Changes In Resting-state Connectivity Research Articles

Resting-State Connectivity Changes After Goal-Oriented Attentional Self-Regulation Training in Veterans With Mild Traumatic Brain Injury: Preliminary Findings from a Randomized Controlled Trial.

Mild traumatic brain injury (mTBI) can have lasting consequences on cognitive functioning and well-being. Goal-Oriented Attentional Self-Regulation (GOALS) training has been shown to improve attention and executive functioning, as well as emotional functioning, in veterans with chronic TBI. An ongoing clinical trial (NCT02920788) is further evaluating GOALS training, including underlying neural mechanisms of change. The present study aimed to examine training-induced neuroplasticity by resting-state functional connectivity (rsFC) changes in GOALS versus active control. Veterans with a history of mTBI ≥6 months post-injury (N = 33) were randomly assigned to GOALS (n = 19) or an intensity-matched active control group (Brain Health Education [BHE] training; n = 14). GOALS consists of attention regulation and problem solving applied to individually defined, relevant goals through a combination of group, individual, and home practice sessions. Participants underwent multi-band resting-state functional magnetic resonance imaging at baseline and post-intervention. Exploratory 2 × 2 mixed analyses of variance identified pre-to-post changes in seed-based connectivity for GOALS versus BHE in five significant clusters. GOALS versus BHE demonstrated a significant increase in right lateral pre-frontal cortex connectivity with the right frontal pole and right middle temporal gyrus, as well as increased posterior cingulate connectivity with the pre-central gyrus. Rostral pre-frontal cortex connectivity with the right precuneus and the right frontal pole decreased in GOALS versus BHE. These GOALS-related changes in rsFC point to potential neural mechanisms underlying the intervention. This training-induced neuroplasticity may play a role in improved cognitive and emotional functioning post-GOALS.

Effects of gastric bypass surgery on brain connectivity responses to hypoglycemia

IntroductionRoux-en-Y gastric bypass (RYGB) leads to beneficial effects on glucose homeostasis, and attenuated hormonal counterregulatory responses to hypoglycemia are likely to contribute. RYGB also induces alterations in neural activity of cortical and subcortical brain regions. We aimed to characterize RYGB-induced changes in resting-state connectivity of specific brain regions of interest for energy homeostasis and behavioral control during hypoglycemia.MethodTen patients with BMI > 35 kg/m2 were investigated with brain PET/MR imaging during a hyperinsulinemic normo- and hypoglycemic clamp, before and 4 months after RYGB. Hormonal levels were assessed throughout the clamp. Resting-state (RS) fMRI scans were acquired in the glucose-lowering phase of the clamp, and they were analyzed with a seed-to-voxel approach.ResultsRS connectivity during initiation of hypoglycemia was significantly altered after RYGB between nucleus accumbens, thalamus, caudate, hypothalamus and their crosstalk with cortical and subcortical regions. Connectivity between the nucleus accumbens and the frontal pole was increased after RYGB, and this was associated with a reduction of ACTH (r = −0.639, p = 0.047) and cortisol (r = −0.635, p = 0.048) responses. Instead, connectivity between the caudate and the frontal pole after RYGB was reduced and this was associated with less attenuation of glucagon response during the hypoglycemic clamp (r = −0.728, p = 0.017), smaller reduction in fasting glucose (r = −0.798, p = 0.007) and less excess weight loss (r = 0.753, p = 0.012). No other significant associations were found between post-RYGB changes in ROI-to-voxel regional connectivity hormonal responses and metabolic or anthropometric outcomes.ConclusionRYGB alters brain connectivity during hypoglycemia of several neural pathways involved in reward, inhibitory control, and energy homeostasis. These changes are associated with altered hormonal responses to hypoglycemia and may be involved in the glucometabolic outcome of RYGB.

EEG Based Resting State Connectivity Changes in the Motor Cortex Associated with Upper Limb Motor Recovery in the Subacute Period Post-Stroke.

Stroke is a heterogeneous condition that would benefit from valid biomarkers of recovery for research and in the clinic. We evaluated the change in resting state connectivity (RSC) via electroencephalography (EEG) in motor areas, as well as motor recovery of the affected upper limb, in the subacute phase post-stroke. Fifteen participants who had sustained a subcortical stroke were included in this study. The group made significant gains in upper limb impairment as measured by the Upper Extremity Fugl-Meyer Assessment (UEFMA) from baseline to four months post-stroke (24.78 (SD 5.4)). During this time, there was a significant increase in RSC in the beta band from contralesional M1 to ipsilesional M1. We propose that this change in RSC may have contributed to the motor recovery seen in this group. Clinical Relevance- This study evaluates resting state connectivity measured via EEG as a neural biomarker of recovery post-stroke. Biomarkers can help clinicians understand the potential for recovery after stroke and thus help them to establish therapy goals and determine treatment plans.

Altered resting-state neural networks in children and adolescents with functional neurological disorder

ObjectivesPrevious studies with adults suggest that aberrant communication between neural networks underpins functional neurological disorder (FND). The current study adopts a data-driven approach to investigate the extent that functional resting-state networks are disrupted in a pediatric mixed-FND cohort. Methods31 children with mixed FND and 33 age- and sex-matched healthy controls completed resting-state fMRI scans. Whole-brain independent component analysis (pFWE < 0.05) was then used to identify group differences in resting-state connectivity. Self-report measures included the Depression, Anxiety and Stress Scale (DASS-21) and Early Life Stress Questionnaire (ELSQ). Resting-state heart rate (HR) and cortisol-awakening response (CAR) were available in a subset. ResultsChildren with FND showed wide-ranging connectivity changes in eight independent components corresponding to eight resting-state neural networks: language networks (IC6 and IC1), visual network, frontoparietal network, salience network, dorsal attention network, cerebellar network, and sensorimotor network. Children whose clinical presentation included functional seizures (vs children with other FND symptoms) showed greater connectivity decreases in the frontoparietal and dorsal attentional networks. Subjective distress (total DASS score), autonomic arousal (indexed by HR), and HPA dysregulation (attenuated/reversed CAR) contributed to changes in neural network connectivity. Children with FND (vs controls) reported more subjective distress (total DASS score) and more adverse childhood experiences (ACEs) across their lifespan. ConclusionsChildren with FND demonstrate changes in resting-state connectivity. Identified network alterations underpin a broad range of functions typically disrupted in children with FND. This study complements the adult literature by suggesting that FND in children and adolescents emerges in the context of their lived experience and that it reflects aberrant communication across neural networks.

Functional Resting-State Connectivity Changes After Post-Operative Delirium in the Elderly

Post-operative delirium (POD) represents a confusional state during days/weeks after surgery and is particularly frequent in elderly patients. Hardly any fMRI studies were conducted to understand the underlying pathophysiology of POD patients. This study aims to examine changes of specific resting-state neuronal networks across different time points (before and 3 months after surgery) in delirious patients compared to no-POD patients.

A Dose Relationship Between Brain Functional Connectivity and Cumulative Head Impact Exposure in Collegiate Water Polo Players.

A growing body of evidence suggests that chronic, sport-related head impact exposure can impair brain functional integration and brain structure and function. Evidence of a robust inverse relationship between the frequency and magnitude of repeated head impacts and disturbed brain network function is needed to strengthen an argument for causality. In pursuing such a relationship, we used cap-worn inertial sensors to measure the frequency and magnitude of head impacts sustained by eighteen intercollegiate water polo athletes monitored over a single season of play. Participants were evaluated before and after the season using computerized cognitive tests of inhibitory control and resting electroencephalography. Greater head impact exposure was associated with increased phase synchrony [r(16) > 0.626, p < 0.03 corrected], global efficiency [r(16) > 0.601, p < 0.04 corrected], and mean clustering coefficient [r(16) > 0.625, p < 0.03 corrected] in the functional networks formed by slow-wave (delta, theta) oscillations. Head impact exposure was not associated with changes in performance on the inhibitory control tasks. However, those with the greatest impact exposure showed an association between changes in resting-state connectivity and a dissociation between performance on the tasks after the season [r(16) = 0.481, p = 0.043] that could also be attributed to increased slow-wave synchrony [F(4, 135) = 113.546, p < 0.001]. Collectively, our results suggest that athletes sustaining the greatest head impact exposure exhibited changes in whole-brain functional connectivity that were associated with altered information processing and inhibitory control.

Growth Hormone Alters Brain Morphometry, Connectivity, and Behavior in Subjects with Fatigue after Mild Traumatic Brain Injury.

Pituitary dysfunction with reduced growth hormone (GH) secretion is common in patients following traumatic brain injury (TBI), and these patients often develop chronic symptoms including fatigue and altered cognition. We examined 18 subjects with a history of mild TBI, fatigue, and insufficient GH secretion. Subjects received GH replacement in a year-long, double-blind, placebo-controlled, crossover study, and were assessed for changes in physical performance, body composition, resting energy expenditure, fatigue, sleep, mood, and neuropsychological status. Additionally, magnetic resonance imaging (MRI) was used to assess changes in brain structure and resting state functional connectivity. GH replacement resulted in decreased fatigue, sleep disturbance, and anxiety, as well as increased resting energy expenditure, improved body composition, and altered perception of submaximal effort when performing exercise testing. Associated brain changes included increased frontal cortical thickness and gray matter volume and resting state connectivity changes in regions associated with somatosensory networks. GH replacement altered brain morphology and connectivity and reduced fatigue and related symptoms in mild TBI patients. Additional studies are needed to understand the mechanisms causing TBI-related fatigue and symptom relief with GH replacement.

Decreased Hand Motor Resting-State Functional Connectivity in Patients with Glioma: Analysis of Factors including Neurovascular Uncoupling.

Background Resting-state functional MRI holds substantial potential for clinical application, but limitations exist in current understanding of how tumors exert local effects on resting-state functional MRI readings. Purpose To investigate the association between tumors, tumor characteristics, and changes in resting-state connectivity, to explore neurovascular uncoupling as a mechanism underlying these changes, and to evaluate seeding methodologies as a clinical tool. Materials and Methods Institutional review board approval was obtained for this HIPAA-compliant observational retrospective study of patients with glioma who underwent MRI and resting-state functional MRI between January 2016 and July 2017. Interhemispheric symmetry of connectivity was assessed in the hand motor region, incorporating tumor position, perfusion, grade, and connectivity generated from seed-based correlation. Statistical analysis was performed by using one-tailed t tests, Wilcoxon rank sum tests, one-way analysis of variance, Pearson correlation, and Spearman rank correlation, with significance at P < .05. Results Data in a total of 45 patients with glioma (mean age, 51.3 years ± 14.3 [standard deviation]) were compared with those in 10 healthy control subjects (mean age, 50.3 years ± 17.2). Patients showed loss of symmetry in measures of hand motor resting-state connectivity compared with control subjects (P < .05). Tumor distance from the ipsilateral hand motor (IHM) region correlated with the degree (R = 0.38, P = .01) and strength (R = 0.33, P = .03) of resting-state connectivity. In patients with World Health Organization grade IV glioblastomas 40 mm or less from the IHM region, loss of symmetry in strength of resting-state connectivity was correlated with tumor perfusion (R = 0.74, P < .01). In patients with gliomas 40 mm or less from the IHM region, seeding the nontumor hemisphere yielded less asymmetric hand motor resting-state connectivity than seeding the tumor hemisphere (connectivity seeded:contralateral = 1.34 nontumor vs 1.38 tumor hemisphere seeded; P = .03, false discovery rate threshold = 0.01). Conclusion Hand motor resting-state connectivity was less symmetrical in a tumor distance-dependent manner in patients with glioma. Differences in resting-state connectivity may be false-negative results driven by a neurovascular uncoupling mechanism. Seeding from the nontumor hemisphere may attenuate asymmetry in patients with tumors near ipsilateral hand motor cortices. © RSNA, 2020 Online supplemental material is available for this article.

Theta-burst TMS to the posterior superior temporal sulcus decreases resting-state fMRI connectivity across the face processing network.

Humans process faces by using a network of face-selective regions distributed across the brain. Neuropsychological patient studies demonstrate that focal damage to nodes in this network can impair face recognition, but such patients are rare. We approximated the effects of damage to the face network in neurologically normal human participants by using theta burst transcranial magnetic stimulation (TBS). Multi-echo functional magnetic resonance imaging (fMRI) resting-state data were collected pre- and post-TBS delivery over the face-selective right superior temporal sulcus (rpSTS), or a control site in the right motor cortex. Results showed that TBS delivered over the rpSTS reduced resting-state connectivity across the extended face processing network. This connectivity reduction was observed not only between the rpSTS and other face-selective areas, but also between nonstimulated face-selective areas across the ventral, medial, and lateral brain surfaces (e.g., between the right amygdala and bilateral fusiform face areas and occipital face areas). TBS delivered over the motor cortex did not produce significant changes in resting-state connectivity across the face processing network. These results demonstrate that, even without task-induced fMRI signal changes, disrupting a single node in a brain network can decrease the functional connectivity between nodes in that network that have not been directly stimulated.

P.788 Associative learning and resting-state connectivity changes in the adult brain

Label distribution learning (LDL) is one of the paradigms for dealing with label ambiguity, and it can learn the relative importance of each label to a particular instance. Most of the existing LDL approaches require strong supervision information, which always involves high cost of the data-labeling process. To this end, we propose a novel transductive weakly supervised LDL algorithm based on matrix completion, which simultaneously explores the discriminant knowledge of both training instances and testing instances. Moreover, the manifold regularization is exploited to capture the samples’ relevance to enhance the performance of matrix completion. Experimental results on real-world data sets with various missing percentages validate the effectiveness of our method.

Neurofeedback of core language network nodes modulates connectivity with the default-mode network: A double-blind fMRI neurofeedback study on auditory verbal hallucinations

BackgroundThe experience of auditory verbal hallucinations in schizophrenia is associated with changes in brain network function. In particular, studies indicate altered functional coupling between nodes of the language and default mode networks. Neurofeedback based on real-time functional magnetic resonance imaging (rtfMRI) can be used to modulate such aberrant network connectivity. MethodsWe investigated resting-state connectivity changes after neurofeedback (NF) in 21 patients with schizophrenia and 35 healthy individuals. All participants underwent two days of neurofeedback training of important nodes of the left-hemispheric language network including the inferior frontal gyrus (IFG) and posterior superior temporal gyrus (pSTG). In a double-blind randomized cross-over design, participants learned to down- and up-regulate their brain activation in the designated target regions based on NF. Prior to and after each training day, a resting state measurement took place. ResultsCoupling between nodes of the language and the default mode network (DMN) selectively increased after down-as compared to up-regulation NF. Network analyses revealed more pronounced increases in functional connectivity between nodes of the language network and the DMN in patients compared to healthy individuals. In particular, down-regulation NF led to increased coupling between nodes of the language network and bilateral inferior parietal lobe (IPL) as well as posterior cingulate cortex (PCC)/precuneus in patients. Up-regulation strengthened connectivity with the medial prefrontal cortex (mPFC). Improved well-being four weeks after the training predicted increased functional coupling between the left IFG and left IPL. ConclusionModulatory effects emerged as increased internetwork communication, indicating that down-regulation NF selectively enhances coupling between language and DM network nodes in patients with AVH. RtfMRI NF may thus be used to modulate brain network function that is relevant to the phenomenology of AVH. Specific effects of self-regulation on symptom improvement have to be explored in therapeutic interventions.

Valerian extract alters functional brain connectivity: A randomized double-blind placebo-controlled trial.

Valerian root is the most commonly used herbal supplement for sedation and anxiolysis, but it is unknown whether it may affect functional brain connectivity. Our goal was to use electroencephalography (EEG) to investigate whether valerian root extract (VRE) affects resting-state connectivity changes and whether such changes are associated with clinical symptoms. This 4-week, double-blinded, randomized, placebo-controlled clinical trial was conducted with 64 nonclinical volunteers suffering psychological stress. The participants received VRE (100mg) or a placebo thrice daily. We examined VRE's therapeutic effects on anxiety and stress-related psychological constructs. Functional brain connectivity changes were measured as EEG coherence in the alpha and theta frequency bands. The VRE and placebo groups both exhibited significant postintervention improvements on all clinical scales, but no significant between-group differences in these changes were noted. Compared with the placebo group, the VRE group exhibited significantly greater increases in frontal brain region alpha coherence across four electrode pairs, and these changes were significantly correlated with anxiolysis. The VRE group also exhibited significantly greater decreases in theta coherence across another four electrodes pairs. Our findings indicate that VRE alters functional brain connectivity in relation to anxiety. Further EEG studies are needed to confirm VRE's neurophysiological effects.

Changes in resting-state connectivity in pediatric temporal lobe epilepsy.

OBJECTIVE Functional connectivity magnetic resonance imaging (fcMRI) is a form of fMRI that allows for analysis of blood oxygen level-dependent signal changes within a task-free, resting paradigm. This technique has been shown to have efficacy in evaluating network connectivity changes with epilepsy. Presurgical data from patients with unilateral temporal lobe epilepsy were evaluated using the fcMRI technique to define connectivity changes within and between the diseased and healthy temporal lobes using a within-subjects design. METHODS Using presurgical fcMRI data from pediatric patients with unilateral temporal lobe epilepsy, the authors performed seed-based analyses within the diseased and healthy temporal lobes. Connectivity within and between temporal lobe seeds was measured and compared. RESULTS In the cohort studied, local ipsilateral temporal lobe connectivity was significantly increased on the diseased side compared to the healthy temporal lobe. Connectivity of the diseased side to the healthy side, on the other hand, was significantly reduced when compared to connectivity of the healthy side to the diseased temporal lobe. A statistically significant regression was observed when comparing the changes in local ipsilateral temporal lobe connectivity to the changes in inter-temporal lobe connectivity. A statistically significant difference was also noted in ipsilateral connectivity changes between patients with and those without mesial temporal sclerosis. CONCLUSIONS Using fcMRI, significant changes in ipsilateral temporal lobe and inter-temporal lobe connectivity can be appreciated in unilateral temporal lobe epilepsy. Furthermore, fcMRI may have a role in the presurgical evaluation of patients with intractable temporal lobe epilepsy.

Resting State Functional Connectivity After Sphenopalatine Ganglion Blocks in Chronic Migraine With Medication Overuse Headache: A Pilot Longitudinal fMRI Study.

In this pilot study, the purpose is to investigate if a series of sphenopalatine ganglion (SPG) blockade treatments modulate the functional connectivity within the salience and central executive network (CEN) in chronic migraine with medication overuse headaches (CMw/MOH ). Using intranasal local anesthesia to block the SPG for the treatment of various headache disorders has been employed in clinical practice since the early 1900s. However, the exact mechanism of how SPG modulate resting state intrinsic functional brain networks connectivity remains to be elucidated. This pilot study seeks to understand the resting state connectivity changes in salience and CENs, with emphasis on the mesocorticolimbic systems, before and after a series of SPG block treatments. Using fMRI, resting state connectivity was derived from predefined networks of nodes (regions of interests) for the salience (27 nodes, 351 connections) and CENs (17 nodes, 136 connections). After treatments, a paired samples t-test (with 10,000 permutations to correct for multiple comparison) was used to evaluate changes in the intranetwork resting state functional connectivity within the salience and executive networks, as well as the overall network connectivity strength. When comparing connectivity strength at baseline to that at the end of treatment in our cohort of 10 CMw/MOH participants, there were several connections within the salience (n = 9) and executive (n = 8) networks that were significantly improved. Within the salience network, improved connectivity was observed between the prefrontal cortex and various regions of the insula, basal ganglia, motor, and frontal cortex. Additionally, changes in connectivity were observed between regions of the temporal cortex with the basal ganglia and supramarginal gyrus. Within the CEN, improved connectivity was observed between the prefrontal cortex and regions of the anterior thalamus, caudate, and frontal cortex. After treatment, the overall CEN connectivity was significantly improved (Baseline 0.00 ± 0.08; 6 weeks 0.03 ± 0.09, P = .01); however, the overall salience network connectivity was not significantly improved (Baseline -0.01 ± 0.10; 6 weeks 0.01 ± 0.12, P = .26). Additionally, after treatment, there was a significant reduction in the number of moderate/severe headache days per month (Baseline 21.1 ± 6.6; 6 weeks 11.2 ± 6.5, P < .001), HIT-6 (Baseline 66.1 ± 2.6; 6 weeks 60.2 ± 3.6, P < .001), and PHQ-9 (Baseline 12.4 ± 5.7; 6 weeks 6.1 ± 3.6, P = .008) scores. In this longitudinal fMRI study, we observed improved functional connectivity within both networks, primarily involving connectivity between regions of the prefrontal cortex and limbic (cortical-limbic) structures, and between different cortical (cortical-cortical) regions after a series of repetitive SPG blockades. The overall CEN strength was also improved. Our results suggest that recurrent parasympathetic inhibition via SPG is associated with improved functional connectivity in brain regions critical to pain processing in CMw/MOH .

P.3.007 - Resting-state connectivity changes in self-control networks in obese before and after bariatric surgery compared to lean

Background/aims Obesity remains a major global challenge that is a risk factor for various diseases and one of the leading causes of preventable death. Currently, one of the most successful weight loss interventions is bariatric surgery, which triggers substantial weight loss and restores metabolic balance in the patient [1]. In this project, we investigated whether bariatric surgery impacts resting state activity in brain regions related to dietary self-control and whether there are group differences between obese and lean participants. Participants 16 morbidly obese (BMI: 36.5-63.5 kg/m2, mean±SD: 45.6±5.2) and 40 normal-weight (BMI: 19-26 kg/m2, mean±SD: 22.3±1.9) women underwent a battery of experimental procedures, including resting-state functional magnetic imaging to examine task-independent functional brain connectivity at two time points. 13 obese and 33 lean participants returned for the second part of the experiments about 6 months later, which was surgery-dependent for the obese group. Bariatric bypass surgery Surgery achieves substantial weight loss in obese patients, reducing mean body weight from 119 to 87 kg six months after surgery, which equals a reduction of 27% in body weight. Statistical analyses Based on prior task-dependent work on dietary self-control, we applied ROI-to-ROI and seed-to-voxel analysis in our two regions of interest, i.e. ventromedial (vmPFC) and dorsolateral (dlPFC) prefrontal cortex, that are related to self-control success and valuation in task-based fMRI studies [2,3]. Masks for those regions were constructed based on Neurosynth data (neurosynth.org) and transformed using previously established methods to create strict and liberal regional masks [4]. Seed-to-voxel connectivity scores were extracted as mean connectivity values per subject, yielding one connectivity measure for each seed region connected to multiple clusters per subject. All analyses were corrected for age due to its effect on resting-state connectivity [5], by integrating it as a co-variate of no interest. All results were obtained applying multiple comparisons using FDR and were considered significant at a threshold for p-FDR Results ROI-to-ROI connectivity between vmPFC and dlPFC at rest related to self-control success in task based fMRI studies is stronger in obesity compared to lean independent of surgery (two-way ANOVA [F(1,84)=5.8, p=0.02]). Seed-to-voxel connectivity of the vmPFC shows that after bariatric surgery the striatum is reintegrated into reward-related circuits in the obese group compared to the difference over time in the lean group (pFWE Conclusion This is the first longitudinal study investigating functional brain connectivity at rest demonstrating the effect of bariatric surgery six months after the operation in morbidly obese individuals. Our findings suggest bariatric surgery as an effective treatment not only on weight status but also on brain circuits in obese patients. The reintegration of the striatum within the brain’s reward circuit indicates that bariatric surgery could help to counteract brain connectivity patterns that resemble those seen in addictions, namely a hypofunctioning of the reward circuit.

Network-specific resting-state connectivity changes in the premotor-parietal axis in writer's cramp

BackgroundWriter's cramp is a task-specific dystonia impairing writing and sometimes other fine motor tasks. Neuroimaging studies using manifold designs have shown varying results regarding the nature of changes in the disease.ObjectiveTo clarify and extend the knowledge of underlying changes by investigating functional connectivity (FC) in intrinsic connectivity networks with putative sensorimotor function at rest in an increased number of study subjects.MethodsResting-state functional magnetic resonance imaging with independent component analysis was performed in 26/27 writer's cramp patients/healthy controls, and FC within and between resting state networks with putative sensorimotor function was compared. Additionally, voxel-based morphometry was carried out on the subjects' structural images.ResultsPatients displayed increased left- and reduced right-hemispheric primary sensorimotor FC in the premotor-parietal network. Mostly bilaterally altered dorsal/ventral premotor FC, as well as altered parietal FC were observed within multiple sensorimotor networks and showed differing network-dependent directionality. Beyond within-network FC changes and reduced right cerebellar grey matter volume in the structural analysis, the positive between-network FC of the cerebellar network and the basal ganglia network was reduced.ConclusionsAbnormal resting-state FC in multiple networks with putative sensorimotor function may act as basis of preexisting observations made during task-related neuroimaging. Further, altered connectivity between the cerebellar and basal ganglia network underlines the important role of these structures in the disease.

Graph Lasso-Based Test for Evaluating Functional Brain Connectivity in Sickle Cell Disease.

Sickle cell disease (SCD) is a vascular disorder that is often associated with recurrent ischemia-reperfusion injury, anemia, vasculopathy, and strokes. These cerebral injuries are associated with neurological dysfunction, limiting the full developing potential of the patient. However, recent large studies of SCD have demonstrated that cognitive impairment occurs even in the absence of brain abnormalities on conventional magnetic resonance imaging (MRI). These observations support an emerging consensus that brain injury in SCD is diffuse and that conventional neuroimaging often underestimates the extent of injury. In this article, we postulated that alterations in the cerebral connectivity may constitute a sensitive biomarker of SCD severity. Using functional MRI, a connectivity study analyzing the SCD patients individually was performed. First, a robust learning scheme based on graphical lasso model and Fréchet mean was used for estimating a consistent descriptor of healthy brain connectivity. Then, we tested a statistical method that provides an individual index of similarity between this healthy connectivity model and each SCD patient's connectivity matrix. Our results demonstrated that the reference connectivity model was not appropriate to model connectivity for only 4 out of 27 patients. After controlling for the gender, two separate predictors of this individual similarity index were the anemia (p = 0.02) and white matter hyperintensities (WMH) (silent stroke) (p = 0.03), so that patients with low hemoglobin level or with WMH have the least similarity to the reference connectivity model. Further studies are required to determine whether the resting-state connectivity changes reflect pathological changes or compensatory responses to chronic anemia.

Investigating Changes in Resting-State Connectivity from Functional MRI Data in Patients with HIV Associated Neurocognitive Disorder Using MCA and Machine Learning.

Infection of the brain by the Human Immunodeficiency Virus (HIV) causes irreversible damage to the synaptic connections resulting in cognitive impairment. Patients with HIV infection, showing signs of impairment in multiple cognitive domains, as assessed by neuropsychological testing, are said to exhibit symptoms of HIV Associated Neurocognitive Disorder (HAND). In this study, we use resting-state functional MRI (fMRI) data to distinguish between healthy subjects and subjects with symptoms of HAND. To this end, we first establish a measure of interaction between pairs of regional time-series by quantifying their non-linear functional connectivity using Mutual Connectivity Analysis (MCA). Subsequently, we use a classifier to distinguish patterns of interaction between healthy and diseased individuals. Our results, quantified as the mean Area under the ROC curve (AUC) over 75 iterations, indicate that, using fMRI data, we can discriminate between the two cohorts well (AUC > 0.8). Specifically, we find that MCA (mean AUC = 0.89) based connectivity features perform significantly better (p < 0.05) when compared to cross-correlation (mean AUC = 0.82) at the classification task. A higher AUC using our approach suggests that such a nonlinear approach is better able to capture connectivity changes between brain regions and has potential for the development of novel neuro-imaging biomarkers.

Increases in Intrinsic Thalamocortical Connectivity and Overall Cognition Following Cognitive Remediation in Chronic Schizophrenia

BackgroundThalamic projections to the prefrontal cortex (PFC) are critical for cognition, and disruptions in these circuits are thought to underlie the pathophysiology of schizophrenia. Cognitive remediation training (REM) is a behavioral intervention that holds promise for improving cognition and functioning in schizophrenia; however, the extent to which it affects thalamo-prefrontal connections has not been researched. This study sought to determine whether patients with schizophrenia who undergo a placebo-controlled trial of REM show increased functional connectivity between the thalamus and PFC, and whether these changes correspond to improvements in cognition. MethodsTwenty-six patients with chronic schizophrenia were randomized to either 48 hours (over 16 weeks) of a drill-and-practice working memory–focused REM condition or an active placebo condition. All participants underwent cognitive assessment (MATRICS), as well as both resting and task-based functional magnetic resonance imaging before and after their respective intervention. All clinicians, technicians, and raters were blinded to participant condition. ResultsWe observed changes in resting-state connectivity in the PFC for the REM group but not for the placebo group. Increased intrinsic connectivity between the thalamus and right middle frontal gyrus correlated with improvements in overall cognition. Additionally, lower baseline cognition correlated with greater increases in connectivity between the thalamus and PFC. Similar findings were observed when patients were scanned during a working memory task. ConclusionsThese results suggest that increases in thalamo-prefrontal circuitry correspond with training-related improvements of the cognitive deficits associated with schizophrenia.

Menstrual Cycle and Hormonal Contraceptive-Dependent Changes in Intrinsic Connectivity of Resting-State Brain Networks Correspond to Behavioral Changes Due to Hormonal Status

Menstrual cycle-dependent changes have been reported for a variety of functions, including cognition, attention, emotion, inhibition, and perception. For several of these functions, an effect of hormonal contraceptives has also been discussed. Cognitive, attentional, emotional, inhibitory, and perceptual functions have been linked to distinct intrinsic connectivity networks during the resting state. However, changes in resting-state connectivity across the menstrual cycle phase and due to hormonal contraceptive use have only been investigated in two selected networks and without controlling for the type of hormonal contraceptives. In the present study, we demonstrate menstrual cycle and hormonal contraceptive-dependent changes in several intrinsic connectivity networks, including networks that have been related to emotion processing, olfaction, audition, vision, coordination, and two lateralized frontoparietal networks related to a variety of cognitive functions. These changes parallel behavioral changes in the functions associated with these networks. Changes in connectivity and changes in behavior occur during the same cycle phases. Furthermore, hormonal contraceptive-dependent effects were observed in the same networks and same target sites as menstrual cycle-related changes and were dependent on the androgenicity of the progestin component contained in the hormonal contraceptive.