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.

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.

Awake brain surgery in children-a single-center experience.

INTRODUCTION: Awake brain surgery (ABS) represents a rare surgical procedure in children as age and psychological aspects, which are considered to interfere with its feasibility and psychological outcome and limit its application. Only few pediatric case series have been reported so far, indicating a more complex translation of this surgical approach to children. However, the advances in neuropsychological testing and monitoring may have a substantial impact on ameliorating the eligibility of children undergoing awake procedures. This study addresses the condition of ABS in a pediatric cohort, focusing on its practicability and diversified outcome aspects. METHODS: We performed a retrospective review and prospective outcome analysis of pediatric patients with CNS lesions undergoing ABS between 2005 and 2018, completed at the University of Lyon, France. RESULTS: Eighteen children were considered for ABS with respect to the eloquent location of their CNS lesions documented in their pre-operative MRI. Seventeen of them underwent asleep-awake-asleep brain surgery. The cohort included 5 males and 12 females. The median age at surgery was 14.8 years, (range 9.4 to 17.6 years). Intraoperative testing included electrocortical stimulation while pursuing speech or motor activity. Most of the lesions were intrinsic tumors of glial origin. A complete tumor removal was achieved in 11 patients (65%). Post-operative neurological deficits were transiently observed in 2 patients, whereas severe psychological reactions occurred in 1 child. Persistent attention deficits were found in 2 patients. One patient experienced an infectious complication requiring antibiotic treatment. Two patients died during follow-up due to tumor progression. The mean duration of follow up was 22.2 months (range 3.4 to 46.8 months). CONCLUSIONS: ABS was shown to be beneficial in terms of efficient tumor resection besides simultaneous preservation of neurological functions. Psychological preparation of the families and the children is essential to increase the number and age range of patients, who can benefit from this technique. Neuropsychological testing before and after surgery is essential to determine cognitive outcome, which can be altered in a minority of patients.

The effects of expected reward on creative problem solving.

Creative problem solving involves search processes, and it is known to be hard to motivate. Reward cues have been found to enhance performance across a range of tasks, even when cues are presented subliminally, without being consciously detected. It is uncertain whether motivational processes, such as reward, can influence problem solving. We tested the effect of supraliminal and subliminal reward on participant performance on problem solving that can be solved by deliberate analysis or by insight. Forty-one participants attempted to solve 100 compound remote associate problems. At the beginning of each problem, a potential reward cue (1 or 25 cents) was displayed, either subliminally (17 ms) or supraliminally (100 ms). Participants earned the displayed reward if they solved the problem correctly. Results showed that the higher subliminal reward increased the percentage of problems solved correctly overall. Second, we explored if subliminal rewards preferentially influenced solutions that were achieved via a sudden insight (mostly processed below awareness) or via a deliberate analysis. Participants solved more problems via insight following high subliminal reward when compared with low subliminal reward, and compared with high supraliminal reward, with no corresponding effect on analytic solving. Striatal dopamine (DA) is thought to influence motivation, reinforce behavior, and facilitate cognition. We speculate that subliminal rewards activate the striatal DA system, enhancing the kinds of automatic integrative processes that lead to more creative strategies for problem solving, without increasing the selectivity of attention, which could impede insight.

Brain Regions Influencing Implicit Violent Attitudes: A Lesion-Mapping Study.

Increased aggression is common after traumatic brain injuries and may persist after cognitive recovery. Maladaptive aggression and violence are associated with dysfunction in the prefrontal and temporal cortex, but such dysfunctional behaviors are typically measured by explicit scales and history. However, it is well known that answers on explicit scales on sensitive topics--such as aggressive thoughts and behaviors--may not reveal true tendencies. Here, we investigated the neural basis of implicit attitudes toward aggression in humans using a modified version of the Implicit Association Task (IAT) with a unique sample of 112 Vietnam War veterans who suffered penetrating brain injury and 33 healthy controls who also served in combat in Vietnam but had no history of brain injury. We hypothesized that dorsolateral prefrontal cortex (dlPFC) lesions, due to the crucial role of the dlPFC in response inhibition, could influence performance on the IAT. In addition, we investigated the causal contribution of specific brain areas to implicit attitudes toward violence. We found a more positive implicit attitude toward aggression among individuals with lesions to the dlPFC and inferior posterior temporal cortex (ipTC). Furthermore, executive functions were critically involved in regulating implicit attitudes toward violence and aggression. Our findings complement existing evidence on the neural basis of explicit aggression centered on the ventromedial prefrontal cortex. These findings highlight that dlPFC and ipTC play a causal role in modulating implicit attitudes about violence and are crucially involved in the pathogenesis of aggressive behavior. SIGNIFICANCE STATEMENT: Maladaptive aggression and violence can lead to interpersonal conflict and criminal behavior. Surprisingly little is known about implicit attitudes toward violence and aggression. Here, we used a range of techniques, including voxel-based lesion-symptom mapping, to examine the causal role of brain structures underpinning implicit attitudes toward aggression in a unique sample of combat veterans with traumatic brain injury. We found that damage to the dorsolateral prefrontal cortex (dlPFC) led to a more positive implicit attitude toward violence that under most normal situations would be considered inappropriate. These results suggest that treatments aimed at increasing cognitive control using cognitive behavioral therapies dependent on the intact dlPFC could treat aggressive and violent behavior.

Acute Isolated Paraplegia Revealing an Ewing Sarcoma of the Thoracic Spine.

Ewing sarcoma (ES) infrequently affects the spine. Diagnosis is usually made several weeks following growing symptoms. In this report, we present the case of a child with ES localized at the upper thoracic level. ES was revealed by isolated acute complete paraplegia mimicking medullary stroke. The girl was operated for decompressive laminectomy and tumor removal. Afterwards, she received adjuvant therapy. Subsequently, the child showed a slow improvement of her leg sensitivity associated with a partial motor recovery. ES can affect the mobile spine. Acute symptomatology due to intratumoral hemorrhage and sudden spinal cord compression may suggest the diagnosis. Neurological outcomes following ES are generally poor.

The effect of claustrum lesions on human consciousness and recovery of function.

Crick and Koch proposed that the claustrum plays a crucial role in consciousness. Their proposal was based on the structure and connectivity of the claustrum that suggested it had a role in coordinating a set of diverse brain functions. Given the few human studies investigating this claim, we decided to study the effects of claustrum lesions on consciousness in 171 combat veterans with penetrating traumatic brain injuries. Additionally, we studied the effects of claustrum lesions and loss of consciousness on long-term cognitive abilities. Claustrum damage was associated with the duration, but not frequency, of loss of consciousness, indicating that the claustrum may have an important role in regaining, but not maintaining, consciousness. Total brain volume loss, but not claustrum lesions, was associated with long-term recovery of neurobehavioral functions. Our findings constrain the current understanding of the neurobehavioral functions of the claustrum and its role in maintaining and regaining consciousness.

Theta signal as the neural signature of social exclusion.

The feeling of being excluded from a social interaction triggers social pain, a sensation as intense as actual physical pain. Little is known about the neurophysiological underpinnings of social pain. We addressed this issue using intracranial electroencephalography in 15 patients performing a ball game where inclusion and exclusion blocks were alternated. Time-frequency analyses showed an increase in power of theta-band oscillations during exclusion in the anterior insula (AI) and posterior insula, the subgenual anterior cingulate cortex (sACC), and the fusiform "face area" (FFA). Interestingly, the AI showed an initial fast response to exclusion but the signal rapidly faded out. Activity in the sACC gradually increased and remained significant thereafter. This suggests that the AI may signal social pain by detecting emotional distress caused by the exclusion, whereas the sACC may be linked to the learning aspects of social pain. Theta activity in the FFA was time-locked to the observation of a player poised to exclude the participant, suggesting that the FFA encodes the social value of faces. Taken together, our findings suggest that theta activity represents the neural signature of social pain. The time course of this signal varies across regions important for processing emotional features linked to social information.

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.

Culture-free perceptual invariant for trustworthiness.

Humans beings decide to trust others selectively, often based on the appearance of a face. But how do observers deal with the wide variety of facial morphologies and, in particular, those outside their own familiar cultural group? Using reverse correlation, a data-driven approach to explore how individuals create internal representations without external biases, we studied the generation of trustworthy faces by French and Chinese participants (N = 160) within and outside their own cultural group. Participants selected the most trustworthy or attractive (control condition) face from two identical European or Asian descent faces that had been modified by different noise masks. A conjunction analysis to reveal facial features common to both cultures showed that Chinese and French participants unconsciously increased the contrast of the "pupil-iris area" to make the face appear more trustworthy. No significant effects common to both groups were found for the attraction condition suggesting that attraction judgements are dependent on cultural processes. These results suggest the presence of universal cross-cultural mechanisms for the construction of implicit first impressions of trust, and highlight the importance of the eyes area in this process.

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.

Cerebellar lesions at a young age predict poorer long-term functional recovery.

Early studies on long-term functional recovery after motor and premotor lesions showed better outcomes in younger monkeys than in older monkeys. This finding led to the widespread belief that brain injuries cause less impairment in children than adults. However, this view has limitations and a large body of evidence now indicates that cerebral damages can be more harmful when inflicted at young age, during critical periods of neural development. To date, this issue has been mainly investigated in the context of focal and diffuse cortical lesions. Much less is known about the potential influence of early cerebellar damages. Several studies exist in survivor of posterior fossa tumours. However, in these studies, critical confounders were not always considered and contradictory conclusions were provided. We studied the impact or early cerebellar damage on long-term functional recovery in three groups of 15 posterior fossa survivors, comparable with respect to their tumour characteristics (type, size and location) but operated at different ages: young (≤7 years), middle (>7 and ≤13 years) and older (>13 years). Daily (health-related quality of life scale, performance status scale), motor (International Cooperative Ataxia Rating Scale, Pegboard Purdue Test) and cognitive (full-scale intelligence quotient) functioning were assessed. A general linear model controlling for age at surgery, radiotherapy, preservation of deep cerebellar nuclei, tumour volume and delay between surgery and assessment was used to investigate significant variations in outcome measures. Early age at surgery, lesion of deep cerebellar nuclei and postoperative radiotherapy had a significant, independent negative influence on long-term recovery. Tumour volume and delay between surgery and assessment had no statistically detectable impact. The negative influence of early age at surgery was significant in all domains: daily functioning (health-related quality of life scale, performance status scale), motor functioning (International Cooperative Ataxia Rating Scale, Pegboard Purdue Test) and cognitive functioning (full-scale intelligence quotient). These results support the existence of an early critical period of development during which the cerebellar 'learning machine' is of critical importance. Although the extent to which the early deficits here observed can be reversed needs now to be established, our data plead for the implementation of prompt and intense rehabilitation interventions in children operated before 7 years of age.

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.

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.

Biological and cognitive underpinnings of religious fundamentalism.

Beliefs profoundly affect people's lives, but their cognitive and neural pathways are poorly understood. Although previous research has identified the ventromedial prefrontal cortex (vmPFC) as critical to representing religious beliefs, the means by which vmPFC enables religious belief is uncertain. We hypothesized that the vmPFC represents diverse religious beliefs and that a vmPFC lesion would be associated with religious fundamentalism, or the narrowing of religious beliefs. To test this prediction, we assessed religious adherence with a widely-used religious fundamentalism scale in a large sample of 119 patients with penetrating traumatic brain injury (pTBI). If the vmPFC is crucial to modulating diverse personal religious beliefs, we predicted that pTBI patients with lesions to the vmPFC would exhibit greater fundamentalism, and that this would be modulated by cognitive flexibility and trait openness. Instead, we found that participants with dorsolateral prefrontal cortex (dlPFC) lesions have fundamentalist beliefs similar to patients with vmPFC lesions and that the effect of a dlPFC lesion on fundamentalism was significantly mediated by decreased cognitive flexibility and openness. These findings indicate that cognitive flexibility and openness are necessary for flexible and adaptive religious commitment, and that such diversity of religious thought is dependent on dlPFC functionality.

The politics of insight.

Previous studies showed that liberals and conservatives differ in cognitive style. Liberals are more flexible, and tolerant of complexity and novelty, whereas conservatives are more rigid, are more resistant to change, and prefer clear answers. We administered a set of compound remote associate problems, a task extensively used to differentiate problem-solving styles (via insight or analysis). Using this task, several researches have proven that self-reports, which differentiate between insight and analytic problem-solving, are reliable and are associated with two different neural circuits. In our research we found that participants self-identifying with distinct political orientations demonstrated differences in problem-solving strategy. Liberals solved significantly more problems via insight instead of in a step-by-step analytic fashion. Our findings extend previous observations that self-identified political orientations reflect differences in cognitive styles. More specifically, we show that type of political orientation is associated with problem-solving strategy. The data converge with previous neurobehavioural and cognitive studies indicating a link between cognitive style and the psychological mechanisms that mediate political beliefs.

Neural correlates of mystical experience.

Mystical experiences, or subjectively believed encounters with a supernatural world, are widely reported across cultures and throughout human history. Previous theories speculate that executive brain functions underpin mystical experiences. To evaluate causal hypotheses, structural studies of brain lesion are required. Previous studies suffer from small samples or do not have valid measures of cognitive functioning prior to injury. We investigated mystical experience among participants from the Vietnam Head Injury Study and compared those who suffered penetrating traumatic brain injury (pTBI; n=116) with matched healthy controls (HC; n=32). Voxel-based lesion-symptom mapping analysis showed that lesions to frontal and temporal brain regions were linked with greater mystical experiences. Such regions included the dorsolateral prefrontal cortex (dlPFC) and middle/superior temporal cortex (TC). In a confirmatory analysis, we grouped pTBI patients by lesion location and compared mysticism experiences with the HC group. The dlPFC group presented markedly increased mysticism. Notably, longitudinal analysis of pre-injury data (correlating with general intelligence and executive performance) excludes explanations from individual differences. Our findings support previous speculation linking executive brain functions to mystical experiences, and reveal that executive functioning (dlPFC) causally contributes to the down-regulation of mystical experiences.

Traumatic brain injury and cognition.

Traumatic brain injury (TBI) is a major cause of death and disability, and therefore an important health and socioeconomic problem for our society. Individuals surviving from a moderate to severe TBI frequently suffer from long-lasting cognitive deficits. Such deficits include different aspects of cognition such as memory, attention, executive functions, and awareness of their deficits. This chapter presents a review of the main neuropsychological and neuroimaging studies of patients with TBI. These studies found that patients evolve differently according to the severity of the injury, the mechanism causing the injury, and the lesion location. Further research is necessary to develop rehabilitation methods that enhance brain plasticity and recovery after TBI. In this chapter, we summarize current knowledge and controversies, focusing on cognitive sequelae after TBI. Recommendations from the Common Data Elements are provided, with an emphasis on diagnosis, outcome measures, and studies organization to make data more comparable across studies. Final considerations on neuroimaging advances, rehabilitation approaches, and genetics are described in the final section of the chapter.