Resting-state Functional Connectivity Measures Research Articles

A Comprehensive and Broad Approach to Resting-State Functional Connectivity in Adult Patients with Mild Traumatic Brain Injury.

Several recent works using resting-state fMRI suggest possible alterations of resting-state functional connectivity after mild traumatic brain injury. However, the literature is plagued by various analysis approaches and small study cohorts, resulting in an inconsistent array of reported findings. In this study, we aimed to investigate differences in whole-brain resting-state functional connectivity between adult patients with mild traumatic brain injury within 1 month of injury and healthy control subjects using several comprehensive resting-state functional connectivity measurement methods and analyses. A total of 123 subjects (72 patients with mild traumatic brain injury and 51 healthy controls) were included. A standard fMRI preprocessing pipeline was used. ROI/seed-based analyses were conducted using 4 standard brain parcellation methods, and the independent component analysis method was applied to measure resting-state functional connectivity. The fractional amplitude of low-frequency fluctuations was also measured. Group comparisons were performed on all measurements with appropriate whole-brain multilevel statistical analysis and correction. There were no significant differences in age, sex, education, and hand preference between groups as well as no significant correlation between all measurements and these potential confounders. We found that each resting-state functional connectivity measurement revealed various regions or connections that were different between groups. However, after we corrected for multiple comparisons, the results showed no statistically significant differences between groups in terms of resting-state functional connectivity across methods and analyses. Although previous studies point to multiple regions and networks as possible mild traumatic brain injury biomarkers, this study shows that the effect of mild injury on brain resting-state functional connectivity has not survived after rigorous statistical correction. A further study using subject-level connectivity analyses may be necessary due to both subtle and variable effects of mild traumatic brain injury on brain functional connectivity across individuals.

Measurement of Functional Brain Network Connectivity in People with Orthostatic Tremor.

Orthostatic tremor is a rare movement disorder characterized by a sensation of unsteadiness and leg tremor while standing. It has been hypothesized that the disorder is attributable to dysregulation of a central oscillatory network in the brain. This putative network includes primary motor cortex, supplementary motor area, cerebellum, thalamus, and pontine tegmentum. We studied this brain network by recording resting-state functional MRI data from individuals with orthostatic tremor. For each participant, we measured resting-state functional connectivity using a seed-based approach. Regions of interest included were components of the putative central oscillatory network and a primary motor thumb region (identified via transcranial magnetic stimulation). A non-central oscillatory network region of interest-posterior cingulate cortex-was included for comparative analysis of a well-characterized intrinsic network, the default mode network. Demographic information, medical history, and tremor characteristics were collected to test associations with functional connectivity. For normative context, data from the 1000 Functional Connectomes Project were analyzed using an identical approach. We observed that tremor and demographic variables were correlated with functional connectivity of central oscillatory network components. Furthermore, relative to healthy comparison participants, patients with orthostatic tremor exhibited qualitatively different patterns of cerebellar resting state functional connectivity. Our study enhances the current understanding of brain network differences related to orthostatic tremor and is consistent with a hypothesized selective decoupling of cerebellum. Additionally, associations observed between functional connectivity and factors including medical history and tremor features may suggest targets for treatment of orthostatic tremor.

Comparison of Resting State Functional Connectivity in Persons With and Without HIV: A Cross-sectional Study.

This study examined the effects of human immunodeficiency virus (HIV) on resting state functional connectivity (RSFC) in a large cohort of people with HIV (PWH) and healthy controls without HIV (PWoH). Within PWH analyses focused on the effects of viral suppression and cognitive impairment on RSFC. A total of 316 PWH on stable combination antiretroviral therapy and 209 demographically matched PWoH were scanned at a single institution. Effects of the virus were examined by grouping PWH by detectable (viral load > 20 copies/mL; VLD) and undetectable (VLU) viral loads and as being cognitively impaired (CI) (Global Deficit Score ≥ 0.5) or cognitively normal (CN). Regression analysis, object oriented data analysis, and spring embedded graph models were applied to RSFC measures from 298 established brain regions of interest comprising 13 brain networks to examine group differences. No significant RSFC differences were observed between PWH and PWoH. Within PWH, there were no significant differences in RSFC between VLD and VLU subgroups and CI and CN subgroups. There were no significant effects of HIV on RSFC in our relatively large cohort of PWH and PWoH. Future studies could increase the sample size and combine with other imaging modalities.

An examination of the reliability of seed-to-seed resting state functional connectivity in tinnitus patients

Resting state functional connectivity (RS-FC) studies of tinnitus over the years have produced inconsistent results. While findings can be organized into broad categories, such as increased correlations between auditory and limbic areas in tinnitus patients and a disrupted default mode network, there has been little one-to-one correspondence of results across RS-FC studies of tinnitus. While some of this variation can be explained by the heterogeneity of the tinnitus population, including tinnitus severity, the sources of variability in RS-FC of tinnitus patients are unclear. To directly assess the reliability of RS-FC measures in tinnitus, both tinnitus and control participants from two different sites (University of Illinois at Urbana-Champaign, or UIUC, and the Wilford Hall Ambulatory Surgical Center, or WHASC, at the Lackland Airforce Base in San Antonio, Texas) participated in two resting state MRI scans separated by exactly one week. Seed-to-seed analysis assessing correlations between the fMRI activity of 27 regions in the default mode, dorsal attention, auditory, visual, salience, and emotional processing networks were examined in control and tinnitus participants separately for each site. Additionally, heart rate and respiration measures were collected at UIUC, and the effect of extra physiological corrections using these measures on reliability was examined within the UIUC participants. Intra-class correlation coefficients (ICCs) were used as the measure of reliability. Overall, RS-FC in a seed-to-seed analysis was as reliable in tinnitus participants as it was in control participants in the seed regions examined. As previously shown in studies of participants with normal hearing sensitivity, intra-network reliability was higher than inter-network reliability. Related to this, stronger correlations between two seed regions were predictive of stronger reliability of the connectivity between those regions. These effects were seen in both control and tinnitus populations. Additional physiological corrections did not have a significant impact on the ICC values. The current study demonstrates that, on a whole-brain level, RS-FC assessed via seed-to-seed analysis is reliable in tinnitus participants. We therefore must look to other sources as potential causes of discrepancies across studies, such as variability within analysis techniques or within the behavioral characteristics of tinnitus participants.

Reliability and similarity of resting state functional connectivity networks imaged using wearable, high-density diffuse optical tomography in the home setting

BackgroundWhen characterizing the brain's resting state functional connectivity (RSFC) networks, demonstrating networks' similarity across sessions and reliability across different scan durations is essential for validating results and possibly minimizing the scanning time needed to obtain stable measures of RSFC. Recent advances in optical functional neuroimaging technologies have resulted in fully wearable devices that may serve as a complimentary tool to functional magnetic resonance imaging (fMRI) and allow for investigations of RSFC networks repeatedly and easily in non-traditional scanning environments. MethodsResting-state cortical hemodynamic activity was repeatedly measured in a single individual in the home environment during COVID-19 lockdown conditions using the first ever application of a 24-module (72 sources, 96 detectors) wearable high-density diffuse optical tomography (HD-DOT) system. Twelve-minute recordings of resting-state data were acquired over the pre-frontal and occipital regions in fourteen experimental sessions over three weeks. As an initial validation of the data, spatial independent component analysis was used to identify RSFC networks. Reliability and similarity scores were computed using metrics adapted from the fMRI literature. ResultsWe observed RSFC networks over visual regions (visual peripheral, visual central networks) and higher-order association regions (control, salience and default mode network), consistent with previous fMRI literature. High similarity was observed across testing sessions and across chromophores (oxygenated and deoxygenated haemoglobin, HbO and HbR) for all functional networks, and for each network considered separately. Stable reliability values (described here as a <10% change between time windows) were obtained for HbO and HbR with differences in required scanning time observed on a network-by-network basis. DiscussionUsing RSFC data from a highly sampled individual, the present work demonstrates that wearable HD-DOT can be used to obtain RSFC measurements with high similarity across imaging sessions and reliability across recording durations in the home environment. Wearable HD-DOT may serve as a complimentary tool to fMRI for studying RSFC networks outside of the traditional scanning environment and in vulnerable populations for whom fMRI is not feasible.

Outcomes of Babies with Opioid Exposure (OBOE): protocol of a prospective longitudinal cohort study

BackgroundWhile the health, social, and economic impacts of opioid addiction on adults and their communities are well known, the impact of maternal opioid use on the fetus exposed in utero is less well understood.MethodsThis paper presents the protocol of the ACT NOW Outcomes of Babies with Opioid Exposure (OBOE) Study, a multi-site prospective longitudinal cohort study of infants with antenatal opioid exposure and unexposed controls. Study objectives are to determine the impact of antenatal opioid exposure on brain development and neurodevelopmental outcomes over the first 2 years of life and explore whether family, home, and community factors modify developmental trajectories during this critical time period.ResultsPrimary outcomes related to brain development include cortical volumes, deep cerebral gray matter volumes, resting-state functional connectivity measures, and structural connectivity measures using diffusion tensor imaging. Primary neurodevelopmental outcomes include visual abnormalities, cognitive, language, and motor skills measured using the Bayley Scales of Infant Development and social–emotional and behavioral problems and competence measured by the Brief Infant-Toddler Social and Emotional Assessment.ConclusionsThe OBOE study has been designed to overcome challenges of previous studies and will help further understanding of the effects of antenatal opioid exposure on early infant development.ImpactThis study will integrate MRI findings and comprehensive neurodevelopmental assessments to provide early insights into the functional topography of the brain in this high-risk population and assess MRI as a potential biomarker.Rather than conducting neuroimaging at a single time point, the study will include serial MRI assessments from birth to 2 years, allowing for the examination of trajectories throughout this period of rapid brain development.While previous studies often have had limited information on exposures, this study will use umbilical cord assays to accurately measure amounts of opioids and other substances from 20 weeks of gestation to birth.

Examining the Role of Socioeconomic Status and Maternal Sensitivity in Predicting Functional Brain Network Connectivity in 5-Month-Old Infants.

Infancy is a sensitive period of human brain development that is plastically shaped by environmental factors. Both proximal factors, such as sensitive parenting, and distal factors, such as socioeconomic status (SES), are known predictors of individual differences in structural and functional brain systems across the lifespan, yet it is unclear how these familial and contextual factors work together to shape functional brain development during infancy, particularly during the first months of life. In the current study, we examined pre-registered hypotheses regarding the interplay between these factors to assess how maternal sensitivity, within the broader context of socioeconomic variation, relates to the development of functional connectivity in long-range cortical brain networks. Specifically, we measured resting-state functional connectivity in three cortical brain networks (fronto-parietal network, default mode network, homologous-interhemispheric connectivity) using functional near-infrared spectroscopy (fNIRS), and examined the associations between maternal sensitivity, SES, and functional connectivity in a sample of 5-month-old infants and their mothers (N = 50 dyads). Results showed that all three networks were detectable during a passive viewing task, and that maternal sensitivity was positively associated with functional connectivity in the default mode network, such that infants with more sensitive mothers exhibited enhanced functional connectivity in this network. Contrary to hypotheses, we did not observe any associations of SES with functional connectivity in the brain networks assessed in this study. This suggests that at 5 months of age, maternal sensitivity is an important proximal environmental factor associated with individual differences in functional connectivity in a long-range cortical brain network implicated in a host of emotional and social-cognitive brain processes.

P 63 Does the Anna Karenina principle apply to vestibular migraine and Meniere's disease?

Introduction: To date it is unclear how Meniere’s disease (MD) and vestibular migraine (VM), which often appear in clinically similar attacks, differ from healthy controls (HC) in functional brain connectivity (measured by fcMRI), especially during the interictal phase. The central functional connectivity feature of VM and MD might be “disorganization” relative to HC, due to unpredictable attacks that cannot be compensated for. This “Anna Karenina principle” states that all HCs are very alike while all patients are very dissimilar from each other and the HCs. Here we examined the distribution parameters of functional connectivity between HC, VM and MD to elucidate the state of disorganization in the interictal phase. Methods: 93 patients (42 VM, 51 MD) and 50 HCs underwent fMRI while resting in a 3T MRI (Siemens). Resting-state fMRI connectivity measures were extracted via dual regression and normalized in mean and standard deviation relative to HCs. Robust distribution parameters for all voxels in the grey matter were compared between groups. Results: Distribution parameters were compact for HCs, while those of VM and MD patient groups were significantly more dispersed, i.e., disorganized (Figure 1), permutation test with 10000 permutations. In Figure 1 the bulk of values for the HCs were marked by black outline and superimposed onto the values for the MD and VM groups. Conclusion: Resting-state functional connectivity measures imply disorganized interactions between patients relative to HCs, even in the interictal phase. VM and MD patients are very different in functional connectivity, suggesting that the Anna Karenina principle might apply to these patients. References 1) Dieterich et.al. J Neurol (2016); 2) Liu & Xu, Behav Neurol (2016); 3) Tabet & Saliba, J Clin Med Res (2017) Figure 1. Distribution parameters per voxel relative to healthy control (HC) group. Values for healthy controls (HC) were marked with a black line and superimposed on Meniere disease (MD) and vestibular migraine (VM) group data. Color of dots indicates the median relative to the HC group (blue to yellow). The data of the healthy controls was normalized to mean of 0 and standard deviation 1, and these parameters were used to normalize the MD and VM patients, i.e., everything is presented in the scale of the HC group such that parameters can be compared visually.

Perceived Stress, Cortical GABA, and Functional Connectivity Correlates: A Hypothesis-Generating Preliminary Study.

Stress exposures and dysregulated responses to stress are implicated in psychiatric disorders of mood, anxiety, and cognition. Perceived stress, an individual's appraisal of experienced stress and ability for coping, relates to dysregulated functioning in resting state brain networks. Alterations in GABAergic function may underlie perceived stress-related functional dysregulation in resting state networks but this has not yet been explored. Therefore, the current study examined the association of perceived stress, via the Perceived Stress Scale (PSS), with prefrontal GABA levels and corresponding resting state functional connectivity (RSFC) alterations. Twelve women and five men, ages 35–61, participated. MR spectroscopy was used to measure brain GABA levels in the anterior cingulate cortex (ACC), left dorsolateral prefrontal cortex (DLPFC), and ventromedial prefrontal cortex (VMPFC). Resting state functional scans acquired at 3 Tesla were used to measure RSFC within and between the default mode (DMN), salience (SN), and central executive networks (CEN), hippocampus and amygdala. We observed significant negative correlations between total PSS scores and left DLPFC GABA levels (r = −0.62, p = 0.023). However, PSS scores were not significantly correlated with RSFC measures (all p > 0.148). These preliminary results support a relationship between perceived stress and GABAergic functioning in DLPFC, a core node of the CEN, an intrinsic network thought to underlie goal-directed attentional processes. Our findings extend previous work suggesting that functioning in the CEN is related to perceived stress and may inform treatment strategies to improve outcomes in stress-related conditions.

Multimodal investigation of the association between shift work and the brain in a population-based sample of older adults

Neuropsychological studies reported that shift workers show reduced cognitive performance and circadian dysfunctions which may impact structural and functional brain networks. Here we tested the hypothesis whether night shift work is associated with resting-state functional connectivity (RSFC), cortical thickness and gray matter volume in participants of the 1000BRAINS study for whom information on night shift work and imaging data were available. 13 PRESENT and 89 FORMER night shift workers as well as 430 control participants who had never worked in shift (NEVER) met these criteria and were included in our study. No associations between night shift work, three graph-theoretical measures of RSFC of 7 functional brain networks and brain morphology were found after multiple comparison correction. Preceding multiple comparison correction, our results hinted at an association between more years of shift work and higher segregation of the visual network in PRESENT shift workers and between shift work experience and lower gray matter volume of the left thalamus. Extensive neuropsychological investigations supplementing objective imaging methodology did not reveal an association between night shift work and cognition after multiple comparison correction. Our pilot study suggests that night shift work does not elicit general alterations in brain networks and affects the brain only to a limited extent. These results now need to be corroborated in studies with larger numbers of participants.

Reducing false discoveries in resting-state functional connectivity using short channel correction: an fNIRS study.

.SignificanceFunctional near-infrared spectroscopy (fNIRS) is a neuroimaging tool that can measure resting-state functional connectivity; however, non-neuronal components present in fNIRS signals introduce false discoveries in connectivity, which can impact interpretation of functional networks.AimWe investigated the effect of short channel correction on resting-state connectivity by removing non-neuronal signals from fNIRS long channel data. We hypothesized that false discoveries in connectivity can be reduced, hence improving the discriminability of functional networks of known, different connectivity strengths.ApproachA principal component analysis-based short channel correction technique was applied to resting-state data of 10 healthy adult subjects. Connectivity was analyzed using magnitude-squared coherence of channel pairs in connectivity groups of homologous and control brain regions, which are known to differ in connectivity.ResultsBy removing non-neuronal components using short channel correction, significant reduction of coherence was observed for oxy-hemoglobin concentration changes in frequency bands associated with resting-state connectivity that overlap with the Mayer wave frequencies. The results showed that short channel correction reduced spurious correlations in connectivity measures and improved the discriminability between homologous and control groups.ConclusionsResting-state functional connectivity analysis with short channel correction performs better than without correction in its ability to distinguish functional networks with distinct connectivity characteristics.

Imbalance between default mode and sensorimotor connectivity is associated with perseverative thinking in obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is highly heterogeneous. Although perseverative negative thinking (PT) is a feature of OCD, little is known about its neural mechanisms or relationship to clinical heterogeneity in the disorder. In a sample of 85 OCD patients, we investigated the relationships between self-reported PT, clinical symptom subtypes, and resting-state functional connectivity measures of local and global connectivity. Results indicated that PT scores were highly variable within the OCD sample, with greater PT relating to higher severity of the “unacceptable thoughts” symptom dimension. PT was positively related to local connectivity in subgenual anterior cingulate cortex (ACC), pregenual ACC, and the temporal poles—areas that are part of, or closely linked to, the default mode network (DMN)—and negatively related to local connectivity in sensorimotor cortex. While the majority of patients showed higher local connectivity strengths in sensorimotor compared to DMN regions, OCD patients with higher PT scores had less of an imbalance between sensorimotor and DMN connectivity than those with lower PT scores, with healthy controls exhibiting an intermediate pattern. Clinically, this imbalance was related to both the “unacceptable thoughts” and “symmetry/not-just-right-experiences” symptom dimensions, but in opposite directions. These effects remained significant after accounting for variance related to psychiatric comorbidity and medication use in the OCD sample, and no significant relationships were found between PT and global connectivity. These data indicate that PT is related to symptom and neural variability in OCD. Future work may wish to target this circuity when developing personalized interventions for patients with these symptoms.

Attention network modulation via tRNS correlates with attention gain.

Transcranial random noise stimulation (tRNS) can enhance vision in the healthy and diseased brain. Yet, the impact of multi-day tRNS on large-scale cortical networks is still unknown. We investigated the impact of tRNS coupled with behavioral training on resting-state functional connectivity and attention. We trained human subjects for 4 consecutive days on two attention tasks, while receiving tRNS over the intraparietal sulci, the middle temporal areas, or Sham stimulation. We measured resting-state functional connectivity of nodes of the dorsal and ventral attention network (DVAN) before and after training. We found a strong behavioral improvement and increased connectivity within the DVAN after parietal stimulation only. Crucially, behavioral improvement positively correlated with connectivity measures. We conclude changes in connectivity are a marker for the enduring effect of tRNS upon behavior. Our results suggest that tRNS has strong potential to augment cognitive capacity in healthy individuals and promote recovery in the neurological population.

Lasting effects of a single psilocybin dose on resting-state functional connectivity in healthy individuals.

Background:Psilocybin is a psychedelic drug that has shown lasting positive effects on clinical symptoms and self-reported well-being following a single dose. There has been little research into the long-term effects of psilocybin on brain connectivity in humans.Aim:Evaluate changes in resting-state functional connectivity (RSFC) at 1 week and 3 months after one psilocybin dose in 10 healthy psychedelic-naïve volunteers and explore associations between change in RSFC and related measures.Methods:Participants received 0.2–0.3 mg/kg psilocybin in a controlled setting. Participants completed resting-state functional magnetic resonance imaging (fMRI) scans at baseline, 1-week and 3-month post-administration and [11C]Cimbi-36 PET scans at baseline and 1 week. We examined changes in within-network, between-network and region-to-region RSFC. We explored associations between changes in RSFC and psilocybin-induced phenomenology as well as changes in psychological measures and neocortex serotonin 2A receptor binding.Results:Psilocybin was well tolerated and produced positive changes in well-being. At 1 week only, executive control network (ECN) RSFC was significantly decreased (Cohen’s d = −1.73, pFWE = 0.010). We observed no other significant changes in RSFC at 1 week or 3 months, nor changes in region-to-region RSFC. Exploratory analyses indicated that decreased ECN RSFC at 1 week predicted increased mindfulness at 3 months (r = −0.65).Conclusions:These findings in a small cohort indicate that psilocybin affects ECN function within the psychedelic ‘afterglow’ period. Our findings implicate ECN modulation as mediating psilocybin-induced, long-lasting increases in mindfulness. Although our findings implicate a neural pathway mediating lasting psilocybin effects, it is notable that changes in neuroimaging measures at 3 months, when personality changes are observed, remain to be identified.

Network dysfunction in cognitively normal APOE ε4 carriers is related to subclinical tau.

Apolipoprotein E (APOE) ε4 allele status is associated with amyloid and tau-related pathological changes related to Alzheimer's disease (AD). However, it is unknown whether brain network changes are related to amyloid beta (Aβ) and/or tau-related pathology in cognitively normal APOE ε4 carriers with subthreshold Aβ accumulation. Resting state functional connectivity measures of network integrity were evaluated in cognitively normal individuals (n=121, mean age 76.6 ± 7.8 years, 15% APOE ε4 carriers, 65% female) with minimal Aβ per cerebrospinal fluid (CSF) or amyloid positron emission tomography. APOE ε4 carriers had increased lateralized connections relative to callosal connections within the default-mode, memory, and salience networks (P=.02), with significant weighting on linear regression toward CSF total tau (P=.03) and CSF phosphorylated tau at codon 181 (P=.03), but not CSF Aβ42 . Cognitively normal APOE ε4 carriers with subthreshold amyloid accumulation may have network reorganization associated with tau.

Distinct effects of prematurity on MRI metrics of brain functional connectivity, activity, and structure: Univariate and multivariate analyses.

Premature birth affects the developmental trajectory of the brain during a period of intense maturation with possible lifelong consequences. To better understand the effect of prematurity on brain structure and function, we performed blood‐oxygen‐level dependent (BOLD) and anatomical magnetic resonance imaging (MRI) at 40 weeks of postmenstrual age on 88 newborns with variable gestational age (GA) at birth and no evident radiological alterations. We extracted measures of resting‐state functional connectivity and activity in a set of 90 cortical and subcortical brain regions through the evaluation of BOLD correlations between regions and of fractional amplitude of low‐frequency fluctuation (fALFF) within regions, respectively. Anatomical information was acquired through the assessment of regional volumes. We performed univariate analyses on each metric to examine the association with GA at birth, the spatial distribution of the effects, and the consistency across metrics. Moreover, a data‐driven multivariate analysis (i.e., Machine Learning) framework exploited the high dimensionality of the data to assess the sensitivity of each metric to the effect of premature birth. Prematurity was associated with bidirectional alterations of functional connectivity and regional volume and, to a lesser extent, of fALFF. Notably, the effects of prematurity on functional connectivity were spatially diffuse, mainly within cortical regions, whereas effects on regional volume and fALFF were more focal, involving subcortical structures. While the two analytical approaches delivered consistent results, the multivariate analysis was more sensitive in capturing the complex pattern of prematurity effects. Future studies might apply multivariate frameworks to identify premature infants at risk of a negative neurodevelopmental outcome.

Distinct neural circuits are associated with subclinical neuropsychiatric symptoms in Parkinson's disease

BackgroundParkinson's disease (PD) can present with neuropsychiatric symptoms (here, anxiety, depression, and apathy) at any stage of the disease. We investigated the neural correlates of subclinical neuropsychiatric symptoms in relation to motor and cognitive symptoms in a high-functioning PD cohort. MethodsBrain morphometry of the cognitively intact, early-stage (Hoehn & Yahr 2) PD group (n = 48) was compared to matched controls (n = 37). Whole-brain, pairwise, resting-state functional connectivity measures were correlated with neuropsychiatric symptom, motor exam, and global cognitive scores of the PD group. ResultsFactor analysis of highly collinear anxiety, depression, and apathy scores revealed a single principal component (i.e., composite neuropsychiatric symptom score) explaining 71.6% of variance. There was no collinearity between the neuropsychiatric, motor, and cognitive scores. Compared to controls, PD group showed only subcortical changes including amygdala and nucleus accumbens atrophy, and greater pallidal volume. Reduced functional connectivity in the limbic cortical-striatal circuits and increased functional connectivity between the cerebellum and occipito-temporal regions were associated with a more impaired neuropsychiatric profile. This functional connectivity pattern was distinct from those associated with motor deficits and global cognitive functioning. The individual components of the neuropsychiatric symptoms also exhibited unique connectivity patterns. LimitationsPatients were scanned in “on-medication” state only and a control group with similar neuropsychiatric symptoms was not included. ConclusionAbnormal functional connectivity of distinct neural circuits is present even at the subclinical stage of neuropsychiatric symptoms in PD. Neuropsychiatric phenotyping is important and may facilitate early interventions to “reorganize” these circuits and delay/prevent clinical symptom onset.

Tinnitus and auditory cortex: using adapted functional near-infrared spectroscopy to measure resting-state functional connectivity.

ObjectiveTinnitus, phantom sound perception, arises from aberrant brain activity within auditory cortex. In tinnitus animal models, auditory cortex neurons show increased spontaneous firing and neural synchrony. In humans, similar hyperactivation in auditory cortex has been displayed with functional near-infrared spectroscopy (fNIRS). Resting-state functional connectivity (RSFC) or increased connectivity between brain regions has also been shown in tinnitus using fNIRS. However, current fNIRS technology utilizes infrared (IR)-sources and IR-detectors placed on the scalp that restricts (~3 cm depth IR penetration) signal capture to outer cerebral cortex due to skin and skull bone. To overcome this limitation, in this proof of concept study, we adapted fNIRS probes to fit in the external auditory canal (EAC) to physically place IR-probes deeper within the skull thereby extracting neural signals from deeper auditory cortex.MethodsTwenty adults with tinnitus and 20 nontinnitus controls listened to periods of silence and broadband noise before and after 5 min of silence to calculate RSFC. Concurrent scalp probes over auditory cortex and an adapted probe placed in the right EAC were utilized.ResultsFor standard probes, left and right auditory cortex in tinnitus showed increased RSFC to each other and to other nonauditory cortices. Interestingly, adapted fNIRS probes showed trends toward increased RSFC.ConclusionWhile many areas for the adapted probes did not reach significance, these data using a highly innovative and newly created probe adapting fNIRS technology to the EAC substantiates our previously published data in human tinnitus and concurrently validates this technology as a useful and expanded brain imaging modality.

Resting state functional atlas and cerebral networks in mouse lemur primates at 11.7 Tesla

Measures of resting-state functional connectivity allow the description of neuronal networks in humans and provide a window on brain function in normal and pathological conditions. Characterizing neuronal networks in animals is complementary to studies in humans to understand how evolution has modelled network architecture. The mouse lemur (Microcebus murinus) is one of the smallest and more phylogenetically distant primates as compared to humans. Characterizing the functional organization of its brain is critical for scientists studying this primate as well as to add a link for comparative animal studies. Here, we created the first functional atlas of mouse lemur brain and describe for the first time its cerebral networks. They were classified as two primary cortical networks (somato-motor and visual), two high-level cortical networks (fronto-parietal and fronto-temporal) and two limbic networks (sensory-limbic and evaluative-limbic). Comparison of mouse lemur and human networks revealed similarities between mouse lemur high-level cortical networks and human networks as the dorsal attentional (DAN), executive control (ECN), and default-mode networks (DMN). These networks were however not homologous, possibly reflecting differential organization of high-level networks. Finally, cerebral hubs were evaluated. They were grouped along an antero-posterior axis in lemurs while they were split into parietal and frontal clusters in humans.

Time-Varying Functional Connectivity Decreases as a Function of Acute Nicotine Abstinence

BackgroundThe nicotine withdrawal syndrome (NWS) includes affective and cognitive disruptions whose incidence and severity vary across time during acute abstinence. However, most network-level neuroimaging uses static measures of resting-state functional connectivity and assumes time-invariance and is thus unable to capture dynamic brain-behavior relationships. Recent advances in resting-state functional connectivity signal processing allow characterization of time-varying functional connectivity (TVFC), which characterizes network communication between networks that reconfigure over the course of data collection. Therefore, TVFC may more fully describe network dysfunction related to the NWS. MethodsTo isolate alterations in the frequency and diversity of communication across network boundaries during acute nicotine abstinence, we scanned 25 cigarette smokers in the nicotine-sated and abstinent states and applied a previously validated method to characterize TVFC at a network and a nodal level within the brain. ResultsDuring abstinence, we found brain-wide decreases in the frequency of interactions between network nodes in different modular communities (i.e., temporal flexibility). In addition, within a subset of the networks examined, the variability of these interactions across community boundaries (i.e., spatiotemporal diversity) also decreased. Finally, within 2 of these networks, the decrease in spatiotemporal diversity was significantly related to NWS clinical symptoms. ConclusionsUsing multiple measures of TVFC in a within-subjects design, we characterized a novel set of changes in network communication and linked these changes to specific behavioral symptoms of the NWS. These reductions in TVFC provide a meso-scale network description of the relative inflexibility of specific large-scale brain networks during acute abstinence.