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.

The shifting role of the cerebellum in executive, emotional and social processing across the lifespan.

The cerebellum's anatomical and functional organization and network interactions between the cerebellum and the cerebral cortex and subcortical structures are dynamic across the lifespan. Executive, emotional and social (EES) functions have likewise evolved during human development from contributing to primitive behaviors during infancy and childhood to being able to modulate complex actions in adults. In this review, we address how the importance of the cerebellum in the processing of EES functions might change across development. This evolution is driven by the macroscopic and microscopic modifications of the cerebellum that are occurring during development including its increasing connectivity with distant supra-tentorial cortical and sub-cortical regions. As a result of anatomical and functional changes, neuroimaging and clinical data indicate that the importance of the role of the cerebellum in human EES-related networks shifts from being crucial in newborns and young children to being only supportive later in life. In early life, given the immaturity of cortically mediated EES functions, EES functions and motor control and perception are more closely interrelated. At that time, the cerebellum due to its important role in motor control and sequencing makes EES functions more reliant on these computational properties that compute spatial distance, motor intent, and assist in the execution of sequences of behavior related to their developing EES expression. As the cortical brain matures, EES functions and decisions become less dependent upon these aspects of motor behavior and more dependent upon high-order cognitive and social conceptual processes. At that time, the cerebellum assumes a supportive role in these EES-related behaviors by computing their motor and sequential features. We suspect that this evolving role of the cerebellum has complicated the interpretation of its contribution to EES computational demands.

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.

Measuring visual electrophysiological responses in individuals with low-functioning autism: a feasibility and pilot study.

BACKGROUND: Although visual abnormalities are considered common in individuals with autism spectrum disorders, the associated electrophysiological markers have remained elusive. One impediment has been that methodological challenges often preclude testing individuals with low-functioning autism (LFA). METHODS: In this feasibility and pilot study, we tested a hybrid visual evoked potential paradigm tailored to individuals with LFA that combines passively presented visual stimuli to elicit scalp-recorded evoked responses with a behavioral paradigm to maintain visual attention. We conducted a pilot study to explore differences in visual evoked response patterns across three groups: individuals with LFA, with high-functioning autism (HFA), and with typical development. RESULTS: All participants with LFA met criteria for study feasibility by completing the recordings and producing measurable cortical evoked waveform responses. The LFA group had longer (delayed) cortical response latencies on average as compared with the HFA and typical development groups. We also observed group differences in visually induced alpha spectral power: the LFA group showed little to no prestimulus alpha activity in contrast to the HFA and typical development groups that showed increased prestimulus alpha activity. This observation was confirmed by the bootstrapped confidence intervals, suggesting that the absence of prestimulus alpha power may be a potential electrophysiological marker of LFA. CONCLUSION: Our results confirm the utility of tailoring visual electrophysiology paradigms to individuals with LFA in order to facilitate inclusion of individuals across the autism spectrum in studies of visual processing.

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.

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.

Lack of awareness despite complex visual processing: Evidence from event-related potentials in a case of selective metamorphopsia.

Visual awareness is thought to result from integration of low- and high-level processing; instances of integration failure provide a crucial window into the cognitive and neural bases of awareness. We present neurophysiological evidence of complex cognitive processing in the absence of awareness, raising questions about the conditions necessary for visual awareness. We describe an individual with a neurodegenerative disease who exhibits impaired visual awareness for the digits 2 to 9, and stimuli presented in close proximity to these digits, due to perceptual distortion. We identified robust event-related potential responses indicating 1) face detection with the N170 component and 2) task-dependent target-word detection with the P3b component, despite no awareness of the presence of faces or target words. These data force us to reconsider the relationship between neural processing and visual awareness; even stimuli processed by a workspace-like cognitive system can remain inaccessible to awareness. We discuss how this finding challenges and constrains theories of visual awareness.

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.

Psychoeducational Interventions for Adults With Level 3 Autism Spectrum Disorder: A 50-Year Systematic Review.

There is face validity to the expectation that adults with level 3 autism spectrum disorder (ASD-3) will benefit from a range of psychoeducational interventions. This paper reviews the empirical evidence supporting the effectiveness of these interventions, many of which are currently used in clinical settings. We reviewed 56 peer-reviewed studies of psychoeducational interventions for adults with ASD-3, written in English and since 1968, that met our criteria. The reviewing team included educators, clinicians, researchers, and a biostatistician. The available literature was limited, and most, if not all, of the studies presented some significant methodological limitations. When using Cochrane's criteria to assess seven key outcome domains-activities of daily living, aggressive/destructive behaviors, emotional functioning, language/communication skills, self-injurious behaviors, stereotypy/mannerisms, and vocational skills-we found only moderately reliable evidence to support the effectiveness of interventions designed to improve emotional functioning in adults with ASD-3. The reliability of evidence relevant to the six other outcome domains was rated as low or very low. Based on this review, we suggest directions for future study of interventions for adults with ASD-3, including topics, subpopulations, and approaches that should be explored. We also propose some crucial changes in how future studies regarding this population should be designed, analyzed, and documented, while balancing clinical considerations with scientific/educational utility.

Implicit Measures of Receptive Vocabulary Knowledge in Individuals With Level 3 Autism.

Implicit measures of cognition are essential for assessing knowledge in people with Level 3 autism because such individuals are often unable to make reliable overt behavioral responses. In this study, we investigated whether three implicit measures-eye movement (EM) monitoring, pupillary dilation (PD), and event-related potentials (ERPs)-can be used to reliably estimate vocabulary knowledge in individuals with Level 3 autism. Five adults with Level 3 autism were tested in a repeated-measures design with two tasks. High-frequency 'known' words (eg, bus, airplane) and low-frequency 'unknown' words (eg, ackee, cherimoya) were presented in a visual world task (during which EM and PD data were collected) and a picture-word congruity task (during which ERP data were collected). Using a case-study approach with single-subject analyses, we found that these implicit measures have the potential to provide estimates of receptive vocabulary knowledge in individuals with Level 3 autism. Participants differed with respect to which measures were the most sensitive and which variables best predicted vocabulary knowledge. These implicit measures may be useful to assess language abilities in individuals with Level 3 autism, but their use should be tailored to each individual.

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.

The lonely brain: evidence from studying patients with penetrating brain injury.

Loneliness is perceived as social isolation and exclusion. The neural substrate of loneliness has been investigated with functional neuroimaging; however, lesion-based studies and their associated outcomes are needed to infer causal involvement between brain regions and function. Here, we applied voxel-based lesion-symptom mapping (VLSM) analyses to investigate the causal role of brain lesions on self-report of loneliness (UCLA Loneliness Scale) in a unique sample from the Vietnam Head Injury Study, including veterans with penetrating traumatic brain injuries (pTBI) (n = 132) and healthy controls (HCs) (n = 35). Our results revealed that the right anterior insula (AI) and right prefrontal cortex (PFC) are key brain regions underpinning loneliness perception. Individuals with selective lesions to the right AI and right PFC were less likely to report loneliness compared to patients with selective lesions to the posterior cortex and HCs. Therefore, it appears that lesions to key regions involved in processing social pain act to lower the perception of loneliness. Reporting loneliness was associated with executive dysfunction, apathy, disinhibition, and lower life satisfaction. In conclusion, the reported findings broaden our understanding of how loneliness is processed in the social brain, and how behavioral and cognitive factors can influence this perception.

Visual and linguistic narrative comprehension in autism spectrum disorders: Neural evidence for modality-independent impairments.

Individuals with autism spectrum disorders (ASD) have notable language difficulties, including with understanding narratives. However, most narrative comprehension studies have used written or spoken narratives, making it unclear whether narrative difficulties stem from language impairments or more global impairments in the kinds of general cognitive processes (such as understanding meaning and structural sequencing) that are involved in narrative comprehension. Using event-related potentials (ERPs), we directly compared semantic comprehension of linguistic narratives (short sentences) and visual narratives (comic panels) in adults with ASD and typically-developing (TD) adults. Compared to the TD group, the ASD group showed reduced N400 effects for both linguistic and visual narratives, suggesting comprehension impairments for both types of narratives and thereby implicating a more domain-general impairment. Based on these results, we propose that individuals with ASD use a more bottom-up style of processing during narrative comprehension.

Anterior insula lesions and alexithymia reduce the endorsements of everyday altruistic attitudes.

Neuroimaging studies have reported a large network of brain regions involved in altruism. However, these studies are unable to determine if these regions are necessary for altruistic attitudes. Here, we examined the brain-basis of everyday altruistic attitudes ([Self-Report Altruism Scale]; e.g., helping a stranger with car troubles) and potential factors (i.e., alexithymia [Toronto Alexithymia Scale] such as empathic concern [Interpersonal Reactivity Index]) that may moderate this relationship. We carried out whole-brain voxel-based lesion-symptom mapping and region of interest analyses to study a large sample of patients (n = 130) with penetrating traumatic brain injuries. Our results showed that the effect of anterior insula (AI) lesions was moderated by alexithymia, but not empathic concern. The presence of AI lesions, as well as increased alexithymia, were associated with fewer endorsements of resource-costly altruistic attitudes. Empathic concern was positively correlated with endorsements of resource-costly altruistic attitudes. Taken together, our study provides direct evidence that the AI and alexithymia play crucial roles in everyday altruistic attitudes and reinforces the importance of the emotional experience in altruism.