Recently, a great deal of interest has arisen in resting state fMRI as a measure of tonic brain function in clinical populations. Most studies have focused on the examination of temporal correlation between resting state fMRI low-frequency oscillations (LFOs). Studies on the amplitudes of these low-frequency oscillations are rarely reported. Here, we used amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF; the relative amplitude that resides in the low frequencies) to examine the amplitude of LFO in schizophrenia. Twenty-six healthy controls and 29 patients with schizophrenia or schizoaffective disorder participated. Our findings show that patients showed reduced low-frequency amplitude in proportion to the total frequency band investigated (i.e., fALFF) in the lingual gyrus, left cuneus, left insula/superior temporal gyrus, and right caudate and increased fALFF in the medial prefrontal cortex and the right parahippocampal gyrus. ALFF was reduced in patients in the lingual gyrus, cuneus, and precuneus and increased in the left parahippocampal gyrus. These results suggest LFO abnormalities in schizophrenia. The implication of these abnormalities for schizophrenic symptomatology is further discussed.

Schizophrenia has been increasingly conceptualized as a disorder of brain connectivity, in large part due to findings emerging from white matter and functional connectivity (FC) studies. This work has focused primarily on within-hemispheric connectivity, however some evidence has suggested abnormalities in callosal structure and interhemispheric interaction. Here we examined functional connectivity between homotopic points in the brain using a technique called voxel-mirrored homotopic connectivity (VMHC). We performed VMHC analyses on resting state fMRI data from 23 healthy controls and 25 patients with schizophrenia or schizoaffective disorder. We found highly significant reductions in VMHC in patients for a number of regions, particularly the occipital lobe, the thalamus, and the cerebellum. No regions of increased VMHC were detected in patients. VMHC in the postcentral gyrus extending into the precentral gyrus was correlated with PANSS Total scores. These results show substantial impairment of interhemispheric coordination in schizophrenia.

Objective Aggression in schizophrenia is a major societal issue, leading to physical harm, stigmatization, patient distress, and higher healthcare costs. Impulsivity is associated with aggression in schizophrenia, but it is multidetermined. The subconstruct of urgency is likely to play an important role in this aggression, with positive urgency referring to rash action in context of positive emotion, and negative urgency to rash action in context of negative emotion. Method We examined urgency and its neural correlates in 33 patients with schizophrenia or schizoaffective disorder and 31 healthy controls. Urgency was measured using the Urgency, Premeditation, Perseverance and Sensation Seeking scale. Aggressive attitudes were measured using the Buss Perry Aggression Questionnaire. Results Positive urgency, negative urgency, and aggressive attitudes were significantly and selectively elevated in patients (1.21< Cohen’s ds < 1.50). Positive and negative urgency significantly correlated with Aggression Questionnaire total score (rs>.48) and each uniquely accounted for a significant portion of the variance in aggression over and above the effect of group. Urgency measures correlated with reduced cortical thickness in ventral prefrontal regions including right frontal pole, medial and lateral orbitofrontal gyrus and inferior frontal gyri, and rostral anterior cingulate cortex. In patients, reduced resting state functional connectivity in some of these regions was associated with higher urgency. Conclusions Findings highlight the key role of urgency in aggressive attitudes in people with schizophrenia and suggest neural substrates of these behaviors. They also suggest behavioral and neural targets for interventions to remediate urgency and aggression.

A significant proportion of patients with schizophrenia demonstrate abnormalities in dorsal prefrontal regions including the dorsolateral prefrontal and dorsal anterior cingulate cortices. However, it is less clear to what extent abnormalities are exhibited in ventral prefrontal and limbic regions, despite their involvement in social cognitive dysfunction and aggression, which represent problem domains for patients with schizophrenia. Previously, we found that reduced white matter integrity in right inferior frontal regions was associated with higher levels of aggression. Here, we used resting-state functional magnetic resonance imaging to examine amygdala/ventral prefrontal cortex (vPFC) functional connectivity (FC) and its relation to aggression in schizophrenia. Twenty-one healthy controls and 25 patients with schizophrenia or schizoaffective disorder participated. Aggression was measured using the Buss Perry Aggression Questionnaire. Regions of interest were placed in the amygdala based on previously published work. A voxelwise FC analysis was performed in which the mean time series across voxels for this bilateral amygdala seed was entered as a predictor in a multiple regression model with motion parameters and global, cerebrospinal fluid, and white matter signals as covariates. Patients showed significant reductions in FC between amygdala and vPFC regions. Moreover, in patients, the strength of this connection showed a significant inverse relationship with aggression, such that lower FC was associated with higher levels of self-rated aggression. Similar results were obtained for 2 other measures--Life History of Aggression and total arrests. These results suggest that amygdala/vPFC FC is compromised in schizophrenia and that this compromise is associated with aggression.

Patients with schizophrenia exhibit cognitive and sensory impairment, and object recognition deficits have been linked to sensory deficits. The "frame and fill" model of object recognition posits that low spatial frequency (LSF) information rapidly reaches the prefrontal cortex (PFC) and creates a general shape of an object that feeds back to the ventral temporal cortex to assist object recognition. Visual dysfunction findings in schizophrenia suggest a preferential loss of LSF information. This study used functional magnetic resonance imaging (fMRI) and resting state functional connectivity (RSFC) to investigate the contribution of visual deficits to impaired object "framing" circuitry in schizophrenia. Participants were shown object stimuli that were intact or contained only LSF or high spatial frequency (HSF) information. For controls, fMRI revealed preferential activation to LSF information in precuneus, superior temporal, and medial and dorsolateral PFC areas, whereas patients showed a preference for HSF information or no preference. RSFC revealed a lack of connectivity between early visual areas and PFC for patients. These results demonstrate impaired processing of LSF information during object recognition in schizophrenia, with patients instead displaying increased processing of HSF information. This is consistent with findings of a preference for local over global visual information in schizophrenia.