Dataset Information

Phase-specific brain change of spatial working memory processing in genetic and ultra-high risk groups of schizophrenia.

ABSTRACT: Spatial working memory (WM) processing has 3 distinct phases: encoding, maintenance, and retrieval and its dysfunction is a core feature in schizophrenia. We examined phase-specific brain activations associated with spatial WM in first-degree relatives of schizophrenia (genetic high risk, GHR), ultra-high risk (UHR) subjects, patients with schizophrenia, and healthy controls. We used an event-related functional magnetic resonance imaging in 17 GHR subjects, 21 UHR subjects, 15 clinically stable patients with schizophrenia and 16 healthy controls, while subjects were performing a spatial delayed-response task. During the encoding phase, the GHR group showed increased activation in the fronto-parietal regions, whereas the UHR and schizophrenia groups showed significantly less activation in these regions than did the healthy control group. Especially, frontal activation was strongest in GHR subjects, followed by healthy controls, and occurred to a lesser degree in the UHR group, with the least activation occurring in the schizophrenia group. During the maintenance phase, the thalamus showed a differential activation, similar to frontal activation pattern during the encoding phase. During the retrieval phase, no prominent differential activations were found. Increased activations were observed in the superior temporal gyrus during the encoding and maintenance phases in the GHR, UHR, and schizophrenia groups relative to healthy controls. Our findings suggest that functional deficits associated with spatial WM processing emerge in the UHR before the onset of schizophrenia and compensatory neural processes exist in the GHR with genetic liability to schizophrenia.

SUBMITTER: Choi JS

PROVIDER: S-EPMC3494057 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Phase-specific brain change of spatial working memory processing in genetic and ultra-high risk groups of schizophrenia.

Choi Jung-Seok JS Park Ji-Young JY Jung Myung Hun MH Jang Joon Hwan JH Kang Do-Hyung DH Jung Wi Hoon WH Han Ji Yeon JY Choi Chi-Hoon CH Hong Kyung Sue KS Kwon Jun Soo JS

Schizophrenia bulletin 20110425 6

Spatial working memory (WM) processing has 3 distinct phases: encoding, maintenance, and retrieval and its dysfunction is a core feature in schizophrenia. We examined phase-specific brain activations associated with spatial WM in first-degree relatives of schizophrenia (genetic high risk, GHR), ultra-high risk (UHR) subjects, patients with schizophrenia, and healthy controls. We used an event-related functional magnetic resonance imaging in 17 GHR subjects, 21 UHR subjects, 15 clinically stable ...[more]

PMID: 21518920

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Project description:BACKGROUND:In most domains of cognition, individuals with schizophrenia are generally found to be one standard deviation below the mean of the controls. As a result, examining the impact of cognitive remediation in individuals with schizophrenia has been a burgeoning area of research. However, the state of the literature remains unclear as to which domains of cognition should be targeted to produce the most widespread and durable benefits for individuals with schizophrenia. One suggestion is that targeting lower-level cognitive processes that are important for higher-level and more complex aspects of cognition may produce the most widespread benefits in cognition and everyday functioning. Relatively few studies have examined the effects of working memory or processing speed training in schizophrenia, as most studies examine broad-based remediation programs. Thus, a need exists for targeted working memory and processing speed training studies to better understand the mechanisms of cognitive enhancement in patients. This study aims to 1) investigate near-transfer gains (that is, the transfer of learning to related contexts) associated with working memory and processing speed training in schizophrenia patients; 2) investigate far-transfer gains (that is, the transfer of learning to new contexts) associated with working memory and processing speed training (that is, gains in other neurocognitive domains and social cognition); and 3) investigate real-world gains associated with training (that is, gains in daily functioning). METHODS/DESIGN:A double-blind randomized controlled trial with a three parallel group design will be conducted. A random sample of 81 patients with schizophrenia or schizoaffective disorder will be recruited through outpatient clinics at Foothills Hospital and community support programs in Calgary, Alberta. Participants will be randomly assigned using a computer-generated program in a 1:1:1 ratio to a working memory-training group, a processing speed-training group, or a no-training control group. Training will be completed at home for 30 minutes per day, 5 days per week, for a total of 10 weeks. Neurocognitive, social cognitive, and daily functioning measures will be administered both pre- and post-training to detect training-related gains. The primary outcome measures will include working memory and processing speed (near-transfer measures), as well as fluid intelligence (far-transfer measure). TRIAL REGISTRATION:Current controlled trials NCT02478827 (ClinicalTrials.gov, registered on 15 June 2015).

Project description:Working memory (WM) is impaired in psychotic disorders and linked to functional outcome. Most neurobiological models emphasize prefrontal cortex (PFC) dysfunction in the etiology of WM impairment. However, WM is composed of multiple processes, including encoding and maintenance, and the delineation of the neurobiology of these sub-processes has not been well characterized in schizophrenia and psychotic bipolar disorder. Functional MRI was obtained during an event-related spatial delayed match-to-sample task from 58 healthy individuals, 72 individuals with schizophrenia and 41 people with bipolar I disorder with psychotic features in order to: 1) characterize neural responses during encoding, maintenance and retrieval stages of WM using complementary region-of-interest and whole brain approaches; 2) determine whether schizophrenia and psychotic bipolar disorder exhibit similar abnormalities in WM-related brain function; and 3) elucidate the associations between WM-related brain function, task performance, and neuropsychological functioning. Both schizophrenia and psychotic bipolar disorder groups showed encoding- and maintenance-related impairments in the posterior parietal cortex (PPC) and frontal eye fields (FEF). BOLD response in the PPC and FEF, during encoding and maintenance respectively, was associated with task performance independent of group. Additionally, encoding-related activation in the PPC correlated with general neuropsychological functioning independent of group. Only encoding-related activation in the right ventral striatum differed between schizophrenia and psychotic bipolar disorder; individuals with schizophrenia showed significantly lower activation than both psychotic bipolar disorder and healthy groups. Our results are consistent with emerging evidence implicating PPC dysfunction in WM impairment and suggest interventions targeting neural activation in PPC may improve WM and neuropsychological functioning across psychotic disorders.

Dataset Information

Phase-specific brain change of spatial working memory processing in genetic and ultra-high risk groups of schizophrenia.

Publications

Phase-specific brain change of spatial working memory processing in genetic and ultra-high risk groups of schizophrenia.

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