Dysregulated but not decreased salience network activity in schizophrenia

Abstract

Effective estimation of the salience of environmental stimuli underlies adaptive behavior, while related aberrance is believed to undermine rational thought processes in schizophrenia. A network including bilateral frontoinsular cortex (FIC) and dorsal anterior cingulate cortex (dACC) has been observed to respond to salient stimuli using functional magnetic resonance imaging (fMRI). To test the hypothesis that activity in this salience network (SN) is less discriminately modulated by contextually-relevant stimuli in schizophrenia than in healthy individuals, fMRI data were collected in 20 individuals with schizophrenia and 13 matched controls during performance of a modified monetary incentive delay (MID) task. After quantitatively identifying spatial components representative of the FIC and dACC features of the SN, two principal analyses were conducted. In the first, modulation of SN activity by salience was assessed by measuring response to trial outcome. First-level general linear models were applied to individual-specific time-courses of SN activity identified using spatial independent component analysis (ICA). This analysis revealed a significant salience-by-performance-by-group interaction on the best-fit FIC component's activity at trial outcome, whereby healthy individuals but not individuals with schizophrenia exhibited greater distinction between the response to hits and misses in high salience trials than in low salience trials. The second analysis aimed to ascertain whether SN component amplitude differed between the study groups over the duration of the experiment. Independent-samples T-tests on back-projected, percent-signal-change scaled SN component images importantly showed that the groups did not differ in the overall amplitude of SN expression over the entire dataset. These findings of dysregulated but not decreased SN activity in schizophrenia provide physiological support for mechanistic conceptual frameworks of delusional thought formation.

Functional Connectivity of the Caudate in Schizophrenia Evaluated with Simultaneous Resting-State Functional MRI and Electroencephalography Recordings

“…Activation of the ventral striatum and the PFC during reward processing is reduced in schizophrenia [21,22], and critical dysfunction of cortico-striatal connectivity related to information retrieval is observed during working memory performance in patients with schizophrenia [23]. The caudate nucleus and cortical regions connected to the caudate show markedly abnormal hemispheric specialization in patients with schizophrenia, and patients also show weaker specialization in the left caudate and stronger specialization in the right on rsfMRI.…”

Dysfunctional Striatal Systems in Treatment-Resistant Schizophrenia

“…Furthermore, there is convergent evidence for the complementary involvement of these corticostriatal networks in psychotic illness. Compromised ventral circuit function has been well established by consistently reduced activation of ventral striatum and PFC during reward processing in schizophrenia (Heinz and Schlagenhauf, 2010;White et al, 2013), structural changes of ventromedial PFC after or during the transition to a first illness episode (Mechelli et al, 2011), and an upregulation of ventral striatum dopamine concentration in psychotic individuals (Fusar-Poli and Meyer-Lindenberg, 2013). However, preferential elevation of dopamine in dorsal striatum has also been reported in both unmedicated patients and individuals in an at-risk mental state (ARMS) for developing psychosis (Howes et al, 2009;Kegeles et al, 2010).…”

What can the monetary incentive delay task tell us about the neural processing of reward and punishment?

“…75 However, this attenuation has not consistently been replicated in other studies. 79,80 Although there is no clear picture as yet regarding how the reward system may be modified in patients with schizophrenia, probing the integrity of this system may lead to identification of subgroups and tailored treatment concepts.…”