Gary Flynn

Functional disconnections in the direct and indirect amygdala pathways for fear processing in schizophrenia

BACKGROUND Schizophrenia patients show reduced neural activity, relative to controls, in the amygdala and its projection to the medial prefrontal cortex (MPFC) in response to fear perception. In this study we tested the hypothesis that schizophrenia is characterized by abnormal functional connectivity in the amygdala network underlying fear perception. METHODS Functional MRI images were acquired from 14 schizophrenia patients and 14 matched healthy control subjects during an emotion perception task, in which fearful and neutral facial expression stimuli were presented pseudorandomly under nonconscious (using masking) and conscious conditions. Both subtraction and functional connectivity analyses were undertaken using a region of interest approach. RESULTS In response to fearful facial expressions, schizophrenia patients displayed reduced amygdala activity, compared to controls, in both the conscious and nonconscious conditions. The amygdala displayed a reversal of the normal pattern of connectivity with the brainstem, visual cortex, and also with the dorsal and ventral divisions of the MPFC in the schizophrenia patients. CONCLUSIONS The presence of functional disconnections in amygdala pathways suggests that schizophrenia patients have a failure in coordinating their automatic orienting to salient signals and the associated prefrontal monitoring of these signals.

Event-related potential correlates of depression, insight and negative symptoms in males with recent-onset psychosis

OBJECTIVE The neurobiology of clinical characteristics -in particular depression, insight and negative symptoms- in recent-onset psychosis (ROP) was studied using event-related potentials (ERPs). METHODS Twenty right-handed ROP men and 20 controls completed an auditory-oddball task. ROP men had minimum exposure to antipsychotic medication. N100, N200 and P300 were studied to ascertain the effects of (a) diagnosis (patients versus controls), and (b) clinical characteristics. RESULTS ROP men had significantly lower anterior N100, enhanced N200 at T3, and lower P300 at Pz than controls. Lower right-anterior N100 and enhanced right-anterior N200 amplitude explained 47.7% of negative symptoms. Left-central N100 amplitude explained 30.28% of negative symptoms. Lower left-posterior and higher right-posterior P300 amplitude explained 65.99% of total symptoms. Lower left-central N100, enhanced left-central N200 and depression explained 78.8% of impairments in insight and judgement. Impaired insight/judgement correlated positively with right-anterior N200 and was identified as the most significant co-efficient for depression. CONCLUSIONS Disturbed selective-attention and executive function indexed by N100 and N200, respectively, are associated with poor insight and negative symptoms. A complex interaction exists between insight and depression. SIGNIFICANCE The current results demonstrate a biological basis of insight and depression and a complex interaction between the two, perhaps mediated by executive function, in early psychosis.

Spatio-temporal EEG waves in first episode schizophrenia.

OBJECTIVE Schizophrenia is characterized by a deficit in context processing, with physiological correlates of hypofrontality and reduced amplitude P3b event-related potentials. We hypothesized an additional physiological correlate: differences in the spatio-temporal dynamics of cortical activity along the anterior-posterior axis of the scalp. METHODS This study assessed latency topographies of spatio-temporal waves under task conditions that elicit the P3b. EEG was recorded during separate auditory and visual tasks. Event-related spatio-temporal waves were quantified from scalp EEG of subjects with first episode schizophrenia (FES) and matched controls. RESULTS The P3b-related task conditions elicited a peak in spatio-temporal waves in the delta band at a similar latency to the P3b event-related potential. Subjects with FES had fewer episodes of anterior to posterior waves in the 2-4 Hz band compared to controls. Within the FES group, a tendency for fewer episodes of anterior to posterior waves was associated with high Psychomotor Poverty symptom factor scores. CONCLUSIONS Subjects with FES had altered global EEG dynamics along the anterior-posterior axis during task conditions involving context update. SIGNIFICANCE The directional nature of this finding and its association with Psychomotor Poverty suggest this result is related to findings of hypofrontality in schizophrenia.

Absolute Level of Gamma Synchrony is Increased in First- Episode Schizophrenia During Face Processing

Most studies of gamma band synchrony in schizophrenia conclude that it is reduced, relative to what is observed in healthy people, during stimulus processing. However, these findings may, in part, be an artifact of greater absolute levels of synchrony in schizophrenia even at baseline. We examined absolute level of gamma band synchrony before and during emotionally neutral face processing in 28 patients with schizophrenia after their first episode of psychosis (FES) (20 male) and 71 controls (53 male) across a range of frequency bins, brain regions and time-bands. We also examined how absolute synchrony prior to stimulus onset related to synchrony change during stimulus processing, and how it related to symptoms. The FES group showed greater absolute gamma synchrony across all time-points in frontal and temporal regions. Baseline absolute synchrony predicted post-stimulus change in these regions in a pattern consistent with previous reports. However, synchrony change was not related to symptoms. These results support the recommendation that studies in this field should examine baseline absolute synchrony when attempting to characterize task-related gamma synchrony in schizophrenia.

First-episode psychosis and direction of wave propagation at 1 Hz in the EEG.

1Brain Resource Company, Sydney, Australia; 2Brain Dynamics Centre, Westmead Millenium Institute and University of Sydney, Sydney, Australia; 3Neuroscience Institute of Schizophrenia and Allied Disorders, Sydney, Australia; 4Early Psychosis Intervention Program, Liverpool Hospital, NSW, Australia; 5Department of Psychiatry, University of Adelaide, SA, Australia; and 6The University of Sydney, Sydney, Australia