Antipsychotic dose and diminished neural modulation: a multi-site fMRI study

Abstract

Background: The effect of antipsychotics on the blood oxygen level dependent signal in schizophrenia is poorly understood. The purpose of the present investigation is to examine the effect of antipsychotic medication on independent neural networks during a motor task in a large, multi-site functional magnetic resonance imaging investigation.

Methods: Seventy-nine medicated patients with schizophrenia and 114 comparison subjects from the Mind Clinical Imaging Consortium database completed a paced, auditory motor task during functional magnetic resonance imaging (fMRI). Independent component analysis identified temporally cohesive but spatially distributed neural networks. The independent component analysis time course was regressed with a model time course of the experimental design. The resulting beta weights were evaluated for group comparisons and correlations with chlorpromazine equivalents.

Results: Group differences between patients and comparison subjects were evident in the cortical and subcortical motor networks, default mode networks, and attentional networks. The chlorpromazine equivalents correlated with the unimotor/bitemporal (rho=-0.32, P=0.0039), motor/caudate (rho=-0.22, P=0.046), posterior default mode (rho=0.26, P=0.020), and anterior default mode networks (rho=0.24, P=0.03). Patients on typical antipsychotics also had less positive modulation of the motor/caudate network relative to patients on atypical antipsychotics (t(77)=2.01, P=0.048).

Conclusion: The results suggest that antipsychotic dose diminishes neural activation in motor (cortical and subcortical) and default mode networks in patients with schizophrenia. The higher potency, typical antipsychotics also diminish positive modulation in subcortical motor networks. Antipsychotics may be a potential confound limiting interpretation of fMRI studies on the disease process in medicated patients with schizophrenia.

Figure 1

The axial slices (z = + 30, +10, −10 mm from anterior commissure/posterior commissure plane) of the components of interest: a) unimotor/bitemporal, b) posterior default mode network, c) inferior frontal, d) motor/posterior cingulate, e) anterior default mode/medial frontal f) motor/caudate, g) anterior default mode/caudate, h) right fronto-parietal, i) bimotor, j) left fronto-parietal, and k) occipital. The spatial maps represent regions of the brain related to the ICA time course from a one- sample t-test.

Figure 2

A two-sample t-test revealed significant differences between the patients with schizophrenia (SP) and the healthy comparison subjects (HC) in the betas of eight of the eleven selected components. The positively modulated components are in green/dark and the negatively modulated components are in gray/light. The lines represent standard error.

Figure 3

This figure is the scatter plot and linear fit for the chlorpromazine equivalents and the following components: A) unimotor/bitemporal network (rho = −0.32, P = 0.0039), B) motor/caudate (rho = −0.22, P = 0.046), C) posterior default mode network (rho = 0.26, P = 0.020), and D) anterior default mode network (rho = 0.24, P = 0.030).

Figure 4

Patients on typical antipsychotics had significantly less positive modulation in the motor/caudate network relative to the patients on atypicals (t₇₇ = 2.01, P = 0.048). Patients on typical antipsychotics had trend a trend towards less negative modulation in the anterior default mode network/caudate network relative to patients on atypical antipsychotics (t₇₇ = −1.92, P = 0.058).