Resting-state Functional Connectivity In Regions Research Articles

Brain functional connectivity differences between responders and non-responders to sleeve gastrectomy.

To compare resting-state functional connectivity (RSFC) of obese patients responders or non-responders to sleeve gastrectomy (SG) with a group of obese patients with no past medical history of metabolic or bariatric surgery. MR images were acquired at 1.5 Tesla. Resting-state fMRI data were analyzed with statistical significance threshold set at p < 0.05, family-wise error (FWE) corrected. Sixty-two subjects were enrolled: 20 controls (age range 25-64; 14 females), 24 responders (excess weight loss > 50%; age range 23-68; 17 females), and 18 non-responders to sleeve gastrectomy (SG) (excess weight loss < 50%; age range 23-67; 13 females). About within-network RSFC, responders showed significantly lower RSFC with respect to both controls and non-responders in the default mode and frontoparietal networks, positively correlating with psychological scores. Non-responders showed significantly higher (p < 0.05, family-wise error (few) corrected) RSFC in regions of the lateral visual network as compared to controls. Regarding between-network RSFC, responders showed significantly higher anti-correlation between executive control and salience networks (p < 0.05, FWE corrected) with respect to both controls and non-responders. Significant positive correlation (Spearman rho = 0.48, p = 0.0012) was found between % of excess weight loss and executive control-salience network RSFC. There are differences in brain functional connectivity in either responders or non-responders patients to SG. The present results offer new insights into the neural correlates of outcome in patients who undergo SG and expand knowledge about neural mechanisms which may be related to surgical response.

Resilience to acute musculoskeletal pain: resting-state functional connectivity of regions associated with gray matter density differences following induction of low-back pain

Musculoskeletal pain is an aversive experience that exists within a variety of conditions and can result in significant impairment for individuals. Gaining greater understanding of the factors related to pain vulnerability and resilience to musculoskeletal pain may help target at-risk individuals for early intervention. This analysis builds on our previous work identifying regions where lower gray matter density (GMD) was associated with individuals who report pain following standardized, exercise induced musculoskeletal injury. Here we sought to examine the relationship between baseline resting state functional connectivity (rsFC) in a priori regions and networks, and delayed onset muscle soreness (DOMS) pain intensity following a single session of eccentric exercise. The present study is a secondary analysis from a portion of a larger, blinded, randomized experimental trial. All participants were healthy adults between the ages of 18 and 40 years recruited from the university and surrounding community. The primary outcome measure was functional connectivity assessed by using T2 rest image. Participants completed a baseline functional MRI scan and a high intensity trunk exercise protocol to induce DOMS in the erector spinae. Pain intensity ratings were collected 48-hours later. rsFC from four seed regions and three networks were separately regressed on pain intensity scores. Our results revealed that connectivity between left middle frontal gyrus, the left occipital gyrus and cerebellar network seeds and clusters associated with discriminative, emotional, and cognitive aspects of pain were associated with lower post-DOMS pain. Our results provide key support for the role of structural and functional coherence in regional and network connectivity in adaptive pain response and represent an important step in clarifying neural mechanisms of resilience to clinically relevant pain. Resilience to clinically relevant pain is associated with aspects of regional and network neural coherence. Investigations of pain modulatory capacity that integrate multimodal neuroimaging metrics are called for. R01AT006334, PI Dr. Mark Bishop.

MEASURING BRAIN AND COGNITIVE CHANGES IN MEMORY SYSTEMS AFTER TARGETED MULTIDAY REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION OF HEALTHY YOUNG, HEALTHY OLD, AND AMNESTIC MILD COGNITIVE IMPAIRMENT PARTICIPANTS

Healthy and pathological aging processes contribute to declines in memory abilities in older adults, and current treatments offer limited remediation. One novel approach — targeted non-invasive brain stimulation (NBS) of intrinsic memory networks — is reported to enhance memory abilities in healthy young adults by 20% (Wang et al., 2014). To test generalizability of this finding, we are administering a clinical trial (ClinicalTrials.gov #NCT03574207) which replicates previously-reported NBS approaches in healthy young adults, healthy older adults, and patients with amnestic mild cognitive impairment (aMCI). Enrollment is continuing during this interim update; target enrollment for healthy young, healthy old, and aMCI groups is N=16 each. Our approach replicates methods from Wang et al. (2014). Enrolled participants complete two interventions (two weeks apart) consisting of pre-stimulation brain and cognitive measurement, NBS (treatment or sham for five consecutive days), and post-stimulation brain and cognitive measurement. The one-week interventions are identically formatted except for NBS parameters. Pre-/post-stimulation, brain variables measured include structural and resting-state functional MRI data; cognitive variables measured include cognitive abilities (e.g., hippocampal-dependent memory). In both intervention formats, we apply repetitive transcranial magnetic stimulation (rTMS) using β-frequency pulse sequences which alternate 2-sec. 20 Hz stimulation with 28-sec. rest for 20 min; the stimulation location is constant (left lateral parietal cortex coactive with hippocampus). Stimulation intensity is tailored to each participant's resting motor threshold (RMT) and varies by condition: treatment condition, 100% RMT; sham condition, 10% RMT. Participants complete both conditions in a counterbalanced order. Participant condition assignment is currently blinded per our trial design, but we will discuss our design and preliminary findings. We anticipate observing changes in brain and cognitive measures related to stimulation condition. Changes in brain variables are anticipated to include differences in regional resting-state functional connectivity, while changes in cognitive variables are expected to be positive following treatment NBS (vs. sham). Our ongoing clinical trial measures changes in brain and cognitive variables associated with NBS of a functional brain network supporting memory processes. Our expected findings will elucidate the plasticity of intrinsic networks supporting memory — conditioned on age and cognitive status — in response to NBS.

Subjective memory complaints are associated with altered resting-state functional connectivity but not structural atrophy.

Research indicates that a subtle cognitive decline, accompanied by pathological changes, occurs in individuals with subjective memory complaints (SMC). However, there is less evidence regarding the measurement of resting-state functional connectivity to detect subtle brain network alterations in neurodegenerative illnesses before cognitive change manifestation. We investigated the correlation between SMC and cognitive performance and explored functional and structural brain changes underlying SMC severity, using behavioral and brain imaging data-driven approaches. We observed that SMC was associated with depression but not with cognitive test scores, implying that SMC represent the “worried-well”; however, this model explains only 15% of the target variance. Using a conservative threshold, we observed connectivity related to SMC severity in the lingual gyrus, cuneus, anterior insula, and superior parietal lobule. Post-hoc analysis indicated that occipital and parietal functional connectivity increased with SMC severity. In contrast, volumetric alterations were not associated with SMC, even after applying a liberal threshold. Our findings suggest that altered resting-state functional connectivity in regions associated with SMC might reflect early compensatory changes that occur before cognitive and structural abnormalities develop.

Changes in resting-state functional connectivity after stroke in a mouse brain lacking extracellular matrix components

In the brain, focal ischemia results in a local region of cell death and disruption of both local and remote functional neuronal networks. Tissue reorganization following stroke can be limited by factors such as extracellular matrix (ECM) molecules that prevent neuronal growth and synaptic plasticity. The brain's ECM plays a crucial role in network formation, development, and regeneration of the central nervous system. Further, the ECM is essential for proper white matter tract development and for the formation of structures called perineuronal nets (PNNs). PNNs mainly surround parvalbumin/GABA inhibitory interneurons, of importance for processing sensory information. Previous studies have shown that downregulating PNNs after stroke reduces the neurite-inhibitory environment, reactivates plasticity, and promotes functional recovery. Resting-state functional connectivity (RS-FC) within and across hemispheres has been shown to correlate with behavioral recovery after stroke. However, the relationship between PNNs and RS-FC has not been examined. Here we studied a quadruple knock-out mouse (Q4) that lacks four ECM components: brevican, neurocan, tenascin-C and tenascin-R. We applied functional connectivity optical intrinsic signal (fcOIS) imaging in Q4 mice and wild-type (129S1 mice) before and 14 days after photothrombotic stroke (PT) to understand how the lack of crucial ECM components affects neuronal networks and functional recovery after stroke. Limb-placement ability was evaluated at 2, 7 and 14 days of recovery through the paw-placement test. Q4 mice exhibited significantly impaired homotopic RS-FC compared to wild-type mice, especially in the sensory and parietal regions. Changes in RS-FC were significantly correlated with the number of interhemispheric callosal crossings in those same regions. PT caused unilateral damage to the sensorimotor cortex and deficits of tactile-proprioceptive placing ability in contralesional fore- and hindlimbs, but the two experimental groups did not present significant differences in infarct size. Two weeks after PT, a general down-scaling of regional RS-FC as well as the number of regional functional connections was visible for all cortical regions and most notable in the somatosensory areas of both Q4 and wild-type mice. Q4 mice exhibited higher intrahemispheric RS-FC in contralesional sensory and motor cortices compared to control mice. We propose that the lack of growth inhibiting ECM components in the Q4 mice potentially worsen behavioral outcome in the early phase after stroke, but subsequently facilitates modulation of contralesional RS-FC which is relevant for recovery of sensory motor function. We conclude that Q4 mice represent a valuable model to study how the elimination of ECM genes compromises neuronal function and plasticity mechanisms after stroke.

Multisensory stimulation improves functional recovery and resting-state functional connectivity in the mouse brain after stroke.

Stroke causes direct structural damage to local brain networks and indirect functional damage to distant brain regions. Neuroplasticity after stroke involves molecular changes within perilesional tissue that can be influenced by regions functionally connected to the site of injury. Spontaneous functional recovery can be enhanced by rehabilitative strategies, which provides experience-driven cell signaling in the brain that enhances plasticity. Functional neuroimaging in humans and rodents has shown that spontaneous recovery of sensorimotor function after stroke is associated with changes in resting-state functional connectivity (RS-FC) within and across brain networks. At the molecular level, GABAergic inhibitory interneurons can modulate brain plasticity in peri-infarct and remote brain regions. Among this cell-type, a decrease in parvalbumin (PV)-immunoreactivity has been associated with improved behavioral outcome. Subjecting rodents to multisensory stimulation through exposure to an enriched environment (EE) enhances brain plasticity and recovery of function after stroke. Yet, how multisensory stimulation relates to RS-FC has not been determined. In this study, we investigated the effect of EE on recovery of RS-FC and behavior in mice after stroke, and if EE-related changes in RS-FC were associated with levels of PV-expressing neurons. Photothrombotic stroke was induced in the sensorimotor cortex. Beginning 2 days after stroke, mice were housed in either standard environment (STD) or EE for 12 days. Housing in EE significantly improved lost tactile-proprioceptive function compared to mice housed in STD environment. RS-FC in the mouse was measured by optical intrinsic signal imaging 14 days after stroke or sham surgery. Stroke induced a marked reduction in RS-FC within several perilesional and remote brain regions. EE partially restored interhemispheric homotopic RS-FC between spared motor regions, particularly posterior secondary motor. Compared to mice housed in STD cages, EE exposure lead to increased RS-FC between posterior secondary motor regions and contralesional posterior parietal and retrosplenial regions. The increased regional RS-FC observed in EE mice after stroke was significantly correlated with decreased PV-immunoreactivity in the contralesional posterior motor region. In conclusion, experimental stroke and subsequent housing in EE induces dynamic changes in RS-FC in the mouse brain. Multisensory stimulation associated with EE enhances RS-FC among distinct brain regions relevant for recovery of sensorimotor function and controlled movements that may involve PV/GABA interneurons. Our results indicate that targeting neural circuitry involving spared motor regions across hemispheres by neuromodulation and multimodal sensory stimulation could improve rehabilitation after stroke.

Fronto-temporal interactions are functionally relevant for semantic control in language processing.

Semantic cognition, i.e. processing of meaning is based on semantic representations and their controlled retrieval. Semantic control has been shown to be implemented in a network that consists of left inferior frontal (IFG), and anterior and posterior middle temporal gyri (a/pMTG). We aimed to disrupt semantic control processes with continuous theta burst stimulation (cTBS) over left IFG and pMTG and to study whether behavioral effects are moderated by induced alterations in resting-state functional connectivity. To this end, we applied real cTBS over left IFG and left pMTG as well as sham stimulation on 20 healthy participants in a within-subject design. Stimulation was followed by resting-state functional magnetic resonance imaging and a semantic priming paradigm. Resting-state functional connectivity of regions of interest in left IFG, pMTG and aMTG revealed highly interconnected left-lateralized fronto-temporal networks representing the semantic system. We did not find any significant direct modulation of either task performance or resting-state functional connectivity by effective cTBS. However, after sham cTBS, functional connectivity between IFG and pMTG correlated with task performance under high semantic control demands in the semantic priming paradigm. These findings provide evidence for the functional relevance of interactions between IFG and pMTG for semantic control processes. This interaction was functionally less relevant after cTBS over aIFG which might be interpretable in terms of an indirect disruptive effect of cTBS.

Cortico-Striato-Thalamo-Cortical Circuitry, Working Memory, and Obsessive-Compulsive Disorder.

Cortico-Striato-Thalamo-Cortical Circuitry, Working Memory, and Obsessive-Compulsive Disorder.

Large-scale neuronal network dysfunction in relapsing-remitting multiple sclerosis

Given that multiple sclerosis (MS) hits diffusely the brain hemispheres, we hypothesized that this should result in a distributed pattern of functional connectivity (FC) abnormalities. To this aim, we assessed, using resting-state (RS) fMRI, intrinsic FC and functional network connectivity (FNC) of brain large-scale neuronal networks from 85 patients with relapsing-remitting MS (RRMS) and 40 matched controls. Independent component analysis was used to analyze RS fMRI data. Intrinsic FC of each cluster of each RS network (RSN) was compared between controls and patients (analysis of variance adjusted for age, gender, and gray matter volume). The FNC toolbox was used to assess interactions among RSNs. Compared to controls, patients with RRMS experienced a decreased RS FC in regions of the salience (SN), executive control (ECN), working memory (WMN), default mode (DMN), sensorimotor, and visual networks. They also had an increased RS FC in regions of the ECN and auditory RSN. Decreased RS FC was significantly correlated with disability and T2 lesion volumes. In patients with RRMS, when compared to controls, FNC analysis showed that the ECN had an increased connectivity with the SN and a decreased connectivity with the DMN. An abnormal connectivity between the WMNs and sensory networks was also found. Functional abnormalities within and between large-scale neuronal networks occur in patients with RRMS and are related to the extent of T2 lesions and the severity of disability. Longitudinal studies should ascertain whether such functional abnormalities confer a systematic vulnerability to disease progression or, conversely, protect against the onset of clinical deficits.