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, Oct 04, 2015
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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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    ABSTRACT: Intractable focal epilepsy is a devastating disorder with profound effects on cognition and quality of life. Epilepsy surgery can lead to seizure freedom in patients with focal epilepsy; however, sometimes it fails owing to an incomplete delineation of the epileptogenic zone (EZ). Brain networks in epilepsy can be studied with resting-state functional connectivity (RSFC) analysis, yet previous investigations using functional MRI or electrocorticography have produced inconsistent results. Magnetoencephalography (MEG) allows noninvasive whole-brain recordings, and can be used to study both long-range network disturbances in focal epilepsy and regional connectivity at the EZ. In MEG recordings from presurgical epilepsy patients, we examined: (1) global functional connectivity maps in patients vs controls, and (2) regional functional connectivity maps at the region of resection, compared with the homotopic nonepileptogenic region in the contralateral hemisphere. Sixty-one patients were studied, including 30 with mesial temporal lobe epilepsy and 31 with focal neocortical epilepsy. Compared with a group of 31 controls, epilepsy patients had decreased RSFC in widespread regions, including perisylvian, posterior temporoparietal, and orbitofrontal cortices (P < .01, false discovery rate-corrected). Decreased mean global connectivity was related to longer duration of epilepsy and higher frequency of consciousness-impairing seizures (P < .01, linear regression). Furthermore, patients with increased regional connectivity within the resection site (n = 24) were more likely to achieve postoperative seizure freedom (87.5% with Engel I outcome) than those with neutral (n = 15, 64.3% seizure free) or decreased (n = 23, 47.8% seizure free) regional connectivity (P < .02, χ). Widespread global decreases in functional connectivity are observed in patients with focal epilepsy and may reflect deleterious long-term effects of recurrent seizures. Furthermore, enhanced regional functional connectivity at the area of resection may help predict seizure outcome and aid surgical planning.
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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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    ABSTRACT: Brain signals recorded from the primary motor cortex (M1) are known to serve a significant role in coding the information brain-machine interfaces (BMIs) need to perform real and imagined movements, and also to form several functional networks with motor association areas. However, whether functional networks between M1 and other brain regions, such as these motor association areas, are related to the performance of BMIs is unclear. To examine the relationship between functional connectivity and performance of BMIs, we analyzed the correlation coefficient between performance of neural decoding and functional connectivity over the whole brain using magnetoencephalography. Ten healthy participants were instructed to execute or imagine three simple right upper limb movements. To decode the movement type, we extracted 40 virtual channels in the left M1 via the beam forming approach, and used them as a decoding feature. In addition, seed-based functional connectivities of activities in the alpha band during real and imagined movements were calculated using imaginary coherence. Seed voxels were set as the same virtual channels in M1. After calculating the imaginary coherence in individuals, the correlation coefficient between decoding accuracy and strength of imaginary coherence was calculated over the whole brain. The significant correlations were distributed mainly to motor association areas for both real and imagined movements. These regions largely overlapped with brain regions that had significant connectivity to M1. Our results suggest that use of the strength of functional connectivity between M1 and motor association areas has the potential to improve the performance of BMIs to perform real and imagined movements.
    Frontiers in Human Neuroscience 08/2014; 8:620. DOI:10.3389/fnhum.2014.00620 · 2.99 Impact Factor
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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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    ABSTRACT: The primary objective of this review article is to summarize how the neuroscience of brain plasticity, exploiting new findings in fundamental, integrative and cognitive neuroscience, is changing the therapeutic landscape for professional communities addressing brain-based disorders and disease. After considering the neurological bases of training-driven neuroplasticity, we shall describe how this neuroscience-guided perspective distinguishes this new approach from (a) the more-behavioral, traditional clinical strategies of professional therapy practitioners, and (b) an even more widely applied pharmaceutical treatment model for neurological and psychiatric treatment domains. With that background, we shall argue that neuroplasticity-based treatments will be an important part of future best-treatment practices in neurological and psychiatric medicine.
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