Patterns Of Connectivity Changes Research Articles

6 Adjunctive Transcranial Direct Current Stimulation and Cognitive Training Alters Default Mode and Frontoparietal Control Network Connectivity in Older Adults

Objective:Aging is associated with disruptions in functional connectivity within the default mode (DMN), frontoparietal control (FPCN), and cingulo-opercular (CON) resting-state networks. Greater within-network connectivity predicts better cognitive performance in older adults. Therefore, strengthening network connectivity, through targeted intervention strategies, may help prevent age-related cognitive decline or progression to dementia. Small studies have demonstrated synergistic effects of combining transcranial direct current stimulation (tDCS) and cognitive training (CT) on strengthening network connectivity; however, this association has yet to be rigorously tested on a large scale. The current study leverages longitudinal data from the first-ever Phase III clinical trial for tDCS to examine the efficacy of an adjunctive tDCS and CT intervention on modulating network connectivity in older adults.Participants and Methods:This sample included 209 older adults (mean age = 71.6) from the Augmenting Cognitive Training in Older Adults multisite trial. Participants completed 40 hours of CT over 12 weeks, which included 8 attention, processing speed, and working memory tasks. Participants were randomized into active or sham stimulation groups, and tDCS was administered during CT daily for two weeks then weekly for 10 weeks. For both stimulation groups, two electrodes in saline-soaked 5x7 cm2 sponges were placed at F3 (cathode) and F4 (anode) using the 10-20 measurement system. The active group received 2mA of current for 20 minutes. The sham group received 2mA for 30 seconds, then no current for the remaining 20 minutes.Participants underwent resting-state fMRI at baseline and post-intervention. CONN toolbox was used to preprocess imaging data and conduct region of interest (ROI-ROI) connectivity analyses. The Artifact Detection Toolbox, using intermediate settings, identified outlier volumes. Two participants were excluded for having greater than 50% of volumes flagged as outliers. ROI-ROI analyses modeled the interaction between tDCS group (active versus sham) and occasion (baseline connectivity versus postintervention connectivity) for the DMN, FPCN, and CON controlling for age, sex, education, site, and adherence.Results:Compared to sham, the active group demonstrated ROI-ROI increases in functional connectivity within the DMN following intervention (left temporal to right temporal [T(202) = 2.78, pFDR < 0.05] and left temporal to right dorsal medial prefrontal cortex [T(202) = 2.74, pFDR < 0.05]. In contrast, compared to sham, the active group demonstrated ROI-ROI decreases in functional connectivity within the FPCN following intervention (left dorsal prefrontal cortex to left temporal [T(202) = -2.96, pFDR < 0.05] and left dorsal prefrontal cortex to left lateral prefrontal cortex [T(202) = -2.77, pFDR < 0.05]). There were no significant interactions detected for CON regions.Conclusions:These findings (a) demonstrate the feasibility of modulating network connectivity using tDCS and CT and (b) provide important information regarding the pattern of connectivity changes occurring at these intervention parameters in older adults. Importantly, the active stimulation group showed increases in connectivity within the DMN (a network particularly vulnerable to aging and implicated in Alzheimer’s disease) but decreases in connectivity between left frontal and temporal FPCN regions. Future analyses from this trial will evaluate the association between these changes in connectivity and cognitive performance post-intervention and at a one-year timepoint.

Shared and Unique Changes in Brain Connectivity Among Depressed Patients After Remission With Pharmacotherapy Versus Psychotherapy.

The authors sought to determine the shared and unique changes in brain resting-state functional connectivity (rsFC) between patients with major depressive disorder who achieved remission with cognitive-behavioral therapy (CBT) or with antidepressant medication. The Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) trial randomized adults with treatment-naive major depressive disorder to 12 weeks of treatment with CBT (16 1-hour sessions) or medication (duloxetine 30-60 mg/day or escitalopram 10-20 mg/day). Resting-state functional MRI scans were performed at baseline and at week 12. The primary outcome was change in the whole-brain rsFC of four seeded brain networks among participants who achieved remission. Of the 131 completers with usable MRI data (74 female; mean age, 39.8 years), remission was achieved by 19 of 40 CBT-treated and 45 of 91 medication-treated patients. Three patterns of connectivity changes were observed. First, those who remitted with either treatment shared a pattern of reduction in rsFC between the subcallosal cingulate cortex and the motor cortex. Second, reciprocal rsFC changes were observed across multiple networks, primarily increases in CBT remitters and decreases in medication remitters. And third, in CBT remitters only, rsFC increased within the executive control network and between the executive control network and parietal attention regions. Remission from major depression via treatment with CBT or medication is associated with changes in rsFC that are mostly specific to the treatment modality, providing biological support for the clinical practice of switching between or combining these treatment approaches. Medication is associated with broadly inhibitory effects. In CBT remitters, the increase in rsFC strength between networks involved in cognitive control and attention provides biological support for the theorized mechanism of CBT. Reducing affective network connectivity with motor systems is a shared process important for remission with both CBT and medication.

Reduced functional connectivity between salience and visual networks in migraine with aura

Migraine with visual aura (MA) is associated with distinct visual disturbances preceding migraine attacks, but shares other visual deficits in between attacks with migraine without aura (MO). Here, we seek to determine if abnormalities specific to interictal MA patients exist in functional brain connectivity of intrinsic cognitive networks. In particular, these networks are involved in top-down modulation of visual processing. Using resting-state functional magnetic resonance imaging, whole-brain functional connectivity maps were derived from seeds placed in the anterior insula and the middle frontal gyrus, key nodes of the salience and dorsal attention networks, respectively. Twenty-six interictal MA patients were compared with 26 matched MO patients and 26 healthy matched controls. The major findings were: connectivity between the anterior insula and occipital areas, including area V3A, was reduced in MA but not in MO. Connectivity changes between the anterior insula and occipital areas further correlated with the headache severity in MA only. The unique pattern of connectivity changes found in interictal MA patients involved area V3A, an area previously implicated in aura generation. Hypoconnectivity to this and other occipital regions may either represent a compensatory response to occipital dysfunctions or predispose MA patients to the development of aura.

Altered basal ganglia functional connectivity in multiple sclerosis patients with fatigue

Background: Fatigue is one of the most frequent and disabling symptoms in multiple sclerosis, but its pathophysiological mechanisms are poorly understood. It is in particular unclear whether and how fatigue relates to structural and functional brain changes. Objective: We aimed to analyse the association of fatigue severity with basal ganglia functional connectivity, basal ganglia volumes, white matter integrity and grey matter density. Methods: In 44 patients with relapsing–remitting multiple sclerosis and 20 age- and gender-matched healthy controls, resting-state fMRI, diffusion tensor imaging and voxel-based morphometry was performed. Results: In comparison with healthy controls, patients showed alteration of grey matter density, white matter integrity, basal ganglia volumes and basal ganglia functional connectivity. No association of fatigue severity with grey matter density, white matter integrity and basal ganglia volumes was observed within patients. In contrast, fatigue severity was negatively correlated with functional connectivity of basal ganglia nuclei with medial prefrontal cortex, precuneus and posterior cingulate cortex in patients. Furthermore, fatigue severity was positively correlated with functional connectivity between caudate nucleus and motor cortex. Conclusion: Fatigue is associated with distinct alterations of basal ganglia functional connectivity independent of overall disability. The pattern of connectivity changes suggests that disruption of motor and non-motor basal ganglia functions, including motivation and reward processing, contributes to fatigue pathophysiology in multiple sclerosis.

P01. Transient spike-related connectivity changes in temporal lobe epilepsy: A high density EEG study

Purpose We aimed to analyze the dynamic behavior of epileptic networks through the study of the effective connectivity at a whole-brain scale during interictal spikes in temporal lobe epilepsy patients (TLE) using high-resolution EEG signals. We aimed to understand the connectivity pattern differences in right versus left TLE (RTLE vs LTLE). Method Sixteen patients, 8 with RTLE and 8 with LTLE, were selected for the study. We assessed the connectivity changes of cortical networks during interictal spikes compared to baseline periods at high-temporal resolution, using high-density EEG recordings. The source activity was obtained for 82 regions of interest using an individual head model and a distributed linear inverse solution. A multivariate, time-varying and frequency-resolved Granger causality analysis was applied to the source signal of all ROIs. A non-parametric statistical test was carried out to assess the difference in outflow between interictal spikes vs baseline in each ROI. Results In both groups, the key driving structures were located in the anterior temporal pole, and their driving towards other regions was higher at the time of the spike. In LTLE the keys drivers were only ipsilateral while in RTLE the key drivers were both ipsilateral and contralateral. Moreover, in RTLE we observed a driving pattern from the ipsilateral to the contralateral regions that was not seen in LTLE. Both groups showed driving from the anterior temporal structures to the frontal lobe. In the RTLE and LTLE groups, the pattern of connectivity changes was concordant with the cognitive impairment. Conclusion The used approach was able to identify the major contributors to interictal epileptic activity in both RTLE and LTLE, concordant with invasive electro-clinical findings. Furthermore, a different connectivity pattern was observed in RTLE and LTLE, suggesting that they are not simply symmetrical entities. This enhanced characterization of the epileptic networks increases our understanding of these conditions and could have clinical implications for epilepsy surgery.

Whole-Brain Mapping of Structural Connectivity in Infants Reveals Altered Connection Strength Associated with Growth and Preterm Birth

Cerebral white-matter injury is common in preterm-born infants and is associated with neurocognitive impairments. Identifying the pattern of connectivity changes in the brain following premature birth may provide a more comprehensive understanding of the neurobiology underlying these impairments. Here, we characterize whole-brain, macrostructural connectivity following preterm delivery and explore the influence of age and prematurity using a data-driven, nonsubjective analysis of diffusion magnetic resonance imaging data. T1- and T2-weighted and -diffusion MRI were obtained between 11 and 31 months postconceptional age in 49 infants, born between 25 and 35 weeks postconception. An optimized processing pipeline, combining anatomical, and tissue segmentations with probabilistic diffusion tractography, was used to map mean tract anisotropy. White-matter tracts where connection strength was related to age of delivery or imaging were identified using sparse-penalized regression and stability selection. Older children had stronger connections in tracts predominantly involving frontal lobe structures. Increasing prematurity at birth was related to widespread reductions in connection strength in tracts involving all cortical lobes and several subcortical structures. This nonsubjective approach to mapping whole-brain connectivity detected hypothesized changes in the strength of intracerebral connections during development and widespread reductions in connectivity strength associated with premature birth.

Functional connectivity changes in multiple sclerosis patients: A graph analytical study of MEG resting state data

Multiple sclerosis (MS) is characterized by extensive damage in the central nervous system. Within this field, there is a strong need for more advanced, functional imaging measures, as abnormalities measured with structural imaging insufficiently explain clinicocognitive decline in MS. In this study we investigated functional connectivity changes in MS using resting-state magnetoencephalography (MEG). Data from 34 MS patients and 28 age and gender-matched controls was assessed using synchronization likelihood (SL) as a measure of functional interaction strength between brain regions, and graph analysis to characterize topological patterns of connectivity changes. Cognition was assessed using extensive neuropsychological evaluation. Structural measures included brain and lesion volumes, using MRI. Results show SL increases in MS patients in theta, lower alpha and beta bands, with decreases in the upper alpha band. Graph analysis revealed a more regular topology in the lower alpha band in patients, indicated by an increased path length (λ) and clustering coefficient (γ). Attention and working memory domains were impaired, with decreased brain volumes. A stepwise linear regression model using clinical, MRI and MEG parameters as predictors revealed that only increases in lower alpha band γ predicted impaired cognition. Cognitive impairments and related altered connectivity patterns were found to be especially predominant in male patients. These results show specific functional changes in MS as measured with MEG. Only changes in network topology were related to poorer cognitive outcome. This indicates the value of graph analysis beyond traditional structural and functional measures, with possible implications for diagnostic and/or prognostic purposes in MS.