Repetitive Transcranial Magnetic Stimulation Modulates Frontal and Temporal Time-Varying EEG Network in Generalized Anxiety Disorder: A Pilot Study

Generalized Anxiety Disorder (GAD) is a highly prevalent yet poorly understood chronic mental disorder. Previous studies have associated GAD with excessive activation of the right dorsolateral prefrontal cortex (DLPFC). This study aimed to investigate the effect of low-frequency repetitive transcranial magnetic stimulation (repetitive TMS, rTMS) targeting the right DLPFC on clinical symptoms and TMS-evoked time-varying brain network connectivity in patients with GAD. Eleven patients with GAD received 1 Hz rTMS treatment targeting the right DLPFC for 10 days. The severity of the clinical symptoms was evaluated using the Hamilton Anxiety Scale (HAMA) and the Hamilton Depression Scale (HAMD) at baseline, right after treatment, and at the one-month follow-up. Co-registration of single-pulse TMS (targeting the right DLPFC) and electroencephalography (TMS-EEG) was performed pre- and post-treatment in these patients and 11 healthy controls. Time-varying brain network connectivity was analyzed using the adaptive directed transfer function. The scores of HAMA and HAMD significantly decreased after low-frequency rTMS treatment, and these improvements in ratings remained at the one-month follow-up. Analyses of the time-varying EEG network in the healthy controls showed a continuous weakened connection information outflow in the left frontal and mid-temporal regions. Compared with the healthy controls, the patients with GAD showed weakened connection information outflow in the left frontal pole and the posterior temporal pole at baseline. After 10-day rTMS treatment, the network patterns showed weakened connection information outflow in the left frontal and temporal regions. The time-varying EEG network changes induced by TMS perturbation targeting right DLPFC in patients with GAD were characterized by insufficient information outflow in the left frontal and temporal regions. Low-frequency rTMS targeting the right DLPFC reversed these abnormalities and improved the clinical symptoms of GAD.

Disrupting The Resting State: Meta-Analytic Evidence That Mindfulness Training Alters Default Mode Network Connectivity

This meta-analysis sought to expand upon neurobiological models of mindfulness through investigation of inherent brain network connectivity outcomes, indexed via resting state functional connectivity (rsFC). We conducted a systematic review and meta-analysis of rsFC as an outcome of mindfulness training (MT) relative to structurally-equivalent programs, with the hypothesis that that MT would increase cross-network connectivity between nodes of the Default Mode Network (DMN), Salience Network (SN), and Frontoparietal Control Network (FPCN) as a mechanism of internally-oriented attentional control. Texts were identified from the databases: MEDLINE/PubMed, ERIC, PSYCINFO, ProQuest, Scopus, and Web of Sciences; and were screened for inclusion based on experimental/quasi-experimental trial design and use of standardized mindfulness-based interventions. RsFC effects were extracted from twelve studies (mindfulness n = 226; control n = 204). Voxel-based meta-analysis revealed significantly greater rsFC (MT > control) between the left middle cingulate (Hedge’s g = .234, p = 0288, I2 = 15.87), located within the SN, and the posterior cingulate cortex, a focal hub of the DMN. Egger’s test for publication bias was nonsignificant, bias = 2.17, p = .162. In support of our hypothesis, results suggest that MT targets internetwork (SN-DMN) connectivity implicated in the flexible control of internally-oriented attention.

Six-Month Lower-Leg Sensory Stimulation Augments Neural Network Connectivity Associated With Improved Gait

Foot sole somatosensory impairment associated with peripheral neuropathy (PN) is prevalent and a strong independent risk factor for gait disturbance and falls in older adults. A lower-limb sensory prosthesis providing afferent input related to foot sole pressure distributions via lower-leg vibrotactile stimulation has been demonstrated to improve gait in people with PN. The effects of this device on brain function related to motor control, however, remains equivocal. This study aimed to explore changes in brain network connectivity after six months of daily use of the prosthesis among individuals with diagnosed PN and balance problems. Functional Gait Assessment (FGA) and resting-state functional magnetic resonance imaging were completed before and after the intervention. Preliminary analysis on participants who have completed the study to date (N=5; mean age 76 years) indicated altered connectivity of the sensorimotor network (SMN), frontoparietal network (FPN), and the default mode network (DMN) post-intervention (Z>3.11, unadjusted p<0.05). Participants displayed an average improvement of 5.5 point in the FGA (Minimal Clinically Important Differences>4 for community-dwelling older adults) that was correlated with connectivity changes (unadjusted p<0.05). Specifically, improved FGA was associated with: 1) increased connectivity between the SMN, cerebellum, and occipital cortex; 2) increased connectivity between the FPN, cerebellum, calcarine and intracalcarine; and 3) decreased connectivity between DMN and intracalcarine. These early findings suggest that long-term use of a lower-limb sensory prosthesis may induce neuroplastic changes in brain network connectivity reflecting enhanced bottom-up sensory-attentional processing and suppression of the DMN that are relevant to gait improvements among older adults with PN.

Altered electroencephalography resting state network coherence in remitted MDD

Individuals with remitted depression are at greater risk for subsequent depression and therefore may provide a unique opportunity to understand the neurophysiological correlates underlying the risk of depression. Research has identified abnormal resting-state electroencephalography (EEG) power metrics and functional connectivity patterns associated with major depression, however little is known about these neural signatures in individuals with remitted depression. We investigate the spectral dynamics of 64-channel EEG surface power and source-estimated network connectivity during resting states in 37 individuals with depression, 56 with remitted depression, and 49 healthy adults that did not differ on age, education, and cognitive ability across theta, alpha, and beta frequencies. Average reference spectral EEG surface power analyses identified greater left and midfrontal theta in remitted depression compared to healthy adults. Using Network Based Statistics, we also demonstrate within and between network alterations in LORETA transformed EEG source-space coherence across the default mode, fronto-parietal, and salience networks where individuals with remitted depression exhibited enhanced coherence compared to those with depression, and healthy adults. This work builds upon our currently limited understanding of resting EEG connectivity in depression, and helps bridge the gap between aberrant EEG power and brain network connectivity dynamics in this disorder. Further, our unique examination of remitted depression relative to both healthy and depressed adults may be key to identifying brain-based biomarkers for those at high risk for future, or subsequent depression.

Advanced Meditation Alters Resting-State Brain Network Connectivity Correlating With Improved Mindfulness

Purpose: The purpose of this study was to investigate the effect of an intensive 8-day Samyama meditation program on the brain functional connectivity using resting-state functional MRI (rs-fMRI).Methods: Thirteen Samyama program participants (meditators) and 4 controls underwent fMRI brain scans before and after the 8-day residential meditation program. Subjects underwent fMRI with a blood oxygen level dependent (BOLD) contrast at rest and during focused breathing. Changes in network connectivity before and after Samyama program were evaluated. In addition, validated psychological metrics were correlated with changes in functional connectivity.Results: Meditators showed significantly increased network connectivity between the salience network (SN) and default mode network (DMN) after the Samyama program (p < 0.01). Increased connectivity within the SN correlated with an improvement in self-reported mindfulness scores (p < 0.01).Conclusion: Samyama, an intensive silent meditation program, favorably increased the resting-state functional connectivity between the salience and default mode networks. During focused breath watching, meditators had lower intra-network connectivity in specific networks. Furthermore, increased intra-network connectivity correlated with improved self-reported mindfulness after Samyama.Clinical Trials Registration: [https://clinicaltrials.gov], Identifier: [NCT04366544]. Registered on 4/17/2020.

Altered functional connectivity is related to impaired cognition in left unilateral asymptomatic carotid artery stenosis patients

Background Asymptomatic carotid artery stenosis (aCAS) impairs haemodynamic and cognitive functions; however, the relationship between these changes and brain network connectivity remains largely unknown. This study aimed to determine the relationship between functional connectivity and neurocognition in patients with aCAS. Methods We compared functional status in 14 patients with aCAS and 15 healthy controls using resting state functional magnetic resonance imaging sequences. The subjects underwent a full range of neuropsychological tests and a graphical theoretical analysis of their brain networks. Results Compared with controls, patients with aCAS showed significant decline in neuropsychological functions, particularly short-term memory (word-memory, p = .046 and picture-memory, p = .014). Brain network connectivity was lower in patients with aCAS than in the controls, and the decline of functional connectivity in aCAS patients was mainly concentrated in the left and right inferior frontal gyri, temporal lobe, left cingulate gyrus, and hippocampus. Decreased connectivity between various brain regions was significantly correlated with impaired short-term memory. Patients with aCAS showed cognitive impairment independent of known vascular risk factors for vascular cognitive impairment. The cognitive defects were mainly manifested in the short-term memory of words and pictures. Conclusions This study is the first of its kind to identify an association between disruption of functional connections in left carotid stenosis and impairment of short-term memory. The findings suggest that alterations in network connectivity may be an essential mechanism underlying cognitive decline in aCAS patients. Clinical trial registration-URL Unique identifier: 04/06/2019, ChiCTR1900023610.