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Age-related differences in default-mode network connectivity in response to intermittent theta-burst stimulation and its relationships with maintained cognition and brain integrity in healthy aging.

ABSTRACT: The default-mode network (DMN) is affected by advancing age, where particularly long-range connectivity has been consistently reported to be reduced as compared to young individuals. We examined whether there were any differences in the effects of intermittent theta-burst stimulation (iTBS) in DMN connectivity between younger and older adults, its associations with cognition and brain integrity, as well as with long-term cognitive status. Twenty-four younger and 27 cognitively normal older adults were randomly assigned to receive real or sham iTBS over the left inferior parietal lobule between two resting-state functional magnetic resonance imaging (rs-fMRI) acquisitions. Three years later, those older adults who had received real iTBS underwent a cognitive follow-up assessment. Among the younger adults, functional connectivity increased following iTBS in distal DMN areas from the stimulation site. In contrast, older adults exhibited increases in connectivity following iTBS in proximal DMN regions. Moreover, older adults with functional responses to iTBS resembling those of the younger participants exhibited greater brain integrity and higher cognitive performance at baseline and at the 3-year follow-up, along with less cognitive decline. Finally, we observed that 'young-like' functional responses to iTBS were also related to the educational background attained amongst older adults. The present study reveals that functional responses of the DMN to iTBS are modulated by age. Furthermore, combining iTBS and rs-fMRI in older adults may allow characterizing distinctive cognitive profiles in aging and its progression, probably reflecting network plasticity systems that may entail a neurobiological substrate of cognitive reserve.

SUBMITTER: Abellaneda-Perez K

PROVIDER: S-EPMC6401253 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Age-related differences in default-mode network connectivity in response to intermittent theta-burst stimulation and its relationships with maintained cognition and brain integrity in healthy aging.

Abellaneda-Pérez Kilian K Vaqué-Alcázar Lídia L Vidal-Piñeiro Dídac D Jannati Ali A Solana Elisabeth E Bargalló Núria N Santarnecchi Emiliano E Pascual-Leone Alvaro A Bartrés-Faz David D

NeuroImage 20181122

The default-mode network (DMN) is affected by advancing age, where particularly long-range connectivity has been consistently reported to be reduced as compared to young individuals. We examined whether there were any differences in the effects of intermittent theta-burst stimulation (iTBS) in DMN connectivity between younger and older adults, its associations with cognition and brain integrity, as well as with long-term cognitive status. Twenty-four younger and 27 cognitively normal older adult ...[more]

PMID: 30472372

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Project description:IntroductionCannabis is the most commonly used illicit substance in the United States, and nearly 1 in 4 young adults are current cannabis users. Chronic cannabis use is associated with changes in resting state functional connectivity (RSFC) in the default mode network (DMN) in adolescents and young adults; results are somewhat inconsistent across studies, potentially due to methodological differences. The aims of the present study were to examine potential differences in DMN RSFC between cannabis users and controls, and to examine, as an exploratory analysis, if gender moderated any findings. We further examined whether differences in RSFC related to differences in performance on selected neuropsychological measures.Materials and methodsSeventy-seven 16-26-year-old participants underwent an MRI scan (including resting state scan), neuropsychological battery, toxicology screening, and drug use interview. Differences in DMN connectivity were examined between groups (cannabis vs. control) and with an exploratory group by gender interaction, using a left posterior cingulate cortex (PCC) seed-based analysis conducted in AFNI.ResultsCannabis users demonstrated weaker connectivity than controls between the left PCC and various DMN nodes, and the right Rolandic operculum/Heschl's gyrus. Cannabis users demonstrated stronger connectivity between the left PCC and the cerebellum and left supramarginal gyrus. The group by gender interaction was not significantly associated with connectivity differences. Stronger left PCC-cerebellum connectivity was associated with poorer performance on cognitive measures in cannabis users. In controls, intra-DMN connectivity was positively correlated with performance on a speeded selective/sustained attention measure.DiscussionConsistent with our hypotheses and other studies, cannabis users demonstrated weaker connectivity between the left PCC and DMN nodes. Chronic THC exposure may alter GABA and glutamate concentrations, which may alter brain communication. Future studies should be conducted with a larger sample size and examine gender differences and the mechanism by which these differences may arise.

Project description:PurposeThe utility of transcranial magnetic stimulation (TMS) has been growing rapidly in both neurocognitive studies and clinical applications in decades. However, it remains unclear how the responses of the stimulated site and the site-related functional network to the external TMS manipulation dynamically change over time.MethodsA multi-session combining TMS-fMRI experiment was conducted to explore the spatiotemporal effects of TMS within the fronto-limbic network. Ten healthy volunteers were modulated by intermittent theta-burst stimulation (iTBS) at a precise site within the left dorsolateral prefrontal cortex (DLPFC, MNI coordinate [-44 36 20]), navigated by individual structural MRI image. Three-session resting-state fMRI images were acquired before iTBS (TP1), immediately after iTBS (TP2), and 15 min after iTBS (TP3) for each participant. Seventy-four regions of interests (ROIs) within the fronto-limbic network were chosen including the bilateral superior frontal gyrus (SFG), middle frontal gyrus (MidFG), inferior frontal gyrus (IFG), orbital gyrus (OrG), cingulate gyrus (CG), and subcortical nuclei (hippocampus and amygdala). Regional fractional amplitude of low-frequency fluctuation (fALFF) and ROI-to-ROI functional connectivity (FC) were compared among TP1, TP2, and TP3.ResultsThe immediate iTBS effect was observed at the stimulated site. FC between the left dorsolateral SFG and left dorsal IFG and between the left rostral IFG and right MidFG increased at TP2 as compared to at TP1 (all FDR-p < 0.05), while FC within the left OrG decreased. The relatively long-term iTBS effect transmitted with decreased FC between the left IFG and right amygdala, increased FC between the left MidFG and left OrG, and decreased FC between bilateral IFG and OrG at TP3 than at TP1 (all FDR-p < 0.05). Meanwhile, mean fALFF values over the left SFG, MidFG, ventral CG, and IFG were significantly increased at TP3 as compared to those at TP2 (all p < 0.05 with Bonferroni correction).ConclusionBy combining TMS and fMRI, it becomes possible to track the spatiotemporal dynamics of TMS after-effects within the fronto-limbic network. Our findings suggested that the iTBS effect dynamically changed over time from the local neural activation at the stimulated site to its connected remote regions within the fronto-limbic network.

Project description:IntroductionCognitive symptoms from Parkinson's disease cause severe disability and significantly limit quality of life. Little is known about mechanisms of cognitive impairment in PD, although aberrant oscillatory activity in basal ganglia-thalamo-prefrontal cortical circuits likely plays an important role. While continuous high-frequency deep brain stimulation (DBS) improves motor symptoms, it is generally ineffective for cognitive symptoms. Although we lack robust treatment options for these symptoms, recent studies with transcranial magnetic stimulation (TMS), applying intermittent theta-burst stimulation (iTBS) to dorsolateral prefrontal cortex (DLPFC), suggest beneficial effects for certain aspects of cognition, such as memory or inhibitory control. While TMS is non-invasive, its results are transient and require repeated application. Subcortical DBS targets have strong reciprocal connections with prefrontal cortex, such that iTBS through the permanently implanted lead might represent a more durable solution. Here we demonstrate safety and feasibility for delivering iTBS from the DBS electrode and explore changes in DLPFC electrophysiology.MethodsWe enrolled seven participants with medically refractory Parkinson's disease who underwent DBS surgery targeting either the subthalamic nucleus (STN) or globus pallidus interna (GPi). We temporarily placed an electrocorticography strip over DLPFC through the DBS burr hole. After placement of the DBS electrode into either GPi (n = 3) or STN (n = 4), awake subjects rested quietly during iTBS (three 50-Hz pulses delivered at 5 Hz for 2 s, followed by 8 s of rest). We contrasted power spectra in DLPFC local field potentials during iTBS versus at rest, as well as between iTBS and conventional high-frequency stimulation (HFS).ResultsDominant frequencies in DLPFC at rest varied among subjects and along the subdural strip electrode, though they were generally localized in theta (3-8 Hz) and/or beta (10-30 Hz) ranges. Both iTBS and HFS were well-tolerated and imperceptible. iTBS increased theta-frequency activity more than HFS. Further, GPi stimulation resulted in significantly greater theta-power versus STN stimulation in our sample.ConclusionAcute subcortical iTBS from the DBS electrode was safe and well-tolerated. This novel stimulation pattern delivered from the GPi may increase theta-frequency power in ipsilateral DLPFC. Future studies will confirm these changes in DLPFC activity during iTBS and evaluate whether they are associated with improvements in cognitive or behavioral symptoms from PD.

Project description:Cognitive impairment affects about 50% of multiple sclerosis (MS) patients, but the mechanisms underlying this remain unclear. The default mode network (DMN) has been linked with cognition, but in MS its role is still poorly understood. Moreover, within an extended DMN network including the cerebellum (CBL-DMN), the contribution of cortico-cerebellar connectivity to MS cognitive performance remains unexplored. The present study investigated associations of DMN and CBL-DMN structural connectivity with cognitive processing speed in MS, in both cognitively impaired (CIMS) and cognitively preserved (CPMS) MS patients. 68 MS patients and 22 healthy controls (HCs) completed a symbol digit modalities test (SDMT) and had 3T brain magnetic resonance imaging (MRI) scans that included a diffusion weighted imaging protocol. DMN and CBL-DMN tracts were reconstructed with probabilistic tractography. These networks (DMN and CBL-DMN) and the cortico-cerebellar tracts alone were modeled using a graph theoretical approach with fractional anisotropy (FA) as the weighting factor. Brain parenchymal fraction (BPF) was also calculated. In CIMS SDMT scores strongly correlated with the FA-weighted global efficiency (GE) of the network [GE(CBL-DMN): ρ = 0.87, R 2 = 0.76, p < 0.001; GE(DMN): ρ = 0.82, R 2 = 0.67, p < 0.001; GE(CBL): ρ = 0.80, R 2 = 0.64, p < 0.001]. In CPMS the correlation between these measures was significantly lower [GE(CBL-DMN): ρ = 0.51, R 2 = 0.26, p < 0.001; GE(DMN): ρ = 0.48, R 2 = 0.23, p = 0.001; GE(CBL): ρ = 0.52, R 2 = 0.27, p < 0.001] and SDMT scores correlated most with BPF (ρ = 0.57, R 2 = 0.33, p < 0.001). In a multivariable regression model where SDMT was the independent variable, FA-weighted GE was the only significant explanatory variable in CIMS, while in CPMS BPF and expanded disability status scale were significant. No significant correlation was found in HC between SDMT scores, MRI or network measures. DMN structural GE is related to cognitive performance in MS, and results of CBL-DMN suggest that the cerebellum structural connectivity to the DMN plays an important role in information processing speed decline.

Dataset Information

Age-related differences in default-mode network connectivity in response to intermittent theta-burst stimulation and its relationships with maintained cognition and brain integrity in healthy aging.

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Age-related differences in default-mode network connectivity in response to intermittent theta-burst stimulation and its relationships with maintained cognition and brain integrity in healthy aging.

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