Faculty Bibliography

BACKGROUND AND OBJECTIVE/OBJECTIVE:Changes in cerebral white matter organization have been documented in acute phases of recovery from traumatic brain injury (TBI). However, little is known about reorganization processes in more chronic stages of recovery. The current study identified changes in white matter organization in chronic cases of TBI, and determined the relationship between structural changes and cognitive functioning. METHODS:15 adults with moderate to severe TBI and eight healthy controls completed neuropsychological testing and diffusion tensor imaging (DTI) scanning. Participants returned 3 years from the initial session to complete identical neuropsychological tests and scans. RESULTS:Adults with TBI were found to have significantly reduced fractional anisotropy (FA), a metric of white matter organization, compared to healthy participants at baseline and also at 3-year follow-up. Within the sample of adults with TBI, increases in FA were observed over time. Importantly, increases in FA in the TBI sample were also correlated with improvements in cognitive performance. CONCLUSIONS:This study provides evidence of a dynamic process of white matter change occurring beyond the initial phases of recovery after moderate to severe TBI. The observed relationship between structural reorganization and changes in cognitive performance has implications for rehabilitation potential in more chronic phases of recovery.

Background: The association between schizophrenia and violence is an important issue in psychiatry. The impact of several factors (social cognition, neurocognition, alexithymia, emotion regulation capacity, and the therapeutic milieu) on aggression in schizophrenia creates an opportunity for the development and evaluation of novel treatments for aggression. Previous studies show that cognitive remediation training (CRT) and social cognitive training (SCT) help to decrease hostility. The parent study examined whether cognitive training leads to improvements in cognition emotion regulation capacity, and impulse control in participants with a history of impulsive aggression. The current study examined the effectiveness of CRT alone versus a combination of CRT and SCT in terms of emotion recognition and cognitive improvement.
Method(s): The study recruited participants with schizophrenia or schizoaffective disorder with a past year history of at least one or more violent acts or a significant lifetime history of aggression as indicated by a score of 5 or more on the Life History of Aggression (LHA) interview from two inpatient sites (Manhattan Psychiatric Center and New York Hospital, Westchester Division). Participants were randomized to two groups of 36 one-hour sessions. Participants in the control group had 24 sessions of CRT (BrainHQ) and 12 sessions of Encyclopedia readings. Participants in the treatment group had 24 sessions of CRT (BrainHQ) and 12 sessions of computerized SCT (MindReading). To assess neurocognition, mentalizing, and facial affect recognition abilities, participants were administered the MATRICS Consensus Cognitive Battery (MCCB), Reading the Mind in the Eyes Task (Eyes Task), and the Emotion Recognition-40 (ER-40) respectively. Negative emotionality was captured using the Positive and Negative Affect Schedule (PANAS).
Result(s): The study data included 49 completers and 5 intent-to-treat samples, with 24 and 25 per group, respectively (CRT+ SCT and CRT alone). Results indicated no significant differences between groups at baseline. Significant overall improvements were observed in the ER-40 for all subjects across time (Mean Time 1 = 25.06 (SD = 25.023), Time 2 Mean = 30.86 (SD = 6.849), p < 0.001), the Mind in the Eyes Test - Revised (Time 1 Mean = 19.70 (SD = 7.407), Time 2 Mean = 26.15 (SD = 7.830), p < 0.001), and the PANAS Negative affect Score (Time 1 Mean = 29.40 (SD = 11.836), Time 2 Mean = 18.47 (SD = 2.688), p < 0.001). Both cognitive groups showed improvements from baseline on the composite cognition score of the MCCB composite (F (1,47)=74.51, p<0.001, eta2 =0.61) with a slight edge to the combined CRT+SCT group (F (1,47)=3.61, p=0.064, eta2 =0.07). The Mind in the Eyes Test showed a significant improvement between groups (p = 0.025) with the CRT + SCT group showing greater improvement at endpoint. There were no other significant differences between groups.
Discussion(s): CRT with and without SCT improved both cognitive functions and emotion recognition as well as aspects of emotion regulation in patients with significant histories of impulsive aggression. While social cognition training only added a small increment in emotion recognition, possibly facilitating better emotion regulation control and impulsivity, more direct measures of aggression and impulsivity need to be interrogated to assess the effect on aggressive behaviors

BACKGROUND:Negative self-referential thinking is a common symptom of depression associated with poor treatment response. In late-life depression, white matter abnormalities may contribute to negative self-referential thoughts following antidepressant treatment. We investigated the association of fractional anisotropy (FA) in select regions of the negative valence system (NVS) with residual negative self-referential thoughts following treatment with escitalopram for late-life depression. METHODS:The participants were older adults with major depression and psychiatrically normal controls. Depressed participants received 12 weeks of treatment with escitalopram. To assess self-referential thinking, participants completed a Trait Adjective Task at baseline and at week 12. Baseline MRI scans included a diffusion imaging sequence for FA analyses. RESULTS:Participants with late-life depression differed from controls on all performance measures of the Trait Adjective Task at baseline and at 12 weeks. Depressed participants endorsed fewer negative personality traits and more positive personality traits at week 12 compared to baseline. Lower FA in the dorsal anterior cingulate and in the uncinate fasciculus in depressed participants was correlated with residual negative self-referential thinking (e.g., more endorsed negative adjectives, fewer rejected negative adjectives) at treatment end. LIMITATIONS/CONCLUSIONS:The sample size is modest so the findings are preliminary. FA analyses were restricted to predetermined regions. CONCLUSIONS:Negative self-referential thinking improved in depressed older adults following 12 weeks of treatment with escitalopram. Baseline FA in select white matter regions of the NVS was associated with residual negative self-referential thinking. These findings may help identify treatment targets for residual negative self-referential thoughts.

BACKGROUND:There is paucity of neurobiological knowledge about major depressive disorder with psychotic features ("psychotic depression"). This study addresses this knowledge gap by using resting state functional magnetic resonance imaging (R-fMRI) to compare functional connectivity in patients with psychotic depression and healthy controls. METHODS:We scanned patients who participated in a randomized controlled trial as well as healthy controls. All patients achieved remission from depressive and psychotic symptoms with sertraline and olanzapine. We employed Independent Component Analysis in independent samples to isolate the default mode network (DMN) and compared patients and controls. FINDINGS/RESULTS:The Toronto sample included 28 patients (mean [SD], age 56·2 [13·7]) and 39 controls (age 55·1 [13·5]). The Replication sample included 29 patients (age 56·1 [17·7]) and 36 controls (age 48·3 [17·9]). Patients in the Toronto sample demonstrated decreased between-network functional connectivity between the DMN and bilateral insular, somatosensory/motor, and auditory cortices with peak activity in the right planum polare (t = 4·831; p = 0·001, Family Wise Error (FWE) corrected). A similar pattern of between-network functional connectivity was present in our Replication sample with peak activity in the right precentral gyrus (t = 4·144; p = 0·003, FWE corrected). INTERPRETATION/CONCLUSIONS:Remission from psychotic depression is consistently associated with an absence of increased DMN-related functional connectivity and presence of decreased between-network functional connectivity. Future research will evaluate this abnormal DMN-related functional connectivity as a potential biomarker for treatment trajectories. FUNDING/BACKGROUND:National Institute of Mental Health.

Schizophrenia is associated with an elevated risk of aggression. Cognitive deficits have been associated with inpatient aggression and future violence. The relationship between cognitive deficits and violent behavior has however been inconsistent across studies. In addition, studies have failed to inform how cognitive deficits may contribute to aggression in schizophrenia. The current study examined the association of cognitive deficits with schizophrenia-related aggression and violent offending. It also explored the putative mediating role of negative emotionality on the impact of cognitive deficits on aggression. People with schizophrenia and schizoaffective disorder (N = 78) were recruited from a state hospital. Participants were classified based on their history of violent offending. Participants completed measures of cognition, symptoms, and aggression. Deficits in working memory, reasoning/problem-solving, and verbal learning were the most prioritized for the prediction of violent offender status. Violent offenders demonstrated greater impairments in most cognitive domains especially working memory and verbal learning. Offenders also demonstrated greater negative emotionality, excitement/agitation, and incidents of verbal and physical aggression. Negative emotionality and excitement/agitation fully transmitted the effect of cognitive deficits on impulsive aggression in meditational models. Cognitive deficits increase the risk of impulsive aggression in schizophrenia via inefficient regulation of negative affective states.

Patients with schizophrenia show response inhibition deficits equal to or greater than those seen in impulse-control disorders, and these deficits contribute to poor outcome. However, little is known about the circuit abnormalities underlying this impairment. To address this, we examined stop signal task performance in 21 patients with schizophrenia and 21 healthy controls using event related potential (ERP) and resting state functional connectivity. Patients showed prolonged stop signal reaction time (SSRT) and reduced N1, N2, and P3 amplitudes compared to controls. Across groups, P3 amplitudes were maximal after SSRT (i.e., after the time associated with the decision to stop occurred), suggesting that this component indexed response monitoring. Multiple regression analyses showed that longer SSRTs were independently related to 1) patient status, 2) reduced N1 amplitude on successful stop trials and 3) reduced anticorrelated resting state functional connectivity between visual and frontoparietal cortical networks. This study used a combined multimodal imaging approach to better understand the network abnormalities that underlie response inhibition in schizophrenia. It is the first of its kind to specifically assess the brain's resting state functional architecture in combination with behavioral and ERP methods to investigate response inhibition in schizophrenia.

Griffanti et al. (2017) provide a rich set of expert-consensus guidelines for how to label components derived from ICA as either belonging to signal of interest or noise to be filtered from fMRI data. These general hypotheses concerning procedures for "hand" classification of components are a good starting point that with further detail would improve reproduction of experiments and facilitate comparisons of alternative hypotheses/procedures. Empirical validation could help to resolve questions by supporting or disconfirming the proposed guidelines.

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.

Background: Restricted global brain connectivity (rGBC) examines mean FC between each voxel and every other voxel within a region. We examined the relationship between rGBC in 7 canonical resting state networks (Yeo et al., 2011) and change in rumination and depression severity following 12 weeks of escitalopram treatment in geriatric patients with depression. Methods: This sample consisted of elderly depressed patients receiving escitalopram treatment during a 12-week clinical trial. Patients received MRI scans at baseline (n=27) and 12 weeks (n=11). Rumination (Ruminative Response Scale) and depression severity (Hamilton Depression Rating Scale; HDRS) were measured at the same time points. Resting state fMRI data was acquired during a 5-minute scan. Data processing involved motion correction, regression of covariates (white matter, CSF, 24 motion parameters, linear/quadratic trends), registration, smoothing (6mm), and filtering (0.01-0.1Hz), and rGBC was computed for each network. Results: Depression and rumination were lower at 12 weeks compared to baseline (os<.01, c/s>0.89). Lower baseline visual and DMN rGBC predicted reduced rumination at 12 weeks (rs<-.68, ps<.02), and lower limbic and DMN rGBC predicted improvement in HDRS (rs<-.62, ps<.04). In addition, poorer treatment response was predicted by reduced (over time) rGBC in 5 out of 7 networks (rs<-.65, ps<.03). Conclusions: The findings suggest that lower baseline levels of self-directed thoughts (as suggested by lower DMN rGBC) may relate to improvement in rumination, and that maintenance of rGBC levels in multiple networks may be necessary for, and/or be a marker for, treatment response. This suggests mechanisms by which escitalopram improves these factors