Clinical Symptoms and Alpha Band Resting-State Functional Connectivity Imaging in Patients With Schizophrenia: Implications for Novel Approaches to Treatment

Department of Radiology and Biomedical Imaging, University of California, San Francisco, California 94143, USA.
Biological psychiatry (Impact Factor: 10.26). 08/2011; 70(12):1134-42. DOI: 10.1016/j.biopsych.2011.06.029
Source: PubMed


Schizophrenia (SZ) is associated with functional decoupling between cortical regions, but we do not know whether and where this occurs in low-frequency electromagnetic oscillations. The goal of this study was to use magnetoencephalography (MEG) to identify brain regions that exhibit abnormal resting-state connectivity in the alpha frequency range in patients with schizophrenia and investigate associations between functional connectivity and clinical symptoms in stable outpatient participants.
Thirty patients with SZ and 15 healthy comparison participants were scanned in resting-state MEG (eyes closed). Functional connectivity MEG source data were reconstructed globally in the alpha range, quantified by the mean imaginary coherence between a voxel and the rest of the brain.
In patients, decreased connectivity was observed in left prefrontal cortex (PFC) and right superior temporal cortex, whereas increased connectivity was observed in left extrastriate cortex and the right inferior PFC. Functional connectivity of left inferior parietal cortex was negatively related to positive symptoms. Low left PFC connectivity was associated with negative symptoms. Functional connectivity of midline PFC was negatively correlated with depressed symptoms. Functional connectivity of right PFC was associated with other (cognitive) symptoms.
This study demonstrates direct functional disconnection in SZ between specific cortical fields within low-frequency resting-state oscillations. Impaired alpha coupling in frontal, parietal, and temporal regions is associated with clinical symptoms in these stable outpatients. Our findings indicate that this level of functional disconnection between cortical regions is an important treatment target in SZ.

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Available from: Adrian G Guggisberg,
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    • "Recently, we have developed techniques to extract global functional connectivity maps across the whole brain from MEG recordings (Guggisberg et al., 2008; Hinkley et al., 2011; Tarapore et al., 2013), and also generate regional functional connectivity maps to relate to behavioural outcomes (Guggisberg et al., 2008; Martino et al., 2011; Tarapore et al., 2012). Here we report the first MEGbased study of RSFC in focal epilepsy to examine both whole brain connectivity and regional connectivity maps associated with the epileptogenic zone. "
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    • "Furthermore, functional connectivities within the range of alpha band activity are suggested to be related to physical and mental fitness (Douw et al., 2014). Such neurophysiological aspects have also been proposed as useful markers of impaired brain states, such as schizophrenia (Hinkley et al., 2011), Alzheimer’s disease (Canuet et al., 2012), and multiple sclerosis (Cover et al., 2006). However, in the field of BMIs, there have been few studies focusing on the relationship between functional connectivity within the range of alpha band activities and the performance of BMIs. "
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    • "By that interpretation, training that improves the neurological abilities that contribute to working memory and neuro-modulatory system functionality in these great brain systems should have substantial prophylactic power in at-risk individuals. From a neurological perspective, schizophrenic brains are: poor signal resolvers, operate sluggishly, struggle to generate sustained activities supporting top-down (working memory, selective attention, associative memory, predictive) processes in prefrontal cortex (Minzenberg et al., 2009), and in frontal, posterior parietal and inferior and medial temporal areas (Heckers, 2001); have distortions in language, visual, source-reference and other operations related to psychotic symptoms (Modinos et al., 2013); have impairments in social cognition that greatly impact quality of life (see Couture et al., 2006); and have changes in fundamental neuronal processes that we associate (along with working memory degradation) with very noisy brain system processing (e.g., Hinkley et al., 2011). Perceptual, cognitive, social, and motor control deficits along with modulatory system abnormalities are obvious, important targets for treatment in schizophrenia. "
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