Article

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

ABSTRACT

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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    • "If spectral measures vary significantly between sessions, the statistical power of these measures is decreased, which limits the attribution of the evaluated effect to the drug, treatment or disease[Deuker et al., 2009;Telesford et al., 2013]. To date, MEG reliability has been addressed for functional connectivity measures[Deuker et al., 2009;Jin et al., 2011;Leighton et al., 2011]whereas the reliability of the power in the classical frequency bands has only been reported with EEG. Overall, power estimates with EEG showed high reliability not only in the different frequency bands[McEvoy et al., 2000], but also across the whole composition of the spectrum as a set[Fingelkurts et al., 2006]. "
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    ABSTRACT: Several studies have reported changes in spontaneous brain rhythms that could be used as clinical biomarkers or in the evaluation of neuropsychological and drug treatments in longitudinal studies using magnetoencephalography (MEG). There is an increasing necessity to use these measures in early diagnosis and pathology progression; however, there is a lack of studies addressing how reliable they are. Here, we provide the first test-retest reliability estimate of MEG power in resting-state at sensor and source space. In this study, we recorded 3 sessions of resting-state MEG activity from 24 healthy subjects with an interval of a week between each session. Power values were estimated at sensor and source space with beamforming for classical frequency bands: delta (2-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), low beta (13-20 Hz), high beta (20-30 Hz), and gamma (30-45 Hz). Then, test-retest reliability was evaluated using the intraclass correlation coefficient (ICC). We also evaluated the relation between source power and the within-subject variability. In general, ICC of theta, alpha, and low beta power was fairly high (ICC > 0.6) while in delta and gamma power was lower. In source space, fronto-posterior alpha, frontal beta, and medial temporal theta showed the most reliable profiles. Signal-to-noise ratio could be partially responsible for reliability as low signal intensity resulted in high within-subject variability, but also the inherent nature of some brain rhythms in resting-state might be driving these reliability patterns. In conclusion, our results described the reliability of MEG power estimates in each frequency band, which could be considered in disease characterization or clinical trials. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Oct 2015 · Human Brain Mapping
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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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    • "They specifically looked at the eye closed condition and found impaired alpha coupling in frontal, parietal, and temporal regions [31]. Previously Rutter et al. [33] preformed a similar MEG study on this population again with the eyes closed and found patients with schizophrenia had significantly reduced activation in the gamma frequency band in the posterior region of the medial parietal cortex. "

    No preview · Article · Jan 2015 · Journal of Behavioral and Brain Science
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