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A disturbance in the frontal-striatal-thalamic circuitry has been proposed for schizophrenia, but this concept has been based primarily on indirect evidence from psychopharmacology and analogies with animal research. Diffusion tensor imaging, a new MRI technique that permits direct assessment of the large axon masses stretching from the prefrontal cortex to the striatum, was used to study white matter axon bundles. Diffusion tensor images, high-resolution structural MRI and positron emission tomography scans with 18-fluorodexoyglucose were obtained on five patients with schizophrenia and six age- and sex-matched normal controls. Significantly lower diffusion anisotropy in the white matter of the prefrontal cortex in schizophrenic patients than in normal controls was observed in statistical probability maps. Co-registered PET scans revealed significantly lower correlation coefficients between metabolic rates in the prefrontal cortex and striatum in patients than in controls. These twin findings provide convergent evidence for diminished fronto-striatal connectivity in schizophrenia.

Abnormal fronto-amygdala circuitry has been implicated in impulsive aggression, a core symptom of borderline personality disorder (BPD). We examined relative glucose metabolic rate (rGMR) at rest and after m-CPP (meta-chloropiperazine) with 18 fluorodeoxyglucose (FDG) with positron emission tomography (PET) in 26 impulsive aggressive (IED)-BPD patients and 24 controls. Brain edges/amygdala were visually traced on MRI scans co-registered to PET scans; rGMR was obtained for ventral and dorsal regions of the amygdala and Brodmann areas within the prefrontal cortex (PFC). Correlation coefficients were calculated between rGMR for dorsal/ventral amygdala regions and PFC. Additionally, amygdala volumes and rGMR were examined in BPD and controls. Correlations PFC/amygdala Placebo: Controls showed significant positive correlations between right orbitofrontal (OFC) and ventral, but not dorsal, amygdala. Patients showed only weak correlations between amygdala and the anterior PFC, with no distinction between dorsal and ventral amygdala. Correlations PFC/amygdala: m-CPP response: Controls showed positive correlations between OFC and amygdala regions, whereas patients showed positive correlations between dorsolateral PFC and amygdala. Group differences between interregional correlational matrices were highly significant. Amygdala volume/metabolism: No group differences were found for amygdala volume, or metabolism in the placebo condition or in response to meta-chloropiperazine (m-CPP). We demonstrated a tight coupling of metabolic activity between right OFC and ventral amygdala in healthy subjects with dorsoventral differences in amygdala circuitry, not present in IED-BPD. We demonstrated no significant differences in amygdala volumes or metabolism between BPD patients and controls.

Background Borderline personality disorder (BPD) is characterized by an inability to regulate emotional responses. The amygdala is important in learning about the valence (goodness and badness) of stimuli and has been reported to function abnormally in BPD. Methods Event-related functional MRI (fMRI) was employed in three groups: unmedicated BPD (n=33) and schizotypal personality disorder (SPD;n=28) participants and healthy controls (n=32) during a task involving an intermixed series of unpleasant, neutral, and pleasant pictures each presented twice within their respective trial block/run. The amygdala was hand-traced on each participant’s structural-MRI scan which was co-registered to their BOLD-scan. Amygdala responses were examined with a mixed-model MANOVA with repeated measures. Results Compared with both control groups, BPD patients showed greater amygdala activation, particularly to the repeated emotional but not neutral pictures and a prolonged return to baseline for the overall BOLD response averaged across all pictures. Despite amygdala overactivation, BPD patients showed a blunted response on the self-report ratings of emotional but not neutral pictures. Fewer dissociative symptoms in both patient groups were associated with greater amygdala activation to repeated unpleasant pictures. Conclusions The increased amygdala response to the repeated emotional pictures observed in BPD was not observed in SPD patients suggesting diagnostic specificity. This BPD-related abnormality is consistent with the well-documented clinical feature of high sensitivity to emotional stimuli with unusually strong and long-lasting reactions. The finding of a mismatch between physiological and self-report measures of emotion reactivity in BPD patients suggests they may benefit from treatments which help them recognize emotions.

The startle reflex (SR) elicited by abrupt stimuli can be modified by attention to nonstartling stimuli that shortly precede the startle-eliciting stimulus. The present study of 15 recent-onset, relatively asymptomatic schizophrenic outpatients and 14 demographically matched normal control subjects demonstrated that attentional modulation of SR is impaired in schizophrenic patients. Specifically, the control group exhibited greater startle eye-blink modification following to-be-attended prestimuli than following to-be-ignored prestimuli, whereas the patients failed to show the attentional modulation effect. These results suggest traitlike attentional deficits in schizophrenia because the patients were relatively asymptomatic. The measurement of attentional modulation of SR may provide a nonverbal, reflexive, state-independent marker of the vulnerability to schizophre-Schizophrenia has long been recognized as involving impaired attention and information processing (Bleuler, 1911/ 1950; Kraepelin, 1913/1919). However, there has been considerable disagreement regarding the nature of these impairments. Paradigms that allow isolation of elementary components of attention and information processing may help refine our understanding of these core schizophrenic impairments. The startle-reflex modification paradigm is one such paradigm. The startle-reflex modification paradigm involves the modification of the acoustic startle reflex by innocuous environmental stimuli that precede the reflex-eliciting stimulus. For example, the size or latency of the eye-blink component of the human startle reflex to a sudden loud noise will vary depending on the stimulus events that immediately precede the startling noise. The amplitude of the startle reflex can be either inhibited or facilitated depending on the stimulus conditions, particularly the interval between onset of the first stimulus (prepulse) and onset of the startle stimulus. When the interval between the prepulse and the startle stimulus is short (i.e., between 30 and 300 ms), there is a reduction in startle amplitude compared with the response elicited in the absence of a prepulse. This phenomenon, called prepulse inhibition, is observed reliably in lower animals when measures of whole-body startle are used (Hoffman & Ison, 1980,1992), as well as in humans when the

Schizophrenia is associated with volume and neuronal changes in the mediodorsal nucleus and pulvinar, the major association nuclei of the thalamus, whereas total thalamic volume and the volumes of anterior and centromedian nuclei were not significantly altered.

The thalamus provides a nodal link for multiple functional circuits that are impaired in schizophrenia (SZ). Despite inconsistencies in the literature, a meta analysis suggests that the volume of the thalamus relative to that of the brain is decreased in SZ. Morphometric neuroimaging studies employing deformation, voxel-based and region of interest methodologies suggest that the volume deficit preferentially affects the thalamic regions containing the anterior and mediodorsal nuclei, and the pulvinar. Postmortem design-based stereological studies have produced mixed results regarding volume and neuronal deficits in these nuclei. This review examines those aspects of thalamic circuitry and function that suggest salience to SZ. Evidence for anomalies of thalamic structure and function obtained from postmortem and neuroimaging studies is then examined and directions for further research proposed.

Reduced serotonergic activity has been associated with impulsive aggression in personality disordered