Matthew J. Hoptman

Quantitative comparison of algorithms for inter-subject registration of 3D volumetric brain MRI scans.

The objective of inter-subject registration of three-dimensional volumetric brain scans is to reduce the anatomical variability between the images scanned from different individuals. This is a necessary step in many different applications such as voxelwise group analysis of imaging data obtained from different individuals. In this paper, the ability of three different image registration algorithms in reducing inter-subject anatomical variability is quantitatively compared using a set of common high-resolution volumetric magnetic resonance imaging scans from 17 subjects. The algorithms are from the automatic image registration (AIR; version 5), the statistical parametric mapping (SPM99), and the automatic registration toolbox (ART) packages. The latter includes the implementation of a non-linear image registration algorithm, details of which are presented in this paper. The accuracy of registration is quantified in terms of two independent measures: (1) post-registration spatial dispersion of sets of homologous landmarks manually identified on images before or after registration; and (2) voxelwise image standard deviation maps computed within the set of images registered by each algorithm. Both measures showed that the ART algorithm is clearly superior to both AIR and SPM99 in reducing inter-subject anatomical variability. The spatial dispersion measure was found to be more sensitive when the landmarks were placed after image registration. The standard deviation measure was found sensitive to intensity normalization or the method of image interpolation.

The 5% difference: early sensory processing predicts sarcasm perception in schizophrenia and schizo-affective disorder.

BACKGROUNDnIntact sarcasm perception is a crucial component of social cognition and mentalizing (the ability to understand the mental state of oneself and others). In sarcasm, tone of voice is used to negate the literal meaning of an utterance. In particular, changes in pitch are used to distinguish between sincere and sarcastic utterances. Schizophrenia patients show well-replicated deficits in auditory function and functional connectivity (FC) within and between auditory cortical regions. In this study we investigated the contributions of auditory deficits to sarcasm perception in schizophrenia.nnnMETHODnAuditory measures including pitch processing, auditory emotion recognition (AER) and sarcasm detection were obtained from 76 patients with schizophrenia/schizo-affective disorder and 72 controls. Resting-state FC (rsFC) was obtained from a subsample and was analyzed using seeds placed in both auditory cortex and meta-analysis-defined core-mentalizing regions relative to auditory performance.nnnRESULTSnPatients showed large effect-size deficits across auditory measures. Sarcasm deficits correlated significantly with general functioning and impaired pitch processing both across groups and within the patient group alone. Patients also showed reduced sensitivity to alterations in mean pitch and variability. For patients, sarcasm discrimination correlated exclusively with the level of rsFC within primary auditory regions whereas for controls, correlations were observed exclusively within core-mentalizing regions (the right posterior superior temporal gyrus, anterior superior temporal sulcus and insula, and left posterior medial temporal gyrus).nnnCONCLUSIONSnThese findings confirm the contribution of auditory deficits to theory of mind (ToM) impairments in schizophrenia, and demonstrate that FC within auditory, but not core-mentalizing, regions is rate limiting with respect to sarcasm detection in schizophrenia.

Functional connectivity fMRI in mouse brain at 7T using isoflurane.

Although many resting state fMRI human studies have been published, the number of such rodent studies is considerably less. The reason for this is the severe technical challenge of high magnetic field small rodent imaging. Local magnetic field susceptibility changes at air tissue boundaries cause image distortion and signal losses. The current study reports measures of functional connectivity in mice using only isoflurane for the anesthetic. Because all anesthetic agents will alter cerebral blood flow and cerebral metabolism, the impact these changes have on neuronal connectivity has yet to be fully understood, however this work reports for the first time that reliable functional connectivity measures in mouse brain can be obtained with isoflurane.

Impulsivity and aggression in schizophrenia: a neural circuitry perspective with implications for treatment

Elevations of impulsive behavior have been observed in a number of serious mental illnesses. These phenomena can lead to harmful behaviors, including violence, and thus represent a serious public health concern. Such violence is often a reason for psychiatric hospitalization, and it often leads to prolonged hospital stays, suffering by patients and their victims, and increased stigmatization. Despite the attention paid to violence, little is understood about its neural basis in schizophrenia. On a psychological level, aggression in schizophrenia has been primarily attributed to psychotic symptoms, desires for instrumental gain, or impulsive responses to perceived personal slights. Often, multiple attributions can coexist during a single aggressive incident. In this review, I discuss the neural circuitry associated with impulsivity and aggression in schizophrenia, with an emphasis on implications for treatment. Impulsivity appears to account for a great deal of aggression in schizophrenia, especially in inpatient settings. Urgency, defined as impulsivity in the context of strong emotion, is the primary focus of this article. It is elevated in several psychiatric disorders, and in schizophrenia, it has been related to aggression. Many studies have implicated dysfunctional frontotemporal circuitry in impulsivity and aggression in schizophrenia, and pharmacological treatments may act via that circuitry to reduce urgency and aggressive behaviors; however, more mechanistic studies are critically needed. Recent studies point toward manipulable neurobehavioral targets and suggest that cognitive, pharmacological, neuromodulatory, and neurofeedback treatment approaches can be developed to ameliorate urgency and aggression in schizophrenia. It is hoped that these approaches will improve treatment efficacy.

S21. EVENT-RELATED REPETITIVE TMS TO RIGHT POSTERIOR STS (BUT NOT OCCIPITAL FACE AREA) IN HEALTHY VOLUNTEERS (HV) BRIEFLY RECAPITULATES FACE EMOTION RECOGNITION (FER) DEFICITS OF SCHIZOPHRENIA (SZ)

Abstract Background Profound FER deficits exist in Sz, causing social disability, though can be partly remediated with computer-based training. Neurostimulation might augment remediation if critical nodes were identified. We aimed to 1) briefly recapitulate FER deficits of Sz in HV using rTMS to rpSTS, 2) identify connectivity patterns of rpSTS regressed by FER, and 3) apply TMS to rpSTS with fMRI as readout. Methods 1) Nine healthy volunteers had rTMS (10 Hz; 500 msec; 110% RMT) to rpSTS or rOFA (counterbalanced; 10/10 system overlay with standard MRI) concurrent (1/3 trials) with stimuli (http://faces.mpdl.mpg.de/) for emotion or gender identification (button press). 14 Sz patients completed these tasks without TMS. 2) Whole-brain resting-connectivity analyses, seeded by rpSTS, was applied in 27 Sz and 35 HV who also completed the UPenn FER task. 3) BOLD fMRI was obtained in 4 HV pre- and post-TMS to rpSTS (1 Hz; 20 minutes). Results 1) In HV, rTMS to rpSTS only (not OFA) significantly slowed reaction time for FER only (not gender identification): overall F test for logRT (p=.001) with post-hoc rpSTS vs.OFA (p=.005) and rpSTS vs. non-stim trials (p=.004). rpSTS recapitulated slowed RT ad lower FER accuracy of Sz. 2) In both HV and Sz, rpSTS had significant resting connectivity with V1 (p= .00013), positively modulated by FER accuracy. 3) Analyses are ongoing. Discussion rpSTS is a critical node in the FER circuit with connectivity to primary visual cortex modulated by FER, whose disruption recapitulates FER deficits, making it a candidate target for remediatory neurostimulation.

T153. CAN COGNITIVE TRAINING DECREASE REACTIVE AGGRESSION IN SCHIZOPHRENIA

Abstract Background Cognitive deficits contribute to aversive social behaviors such as impulsive aggression. Studies have shown that cognitive training interventions may decrease the risk for impulsive aggression. The current study sought to illuminate the underlying mechanism of cognitive training effects on impulsive aggression—particularly, changes in the neural circuitry and in behavioral expressions of emotion regulation and emotion-based impulsivity. Methods Participants (N=28) with schizophrenia or schizoaffective disorder were recruited from New York Presbyterian Hospital and Manhattan Psychiatric Center and randomized into one of two cognitive training groups—a cognitive remediation training plus social cognition training (CRT+SCT) group versus CRT alone. At baseline and following 36 hours of training, participants completed the MATRICS Consensus Cognitive Battery (MCCB), Eyes Task, and the Emotion Recognition-40 (ER-40) as measures of neurocognition, mentalizing, and facial affect recognition. We indexed emotion regulation capacity using the Positive and Negative Affect Scale (PANAS) and by obtaining heart rate, respiration, and electrodermal activity while participants viewed pictures selected from the International Affective Picture System (IAPS). A subsample of participants completed fMRI scans during the completion of the emotion regulation task. The Go No-go task and the Emotional Stop Signal task served as measures of impulsivity. Aggression was measured using the Overt Aggression Scale (OAS), the Point Subtraction Aggression Paradigm (PSAP), and the Taylor Aggression Paradigm (TAP). Results Participants were 31.93 years old (SD=10.46) and had completed 12.07 (SD=2.59) years of education. Both groups showed improvements from baseline on the composite cognition score of the MCCB with a slight edge to the combined CRT+SCT group (Cohen’s d=0.22). Both groups showed pre-to-post reductions in aggression with only minimal differences. Although both groups showed pre-to-post improvements in affect recognition and mentalizing, the CRT+SCT group showed greater improvements in affect recognition (Cohen’s d = 0.21) and mentalizing (Cohen’s d = 0.39). Both groups showed reductions in negative affectivity scores from baseline (Cohen’s d =-0.48) but reductions were greater in the CRT+SCT group (Cohen’s d = -0.24). Both groups demonstrated pre-to-post reductions in their Low Frequency/High Frequency heart rate variability ratio (Cohen’s d=-0.83) and pre-to-post reductions in skin conductance (Cohen’s d = -0.48). Pre-to-post differences in HRV and skin conductance were very minimal. Both groups demonstrated large pre-to-post reductions in misses on the No-Go trials of the Go No-Go Task (Cohen’s d =-1.74). Reductions were greater in the CRT+SCT than the CRT only group (Cohen’s d=0.49) suggesting that the CRT+SCT group show greater improvements in impulse control after cognitive training. Baseline fMRI scans showed that amygdalofrontal network activation was greater when emotionally evocative pictures were preceded by a reappraisal statement compared to conditions in which they were preceded by negative descriptions. This shows that the emotion regulation task engages relevant neural targets. The presentation will include accumulated follow-up fMRI scans. It is expected that there will be increased BOLD signaling following cognitive training. Discussion The study adds to evidence of cognitive training prospects for decreasing aggressive impulses. A mechanistic model with improved emotion regulation and impulse control contributing to reduced aggression may characterize cognitive training effects. Change in neural circuitry of emotion regulation will demonstrate strong proof-of-concept.