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.

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.

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.

Altruistic decisions following penetrating traumatic brain injury.

The cerebral correlates of altruistic decisions have increasingly attracted the interest of neuroscientists. To date, investigations on the neural underpinnings of altruistic decisions have primarily been conducted in healthy adults undergoing functional neuroimaging as they engaged in decisions to punish third parties. The chief purpose of the present study was to investigate altruistic decisions following focal brain damage with a novel altruistic decision task. In contrast to studies that have focused either on altruistic punishment or donation, the Altruistic Decision Task allows players to anonymously punish or donate to 30 charitable organizations involved with salient societal issues such as abortion, nuclear energy and civil rights. Ninety-four Vietnam War veterans with variable patterns of penetrating traumatic brain injury and 28 healthy veterans who also served in combat participated in the study as normal controls. Participants were asked to invest $1 to punish or reward real societal organizations, or keep the money for themselves. Associations between lesion distribution and performance on the task were analysed with multivariate support vector regression, which enables the assessment of the joint contribution of multiple regions in the determination of a given behaviour of interest. Our main findings were: (i) bilateral dorsomedial prefrontal lesions increased altruistic punishment, whereas lesions of the right perisylvian region and left temporo-insular cortex decreased punishment; (ii) altruistic donations were increased by bilateral lesions of the dorsomedial parietal cortex, whereas lesions of the right posterior superior temporal sulcus and middle temporal gyri decreased donations; (iii) altruistic punishment and donation were only weakly correlated, emphasizing their dissociable neuroanatomical associations; and (iv) altruistic decisions were not related to post-traumatic personality changes. These findings indicate that altruistic punishment and donation are determined by largely non-overlapping cerebral regions, which have previously been implicated in social cognition and moral experience such as evaluations of intentionality and intuitions of justice and morality.10.1093/brain/awy064_video1awy064media15758316955001.

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.

Auditory Brainstem Pathology in Autism Spectrum Disorder: A Review.

Atypical responses to sound are common in individuals with autism spectrum disorder (ASD), and growing evidence suggests an underlying auditory brainstem pathology. This review of the literature provides a comprehensive account of the structural and functional evidence for auditory brainstem abnormalities in ASD. The studies reviewed were published between 1975 and 2016 and were sourced from multiple online databases. Indices of both the quantity and quality of the studies reviewed are considered. Findings show converging evidence for auditory brainstem pathology in ASD, although the specific functions and anatomical structures involved remain equivocal. Two main trends emerge from the literature: (1) abnormalities occur mainly at higher levels of the auditory brainstem, according to structural imaging and electrophysiology studies; and (2) brainstem abnormalities appear to be more common in younger than older children with ASD. These findings suggest delayed maturation of neural transmission pathways between lower and higher levels of the brainstem and are consistent with the auditory disorders commonly observed in ASD, including atypical sound sensitivity, poor sound localization, and difficulty listening in background noise. Limitations of existing studies are discussed, and recommendations for future research are offered.

Do clinical features of Lesch-Nyhan disease correlate more closely with hypoxanthine or guanine recycling?

Lesch-Nyhan disease (LND) is a rare, X-linked recessive neurodevelopmental disorder caused by deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGprt), an enzyme in the purine salvage pathway. HGprt has two functions; it recycles hypoxanthine and guanine. Which of these two functions is more relevant for pathogenesis is unclear because some evidence points to hypoxanthine recycling, but other evidence points to guanine recycling. In this study, we selectively assayed hypoxanthine (Hprt) and guanine (Gprt) recycling in skin fibroblasts from 17 persons with LND, 11 with an attenuated variant of the disease (LNV), and 19 age-, sex-, and race-matched healthy controls (HC). Activity levels of both enzymes differed across groups (p < 0.0001), but only Gprt distinguished patients with LND from those with LNV (p < 0.05). Gprt also showed slightly stronger correlations than Hprt with 13 of 14 measures of the clinical phenotype, including the severity of dystonia, cognitive impairment, and behavioral abnormalities. These findings suggest that loss of guanine recycling might be more closely linked to the LND/LNV phenotype than loss of hypoxanthine recycling.

Reproducibility of tDCS Results in a Randomized Trial: Failure to Replicate Findings of tDCS-Induced Enhancement of Verbal Fluency.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been shown to enhance verbal productivity, but the finding and extent of enhancement vary across studies. Few attempts to replicate positive tDCS findings have been reported, suggesting the possibility of publication bias. OBJECTIVE: We aimed to replicate the tDCS methodology and findings of Cattaneo, Pisoni, and Papagno (2011, Neuroscience 183:64-70) in a new population sample. We hypothesized that our study of anodal tDCS would improve verbal fluency production similarly to the original study. METHODS: In our single-blind, sham-controlled crossover experiment, 14 healthy young adults were randomly assigned to receive 2 mA of anodal and sham stimulation to the Broca area in counterbalanced order before completing verbal fluency tasks. RESULTS: Participants tolerated the stimulation well. Despite closely mirroring the original study methods, we saw no main effect of stimulation condition: F1,13=0.002, P=0.97, letter fluency sham mean (standard deviation)=16.8 (2.3), letter fluency anodal=17.5 (3.8), category fluency sham=25.3 (5.4), or category fluency anodal=24.7 (5.2), η≤0.01. CONCLUSIONS: While tDCS may enhance cerebral functions in general, the lack of consistency between studies suggests either that this tDCS protocol does not affect verbal fluency or, at minimum, that tDCS may be more sensitive to experimental conditions than has been thought. Our findings also highlight the need for replication studies in brain stimulation research. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (Identifier NCT01602263).

The concurrent use of three implicit measures (eye movements, pupillometry, and event-related potentials) to assess receptive vocabulary knowledge in normal adults.

Recent years have seen the advent and proliferation of the use of implicit techniques to study learning and cognition. One such application is the use of event-related potentials (ERPs) to assess receptive vocabulary knowledge. Other implicit assessment techniques that may be well-suited to other testing situations or to use with varied participant groups have not been used as widely to study receptive vocabulary knowledge. We sought to develop additional implicit techniques to study receptive vocabulary knowledge that could augment the knowledge gained from the use of the ERP technique. Specifically, we used a simple forced-choice paradigm to assess receptive vocabulary knowledge in normal adult participants using eye movement monitoring (EM) and pupillometry. In the same group of participants, we also used an N400 semantic incongruity ERP paradigm to assess their knowledge of two groups of words: those expected to be known to the participants (high-frequency, familiar words) and those expected to be unknown (low-frequency, unfamiliar words). All three measures showed reliable differences between the known and unknown words. EM and pupillometry thus may provide insight into receptive vocabulary knowledge similar to that from ERPs. The development of additional implicit assessment techniques may increase the feasibility of receptive vocabulary testing across a wider range of participant groups and testing situations, and may make the conduct of such testing more accessible to a wider range of researchers, clinicians, and educators.

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.

Semantic clustering of category fluency in schizophrenia examined with singular value decomposition.

Decreased productivity on verbal fluency tasks by persons with schizophrenia has been attributed to semantic system abnormalities. Semantic structure is often assessed using multidimensional scaling (MDS) to detect normal and aberrant semantic clustering. However, MDS has limitations that may be particularly problematic for such assessments. Here, we introduce a different clustering technique, singular value decomposition (SVD), to elucidate abnormalities of the semantic system in schizophrenia. We compared 102 treated outpatients with schizophrenia to 109 healthy adults on two category-cued word fluency tasks. Patients with schizophrenia showed semantic clustering patterns that differ markedly from those of healthy adults. However, SVD revealed more detailed and critical semantic system abnormalities than previously appreciated using MDS. Patients with schizophrenia showed less coherent semantic clustering of both low- and high-frequency category exemplars than healthy adults. These results suggest the intriguing possibility that impaired automatic activation of semantic information is a key deficit in schizophrenia.

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.