Individual differences in reasoning and visuospatial attention are associated with prefrontal and parietal white matter tracts in healthy older adults.

OBJECTIVE: Although reasoning and attention are 2 cognitive processes necessary for ensuring the efficiency of many everyday activities in older adults, the role of white matter integrity in these processes has been little studied. This is an important question due to the role of white matter integrity as a neural substrate of cognitive aging. Here, we sought to examine the white matter tracts subserving reasoning and visuospatial attention in healthy older adults. METHOD: Sixty-one adults ages 60 and older completed a battery of cognitive tests to assess reasoning and visuospatial attention. In addition, diffusion tensor images were collected to assess fractional anisotropy (FA), a measure of white matter integrity. A principle components analysis of the test scores yielded 2 components: reasoning and visuospatial attention. Whole-brain correlations between FA and the cognitive components were submitted to probabilistic tractography analyses for visualization of cortical targets of tracts. RESULTS: For reasoning, bilateral thalamo-anterior prefrontal, anterior corpus callosum, and corpus callosum body tracts interconnecting the superior frontal cortices and right cingulum bundle were found. For visuospatial attention, a right inferior fronto-parietal tract and bilateral parietal and temporal connections were found. CONCLUSIONS: We conclude that in older adults, prefrontal cortex white matter tracts and interhemispheric communication are important in higher order cognitive functioning. On the other hand, right-sided fronto-parietal tracts appear to be critical for supporting control of cognitive processes, such as redirecting attention. Researchers may use our results to develop neuroscience-based interventions for older adults targeting brain mechanisms involved in cognitive plasticity. (PsycINFO Database Record

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.

Aggression, DRD1 polymorphism, and lesion location in penetrating traumatic brain injury.

OBJECTIVE: This study evaluated whether structural brain lesions modulate the relationship between pathological aggression and the dopaminergic system in traumatic brain injury (TBI). While converging evidence suggests that different areas of the prefrontal cortex modulate dopaminergic activity, to date no evidence exists of a modulation of endogenous dopaminergic tone by lesion localization in penetrating TBI (pTBI). METHODS: This study included 141 male Caucasian veterans who suffered penetrating pTBI during their service in Vietnam and 29 healthy male Caucasian Vietnam veterans. Participants were genotyped for 3 functional single nucleotide polymorphisms (SNPs): dopamine receptor D1 (DRD1) rs686, dopamine receptor D2 (DRD2) rs4648317, and catechol-O-methyltransferase (COMT) Val158Met. Patients underwent brain CT scans and were divided into medial prefrontal cortex, lateral prefrontal cortex, and posterior cortex lesion groups. Long-term aggression levels were evaluated with the agitation/aggression subscale of the Neuropsychiatric Inventory. RESULTS: Our data showed that carriers of more transcriptionally active DRD1 alleles compared to noncarriers demonstrated greater aggression levels due to medial prefrontal cortex lesions but reduced aggression levels due to lateral prefrontal cortex lesions independently of DRD2 rs4648317 or COMT Val158Met genotypes. CONCLUSIONS: Our results suggest that the relationship between pTBI-related aggression and the dopaminergic system is modulated by lesion location. Potentially lesion location could represent an easy-to-use, widely available, para-clinical marker to help in the development of an individualized therapeutic approach to pTBI-related pathological aggression.

Neurocognitive enhancement in older adults: comparison of three cognitive training tasks to test a hypothesis of training transfer in brain connectivity.

The ultimate goal of cognitive enhancement as an intervention for age-related cognitive decline is transfer to everyday cognitive functioning. Development of training methods that transfer broadly to untrained cognitive tasks (far transfer) requires understanding of the neural bases of training and far transfer effects. We used cognitive training to test the hypothesis that far transfer is associated with altered attentional control demands mediated by the dorsal attention network and trained sensory cortex. In an exploratory study, we randomly assigned 42 healthy older adults to six weeks of training on Brain Fitness (BF-auditory perception), Space Fortress (SF-visuomotor/working memory), or Rise of Nations (RON-strategic reasoning). Before and after training, cognitive performance, diffusion-derived white matter integrity, and functional connectivity of the superior parietal cortex (SPC) were assessed. We found the strongest effects from BF training, which transferred to everyday problem solving and reasoning and selectively changed integrity of occipito-temporal white matter associated with improvement on untrained everyday problem solving. These results show that cognitive gain from auditory perception training depends on heightened white matter integrity in the ventral attention network. In BF and SF (which also transferred positively), a decrease in functional connectivity between SPC and inferior temporal lobe (ITL) was observed compared to RON-which did not transfer to untrained cognitive function. These findings highlight the importance for cognitive training of top-down control of sensory processing by the dorsal attention network. Altered brain connectivity - observed in the two training tasks that showed far transfer effects - may be a marker for training success.

Differential contributions of dorso-ventral and rostro-caudal prefrontal white matter tracts to cognitive control in healthy older adults.

Prefrontal cortex mediates cognitive control by means of circuitry organized along dorso-ventral and rostro-caudal axes. Along the dorso-ventral axis, ventrolateral PFC controls semantic information, whereas dorsolateral PFC encodes task rules. Along the rostro-caudal axis, anterior prefrontal cortex encodes complex rules and relationships between stimuli, whereas posterior prefrontal cortex encodes simple relationships between stimuli and behavior. Evidence of these gradients of prefrontal cortex organization has been well documented in fMRI studies, but their functional correlates have not been examined with regard to integrity of underlying white matter tracts. We hypothesized that (a) the integrity of specific white matter tracts is related to cognitive functioning in a manner consistent with the dorso-ventral and rostro-caudal organization of the prefrontal cortex, and (b) this would be particularly evident in healthy older adults. We assessed three cognitive processes that recruit the prefrontal cortex and can distinguish white matter tracts along the dorso-ventral and rostro-caudal dimensions -episodic memory, working memory, and reasoning. Correlations between cognition and fractional anisotropy as well as fiber tractography revealed: (a) Episodic memory was related to ventral prefrontal cortex-thalamo-hippocampal fiber integrity; (b) Working memory was related to integrity of corpus callosum body fibers subserving dorsolateral prefrontal cortex; and (c) Reasoning was related to integrity of corpus callosum body fibers subserving rostral and caudal dorsolateral prefrontal cortex. These findings confirm the ventrolateral prefrontal cortex's role in semantic control and the dorsolateral prefrontal cortex's role in rule-based processing, in accordance with the dorso-ventral prefrontal cortex gradient. Reasoning-related rostral and caudal superior frontal white matter may facilitate different levels of task rule complexity. This study is the first to demonstrate dorso-ventral and rostro-caudal prefrontal cortex processing gradients in white matter integrity.

A voxel-based lesion study on facial emotion recognition after penetrating brain injury.

The ability to read emotions in the face of another person is an important social skill that can be impaired in subjects with traumatic brain injury (TBI). To determine the brain regions that modulate facial emotion recognition, we conducted a whole-brain analysis using a well-validated facial emotion recognition task and voxel-based lesion symptom mapping (VLSM) in a large sample of patients with focal penetrating TBIs (pTBIs). Our results revealed that individuals with pTBI performed significantly worse than normal controls in recognizing unpleasant emotions. VLSM mapping results showed that impairment in facial emotion recognition was due to damage in a bilateral fronto-temporo-limbic network, including medial prefrontal cortex (PFC), anterior cingulate cortex, left insula and temporal areas. Beside those common areas, damage to the bilateral and anterior regions of PFC led to impairment in recognizing unpleasant emotions, whereas bilateral posterior PFC and left temporal areas led to impairment in recognizing pleasant emotions. Our findings add empirical evidence that the ability to read pleasant and unpleasant emotions in other people's faces is a complex process involving not only a common network that includes bilateral fronto-temporo-limbic lobes, but also other regions depending on emotional valence.

Regional brain atrophy and impaired decision making on the balloon analog risk task in behavioral variant frontotemporal dementia.

OBJECTIVE: The goal of this study was 2-fold, first, to compare decision making in behavioral variant frontotemporal dementia (bvFTD) patients and healthy adults using the Balloon Analog Risk Task (BART), and, second, to identify the regions of gray matter atrophy associated with bvFTD patients' BART performance. BACKGROUND: Stimulus-reinforcement learning is required to evaluate the results of previously chosen actions to improve future decisions. Although there is a well established literature suggesting altered decision making in FTD patients and data from lesion studies suggest orbitofrontal cortex (OFC) involvement in decision making, there is very little research looking at the brain correlates of decision making in FTD populations specifically. METHOD: Twenty-seven bvFTD patients and 19 age-matched and education-matched normal controls completed the BART. Voxel-based morphometry analysis was performed on the magnetic resonance imaging scans of a subset of patients. RESULTS: Compared with healthy controls, the bvFTD patients did not learn and pumped less to inflate a balloon to receive a reward, indicating altered stimulus-reinforcement learning. The voxel-based morphometry analysis indicated that bvFTD patients' impaired BART performance was related to atrophy in the right lateral OFC. CONCLUSIONS: The right lateral OFC is crucial for stimulus-reinforcement learning required for the adjustment of behavior under changing reward contingencies.

Fronto-parietal regulation of media violence exposure in adolescents: a multi-method study.

Adolescents spend a significant part of their leisure time watching TV programs and movies that portray violence. It is unknown, however, how the extent of violent media use and the severity of aggression displayed affect adolescents' brain function. We investigated skin conductance responses, brain activation and functional brain connectivity to media violence in healthy adolescents. In an event-related functional magnetic resonance imaging experiment, subjects repeatedly viewed normed videos that displayed different degrees of aggressive behavior. We found a downward linear adaptation in skin conductance responses with increasing aggression and desensitization towards more aggressive videos. Our results further revealed adaptation in a fronto-parietal network including the left lateral orbitofrontal cortex (lOFC), right precuneus and bilateral inferior parietal lobules, again showing downward linear adaptations and desensitization towards more aggressive videos. Granger causality mapping analyses revealed attenuation in the left lOFC, indicating that activation during viewing aggressive media is driven by input from parietal regions that decreased over time, for more aggressive videos. We conclude that aggressive media activates an emotion-attention network that has the capability to blunt emotional responses through reduced attention with repeated viewing of aggressive media contents, which may restrict the linking of the consequences of aggression with an emotional response, and therefore potentially promotes aggressive attitudes and behavior.

Developmental effects of aggressive behavior in male adolescents assessed with structural and functional brain imaging.

Aggressive behavior is common during adolescence. Although aggression-related functional changes in the ventromedial prefrontal cortex (vmPFC) and frontopolar cortex (FPC) have been reported in adults, the neural correlates of aggressive behavior in adolescents, particularly in the context of structural neurodevelopment, are obscure. We used functional and structural magnetic resonance imaging (MRI) to measure the blood oxygenation level-depended signal and cortical thickness. In a block-designed experiment, 14-17-year old adolescents imagined aggressive and non-aggressive interactions with a peer. We show reduced vmPFC activation associated with imagined aggressive behavior as well as enhanced aggression-related activation and cortical thinning in the FPC with increasing age. Changes in FPC activation were also associated with judgments of the severity of aggressive acts. Reduced vmPFC activation was associated with greater aggression indicating its normal function is to exert inhibitory control over aggressive impulses. Concurrent FPC activation likely reflects foresight of harmful consequences that result from aggressive acts. The correlation of age-dependent activation changes and cortical thinning demonstrates ongoing maturation of the FPC during adolescence towards a refinement of social and cognitive information processing that can potentially facilitate mature social behavior in aggressive contexts.

Lower lateral orbitofrontal cortex density associated with more frequent exposure to television and movie violence in male adolescents.

The relationship between cortical grey matter density and media violence exposure in healthy male adolescents was investigated using voxel-based morphometry and the Childrens' Report of Exposure to Violence. Adolescents with more frequent exposure have lower left lateral orbitofrontal cortex density--a possible risk factor for altered socioemotional functioning.

The neural bases of key competencies of emotional intelligence.

Emotional intelligence (EI) refers to a set of competencies that are essential features of human social life. Although the neural substrates of EI are virtually unknown, it is well established that the prefrontal cortex (PFC) plays a crucial role in human social-emotional behavior. We studied a unique sample of combat veterans from the Vietnam Head Injury Study, which is a prospective, long-term follow-up study of veterans with focal penetrating head injuries. We administered the Mayer-Salovey-Caruso Emotional Intelligence Test as a valid standardized psychometric measure of EI behavior to examine two key competencies of EI: (i) Strategic EI as the competency to understand emotional information and to apply it for the management of the self and of others and (ii) Experiential EI as the competency to perceive emotional information and to apply it for the integration into thinking. The results revealed that key competencies underlying EI depend on distinct neural PFC substrates. First, ventromedial PFC damage diminishes Strategic EI, and therefore, hinders the understanding and managing of emotional information. Second, dorsolateral PFC damage diminishes Experiential EI, and therefore, hinders the perception and integration of emotional information. In conclusion, EI should be viewed as complementary to cognitive intelligence and, when considered together, provide a more complete understanding of human intelligence.

Neural correlates of trust.

Trust is a critical social process that helps us to cooperate with others and is present to some degree in all human interaction. However, the underlying brain mechanisms of conditional and unconditional trust in social reciprocal exchange are still obscure. Here, we used hyperfunctional magnetic resonance imaging, in which two strangers interacted online with one another in a sequential reciprocal trust game while their brains were simultaneously scanned. By designing a nonanonymous, alternating multiround game, trust became bidirectional, and we were able to quantify partnership building and maintenance. Using within- and between-brain analyses, an examination of functional brain activity supports the hypothesis that the preferential activation of different neuronal systems implements these two trust strategies. We show that the paracingulate cortex is critically involved in building a trust relationship by inferring another person's intentions to predict subsequent behavior. This more recently evolved brain region can be differently engaged to interact with more primitive neural systems in maintaining conditional and unconditional trust in a partnership. Conditional trust selectively activated the ventral tegmental area, a region linked to the evaluation of expected and realized reward, whereas unconditional trust selectively activated the septal area, a region linked to social attachment behavior. The interplay of these neural systems supports reciprocal exchange that operates beyond the immediate spheres of kinship, one of the distinguishing features of the human species.

Ethics questions raised by the neuropsychiatric, neuropsychological, educational, developmental, and family characteristics of 18 juveniles awaiting execution in Texas.

Eighteen males condemned to death in Texas for homicides committed prior to the defendants' 18th birthdays received systematic psychiatric, neurologic, neuropsychological, and educational assessments, and all available medical, psychological, educational, social, and family data were reviewed. Six subjects began life with potentially compromised central nervous system (CNS) function (e.g., prematurity, respiratory distress syndrome). All but one experienced serious head traumas in childhood and adolescence. All subjects evaluated neurologically and neuropsychologically had signs of prefrontal cortical dysfunction. Neuropsychological testing was more sensitive to executive dysfunction than neurologic examination. Fifteen (83%) had signs, symptoms, and histories consistent with bipolar spectrum, schizoaffective spectrum, or hypomanic disorders. Two subjects were intellectually limited, and one suffered from parasomnias and dissociation. All but one came from extremely violent and/or abusive families in which mental illness was prevalent in multiple generations. Implications regarding the ethics involved in matters of culpability and mitigation are considered.