An fMRI study of prefrontal dysfunction and symptomatic recovery in schizophrenia

Smee, Cori; Krabbendam, Lydia; O’Daly, Owen; Prins, Anne-Marye; Nalesnik, Natasza Dominika; Morley, Lucy; Samson, Gabrielle; Shergill, Sukhwinder S.

doi:10.1111/j.1600-0447.2010.01632.x

Cited by 12 publications

(4 citation statements)

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“…36 Because structural and functional changes within the dorsolateral prefrontal cortex (DLPFC) are consistently replicated across all phases of SZ, 37,38 the DLPFC stands as a principal area worthy of developmental investigation. Previous fMRI studies demonstrated that changes in prefrontal activation during follow-up are associated with reductions in psychotic symptoms, 39,40 improved social functioning, 41 and treatment response. [42][43][44][45] These studies examined small samples, short follow-up periods, and adult patients with chronic illness.…”

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confidence: 99%

Association of Age at Onset and Longitudinal Course of Prefrontal Function in Youth With Schizophrenia

Niendam

Ray

et al. 2018

JAMA Psychiatry

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IMPORTANCEThe extent of cognitive deterioration after schizophrenia (SZ) onset is poorly understood because prior longitudinal studies used small samples of older individuals with established illness. OBJECTIVE To examine the association of age at onset and subsequent longitudinal course of prefrontal activity during the first 2 years of illness in youths with SZ and healthy control participants (HCs). DESIGN, SETTING, AND PARTICIPANTSThis naturalistic, longitudinal, functional magnetic resonance imaging (fMRI) study included patients with recent-onset SZ and HCs aged 12 to 25 years enrolled in an ongoing study of cognition in recent-onset psychosis in the Sacramento, California, area from October 13, 2004, through June 25, 2013. Participants completed clinical assessments and an established measure of cognitive control, the AX Continuous Performance Task (AX-CPT), during fMRI at baseline and at 6-, 12-, and 24-month follow-up. Whole-brain, voxelwise, and an a priori dorsolateral prefrontal cortex (DLPFC) region of interest analyses were performed. Group differences in developmental trajectories were examined by focusing on behavioral performance (d′-context) and cognitive control-associated brain activity. The association of antipsychotic medication and clinical factors were also examined. Data were analyzed from April 15, 2015, through August 29, 2017. MAIN OUTCOMES AND MEASURES Primary outcomes included group differences (HC vs SZ) in behavioral performance (d'-context from AX-CPT) and brain activity for cue B-A trials of the AX-CPT in an a priori DLPFC region of interest at baseline and across the age span. Secondary analysis examined the influence of antipsychotics on behavioral performance and DLPFC activity. RESULTSAmong the sample of 180 participants (66.1% male; mean [SD] age at baseline, 19.2 [3.2] years), 87 patients with SZ (mean [SD] age, 19.6 [3.0] years) showed impaired performance compared with 93 HCs (mean [SD] age, 18.8 [3.4] years) across the age span (estimated difference [SE], −0.571 [0.12], d′-context; P < .001). Patients with SZ showed reduced activation in the DLPFC and parietal cortex (false discovery rate cluster corrected to P < .05) compared with HCs under conditions of high cognitive control at baseline. Region-of-interest analysis showed reduced activation in the DLPFC bilaterally for patients with SZ, with a trajectory that paralleled that of HCs across the age span (left DLPFC β [SE] estimates, 0.409 [0.165] for the HC group and −0.285 [0.130] for the SZ group [main effect of group, P = .03]; right DLPFC β [SE] estimates, 0.350 [0.103] for the HC group and −0.469 [0.157] for the SZ group [P = .003]). Antipsychotic medication, clinical symptoms, and global functioning were associated with SZ performance.CONCLUSIONS AND RELEVANCE During the initial 1 to 2 years after illness onset, young individuals with SZ showed deficits in DLPFC activation and cognitive control, with developmental trajectories comparable to those of HCs. Younger age at onset was not associated with reduced cogniti...

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confidence: 99%

Association of Age at Onset and Longitudinal Course of Prefrontal Function in Youth With Schizophrenia

Niendam

Ray

et al. 2018

JAMA Psychiatry

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“…In addition to reducing the hyperactivity in temporal cortices during hallucinations, rTMS may also extert its beneficial effects on AH by facilitating the functional connectivity between the temporoparietal and frontal cortexes. Changes in frontal cortical activation have recently been demonstrated to covary with positive symptoms over time (Krabbendam et al, 2009; Michalopoulou et al, 2010; Smee et al, 2011). These two different mechanisms of action may underlie change in different patients, perhaps explaining some of the variability in results of rTMS treatment of AH.…”

Section: Discussionmentioning

confidence: 99%

Examining frontotemporal connectivity and rTMS in healthy controls: Implications for auditory hallucinations in schizophrenia.

et al. 2012

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“…Multiple functional magnetic resonance imaging (fMRI) studies have examined neural correlates of clinical [ 10 , 11 ] and symptomatic [ 12 ] recovery in psychotic and schizophrenic patients. They showed altered functional connectivity (FC) [ 11 ], as well as changes in the activities of specific brain regions, while the patients performed tasks [ 10 , 12 ]. However, the participants in those studies did not meet our strict criteria for full recovery [ 3 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Network biomarkers in recovered psychosis patients who discontinued antipsychotics

Odkhuu,

Kim,

Tsogt

et al. 2023

Mol Psychiatry

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There are no studies investigating topological properties of resting-state fMRI (rs-fMRI) in patients who have recovered from psychosis and discontinued medication (hereafter, recovered patients [RP]). This study aimed to explore topological organization of the functional brain connectome in the RP using graph theory approach. We recruited 30 RP and 50 age and sex-matched healthy controls (HC). The RP were further divided into the subjects who were relapsed after discontinuation of antipsychotics (RP-R) and who maintained recovered state without relapse (RP-M). Using graph-based network analysis of rs-fMRI signals, global and local metrics and hub information were obtained. The robustness of the network was tested with random failure and targeted attack. As an ancillary analysis, Network-Based Statistic (NBS) was performed. Association of significant findings with psychopathology and cognitive functioning was also explored. The RP showed intact network properties in terms of global and local metrics. However, higher global functional connectivity strength and hyperconnectivity in the interconnected component were observed in the RP compared to HC. In the subgroup analysis, the RP-R were found to have lower global efficiency, longer characteristic path length and lower robustness whereas no such abnormalities were identified in the RP-M. Associations of the degree centrality of some hubs with cognitive functioning were identified in the RP-M. Even though network properties of the RP were intact, subgroup analysis revealed more altered topological organizations in the RP-R. The findings in the RP-R and RP-M may serve as network biomarkers for predicting relapse or maintained recovery after the discontinuation of antipsychotics.

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An fMRI study of prefrontal dysfunction and symptomatic recovery in schizophrenia

Abstract: The data supports the role of dysfunctional prefronto-parietal relationships in the genesis of positive psychotic symptoms.

Cited by 12 publications

References 73 publications

Association of Age at Onset and Longitudinal Course of Prefrontal Function in Youth With Schizophrenia

Association of Age at Onset and Longitudinal Course of Prefrontal Function in Youth With Schizophrenia

Examining frontotemporal connectivity and rTMS in healthy controls: Implications for auditory hallucinations in schizophrenia.

Network biomarkers in recovered psychosis patients who discontinued antipsychotics

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