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Changes in MEG resting-state networks are related to cognitive decline in type 1 diabetes mellitus patients.

ABSTRACT: OBJECTIVE: Integrity of resting-state functional brain networks (RSNs) is important for proper cognitive functioning. In type 1 diabetes mellitus (T1DM) cognitive decrements are commonly observed, possibly due to alterations in RSNs, which may vary according to microvascular complication status. Thus, we tested the hypothesis that functional connectivity in RSNs differs according to clinical status and correlates with cognition in T1DM patients, using an unbiased approach with high spatio-temporal resolution functional network. METHODS: Resting-state magnetoencephalographic (MEG) data for T1DM patients with (n = 42) and without (n = 41) microvascular complications and 33 healthy participants were recorded. MEG time-series at source level were reconstructed using a recently developed atlas-based beamformer. Functional connectivity within classical frequency bands, estimated by the phase lag index (PLI), was calculated within eight commonly found RSNs. Neuropsychological tests were used to assess cognitive performance, and the relation with RSNs was evaluated. RESULTS: Significant differences in terms of RSN functional connectivity between the three groups were observed in the lower alpha band, in the default-mode (DMN), executive control (ECN) and sensorimotor (SMN) RSNs. T1DM patients with microvascular complications showed the weakest functional connectivity in these networks relative to the other groups. For DMN, functional connectivity was higher in patients without microangiopathy relative to controls (all p < 0.05). General cognitive performance for both patient groups was worse compared with healthy controls. Lower DMN alpha band functional connectivity correlated with poorer general cognitive ability in patients with microvascular complications. DISCUSSION: Altered RSN functional connectivity was found in T1DM patients depending on clinical status. Lower DMN functional connectivity was related to poorer cognitive functioning. These results indicate that functional connectivity may play a key role in T1DM-related cognitive dysfunction.

SUBMITTER: Demuru M

PROVIDER: S-EPMC4081980 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:UNLABELLED:Functional magnetic resonance imaging (fMRI) studies have revealed the existence of robust, interconnected brain networks exhibiting correlated low frequency fluctuations during rest, which can be derived by examining inherent spatio-temporal patterns in functional scans independent of any a priori model. In order to explore the electrophysiological underpinnings of these networks, analogous techniques have recently been applied to magnetoencephalography (MEG) data, revealing similar networks that exhibit correlated low frequency fluctuations in the power envelope of beta band (14-30Hz) power. However, studies to date using this technique have concentrated on healthy subjects, and no method has yet been presented for group comparisons. We extended the ICA resting state MEG method to enable group comparisons, and demonstrate the technique in a sample of subjects with major depressive disorder (MDD). We found that the intrinsic resting state networks evident in fMRI appeared to be disrupted in individuals with MDD compared to healthy participants, particularly in the subgenual cingulate, although the electrophysiological correlates of this are unknown. Networks extracted from a combined group of healthy and MDD participants were examined for differences between groups. Individuals with MDD showed reduced correlations between the subgenual anterior cingulate (sgACC) and hippocampus in a network with primary nodes in the precentral and middle frontal gyri. Individuals with MDD also showed increased correlations between insulo-temporal nodes and amygdala compared to healthy controls. To further support our methods and findings, we present test/re-test reliability on independent recordings acquired within the same session. Our results demonstrate that group analyses are possible with the resting state MEG-independent component analysis (ICA) technique, highlighting a new pathway for analysis and discovery. This study also provides the first evidence of altered sgACC connectivity with a motor network. This finding, reliable across multiple sessions, suggests that the sgACC may partially mediate the psychomotor symptoms of MDD via synchronized changes in beta-band power, and expands the idea of the sgACC as a hub region mediating cognitive and emotional symptomatic domains in MDD. Findings of increased connectivity between the amygdala and cortical nodes further support the role of amygdalar networks in mediated depressive symptomatology. CLINICAL TRIALS IDENTIFIER:NCT00024635 (ZIA-MH002927-04).

Project description:The brain consists of functional units with more-or-less specific information processing capabilities, yet cognitive functions require the co-ordinated activity of these spatially separated units. Magnetoencephalography (MEG) has the temporal resolution to capture these frequency-dependent interactions, although, due to volume conduction and field spread, spurious estimates may be obtained when functional connectivity is estimated on the basis of the extra-cranial recordings directly. Connectivity estimates on the basis of reconstructed sources may similarly be affected by biases introduced by the source reconstruction approach. Here we propose an analysis framework to reliably determine functional connectivity that is based around two main ideas: (i) functional connectivity is computed for a set of atlas-based ROIs in anatomical space that covers almost the entire brain, aiding the interpretation of MEG functional connectivity/network studies, as well as the comparison with other modalities; (ii) volume conduction and similar bias effects are removed by using a functional connectivity estimator that is insensitive to these effects, namely the Phase Lag Index (PLI). Our analysis approach was applied to eyes-closed resting-state MEG data for thirteen healthy participants. We first demonstrate that functional connectivity estimates based on phase coherence, even at the source-level, are biased due to the effects of volume conduction and field spread. In contrast, functional connectivity estimates based on PLI are not affected by these biases. We then looked at mean PLI, or weighted degree, over areas and subjects and found significant mean connectivity in three (alpha, beta, gamma) of the five (including theta and delta) classical frequency bands tested. These frequency-band dependent patterns of resting-state functional connectivity were distinctive; with the alpha and beta band connectivity confined to posterior and sensorimotor areas respectively, and with a generally more dispersed pattern for the gamma band. Generally, these patterns corresponded closely to patterns of relative source power, suggesting that the most active brain regions are also the ones that are most-densely connected. Our results reveal for the first time, using an analysis framework that enables the reliable characterisation of resting-state dynamics in the human brain, how resting-state networks of functionally connected regions vary in a frequency-dependent manner across the cortex.

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Changes in MEG resting-state networks are related to cognitive decline in type 1 diabetes mellitus patients.

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