Aberrant Frontostriatal Connectivity in Negative Symptoms of Schizophrenia

Abstract

Negative symptoms represent a distinct component of psychopathology in schizophrenia (SCZ) and are a stable construct over time. Although impaired frontostriatal connectivity has been frequently described in SCZ, its link with negative symptoms has not been carefully studied. We tested the hypothesis that frontostriatal connectivity at rest may be associated with the severity of negative symptoms in SCZ. Resting state functional connectivity (rsFC) data from 95 mostly medicated patients with SCZ and 139 healthy controls (HCs) were acquired. Negative symptoms were assessed using the Brief Negative Symptom Scale. The study analyzed voxel-wise rsFC between 9 frontal “seed regions” and the entire striatum, with the intention to reduce potential biases introduced by predefining any single frontal or striatal region. SCZ showed significantly reduced rsFC between the striatum and the right medial and lateral orbitofrontal cortex (OFC), lateral prefrontal cortex, and rostral anterior cingulate cortex compared with HCs. Further, rsFC between the striatum and the right medial OFC was significantly associated with negative symptom severity. The involved striatal regions were primarily at the ventral putamen. Our results support reduced frontostriatal functional connectivity in SCZ and implicate striatal connectivity with the right medial OFC in negative symptoms. This task-independent resting functional magnetic resonance imaging study showed that medial OFC–striatum functional connectivity is reduced in SCZ and associated with severity of negative symptoms. This finding supports a significant association between frontostriatal connectivity and negative symptoms and thus may provide a potential circuitry-level biomarker to study the neurobiological mechanisms of negative symptoms.

Genetic Contribution of Synapse-Associated Protein 97 to Orbitofrontal–Striatal–Thalamic Circuitry Connectivity Changes in First-Episode Schizophrenia

“…Combining previous reports and our results suggests that increased connectivity in the FES with the risk allele group may be a compensatory mechanism for the relatively inefficient connectivity of the relevant brain regions to reach near-normal performance (17). Consistent with a recent task-independent fMRI study, we also found abnormal orbitofrontal-putamen functional connectivity in schizophrenia but failed to associate connectivity with the severity of negative symptoms in that study (18). Few previous reports have mentioned abnormal orbitofrontal-pallidum connectivity in schizophrenia.…”

Intermittent theta burst stimulation for negative symptoms of schizophrenia—A double-blind, sham-controlled pilot study

“…Specific prefrontal areas, in particular, the dorsolateral prefrontal cortex (DLPFC), have been identified 10 . More recent studies have suggested that patients with NSS have structural and functional impairments in prefrontal areas and that the connectivity between those areas and the rest of the brain, including striatal regions, is also impacted 11 .…”

Impact of Positive Emotion Regulation Training on Negative Symptoms and Social Functioning in Schizophrenia: A Field Test

“…Behavioral and neuroimaging studies tend to show the underpinnings of these clinical differences (7, 11). Reduced frontostriatal functional connectivity associated with negative symptoms might provide a supplementary hypothesis to study the neurobiological mechanisms of negative symptoms (16).…”