) others agents' intentions (Theory of Mind, ToM) and (2) other agents' feelings (Empathy). Extending previous observations that ToM networks are recruited during prayer, we find that people with vmPFC damage report higher scores on the personal relationship with God inventory even when they are not praying. This result offers evidence that it is the modulation of ToM networks that support beliefs in supernatural agents. With respect to empathetic processing, we observed that vmPFC and pSTS/TPJ lesions mediated by the strength of the personal relationship with God affect empathetic responses. We suggest that the neurological networks underpinning God representations amplify human empathetic responses. The cultural evolutionary study of religion has argued that supernatural beliefs evoke pro-social responses because people fear the wrath of Gods. Our findings imply greater attention should be paid to the mechanisms by which religious cognition may regulate empathetic responses to others.

Determinants of caregiver burden in male patients with epilepsy following penetrating traumatic brain injury.

PURPOSE: We determined burden of caring for patients with post-traumatic epilepsy (PTE) following penetrating traumatic brain injury (TBI) and identified factors predicting higher burden. METHOD: We assessed 331 caregiver-veteran dyads in Phase 2 (136 PTE, 136 non-PTE, and 59 HC dyads), 133 in Phase 4 (47 PTE, 56 non-PTE, and 30 HC dyads) - 30 years later, and 46 dyads in the follow-up study (18 PTE, 19 non-PTE, and 9 HC). Caregiver's burden was measured by Zarit Burden Index and a questionnaire. Veterans completed demographic, mental and physical well-being, quality-of-life, and medical-related information. Caregivers provided information about burden and their assessments of cognitive decline and neuropsychiatric status of the veterans. RESULTS: PTE caregivers perceived significantly more burden than comparison groups at all phases. Bivariate analyses revealed that caregiver distress due to the veteran's neuropsychiatric state including cognitive decline, apathy, and disinhibition and the veteran's characteristics including older age at epilepsy onset and role limitation due to physical problems were associated with higher burden. Finally, we revealed disinhibition distress, and role imitation due to physical problems as the predictors in a model of caregiver burden. CONCLUSION: Elevated PTE caregiver burden is persistent across the life span suggesting that caregivers could benefit from counseling and targeted psychosocial interventions to reduce their burden.

The neural basis for mental state attribution: A voxel-based lesion mapping study.

The ability to infer other persons' mental states, "Theory of Mind" (ToM), is a key function of social cognition and is needed when interpreting the intention of others. ToM is associated with a network of functionally related regions, with reportedly key prominent hubs located in the dorsolateral prefrontal cortex (dlPFC) and the temporoparietal junction (TPJ). The involvement of (mainly the right) TPJ in ToM is based primarily on functional imaging studies that provide correlational evidence for brain-behavior associations. In this lesion study, we test whether certain brain areas are necessary for intact ToM performance. We investigated individuals with penetrating traumatic brain injury (n = 170) and healthy matched controls (n = 30) using voxel-based lesion-symptom mapping (VLSM) and by measuring the impact of a given lesion on white matter disconnections. ToM performance was compared between five patient groups based on lesion location: right TPJ, left TPJ, right dlPFC, left dlPFC, and other lesion, as well as healthy controls. The only group to present with lower ToM abilities was the one with lesions in the right dlPFC. Similarly, VLSM analysis revealed a main cluster in the right frontal middle gyrus and a secondary cluster in the left inferior parietal gyrus. Last, we found that disconnection of the left inferior longitudinal fasciculus and right superior longitudinal fasciculus were associated with poor ToM performance. This study highlights the importance of lesion studies in complementing functional neuroimaging findings and supports the assertion that the right dlPFC is a key region mediating mental state attribution.

Neural underpinning of a personal relationship with God and sense of control: A lesion-mapping study.

A strong personal relationship with God is theoretically and empirically associated with an enhanced sense of control. While a growing body of research is focused on understanding the neural mechanisms underlying religious belief, little is known about the brain basis of the link between a personal relationship with God and sense of control. Here, we used a sample of patients with focal brain lesions (N = 84) and matched healthy controls (N = 22) to determine whether damage to the ventromedial prefrontal cortex (vmPFC)-a region associated with emotionally meaningful religious experiences and with sense of control-will modulate self-reports of a personal relationship with God and sense of control. We also examined potential mediators for these associations. Voxel-based lesion symptom mapping revealed that damage to the right vmPFC resulted in a stronger personal relationship with God, and patients with damage to this region demonstrated an increased sense of control relative to patients with damage to posterior cortex and healthy controls. Moreover, the association between vmPFC damage and greater perceived sense of control was mediated by a stronger personal relationship with God. Collectively, these results suggest that a strong personal relationship with God can serve an important psychological function by affecting sense of control, with both enhanced following damage to the right vmPFC.

A New Insight on the Role of the Cerebellum for Executive Functions and Emotion Processing in Adults.

Objective: We investigated whether the cerebellum plays a critical or supportive role in in executive and emotion processes in adults. Many investigators now espouse the hypothesis that participants with cerebellar lesions experience executive functions and emotions (EE) disorders. But we hypothesized that these disorders would be milder if the damage is relatively limited to the cerebellum compared to damage involving the cerebellum plus additional cortical areas. Methods: We studied veterans with penetrating Traumatic Brain Injury (pTBI) participating in the Vietnam Head Injury Study (VHIS). We selected veterans with a cerebellar lesion (n = 24), a prefrontal cortex lesion (n = 20), along with healthy controls (HC) (n = 55). Tests of executive functions and emotions were analyzed as well as caregiver burden. We performed between-group null hypothesis significance testing, Bayesian hypothesis tests and correlational analyses. Results: Performance of participants with cerebellar lesions which extended to the cerebral cortex was similar to the HC on the Executive Function tests but they were significantly impaired on the Working Memory Index. No differences were found on the emotional processing tasks with one exception-the Facial Expression of Emotion-Test (FEEST). We then examined a sub-group of participants with large cerebellar lesions (>15%) but minimal lesions in the cerebral cortex (<15%). This sub-group of participants performed similarly to the HC on the Working Memory Index and on the FEEST. Conclusions: We suggest that the cerebellar cortex may not be critical for executive functions or processing emotional stimuli in adults as suggested. Instead, we find that the cerebellum has a supportive role characterized by its computing of the motor requirements when EE processing is required.

Executive functions.

Executive functions (EFs) include high-order cognitive abilities such as working memory, inhibitory control, cognitive flexibility, planning, reasoning, and problem solving. EFs enable humans to achieve goals, adapt to novel everyday life situations, and manage social interactions. Traditionally EFs have been associated with frontal lobe functioning. More recent evidence shows that posterior and subcortical regions also play a crucial role in EF processing, especially in the integration of sensory information and emotion. This chapter reviews the variety of EFs and their neural underpinning, based on lesion mapping and neuroimaging studies, as well as the evidence for rehabilitation interventions, neuropsychological assessment based on standard and ecologically valid tests, development, and genetic predisposition for recovery of executive functions after brain injury. Taken together, the EFs are critical for unique human abilities and more careful analyses of their subcomponents may help the development of targeted translational interventions to improve them.

Suicidal ideation and behavior in Huntington's disease: Systematic review and recommendations.

BACKGROUND: An increased risk of suicide in Huntington's disease (HD) patients is well documented, with rates significantly higher than those of the general population as well as other neurodegenerative diseases. However, despite its prevalence, the magnitude of this phenomenon as well as its predictors and etiology are still poorly understood. METHODS: We performed the first systematic review of all the studies published between March 1993 and December 2018 which investigated HD patients and gene carriers that reported suicidal ideation, suicide attempt, or suicide as an outcome. RESULTS: This review reveals that some aspects of suicidality in HD are more clearly understood than others. We confirm an increased risk of suicidal ideation, suicide attempt, and suicide for HD patients. We found that suicidal ideation is elevated throughout the course of the disease, and that psychiatric comorbidities are common risk factors with depression being the most prominent. LIMITATIONS: Important data are still largely missing, specifically regarding cognitive and neuroanatomical mechanisms and potential effective interventions. Moreover, inconsistencies in terminology, assessment tools, and outcome measures limit the comparability of the research and the conclusions that can be drawn. CONCLUSIONS: Incidence of suicidal ideation, suicide attempt, and suicide are higher among those with HD relative to the non-HD population. It is therefore important that suicidal thoughts and behaviors are closely monitored in HD clinics and that clinical trials use standardized scales. Future research should focus on better understanding the etiology of this high suicide risk and on testing the efficacy of potential interventions.

Childhood socioeconomic status predicts cognitive outcomes across adulthood following traumatic brain injury.

OBJECTIVE: To examine the association between childhood socioeconomic status (SES) and the level and rate of change in intelligence scores throughout adulthood following traumatic brain injury (TBI). METHODS: In this longitudinal study we tested 186 patients with TBI and 54 healthy controls from the Vietnam Head Injury Study. Childhood SES was determined for each participant based on parental educational attainment and occupational prestige. General intelligence was initially assessed pre-injury upon induction into the military, and again 15, 35 and 40+ years post-injury. We examined whether childhood SES, total brain volume loss and lesion laterality can predict post-injury intelligence scores and the rate of change in those scores between study phases. RESULTS: For both participants with and without TBI, childhood SES accounted for a significant portion of the variance in intelligence scores pre-injury and in all three post-injury evaluations, however, it was not associated with the rate of cognitive change. Lastly, childhood SES predicted cognitive outcome among patients with left hemisphere damage better than it did for right hemisphere damage patients. CONCLUSIONS: These findings provide the first evidence indicating the persistent effects of childhood SES on intelligence scores later in adulthood following a TBI. Childhood SES should be considered when predicting and assessing cognitive recovery following TBI, even when the injury occurred in adulthood.

Implicit motivation improves executive functions of older adults.

It is widely accepted that while controlled processes (e.g., working memory and executive functions) decline with age, implicit (automatic) processes are not affected by age. In this paper we challenge this view by arguing that high-level automatic processes (e.g., recruiting motivation) decline with age, and that this decline plays an unappreciated role in cognitive aging. Specifically, we hypothesized that due to their decline, automatic motivational processes are less likely to be spontaneously activated in old age; thus, implicit external activation of them should have stronger effects on older (vs. younger) adults. In two experiments we used different methods of implicitly activating motivation, and measured executive functions of younger and older adults using the Wisconsin Card Sorting Test. In both experiments, implicit modulation of motivation resulted in improved executive functioning for older adults. The framework we propose is general and offers a new look at various aspects of cognitive aging.

Intelligence across the seventh decade in patients with brain injuries acquired in young adulthood.

In this longitudinal study, we examined intelligence in a group of Vietnam veterans in their 60 s who suffered combat-related penetrating traumatic brain injuries (pTBI) in their 20 s (n = 120), as well as matched veterans with no brain damage (n = 33). Intelligence was evaluated using the Armed Forces Qualification Test (AFQT) administered before the injury occurred and then again at three points in time over the following 45 years. We tested for potential predictors and correlates of late midlife intelligence score, as well as the recent change in score over the seventh decade. The pTBI group had lower intelligence scores than the control group when currently evaluated. Pre-injury intelligence and the presence of a pTBI were the most consistent predictors of current intelligence scores. While exacerbated intellectual decline occurs following a young-adulthood pTBI and affects everyday life, no evidence for late midlife accelerated cognitive decline or dementia was found.

Machiavellian tendencies increase following damage to the left dorsolateral prefrontal cortex.

Machiavellianism - a personality trait that is characterized by a tendency to distrust, deceive and exploit others - has been the focus of growing attention in psychological research. Neuroimaging studies of Machiavellianism highlight the influence of the dorsolateral prefrontal cortex (dlPFC) on Machiavellianism tendencies. However, knowledge regarding the causal role of the left and right dlPFC on Machiavellianism is still obscure. Here, we measured general Machiavellian tendencies, as well as two subscales (i.e., Machiavellian Views and Machiavellian Tactics) in a large sample of brain-injured patients (N = 129) and non-brain-injured control participants (N = 37) to determine whether Machiavellianism tendencies can be altered by brain damage. We analyzed Machiavellianism tendencies as a function of lesion location, with patients separated into four groups based on dlPFC damage: left dlPFC damage, right dlPFC damage, non-dlPFC damage, and healthy controls. We found that left dlPFC damage increased Machiavellianism in general, and Machiavellian perspective (views) in particular, but did not modulate behavior (tactics). Critically, left dlPFC damage predicted higher levels of Machiavellianism after controlling for general and emotional intelligence, linguistic abilities, empathy and psychopathology. These findings establish a causal role of the left dlPFC in modulating Machiavellian views, and indicate that one can hold Machiavellian views without necessarily endorsing Machiavellian tactics.