An fMRI study of visual attention and sensorimotor function before and after antipsychotic treatment in first-episode schizophrenia

Abstract

While much is known about receptor affinity profiles of antipsychotic medications, less is known about their impact on functional brain systems in patients with schizophrenia. We conducted functional magnetic resonance imaging (fMRI) studies with first-episode schizophrenia patients as they made saccades to unpredictable visual targets before and after 4-6 weeks of antipsychotic treatment. Matched healthy individuals were scanned at similar time intervals. Pretreatment, patients had less activation in frontal and parietal eye fields and cerebellum. After treatment these disturbances were not present, suggesting improved function in attentional and sensorimotor systems. Other pretreatment abnormalities were noted in sensory and ventromedial prefrontal cortex, but after treatment these abnormalities were absent or less prominent, in line with improved function in attentional systems. In addition, although not abnormal at baseline, there was reduced activity after treatment in dorsal prefrontal cortex, dorsal striatum, and dorsomedial thalamus, suggesting a potential adverse effect of treatment on frontostriatal systems, perhaps related to dopamine blockade in the caudate. These findings provide evidence for a complex impact of antipsychotic medication on functional brain systems in schizophrenia and illustrate the potential of neuroimaging biomarkers for both adverse and beneficial drug effects on functional brain systems.

Antipsychotic Drug Effects in Schizophrenia: A Review of Longitudinal fMRI Investigations and Neural Interpretations

“…Changes in symptoms over the 31-day treatment period and symptoms correlations after treatment were not significant. Keedy et al (2009) assessed the impact of 28 to 36 days of antipsychotic treatment in 9 SP and 9 matched HC with unpredictable, visually guided saccades that activated the saccade and spatial attention system [43]. One SP was antipsychotic naïve.…”

“…Instead of anatomic regions, we focus on the generalized pattern of normalization with respect to analysis method. With respect to the general linear model, normalization resulted in both increased [42][43][44] and decreased activation [43,44]. Seed-voxel correlations had mixed results with both increased and decreased connectivity with treatment [40,46].…”

“…Seven of the eight investigations demonstrated normalization of the BOLD signal with antipsychotic treatment reflecting reversal of the aberrant fMRI signal evident at T1 and possible therapeutic benefit of antipsychotic treatment [40][41][42][43][44][45][46][47]. In contrast, five of the eight investigations had concurrent denormalization of different cortical and subcortical regions [40,[43][44][45][46]. Behavioral correlates (symptoms or cognition) were intermittently included among the eight investigations.…”

“…Four of the eight investigations used olanzapine monotherapy [40,41,44,45]. The remaining studies used clinical judgment resulting in a mixture of different antipsychotics with markedly different D 2 binding affinities from clozapine (K i = 63) [46] to haloperidol (K i = 0.55) [43]. D 2 binding affinities may be associated with diminished BOLD signal activity in crosssectional or longitudinal investigations comparing different types of antipsychotics [10].…”

“…Although the included investigations do not permit comparisons of different types or binding affinities of antipsychotics, our results do not appear to entirely support this framework. Several investigations included risperidone (K i = 1.1) and reported normalization of BOLD activity via increased activity in the anterior cingulate [42] as well as the frontal eye fields and cerebellum [43]. Furthermore, Lui et al…”