Everyday function profiles in prodromal stages of MCI: Prospective cohort study.

INTRODUCTION: The nature and course of limitations in everyday function in the early clinical stages of cognitive decline is not well known. METHODS: We compared complex everyday functional profiles at baseline in 59 community-dwelling older individuals with normal cognitive performance who went on to develop incident mild cognitive impairment (MCI) ("pre-MCI") with 284 older individuals who remained cognitively normal over follow-up. RESULTS: The mean number of limitations on complex everyday function at baseline was 3.1 ± 3.0 in the 59 pre-MCI cases and 2.0 ± 2.4 in the 284 normal controls (P = .003). Pre-MCI cases had limitations in traveling, entertaining, remembering appointments, and hobbies compared to normal controls. A progressive increase in mild limitations on complex everyday function preceded the incidence of MCI (mean change: pre-MCI 1.9 ± 3.6 vs normal controls 0.5 ± 2.7, P < .001). DISCUSSION: Prodromal stages of MCI are associated with progressive mild limitations in complex activities of daily living.

Time to move: Brain dynamics underlying natural action and cognition.

Advances in Mobile Brain/Body Imaging (MoBI) technology allows for real-time measurements of human brain dynamics during every day, natural, real-life situations. This special issue Time to Move brings together a collection of experimental papers, targeted reviews and opinion articles that lay out the latest MoBI findings. A wide range of topics across different fields are covered including art, athletics, virtual reality, and mobility. What unites these diverse topics is the common goal to enhance and restore human abilities by reaching a better understanding on how cognition is implemented by the brain-body relationship. The breadth and novelty of paradigms and findings reported here positions MoBI as a new frontier in the field of human cognitive neuroscience.

Aging-related changes in cortical mechanisms supporting postural control during base of support and optic flow manipulations.

Behavioral findings suggest that aging alters the involvement of cortical sensorimotor mechanisms in postural control. However, corresponding accounts of the underlying neural mechanisms remain sparse, especially the extent to which these mechanisms are affected during more demanding tasks. Here, we set out to elucidate cortical correlates of altered postural stability in younger and older adults. 3D body motion tracking and high-density electroencephalography (EEG) were measured while 14 young adults (mean age = 24 years, 43% women) and 14 older adults (mean age = 77 years, 50% women) performed a continuous balance task under four different conditions. Manipulations were applied to the base of support (either regular or tandem (heel-to-toe) stance) and visual input (either static visual field or dynamic optic flow). Standing in tandem, the more challenging position, resulted in increased sway for both age groups, but for the older adults, only this effect was exacerbated when combined with optic flow compared to the static visual display. These changes in stability were accompanied by neuro-oscillatory modulations localized to midfrontal and parietal regions. A cluster of electro-cortical sources localized to the supplementary motor area showed a large increase in theta spectral power (4-7 Hz) during tandem stance, and this modulation was much more pronounced for the younger group. Additionally, the older group displayed widespread mu (8-12 Hz) and beta (13-30 Hz) suppression as balance tasks placed more demands on postural control, especially during tandem stance. These findings may have substantial utility in identifying early cortical correlates of balance impairments in otherwise healthy older adults.

Cognitive load reduces the effects of optic flow on gait and electrocortical dynamics during treadmill walking.

During navigation of complex environments, the brain must continuously adapt to both external demands, such as fluctuating sensory inputs, and internal demands, such as engagement in a cognitively demanding task. Previous studies have demonstrated changes in behavior and gait with increased sensory and cognitive load, but the underlying cortical mechanisms remain largely unknown. In the present study, in a mobile brain/body imaging (MoBI) approach, 16 young adults walked on a treadmill with high-density EEG while 3-dimensional (3D) motion capture tracked kinematics of the head and feet. Visual load was manipulated with the presentation of optic flow with and without continuous mediolateral perturbations. The effects of cognitive load were assessed by the performance of a go/no-go task on half of the blocks. During increased sensory load, participants walked with shorter and wider strides, which may indicate a more restrained pattern of gait. Interestingly, cognitive task engagement attenuated these effects of sensory load on gait. Using an independent component analysis and dipole-fitting approach, we found that cautious gait was accompanied by neuro-oscillatory modulations localized to frontal (supplementary motor area, anterior cingulate cortex) and parietal (inferior parietal lobule, precuneus) areas. Our results show suppression in alpha/mu (8-12 Hz) and beta (13-30 Hz) rhythms, suggesting enhanced activation of these regions with unreliable sensory inputs. These findings provide insight into the neural correlates of gait adaptation and may be particularly relevant to older adults who are less able to adjust to ongoing cognitive and sensory demands while walking. NEW & NOTEWORTHY The neural underpinnings of gait adaptation in humans are poorly understood. To this end, we recorded high-density EEG combined with three-dimensional body motion tracking as participants walked on a treadmill while exposed to full-field optic flow stimulation. Perturbed visual input led to a more cautious gait pattern with neuro-oscillatory modulations localized to premotor and parietal regions. Our findings show a possible brain-behavior link that might further our understanding of gait and mobility impairments.

The aging brain shows less flexible reallocation of cognitive resources during dual-task walking: A mobile brain/body imaging (MoBI) study.

Aging is associated with reduced abilities to selectively allocate attention across multiple domains. This may be particularly problematic during everyday multitasking situations when cognitively demanding tasks are performed while walking. Due to previous limitations in neuroimaging technology, much remains unknown about the cortical mechanisms underlying resource allocation during locomotion. Here, we utilized an EEG-based mobile brain/body imaging (MoBI) technique that integrates high-density event-related potential (ERP) recordings with simultaneously acquired foot-force sensor data to monitor gait patterns and brain activity concurrently. To assess effects of motor load on cognition we evaluated young (N=17; mean age=27.2) and older adults (N=16; mean age=63.9) and compared behavioral and ERP measures associated with performing a Go/No-Go response inhibition task as participants sat stationary or walked on a treadmill. Stride time and variability were also measured during task performance and compared to stride parameters obtained without task performance, thereby assessing effects of cognitive load on gait. Results showed that older, but not young adults' accuracy dropped significantly when performing the inhibitory task while walking. Young adults revealed ERP modulations at relatively early (N2 amplitude reduction) and later (earlier P3 latency) stages within the processing stream as motor load increased while walking. In contrast, older adults' ERP modulations were limited to later processing stages (increased P3 amplitude) of the inhibitory network. The relative delay and attenuation of ERP modulations accompanied by behavioral costs in older participants might indicate an age-associated loss in flexible resource allocation across multiple tasks. Better understanding of the neural underpinnings of these age-related changes may lead to improved strategies to reduce fall risk and enhance mobility in aging.

Recalibration of inhibitory control systems during walking-related dual-task interference: a mobile brain-body imaging (MOBI) study.

Walking while simultaneously performing cognitively demanding tasks such as talking or texting are typical complex behaviors in our daily routines. Little is known about neural mechanisms underlying cortical resource allocation during such mobile actions, largely due to portability limitations of conventional neuroimaging technologies. We applied an EEG-based Mobile Brain-Body Imaging (MOBI) system that integrates high-density event-related potential (ERP) recordings with simultaneously acquired foot-force sensor data to monitor gait patterns and brain activity. We compared behavioral and ERP measures associated with performing a Go/NoGo response-inhibition task under conditions where participants (N=18) sat in a stationary way, walked deliberately or walked briskly. This allowed for assessment of effects of increasing dual-task load (i.e. walking speed) on neural indices of inhibitory control. Stride time and variability were also measured during inhibitory task performance and compared to stride parameters without task performance, thereby assessing reciprocal dual-task effects on gait parameters. There were no task performance differences between sitting and either walking condition, indicating that participants could perform both tasks simultaneously without suffering dual-task costs. However, participants took longer strides under dual-task load, likely indicating an adaptive mechanism to reduce inter-task competition for cortical resources. We found robust differences in amplitude, latency and topography of ERP components (N2 and P3) associated with inhibitory control between the sitting and walking conditions. Considering that participants showed no dual-task performance costs, we suggest that observed neural alterations under increasing task-load represent adaptive recalibration of the inhibitory network towards a more controlled and effortful processing mode, thereby optimizing performance under dual-task situations.

Throwing out the rules: anticipatory alpha-band oscillatory attention mechanisms during task-set reconfigurations.

We assessed the role of alpha-band oscillatory activity during a task-switching design that required participants to switch between an auditory and a visual task, while task-relevant audiovisual inputs were simultaneously presented. Instructional cues informed participants which task to perform on a given trial and we assessed alpha-band power in the short 1.35-s period intervening between the cue and the task-imperative stimuli, on the premise that attentional biasing mechanisms would be deployed to resolve competition between the auditory and visual inputs. Prior work had shown that alpha-band activity was differentially deployed depending on the modality of the cued task. Here, we asked whether this activity would, in turn, be differentially deployed depending on whether participants had just made a switch of task or were being asked to simply repeat the task. It is well established that performance speed and accuracy are poorer on switch than on repeat trials. Here, however, the use of instructional cues completely mitigated these classic switch-costs. Measures of alpha-band synchronisation and desynchronisation showed that there was indeed greater and earlier differential deployment of alpha-band activity on switch vs. repeat trials. Contrary to our hypothesis, this differential effect was entirely due to changes in the amount of desynchronisation observed during switch and repeat trials of the visual task, with more desynchronisation over both posterior and frontal scalp regions during switch-visual trials. These data imply that particularly vigorous, and essentially fully effective, anticipatory biasing mechanisms resolved the competition between competing auditory and visual inputs when a rapid switch of task was required.

Linking Dementia Pathology and Alteration in Brain Activation to Complex Daily Functional Decline During the Preclinical Dementia Stages: Protocol for a Prospective Observational Cohort Study.

BACKGROUND: Progressive difficulty in performing everyday functional activities is a key diagnostic feature of dementia syndromes. However, not much is known about the neural signature of functional decline, particularly during the very early stages of dementia. Early intervention before overt impairment is observed offers the best hope of reducing the burdens of Alzheimer disease (AD) and other dementias. However, to justify early intervention, those at risk need to be detected earlier and more accurately. The decline in complex daily function (CdF) such as managing medications has been reported to precede impairment in basic activities of daily living (eg, eating and dressing). OBJECTIVE: Our goal is to establish the neural signature of decline in CdF during the preclinical dementia period. METHODS: Gait is central to many CdF and community-based activities. Hence, to elucidate the neural signature of CdF, we validated a novel electroencephalographic approach to measuring gait-related brain activation while participants perform complex gait-based functional tasks. We hypothesize that dementia-related pathology during the preclinical period activates a unique gait-related electroencephalographic (grEEG) pattern that predicts a subsequent decline in CdF. RESULTS: We provide preliminary findings showing that older adults reporting CdF limitations can be characterized by a unique gait-related neural signature: weaker sensorimotor and stronger motor control activation. This subsample also had smaller brain volume and white matter hyperintensities in regions affected early by dementia and engaged in less physical exercise. We propose a prospective observational cohort study in cognitively unimpaired older adults with and without subclinical AD (plasma amyloid-ß) and vascular (white matter hyperintensities) pathologies. We aim to (1) establish the unique grEEG activation as the neural signature and predictor of decline in CdF during the preclinical dementia period; (2) determine associations between dementia-related pathologies and incidence of the neural signature of CdF; and (3) establish associations between a dementia risk factor, physical inactivity, and the neural signature of CdF. CONCLUSIONS: By establishing the clinical relevance and biological basis of the neural signature of CdF decline, we aim to improve prediction during the preclinical stages of ADs and other dementias. Our approach has important research and translational implications because grEEG protocols are relatively inexpensive and portable, and predicting CdF decline may have real-world benefits. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56726.

Neural signature of mobility-related everyday function in older adults at-risk of cognitive impairment.

Assessment of everyday activities is central to the diagnosis of dementia. Yet, little is known about brain processes associated with everyday functional limitations, particularly during early stages of cognitive decline. Twenty-six older adults (mean = 74.9 y) were stratified by risk using the Montreal Cognitive Assessment battery (MoCA, range: 0- 30) to classify individuals as higher (22-26) and lower risk (27+) of cognitive impairment. We investigated everyday function using a gait task designed to destabilize posture and applied Mobile Brain/Body Imaging. We predicted that participants would increase step width to gain stability, yet the underlying neural signatures would be different for lower versus higher risk individuals. Step width and fronto-parietal activation increased during visually perturbed input. Frontomedial theta increased in higher risk individuals during perturbed and unperturbed inputs. Left sensorimotor beta decreased in lower risk individuals during visually perturbed input. Modulations in theta and beta power were associated with MoCA scores. Our findings suggest that older adults at-risk of cognitive impairment can be characterized by a unique neural signature of everyday function.

Visual-somatosensory integration (VSI) as a novel marker of Alzheimer's disease: A comprehensive overview of the VSI study.

Identification of novel, non-invasive, non-cognitive based markers of Alzheimer's disease (AD) and related dementias are a global priority. Growing evidence suggests that Alzheimer's pathology manifests in sensory association areas well before appearing in neural regions involved in higher-order cognitive functions, such as memory. Previous investigations have not comprehensively examined the interplay of sensory, cognitive, and motor dysfunction with relation to AD progression. The ability to successfully integrate multisensory information across multiple sensory modalities is a vital aspect of everyday functioning and mobility. Our research suggests that multisensory integration, specifically visual-somatosensory integration (VSI), could be used as a novel marker for preclinical AD given previously reported associations with important motor (balance, gait, and falls) and cognitive (attention) outcomes in aging. While the adverse effect of dementia and cognitive impairment on the relationship between multisensory functioning and motor outcomes has been highlighted, the underlying functional and neuroanatomical networks are still unknown. In what follows we detail the protocol for our study, named The VSI Study, which is strategically designed to determine whether preclinical AD is associated with neural disruptions in subcortical and cortical areas that concurrently modulate multisensory, cognitive, and motor functions resulting in mobility decline. In this longitudinal observational study, a total of 208 community-dwelling older adults with and without preclinical AD will be recruited and monitored yearly. Our experimental design affords assessment of multisensory integration as a new behavioral marker for preclinical AD; identification of functional neural networks involved in the intersection of sensory, motor, and cognitive functioning; and determination of the impact of early AD on future mobility declines, including incident falls. Results of The VSI Study will guide future development of innovative multisensory-based interventions aimed at preventing disability and optimizing independence in pathological aging.

Cognitive control in late-life depression: response inhibition deficits and dysfunction of the anterior cingulate cortex.

OBJECTIVES: Geriatric depression is associated with frontolimbic functional deficits, and this frontal dysfunction may underlie the marked executive control deficits often seen in this population. The authors' goal was to assess the integrity of frontal cortical functioning in geriatric depression, while these individuals performed a standard cognitive control task. The N2 component of the event-related potential (ERP), an evoked response generated within the anterior cingulate cortex (ACC), is significantly enhanced when nondepressed individuals successfully inhibit a response, providing an excellent metric of frontal inhibitory function. DESIGN: The authors used a variant of a demanding Go/NoGo task-switching paradigm that required participants to inhibit response execution during NoGo trials by overcoming a potent response tendency established by frequent Go trials. PARTICIPANTS: The authors compared a cohort of depressed geriatric outpatients (N = 11) with a similarly aged group of nondepressed participants (N = 11). MEASUREMENTS: Reaction times, accuracy, and high-density event-related potential recordings from a 64-channel electrode montage were obtained. RESULTS: A significantly enhanced N2 to NoGo trials was observed in nondepressed elderly participants, with generators localized to the ACC. In contrast, this enhancement was strongly reduced in the depressed sample. Source analysis and topographic mapping pointed to a displacement of N2 generators toward more posterior areas of the middle frontal gyrus in depressed subjects. CONCLUSIONS: Findings confirm previous reports of an inhibitory control deficit in depressed elderly who show significantly increased rates of commission errors (i.e., failures to inhibit responses on NoGo trials). Electrophysiologic data suggest underlying dysfunction in ACC as the basis for this deficit.

Mobile Brain/Body Imaging of cognitive-motor impairment in multiple sclerosis: Deriving EEG-based neuro-markers during a dual-task walking study.

OBJECTIVE: Individuals with a diagnosis of multiple sclerosis (MS) often present with cognitive and motor deficits, and thus the ability to perform tasks that rely on both domains may be particularly impaired. Yet, dual-task walking studies yield mixed results. Individual variance in the ability to cope with brain insult and mobilize additional brain resources may contribute to mixed findings. METHODS: To test this hypothesis, we acquired event-related potentials (ERP) in individuals with MS and healthy controls (HCs) performing a Go/NoGo task while sitting (i.e., single task) or walking (i.e., dual-task) and looked at the relationship between task related modulation of the brain response and performance. RESULTS: On the Go/NoGo task the MS group showed dual-task costs when walking, whereas HCs showed a dual-task benefit. Further, whereas the HC group showed modulation of the brain response as a function of task load, this was not the case in the MS group. Analysis for the pooled sample revealed a positive correlation between load-related ERP effects and dual-task performance. CONCLUSIONS: These data suggest a neurophysiological marker of cognitive-motor dysfunction in MS. SIGNIFICANCE: Understanding neural processes underlying dual-task walking will help identify objective brain measurements of real-world issues and may improve assessment of MS.

Preserved executive function in high-performing elderly is driven by large-scale recruitment of prefrontal cortical mechanisms.

High-density electrical mapping of event-related potentials was used to investigate the neural processes that permit some elderly subjects to preserve high levels of executive functioning. Two possibilities pertain: (1) high-performance in elderly subjects is underpinned by similar processing mechanisms to those seen in young adults; that is, these individuals display minimal functional decay across the lifespan, or (2) preserved function relies on successfully recruiting and amplifying control processes to compensate for normal sensory-perceptual decline with age. Fifteen young and nineteen elderly participants, the latter split into groups of high and low performers, regularly alternated between a letter and a number categorization task, switching between tasks every third trial (AAA-BBB-AAA...). This allowed for interrogation of performance during switch, repeat, and preparatory pre-switch trials. Robust effects of age were observed in both frontal and parietal components of the task-switching network. Greatest differences originated over prefrontal regions, with elderly subjects generating amplified, earlier, and more differentiated patterns of activity. This prefrontal amplification was evident only in high-performing (HP) elderly, and was strongest on pre-switch trials when participants prepared for an upcoming task-switch. Analysis of the early transient and late sustained activity using topographic analyses and source localization collectively supported a unique and elaborated pattern of activity across frontal and parietal scalp in HP-elderly, wholly different to that seen in both young and low-performing elderly. On this basis, we propose that preserved executive function in HP-elderly is driven by large-scale recruitment and enhancement of prefrontal cortical mechanisms.

Long-term test-retest reliability of event-related potential (ERP) recordings during treadmill walking using the mobile brain/body imaging (MoBI) approach.

Advancements in acquisition technology and signal-processing techniques have spurred numerous recent investigations on the electro-cortical signals generated during whole-body motion. This approach, termed Mobile Brain/Body Imaging (MoBI), has the potential to elucidate the neural correlates of perceptual and cognitive processes during real-life activities, such as locomotion. However, as of yet, no one has assessed the long-term stability of event-related potentials (ERPs) recorded under these conditions. Therefore, the objective of the current study was to evaluate the test-retest reliability of cognitive ERPs recorded while walking. High-density EEG was acquired from 12 young adults on two occasions, separated by an average of 2.3years, as they performed a Go/No-Go response inhibition paradigm. During each testing session, participants performed the task while walking on a treadmill and seated. Using the intraclass correlation coefficient (ICC) as a measure of agreement, we focused on two well-established neurophysiological correlates of cognitive control, the N2 and P3 ERPs. Following ICA-based artifact rejection, the earlier N2 yielded good to excellent levels of reliability for both amplitude and latency, while measurements for the later P3 component were generally less robust but still indicative of adequate to good levels of stability. Interestingly, the N2 was more consistent between walking sessions, compared to sitting, for both hits and correct rejection trials. In contrast, the P3 waveform tended to have a higher degree of consistency during sitting conditions. Overall, these results suggest that the electro-cortical signals obtained during active walking are representative of stable indices of neurophysiological function.

Auditory scene analysis: the interaction of stimulation rate and frequency separation on pre-attentive grouping.

Segregation of auditory inputs into meaningful acoustic groups is a key element of auditory scene analysis. Previously, we showed that two interwoven sets of tones differing widely along multiple feature dimensions (duration, pitch and location) were pre-attentively separated into different groups, and that tones separated in this manner did not elicit the mismatch negativity component with respect to each other. Grouping was studied with human subjects using a stimulus rate too slow to induce streaming. Here, we varied the separation of tone sequences along a single feature dimension, i.e. frequency. Frequency differences were either 24 Hz (small) or 1054 Hz (large). Two relatively slow stimulus rates were used (2.7 or 1 tone/s) to explicitly investigate grouping outside the so-called 'streaming effect', which requires rates of about 4 tones/s or faster. Two tones were presented in a quasi-random manner with embedded trains of one to four identical tones in a row. Deviants were defined as frequency switches after trains of four identical tones. Mismatch negativity was only elicited for small frequency switches at the slower stimulation rate. The data indicate that pre-attentive grouping of tones occurred when the frequency difference that separated them was large, regardless of stimulation rate. For small frequency differences, inputs were only grouped separately when the stimulation rate was relatively fast.

Seeing voices: High-density electrical mapping and source-analysis of the multisensory mismatch negativity evoked during the McGurk illusion.

Seeing a speaker's facial articulatory gestures powerfully affects speech perception, helping us overcome noisy acoustical environments. One particularly dramatic illustration of visual influences on speech perception is the "McGurk illusion", where dubbing an auditory phoneme onto video of an incongruent articulatory movement can often lead to illusory auditory percepts. This illusion is so strong that even in the absence of any real change in auditory stimulation, it activates the automatic auditory change-detection system, as indexed by the mismatch negativity (MMN) component of the auditory event-related potential (ERP). We investigated the putative left hemispheric dominance of McGurk-MMN using high-density ERPs in an oddball paradigm. Topographic mapping of the initial McGurk-MMN response showed a highly lateralized left hemisphere distribution, beginning at 175 ms. Subsequently, scalp activity was also observed over bilateral fronto-central scalp with a maximal amplitude at approximately 290 ms, suggesting later recruitment of right temporal cortices. Strong left hemisphere dominance was again observed during the last phase of the McGurk-MMN waveform (350-400 ms). Source analysis indicated bilateral sources in the temporal lobe just posterior to primary auditory cortex. While a single source in the right superior temporal gyrus (STG) accounted for the right hemisphere activity, two separate sources were required, one in the left transverse gyrus and the other in STG, to account for left hemisphere activity. These findings support the notion that visually driven multisensory illusory phonetic percepts produce an auditory-MMN cortical response and that left hemisphere temporal cortex plays a crucial role in this process.

Regulating task-monitoring systems in response to variable reward contingencies and outcomes in cocaine addicts.

BACKGROUND: We investigated anticipatory and consummatory reward processing in cocaine addiction. In addition, we set out to assess whether task-monitoring systems were appropriately recalibrated in light of variable reward schedules. We also examined neural measures of task-monitoring and reward processing as a function of hedonic tone, since anhedonia is a vulnerability marker for addiction that is obviously germane in the context of reward processing. METHOD: High-density event-related potentials were recorded while participants performed a speeded response task that systematically varied anticipated probabilities of reward receipt. The paradigm dissociated feedback regarding task success (or failure) from feedback regarding the value of reward (or loss), so that task-monitoring and reward processing could be examined in partial isolation. Twenty-three active cocaine abusers and 23 age-matched healthy controls participated. RESULTS: Cocaine abusers showed amplified anticipatory responses to reward predictive cues, but crucially, these responses were not as strongly modulated by reward probability as in controls. Cocaine users also showed blunted responses to feedback about task success or failure and did not use this information to update predictions about reward. In turn, they showed clearly blunted responses to reward feedback. In controls and users, measures of anhedonia were associated with reward motivation. In cocaine users, anhedonia was also associated with diminished monitoring and reward feedback responses. CONCLUSION: Findings imply that reward anticipation and monitoring deficiencies in addiction are associated with increased responsiveness to reward cues but impaired ability to predict reward in light of task contingencies, compounded by deficits in responding to actual reward outcomes.

Neuroanatomical Abnormalities in Violent Individuals with and without a Diagnosis of Schizophrenia.

Several structural brain abnormalities have been associated with aggression in patients with schizophrenia. However, little is known about shared and distinct abnormalities underlying aggression in these subjects and non-psychotic violent individuals. We applied a region-of-interest volumetric analysis of the amygdala, hippocampus, and thalamus bilaterally, as well as whole brain and ventricular volumes to investigate violent (n = 37) and non-violent chronic patients (n = 26) with schizophrenia, non-psychotic violent (n = 24) as well as healthy control subjects (n = 24). Shared and distinct volumetric abnormalities were probed by analysis of variance with the factors violence (non-violent versus violent) and diagnosis (non-psychotic versus psychotic), adjusted for substance abuse, age, academic achievement and negative psychotic symptoms. Patients showed elevated vCSF volume, smaller left hippocampus and smaller left thalamus volumes. This was particularly the case for non-violent individuals diagnosed with schizophrenia. Furthermore, patients had reduction in right thalamus size. With regard to left amygdala, we found an interaction between violence and diagnosis. More specifically, we report a double dissociation with smaller amygdala size linked to violence in non-psychotic individuals, while for psychotic patients smaller size was linked to non-violence. Importantly, the double dissociation appeared to be mostly driven by substance abuse. Overall, we found widespread morphometric abnormalities in subcortical regions in schizophrenia. No evidence for shared volumetric abnormalities in individuals with a history of violence was found. Finally, left amygdala abnormalities in non-psychotic violent individuals were largely accounted for by substance abuse. This might be an indication that the association between amygdala reduction and violence is mediated by substance abuse. Our results indicate the importance of structural abnormalities in aggressive individuals.

Disturbances in Response Inhibition and Emotional Processing as Potential Pathways to Violence in Schizophrenia: A High-Density Event-Related Potential Study.

OBJECTIVE: Increased susceptibility to emotional triggers and poor response inhibition are important in the etiology of violence in schizophrenia. Our goal was to evaluate abnormalities in neurophysiological mechanisms underlying response inhibition and emotional processing in violent patients with schizophrenia (VS) and 3 different comparison groups: nonviolent patients (NV), healthy controls (HC) and nonpsychotic violent subjects (NPV). METHODS: We recorded high-density Event-Related Potentials (ERPs) and behavioral responses during an Emotional Go/NoGo Task in 35 VS, 24 NV, 28 HC and 31 NPV subjects. We also evaluated psychiatric symptoms and impulsivity. RESULTS: The neural and behavioral deficits in violent patients were most pronounced when they were presented with negative emotional stimuli: They responded more quickly than NV when they made commission errors (ie, failure of inhibition), and evidenced N2 increases and P3 decreases. In contrast, NVs showed little change in reaction time or ERP amplitude with emotional stimuli. These N2 and P3 amplitude changes in VSs showed a strong association with greater impulsivity. Besides these group specific changes, VSs shared deficits with NV, mostly N2 reduction, and with violent nonpsychotic subjects, particularly P3 reduction. CONCLUSION: Negative affective triggers have a strong impact on violent patients with schizophrenia which may have both behavioral and neural manifestations. The resulting activation could interfere with response inhibition. The affective disruption of response inhibition, identified in this study, may index an important pathway to violence in schizophrenia and suggest new modes of treatment.

Aberrant response inhibition and task switching in psychopathic individuals.

Deficits in cognitive control have been considered a core dysfunction of psychopathy, responsible for disrupted self-control. We investigated cognitive control impairments, including difficulties with task switching, failure of response inhibition, and inability to adjust speed of responding. Participants included 16 subjects with psychopathic traits (Ps), and 22 healthy controls (HCs). We recorded behavioral responses during a Task Switching paradigm, a probe of flexible behavioral adaptation to changing contexts; and a Go/NoGo Task, which assesses response inhibition and indexes behavioral impulsivity. During task switching, Ps evidenced impairments shifting set when conflicting (incongruent) information was presented, but performed as well as HCs in the absence of such conflict. In addition, when they encountered these difficulties, they failed to adjust their speed of responding. Ps presented also with deficits in response inhibition, with many commission errors on the Go/NoGo Task. This study identified impairments in response inhibition and in set shifting in psychopathic individuals. When shifting set, they evidenced difficulties refocusing on a new task when it was incongruent with the previous task. These deficits interfere with regulation of ongoing behavior and disrupt self-regulation. Our findings suggest abnormal neural processing during suppression of inappropriate responses in psychopathic individuals.