Faculty Bibliography

Diffusion tensor imaging (DTI) has widely been used to investigate the microstructural damage of white matter tracts that occur in individuals with traumatic brain injury (TBI). In the current review, we discuss the white matter regions which are commonly affected in adults with TBI. We also describe the current literature that has utilized DTI to investigate the relationship between microstructural integrity with neuropsychological performance and clinical outcome measures. Finally, a model is presented of the potential utilization of DTI as a biomarker of efficacy in neurorehabilitation for individuals with TBI.

The National Institute of Mental Health strategic plan for advancing psychiatric neuroscience calls for an acceleration of discovery and the delineation of developmental trajectories for risk and resilience across the lifespan. To attain these objectives, sufficiently powered datasets with broad and deep phenotypic characterization, state-of-the-art neuroimaging, and genetic samples must be generated and made openly available to the scientific community. The enhanced Nathan Kline Institute-Rockland Sample (NKI-RS) is a response to this need. NKI-RS is an ongoing, institutionally centered endeavor aimed at creating a large-scale (N > 1000), deeply phenotyped, community-ascertained, lifespan sample (ages 6-85 years old) with advanced neuroimaging and genetics. These data will be publically shared, openly, and prospectively (i.e., on a weekly basis). Herein, we describe the conceptual basis of the NKI-RS, including study design, sampling considerations, and steps to synchronize phenotypic and neuroimaging assessment. Additionally, we describe our process for sharing the data with the scientific community while protecting participant confidentiality, maintaining an adequate database, and certifying data integrity. The pilot phase of the NKI-RS, including challenges in recruiting, characterizing, imaging, and sharing data, is discussed while also explaining how this experience informed the final design of the enhanced NKI-RS. It is our hope that familiarity with the conceptual underpinnings of the enhanced NKI-RS will facilitate harmonization with future data collection efforts aimed at advancing psychiatric neuroscience and nosology.

CONTEXT: The AX version of the visual continuous performance task (AX-CPT) is widely used for investigating visual working memory dysfunction in schizophrenia. Event-related potentials (ERP) provide an objective index of brain function and can be used to evaluate brain substrates underlying impaired cognition in schizophrenia. OBJECTIVE: To assess the mechanisms that underlie visual working memory dysfunction in schizophrenia relative to impairment of early visual processing. DESIGN: Case-control study. SETTING: Inpatient and outpatient facilities associated with the Nathan Kline Institute for Psychiatric Research. PARTICIPANTS: A total of 30 individuals with schizophrenia and 17 healthy comparison subjects. INTERVENTIONS: Three versions of the AX-CPT, with parametric variations in the proportions of trial types, were used to test performance and underlying neural activity during differential challenge situations. Contrast sensitivity measures were obtained from most subjects. MAIN OUTCOME MEASURES: Behavioral performance was assessed using d' context scores. Integrity of stimulus- and task-related cortical activation to both cue and probe stimuli was assessed using sensory (C1, P1, N1) and cognitive (N2, contingent negative variation [CNV]) ERP components. Early magnocellular/parvocellular function was assessed using contrast sensitivity. Linear regression and path analyses were used to assess relations between physiological and behavioral parameters. RESULTS: Patients showed reduced amplitude of both early sensory (P1, N1) and later cognitive (N2, CNV) ERP components. Deficits in sensory (N1) and cognitive (N2) component activation to cue stimuli contributed independently to impaired behavioral performance. In addition, sensory deficits predicted impaired cognitive ERP generation. Finally, deficits in performance correlated with impairments in contrast sensitivity to low, but not high, spatial frequency stimuli. CONCLUSIONS: Working memory deficits in schizophrenia have increasingly been attributed to impairments in stimulus encoding rather than to failures in memory retention. This study provides objective physiological support for encoding hypotheses. Further, deficits in sensory processing contribute significantly to impaired working memory performance, consistent with generalized neurochemical models of schizophrenia

Functional connectivity between the piriform cortex and limbic and neocortical areas was assessed using functional magnetic resonance imaging (fMRI) of urethane anesthetized rats that spontaneously cycled between slow-wave and fast-wave states. Slow-wave and fast-wave states were determined indirectly through monitoring of respiration rate, which was confirmed to co-vary with state as determined by electrophysiological recordings. Previous electrophysiological data have suggested that the piriform cortex shifts between responsiveness to afferent odor input during fast-wave states and enhanced functional connectivity with limbic areas during slow-wave state. The present results demonstrate that fMRI-based resting state functional connectivity between the piriform cortex and both limbic and neocortical areas is enhanced during slow-wave state compared to fast-wave state using respiration as an indirect measure of state in urethane anesthetized rats. This state-dependent shift in functional connectivity may be important for sleep-dependent odor memory consolidation

This study examined self-reported impulsivity and aggression and performance on the stop-signal task in patients with schizophrenia or schizoaffective disorder and healthy volunteers. Compared to controls, patients had higher scores on interview and questionnaire measures of impulsivity and aggression and showed increased stop-signal reaction time and greater response variability. These findings are consistent with a specific impairment in response inhibition in schizophrenia

Functional connectivity of an individual human brain is often studied by acquiring a resting state functional magnetic resonance imaging scan, and mapping the correlation of each voxel's BOLD time series with that of a seed region. As large collections of such maps become available, including multisite data sets, there is an increasing need for ways to distill the information in these maps in a readily visualized form. Here we propose a two-step analytic strategy. First, we construct connectivity-distance profiles, which summarize the connectivity of each voxel in the brain as a function of distance from the seed, a functional relationship that has attracted much recent interest. Next, these profile functions are regressed on predictors of interest, whether categorical (e.g., acquisition site or diagnostic group) or continuous (e.g., age). This procedure can provide insight into the roles of multiple sources of variation, and detect large-scale patterns not easily available from conventional analyses. We illustrate the proposed methods with a resting state data set pooled across four imaging sites

OBJECTIVE: Poor insight into illness is commonly associated with schizophrenia and has implications for the clinical outcome of the disease. A better understanding of the neurobiology of these insight deficits may help the development of new treatments targeting insight. Despite the importance of this issue, the neural correlates of insight deficits in schizophrenia remain poorly understood. METHOD: Thirty-six individuals diagnosed with schizophrenia or schizoaffective disorder underwent diffusion tensor imaging (DTI). The subjects were assessed on two dimensions of insight (symptom awareness and attribution of symptoms) using the Scale to Assess Unawareness of Mental Disorder (SUMD). Level of psychosis was assessed with the Positive and Negative Syndrome Scale (PANSS). RESULTS: White matter abnormalities in the right superior frontal gyrus, left middle frontal gyrus, bilateral parahippocampal gyrus, adjacent to the right caudate head, right thalamus, left insula, left lentiform nucleus, left fusiform gyrus, bilateral posterior cingulate, left anterior cingulate, right cingulate gyrus, left lingual gyrus, and bilateral claustrum were associated with symptom unawareness. Misattribution of symptoms was related to deficits in the white matter adjacent to the right lentiform nucleus, left middle temporal gyrus, and the right precuneus. CONCLUSIONS: Impaired insight in schizophrenia implicates a complex neural circuitry: white matter deficits in fronto-temporo brain regions are linked to symptom unawareness; compromised temporal and parietal white matter regions are involved in the misattribution of symptoms. These findings suggest the multidimensional construct of insight has multiple neural determinants

Current cocaine-dependent users show reductions in white matter (WM) integrity, especially in cortical regions associated with cognitive control that have been associated with inhibitory dysfunction. A key question is whether these white matter differences are present following abstinence from drug use. To address this, WM integrity was examined using diffusion tensor imaging (DTI) obtained on 43 cocaine abstinent patients (abstinence duration ranged between five days and 102 weeks) and 43 non-using controls. Additionally, a cross-sectional comparison separated the patients into three groups (short-term, mid-term and long-term) based upon duration of cocaine abstinence. The 43 cocaine abstinent patients showed lower fractional anisotropy (FA) in the left anterior callosal fibers, left genu of the corpus callosum, right superior longitudinal fasciculus, right callosal fibers and the superior corona radiata bilaterally when compared against non-using controls. Higher FA in the cocaine abstinent patients was observed in the splenium of the corpus callosum and right superior longitudinal fasciculus. Differences between the cocaine abstinent groups were observed bilaterally in the inferior longitudinal fasciculus, right anterior thalamic radiation, right ventral posterolateral nucleus of the thalamus, left superior corona radiata, superior longitudinal fasciculus bilaterally, right cingulum and the WM of the right precentral gyrus. The results identified WM differences between cocaine abstinent patients and controls as well as distinct differences between abstinent subgroups. The findings suggest that specific white matter differences persist throughout abstinence while other, spatially distinct, differences discriminate as a function of abstinence duration. These differences may, therefore, represent brain changes that mark recovery from addiction

PURPOSE OF REVIEW: Aggression in schizophrenia is associated with poor treatment outcomes, hospital admissions, and stigmatization of patients. As such it represents an important public health issue. This article reviews recent neuroimaging studies of aggression in schizophrenia, focusing on PET/single photon emission computed tomography and MRI methods. RECENT FINDINGS: The neuroimaging literature on aggression in schizophrenia is in a period of development. This is attributable in part to the heterogeneous nature and basis of that aggression. Radiological methods have consistently shown reduced activity in frontal and temporal regions. MRI brain volumetric studies have been less consistent, with some studies finding increased volumes of inferior frontal structures, and others finding reduced volumes in aggressive individuals with schizophrenia. Functional MRI studies have also had inconsistent results, with most finding reduced activity in inferior frontal and temporal regions, but some also finding increased activity in other regions. Some studies have made a distinction between types of aggression in schizophrenia in the context of antisocial traits, and this appears to be useful in understanding the neuroimaging literature. SUMMARY: Frontal and temporal abnormalities appear to be a consistent feature of aggression in schizophrenia, but their precise nature likely differs because of the heterogeneous nature of that behavior