Machine learning classification of chronic traumatic brain injury using diffusion tensor imaging and NODDI: A replication and extension study.

Individuals with acute and chronic traumatic brain injury (TBI) are associated with unique white matter (WM) structural abnormalities, including fractional anisotropy (FA) differences. Our research group previously used FA as a feature in a linear support vector machine (SVM) pattern classifier, observing high classification between individuals with and without acute TBI (i.e., an area under the curve [AUC] value of 75.50%). However, it is not known whether FA could similarly classify between individuals with and without history of chronic TBI. Here, we attempted to replicate our previous work with a new sample, investigating whether FA could similarly classify between incarcerated men with (n = 80) and without (n = 80) self-reported history of chronic TBI. Additionally, given limitations associated with FA, including underestimation of FA values in WM tracts containing crossing fibers, we extended upon our previous study by incorporating neurite orientation dispersion and density imaging (NODDI) metrics, including orientation dispersion (ODI) and isotropic volume (Viso). A linear SVM based classification approach, similar to our previous study, was incorporated here to classify between individuals with and without self-reported chronic TBI using FA and NODDI metrics as separate features. Overall classification rates were similar when incorporating FA and NODDI ODI metrics as features (AUC: 82.50%). Additionally, NODDI-based metrics provided the highest sensitivity (ODI: 85.00%) and specificity (Viso: 82.50%) rates. The current study serves as a replication and extension of our previous study, observing that multiple diffusion MRI metrics can reliably classify between individuals with and without self-reported history of chronic TBI.

Reduced structural integrity of the uncinate fasciculus in incarcerated women scoring high on psychopathy.

Both men and women scoring high on psychopathy exhibit similar structural and functional neural abnormalities, including reduced volume of the orbitofrontal cortex (OFC) and reduced hemodynamic activity in the amygdala during affective processing experimental paradigms. The uncinate fasciculus (UF) is a white matter (WM) tract that connects the amygdala to the OFC. Reduced structural integrity of the UF, measured via fractional anisotropy (FA), is commonly associated with men scoring high on psychopathy. However, only one study to date has investigated the relationship between psychopathic traits and UF structural integrity in women, recruiting participants from a community sample. Here, we investigated whether Hare Psychopathy Checklist-Revised (PCL-R) facet scores (measuring interpersonal, affective, lifestyle/behavioral, and antisocial psychopathic traits, respectively) were associated with reduced FA in the left and right UF in a sample of 254 incarcerated women characterized by a wide range of psychopathy scores. We observed that PCL-R Facet 3 scores, assessing lifestyle/behavioral psychopathic traits, were associated with reduced FA in the left and right UF, even when controlling for participant's age and history of previous substance use. The results obtained in the current study help improve our understanding of structural abnormalities associated with women scoring high on psychopathy. Specifically, reduced UF structural integrity may contribute to some of the deficits commonly associated with women scoring high on psychopathy, including emotion dysregulation.

Widespread and interrelated gray matter reductions in child sexual offenders with and without pedophilia: Evidence from a multivariate structural MRI study.

AIM: To further investigate the neuroanatomical correlates of child sexual offending and disentangle them from the neural correlates of pedophilia, using a multivariate analytical approach in order to minimize loss of statistical power. METHODS: This study presents structural MRI data on gray matter in an incarcerated, male population of 22 pedophilic and 21 non-pedophilic child sexual offenders, and 20 violent non-sexual offender controls, based on a multivariate whole-brain approach using source-based morphometry. RESULTS: We identify a network of several neuroanatomical regions exhibiting interrelated reduced gray matter in both child sexual offender groups relative to controls, comprising extensive clusters in the bilateral cerebellum and frontal lobe, as well as smaller clusters in the bilateral parietal, temporal, and occipital lobes, the bilateral basal ganglia, the medial cingulate and the hippocampus. CONCLUSION: Our results speak to the interpretation that there are inter- and possibly connectivity-related brain structural abnormalities in child sexual offenders that are not (only) pertaining to pedophilia per se. Interpretations and limitations of the present data are discussed and recommendations for future works are given.

Youth with elevated psychopathic traits exhibit structural integrity deficits in the uncinate fasciculus.

Youth with elevated psychopathic traits represent a particularly severe subgroup of adolescents characterized by extreme behavioral problems and exhibit comparable neurocognitive deficits as adult offenders with psychopathic traits. A consistent finding among adults with elevated psychopathic traits is reduced white matter structural integrity of the right uncinate fasciculus (UF). The UF is a major white matter tract that connects regions of the anterior temporal lobe (i.e., the amygdala) to higher-order executive control regions, including the ventromedial prefrontal cortex. However, the relationship between youth psychopathic traits and structural integrity of the UF has been mixed, with some studies identifying a negative relationship between adolescent psychopathy scores and FA in the UF, and others identifying a positive relationship. Here, we investigated structural integrity of the left and right UF using fractional anisotropy (FA) in a large sample of n = 254 male adolescent offenders recruited from maximum-security juvenile correctional facilities. Psychopathic traits were assessed using the Hare Psychopathy Checklist: Youth Version (PCL:YV). Consistent with hypotheses, interpersonal and affective traits (i.e., PCL:YV Factor 1 and Facet 1 scores) were associated with reduced FA in the right UF. Additionally, lifestyle traits (i.e., PCL:YV Facet 3 scores) were associated with increased FA in the left UF. Results are consistent with previously published studies reporting reduced FA in the right UF in adult psychopathic offenders and increased left UF FA in youth meeting criteria for certain externalizing disorders.

Aberrant brain gray matter in murderers.

Homicide is a significant societal problem with economic costs in the billions of dollars annually and incalculable emotional impact on victims and society. Despite this high burden, we know very little about the neuroscience of individuals who commit homicide. Here we examine brain gray matter differences in incarcerated adult males who have committed homicide (n = 203) compared to other non-homicide offenders (n = 605; total n = 808). Homicide offenders' show reduced gray matter in brain areas critical for behavioral control and social cognition compared with subsets of other violent and non-violent offenders. This demonstrates, for the first time, that unique brain abnormalities may distinguish offenders who kill from other serious violent offenders and non-violent antisocial individuals.

Affective and interpersonal psychopathic traits associated with reduced corpus callosum volume among male inmates - RETRACTED.

BACKGROUND: Psychopathy is a personality disorder associated with severe emotional and interpersonal consequences and persistent antisocial behavior. Neurobiological models of psychopathy emphasize impairments in emotional processing, attention, and integration of information across large-scale neural networks in the brain. One of the largest integrative hubs in the brain is the corpus callosum (CC) - a large white matter structure that connects the two cerebral hemispheres. METHOD: The current study examines CC volume, measured via Freesurfer parcellation, in a large sample (n = 495) of incarcerated men who were assessed for psychopathic traits using the Hare Psychopathy Checklist-Revised (PCL-R). RESULTS: Psychopathy was associated with reduced volume across all five sub-regions of the CC. These relationships were primarily driven by the affective/interpersonal elements of psychopathy (PCL-R Factor 1), as no significant associations were found between the CC and the lifestyle/antisocial traits of psychopathy. The observed effects were not attributable to differences in substance use severity, age, IQ, or total brain volume. CONCLUSIONS: These findings align with suggestions that core psychopathic traits may be fostered by reduced integrative capacity across large-scale networks in the brain.

Callous-Unemotional Traits Modulate Brain Drug Craving Response in High-Risk Young Offenders.

Adults with psychopathy have a high propensity for substance abuse, generally starting from a young age. This investigation tested hypotheses about differences in the neural responses associated with drug craving among high-risk young offenders with histories of abuse of stimulants and other drugs as a function of psychopathic traits. Fifty-four male adolescents (44 with a history of stimulant abuse and 10 controls) incarcerated at a maximum-security facility (M age = 17.08 years) completed a drug-cue exposure task while brain hemodynamic activity was monitored using functional magnetic resonance imaging (fMRI) with a mobile MRI scanner stationed at the facility. Psychopathic traits were assessed using the Hare Psychopathy Checklist: Youth Version (PCL:YV). In the stimulant abuser group, drug cues elicited activity in classic reward circuitry. Consistent with studies of adult psychopathic traits and substance abuse, there was a negative association between PCL-YV scores and hemodynamic response related to drug craving in the amygdala and ACC in youth with a history of stimulant abuse. However, there were considerably more negative associations between the PCL:YV and hemodynamic response among youth than adults and this was primarily due to callous-unemotional traits rather than interpersonal or behavioral traits. The implications for how personality traits modulate motivations for drug-seeking behavior among adolescent offenders are discussed.

Regular cannabis and alcohol use is associated with resting-state time course power spectra in incarcerated adolescents.

Cannabis and alcohol are believed to have widespread effects on the brain. Although adolescents are at increased risk for substance use, the adolescent brain may also be particularly vulnerable to the effects of drug exposure due to its rapid maturation. Here, we examined the association between cannabis and alcohol use duration and resting-state functional connectivity in a large sample of male juvenile delinquents. The present sample was drawn from the Southwest Advanced Neuroimaging Cohort, Youth sample, and from a youth detention facility in Wisconsin. All participants were scanned at the maximum-security facilities using The Mind Research Network's 1.5T Avanto SQ Mobile MRI scanner. Information on cannabis and alcohol regular use duration was collected using self-report. Resting-state networks were computed using group independent component analysis in 201 participants. Associations with cannabis and alcohol use were assessed using Mancova analyses controlling for age, IQ, smoking and psychopathy scores in the complete case sample of 180 male juvenile delinquents. No associations between alcohol or cannabis use and network spatial maps were found. Longer cannabis use was associated with decreased low frequency power of the default mode network, the executive control networks (ECNs), and several sensory networks, and with decreased functional network connectivity. Duration of alcohol use was associated with decreased low frequency power of the right frontoparietal network, salience network, dorsal attention network, and several sensory networks. Our findings suggest that adolescent cannabis and alcohol use are associated with widespread differences in resting-state time course power spectra, which may persist even after abstinence.

Distinct neuronal patterns of positive and negative moral processing in psychopathy.

Psychopathy is a disorder characterized by severe and frequent moral violations in multiple domains of life. Numerous studies have shown psychopathy-related limbic brain abnormalities during moral processing; however, these studies only examined negatively valenced moral stimuli. Here, we aimed to replicate prior psychopathy research on negative moral judgments and to extend this work by examining psychopathy-related abnormalities in the processing of controversial moral stimuli and positive moral processing. Incarcerated adult males (N = 245) completed a functional magnetic resonance imaging protocol on a mobile imaging system stationed at the prison. Psychopathy was assessed using the Hare Psychopathy Checklist-Revised (PCL-R). Participants were then shown words describing three types of moral stimuli: wrong (e.g., stealing), not wrong (e.g., charity), and controversial (e.g., euthanasia). Participants rated each stimulus as either wrong or not wrong. PCL-R total scores were correlated with not wrong behavioral responses to wrong moral stimuli, and were inversely related to hemodynamic activity in the anterior cingulate cortex in the contrast of wrong > not wrong. In the controversial > noncontroversial comparison, psychopathy was inversely associated with activity in the temporal parietal junction and dorsolateral prefrontal cortex. These results indicate that psychopathy-related abnormalities are observed during the processing of complex, negative, and positive moral stimuli.

Abnormal fronto-limbic engagement in incarcerated stimulant users during moral processing.

RATIONALE: Stimulant use is a significant and prevalent problem, particularly in criminal populations. Previous studies found that cocaine and methamphetamine use is related to impairment in identifying emotions and empathy. Stimulant users also have abnormal neural structure and function of the ventromedial prefrontal cortex (vmPFC), amygdala, and anterior (ACC) and posterior cingulate (PCC), regions implicated in moral decision-making. However, no research has studied the neural correlates of stimulant use and explicit moral processing in an incarcerated population. OBJECTIVES: Here, we examine how stimulant use affects sociomoral processing that might contribute to antisocial behavior. We predicted that vmPFC, amygdala, PCC, and ACC would show abnormal neural response during a moral processing task in incarcerated methamphetamine and cocaine users. METHODS: Incarcerated adult males (N = 211) were scanned with a mobile MRI system while completing a moral decision-making task. Lifetime drug use was assessed. Neural responses during moral processing were compared between users and non-users. The relationship between duration of use and neural function was also examined. RESULTS: Incarcerated stimulant users showed less amygdala engagement than non-users during moral processing. Duration of stimulant use was negatively associated with activity in ACC and positively associated with vmPFC response during moral processing. CONCLUSIONS: These results suggest a dynamic pattern of fronto-limbic moral processing related to stimulant use with deficits in both central motive and cognitive integration elements of biological moral processes theory. This increases our understanding of how drug use relates to moral processing in the brain in an ultra-high-risk population.

Paralimbic gray matter reductions in incarcerated adolescent females with psychopathic traits.

Psychopathy-related paralimbic and limbic structural brain abnormalities have been implicated in incarcerated adult and adolescent male samples. However, there have been few neuroimaging studies of psychopathic traits in females in general and no studies from incarcerated female youth in particular. Here we present the first study to examine the relationship between brain gray matter volumes and psychopathic traits (assessed using the Psychopathy Checklist-Youth Version [PCL-YV]) in a sample of maximum-security incarcerated female adolescents (N = 39; mean age = 17.6 years). Consistent with male samples, regional gray matter volumes were negatively related to psychopathic traits in female youth offenders in limbic and paralimbic areas, including orbitofrontal cortex, parahippocampal cortex, temporal poles, and left hippocampus. These results provide evidence that psychopathic traits manifest similar neural abnormalities across sex and age.

Psychopathic traits modulate brain responses to drug cues in incarcerated offenders.

Recent neuroscientific evidence indicates that psychopathy is associated with abnormal function and structure in limbic and paralimbic areas. Psychopathy and substance use disorders are highly comorbid, but clinical experience suggests that psychopaths abuse drugs for different reasons than non-psychopaths, and that psychopaths do not typically experience withdrawal and craving upon becoming incarcerated. These neurobiological abnormalities may be related to psychopaths' different motivations for-and symptoms of-drug use. This study examined the modulatory effect of psychopathic traits on the neurobiological craving response to pictorial drug stimuli. Drug-related pictures and neutral pictures were presented and rated by participants while hemodynamic activity was monitored using functional magnetic resonance imaging. These data were collected at two correctional facilities in New Mexico using the Mind Research Network mobile magnetic resonance imaging system. The sample comprised 137 incarcerated adult males and females (93 females) with histories of substance dependence. The outcome of interest was the relation between psychopathy scores (using the Hare Psychopathy Checklist-Revised) and hemodynamic activity associated with viewing drug-related pictures vs. neutral pictures. There was a negative association between psychopathy scores and hemodynamic activity for viewing drug-related cues in the anterior cingulate, posterior cingulate, hippocampus, amygdala, caudate, globus pallidus, and parts of the prefrontal cortex. Psychopathic traits modulate the neurobiological craving response and suggest that individual differences are important for understanding and treating substance abuse.

A large scale (N=102) functional neuroimaging study of response inhibition in a Go/NoGo task.

We report a functional magnetic resonance imaging (fMRI) study of healthy adult participants who completed a demanding Go/NoGo task. The primary purpose of this study was to delineate the neural systems underlying successful and unsuccessful response inhibition using a large sample (N=102). We identified a number of regions uniquely engaged during successful response inhibition, including a fronto-parietal network involving the anterior cingulate, supplementary motor areas, lateral and inferior prefrontal regions, and the inferior parietal lobule. Unique hemodynamic activity was also noted in the amygdala and in frontostriatal regions including the inferior frontal gyrus and portions of the basal ganglia. Also, contrasts were defined to explore three variants of hemodynamic response allowing for more specificity in identifying the underlying cognitive mechanisms of response inhibition. Addressing issues raised by prior small sample studies, we identified a stable set of regions involved in successful response inhibition. The present results help to incrementally refine the specificity of the neural correlates of response inhibition.

Aberrant paralimbic gray matter in incarcerated male adolescents with psychopathic traits.

OBJECTIVE: To investigate the relationship between brain structure and psychopathic traits in maximum-security incarcerated male adolescents, and to examine whether the associations between brain volumes in paralimbic and limbic regions and psychopathic traits observed in incarcerated adult men extend to an independent sample of incarcerated male adolescents. METHOD: A structural magnetic resonance imaging (MRI) study of regional gray matter volumes by using voxel-based morphometry in maximum-security incarcerated male adolescents (N = 218) assessed for psychopathic traits using the Hare Psychopathy Checklist-Youth Version (PCL-YV). All analyses controlled for effects of age, substance use, and brain size. RESULTS: Consistent with hypotheses and the adult literature, psychopathic traits were associated with decreased regional gray matter volumes in diffuse paralimbic regions, including orbitofrontal cortex, bilateral temporal poles, and posterior cingulate cortex. CONCLUSIONS: These results strengthen the interpretation that paralimbic regions are central for understanding neural dysfunction associated with psychopathic traits and that psychopathy is best conceptualized as a neurodevelopmental disorder.

Examining the effect of psychopathic traits on gray matter volume in a community substance abuse sample.

Psychopathy is believed to be associated with brain abnormalities in both paralimbic (i.e., orbitofrontal cortex, insula, temporal pole, parahippocampal gyrus, posterior cingulate) and limbic (i.e., amygdala, hippocampus, anterior cingulate) regions. Recent structural imaging studies in both community and prison samples are beginning to support this view. Sixty-six participants, recruited from community corrections centers, were administered the Hare psychopathy checklist-revised (PCL-R), and underwent magnetic resonance imaging (MRI). Voxel-based morphometry was used to test the hypothesis that psychopathic traits would be associated with gray matter reductions in limbic and paralimbic regions. Effects of lifetime drug and alcohol use on gray matter volume were covaried. Psychopathic traits were negatively associated with gray matter volumes in right insula and right hippocampus. Additionally, psychopathic traits were positively associated with gray matter volumes in bilateral orbital frontal cortex and right anterior cingulate. Exploratory regression analyses indicated that gray matter volumes within right hippocampus and left orbital frontal cortex combined to explain 21.8% of the variance in psychopathy scores. These results support the notion that psychopathic traits are associated with abnormal limbic and paralimbic gray matter volume. Furthermore, gray matter increases in areas shown to be functionally impaired suggest that the structure-function relationship may be more nuanced than previously thought.

Aberrant paralimbic gray matter in criminal psychopathy.

Psychopaths impose large costs on society, as they are frequently habitual, violent criminals. The pervasive nature of emotional and behavioral symptoms in psychopathy suggests that several associated brain regions may contribute to the disorder. Studies employing a variety of methods have converged on a set of brain regions in paralimbic cortex and limbic areas that appear to be dysfunctional in psychopathy. The present study further tests this hypothesis by investigating structural abnormalities using voxel-based morphometry in a sample of incarcerated men (N=296). Psychopathy was associated with decreased regional gray matter in several paralimbic and limbic areas, including bilateral parahippocampal, amygdala, and hippocampal regions, bilateral temporal pole, posterior cingulate cortex, and orbitofrontal cortex. The consistent identification of paralimbic cortex and limbic structures in psychopathy across diverse methodologies strengthens the interpretation that these regions are crucial for understanding neural dysfunction in psychopathy.

Hemispheric Asymmetries during Processing of Immoral Stimuli.

Evolutionary approaches to dissecting our psychological architecture underscore the importance of both function and structure. Here we focus on both the function and structure of our neural circuitry and report a functional bilateral asymmetry associated with the processing of immoral stimuli. Many processes in the human brain are associated with functional specialization unique to one hemisphere. With respect to emotions, most research points to right-hemispheric lateralization. Here we provide evidence that not all emotional stimuli share right-hemispheric lateralization. Across three studies employing different paradigms, the processing of negative morally laden stimuli was found to be highly left-lateralized. Regions of engagement common to the three studies include the left medial prefrontal cortex, left temporoparietal junction, and left posterior cingulate. These data support the hypothesis that processing of immoral stimuli preferentially engages left hemispheric processes and sheds light on our evolved neural architecture.

Imaging phonological similarity effects on verbal working memory.

Studies of verbal working memory (VWM) report that performance declines as the phonemic similarity of stimuli increases. To determine how phonological similarity affects brain function during VWM, "standard" and "similarity" versions of the 2-Back task were presented to 34 healthy participants during functional magnetic resonance imaging (FMRI). Letter consonants presented during similarity blocks rhymed, while consonants did not rhyme during standard blocks. Empirical ROIs were identified from significant 2-Back-related activity observed during either condition. A priori ROIs were selected from functional neuroimaging literature on phonological processing. Although VWM-related activity was not modulated by similarity in any of four regions recruited (dorsolateral prefrontal, posterior parietal, anterior insular, and supplementary motor cortices), four of five regions of deactivation exhibited significantly greater deactivation during the similarity compared to the standard condition (posterior cingulate, paracentral lobule, posterior insula, and parahippocampal gyrus). In a priori phonological processing-related ROIs, similarity did not affect observed increases in activity (supplementary motor area, Broca's area, and cerebellum), while two of the three regions exhibiting decreased activity (near Wernicke's area and Heschel's Gyrus) also exhibited more deactivation during similarity. Accuracy was lower during the similarity 2-Back, positively related to activity within recruited VWM-related ROIs, and inversely related to activity in regions of VWM-related deactivation. Based on known functions of these ROIs, we conclude that language, audition, and self-reflection processes may disengage during phonological interference, while activity levels are maintained in regions recruited during VWM processing. Similarity effects likely include suspension of attention to unrelated and distracting processes to improve concentration.