Seed-based Correlation Analysis Research Articles

Functional MRI for the Assessment of Brain Connectivity in Neurodegenerative Diseases: An Observational Study in Mexico City

Introduction: Neurodegenerative diseases are characterized by progressive brain dysfunction and structural changes. Functional MRI (fMRI), a non-invasive imaging technique, offers the potential to assess brain connectivity and identify early biomarkers of these diseases. Methods: This observational study included patients with Alzheimer's disease (AD), Parkinson's disease (PD), and healthy controls in Mexico City. Resting-state fMRI data was acquired, and brain connectivity was analyzed using independent component analysis (ICA) and seed-based correlation analysis (SCA). Results: fMRI revealed altered brain connectivity patterns in AD and PD compared to healthy controls. In AD, decreased connectivity was observed within the default mode network (DMN), while PD patients showed reduced connectivity in the motor network. Conclusion: fMRI provides valuable insights into brain connectivity changes in neurodegenerative diseases. These findings contribute to the development of early diagnostic tools and potential therapeutic targets for AD and PD.

Resting-state functional connectivity correlates of brain structural aging in schizophrenia.

A large body of research has shown that schizophrenia patients demonstrate increased brain structural aging. Although this process may be coupled with aberrant changes in intrinsic functional architecture of the brain, they remain understudied. We hypothesized that there are brain regions whose whole-brain functional connectivity at rest is differently associated with brain structural aging in schizophrenia patients compared to healthy controls. Eighty-four male schizophrenia patients and eighty-six male healthy controls underwent structural MRI and resting-state fMRI. The brain-predicted age difference (b-PAD) was a measure of brain structural aging. Resting-state fMRI was applied to obtain global correlation (GCOR) maps comprising voxelwise values of the strength and sign of functional connectivity of a given voxel with the rest of the brain. Schizophrenia patients had higher b-PAD compared to controls (mean between-group difference + 2.9 years). Greater b-PAD in schizophrenia patients, compared to controls, was associated with lower whole-brain functional connectivity of a region in frontal orbital cortex, inferior frontal gyrus, Heschl's Gyrus, plana temporale and polare, insula, and opercular cortices of the right hemisphere (rFTI). According to post hoc seed-based correlation analysis, decrease of functional connectivity with the posterior cingulate gyrus, left superior temporal cortices, as well as right angular gyrus/superior lateral occipital cortex has mainly driven the results. Lower functional connectivity of the rFTI was related to worse verbal working memory and language production. Our findings demonstrate that well-established frontotemporal functional abnormalities in schizophrenia are related to increased brain structural aging.

Brain plasticity and adolescent HIV: A randomised controlled trial protocol investigating behavioural and hemodynamic responses in attention cognitive rehabilitation therapy

Despite advances in antiretroviral pharmacology, neuroHIV in the central nervous system (CNS), causes neuronal dysregulation, which is associated with compromised neurocognition. Non-pharmaceutical interventions such as HIV cognitive rehabilitation training (HIV-CRT), have shown potential to partially reverse cognitive deficits, sequent HIV neuroinvasion. Nonetheless, no studies exist pairing cognitive outcomes with objective neuroimaging biomarkers in adolescent HIV-CRT. This longitudinal pre-post-quasi-experimental protocol examined cognitive outcomes, paired with optimal neuroimaging outcomes following customised attention training in adolescent HIV. Twenty-six adolescents living with HIV were randomly assigned to either the treatment group, which received attention CRT using ACTIVATE™, (n = 13), or to the treatment as usual group (n = 13). Cognitive outcomes were examined using the NEPSY-II, and BRIEF; whilst neuroimaging outcomes were determined by changes in oxygenated haemoglobin (HbO), as determined by functional near-infrared spectrometry (fNIRS). Functional connectivity fNIRS measures were evaluated using seed-based correlation analysis, located in the central executive network (CEN). This study serves to guide the development and identification of objective biomarkers for adolescent neuroHIV, sequent CRT amongst children living with HIV in Sub-Saharan Africa

The long-term intensive gymnastic training influences functional stability and integration: A resting-state fMRI study

IntroductionLong-term motor skill training has been shown to induce anatomical and functional neuroplasticity. World class gymnasts (WCGs) provide a unique opportunity to investigate the effect of long-term intensive training on neuroplasticity. Previous resting-state fMRI studies have demonstrated a high efficient information processing related to motor and cognitive functions in gymnasts compared with healthy controls (HCs). However, most research treated brain signals as static, overlooking the fact that the brain is a complex and dynamic system. In this study, we employed functional stability, a new metric based on dynamic functional connectivity (FC), to examine the impact of long-term intensive training on the functional architecture in the WCGs. MethodsWe first conducted a voxel-wise analysis of functional stability between the WCGs and HCs. Then, we applied FC density (FCD) to explore whether regions with modified functional stability were also accompanied by changes in connection patterns in the WCGs. We identified overlapping regions showing significant differences in both functional stability and FCD. Finally, we applied seed-based correlation analysis (SCA) to determine the detailed changes in connection patterns between the WCGs and HCs within these overlapping regions. ResultsCompared with the HCs, the WCGs exhibited higher functional stability in the bilateral angular gyrus (AG), bilateral inferior temporal gyrus (ITG), bilateral precentral gyrus, and right superior frontal gyrus and lower functional stability in the bilateral hippocampus, bilateral caudate, right rolandic operculum, left superior temporal gyrus, right middle frontal gyrus, right middle cingular cortex, and right precuneus than the HCs. We found that the bilateral AG and ITG not only showed higher functional stability but also increased global and long-range FCD in the WCGs relative to the HCs. The right precuneus displayed lower functional stability as well as decreased local, long-range, and global FCD in the WCGs. Both AG and ITG showed higher FC with regions in the default mode network (DMN) in the WCGs than in the HCs. ConclusionsThe increased functional stability in the AG and ITG might be associated with enhanced functional integration within the DMN in the WCGs. These findings may offer new spatiotemporal evidence for the impact of long-term intensive training on neuroplasticity.

Diffuse optical tomography for mapping cerebral hemodynamics and functional connectivity in delirium.

Delirium is associated with mortality and new onset dementia, yet the underlying pathophysiology remains poorly understood. Development of imaging biomarkers has been difficult given the challenging nature of imaging delirious patients. Diffuse optical tomography (DOT) offers a promising approach for investigating delirium given its portability and three-dimensional capabilities. Twenty-five delirious and matched non-delirious patients (n=50) were examined using DOT, comparing cerebral oxygenation and functional connectivity in the prefrontal cortex during and after an episode of delirium. Total hemoglobin values were significantly decreased in the delirium group, even after delirium resolution. Functional connectivity between the dorsolateral prefrontal cortex and dorsomedial prefrontal cortex was strengthened post-resolution compared to during an episode; however, this relationship was still significantly weaker compared to controls. These findings highlight DOT's potential as an imaging biomarker to measure impaired cerebral oxygenation and functional dysconnectivity during and after delirium. Future studies should focus on the role of cerebral oxygenation in delirium pathogenesis and exploring the etiological link between delirium and dementias. We developed a portable diffuse optical tomography (DOT) system for bedside three-dimensional functional neuroimaging to study delirium in the hospital. We implemented a novel DOT task-focused seed-based correlation analysis. DOT revealed decreased cerebral oxygenation and functional connectivity strength in the delirium group, even after resolution of delirium.

Hypo-connectivity of the primary somatosensory cortex in Parkinson's disease: a resting-state functional MRI study.

Parkinson's disease (PD) is characterized by a range of motor symptoms as well as documented sensory dysfunction. This sensory dysfunction can present itself either as a "pure" sensory disturbance or as a consequence of sensory-motor integration within the central nervous system. This study aims to investigate changes in the functional connectivity of the primary somatosensory cortex (S1) and its clinical significance in Parkinson's disease (PD), an area that has received limited attention in previous neuroimaging studies. This study included thirty-three patients with PD and thirty-four healthy controls (HCs). Clinical evaluations were conducted to assess the clinical manifestations, severity, and functional capacity of all the patients. Resting-state functional MRI (fMRI) was employed to evaluate the functional connectivity of six paired S1 subregions in the participants. Seed-based correlation (SBC) analysis was utilized to construct the correlation matrix among the subregions and to generate connectivity maps between the subregions and the remaining brain voxels. Finally, the study employed partial least-squares (PLS) correlation analysis to investigate the association between modified functional connectivity and clinical characteristics in PD patients. In the correlation matrix, patients with PD demonstrated a notable decrease in functional connectivity across various S1 subregions in comparison to HCs (p < 0.001, corrected using network-based methods). In connectivity maps, hypo-connectivity was primarily observed in the sensorimotor network as common patterns (p < 0.001, corrected for false discovery rate) and in the default mode network (DMN) as distinct patterns. Moreover, this study identified a negative association between the correlation matrix within S1 subregions and the scores for axial symptoms and postural instability/gait difficulty (PIGD) in PD patients. Nevertheless, a direct relationship between the connectivity maps of S1 subregions and clinical assessment scales was not established. This study offers novel insights into the neurobiological mechanisms that contribute to S1 dysfunction in PD, highlighting the significant involvement of S1 hypo-connectivity in the motor disturbances observed in PD patients.

4 Resting State Functional Connectivity Impairments Implicate CNS Mechanisms Underlying Chronic Pain and Depression in Gulf War Veterans’ Illness

Objective:Around 200,000 veterans (up to 32% of those deployed) of the 1991 Gulf War (GW) suffer from GW veterans’ illness (GWVI). GWVI is a poorly understood chronic medical condition, characterized by symptoms indicative of brain function deficits in multiple domains. Among the symptoms of brain impairment GWVI-related chronic headaches and body muscle and joint pain conditions (GWVI-HAP) are the most debilitating, affecting around 64% of the GWVI veterans. Further, depression carries a very high co-morbid rate (&gt;50%) in patients with chronic pain, including GWVI-HAP. In this preliminary study, we examined the integrity of brain function networks in a group of GWI-HAP veterans, with resting state fMRI (rsfMRI).Participants and Methods:Data from the first twenty-two GWVI-HAP veterans from two ongoing parallel clinical trials was examined. Of these 14 subjects (GWVI-HAP-DM) had mild depression (Hamilton Rating Scale for Depression (HSRD &lt; 13); and 8 subjects (GWVI-HAP-DS) had moderate to severe depression (HSRD &gt; 14). Written informed consent was obtained from all participants in the protocol approved by the local Institutional Review Board. RsfMRI data was acquired on a Siemens 3T Prisma-Fit MRI scanner using a 10-minute whole-brain high resolution simultaneous multi-slice (SMS) gradient echo echo-planar imaging (EPI) sequence: TR/TE/FA = 2.2 sec/ 27 msec/80°, and analyzed with well-established image processing pipelines. Functional connectivity (FC) to different regions implicated in depression and chronic pain was assessed with seed-based correlation analysis. Between group differences in FC were obtained with 2-sample t-tests.Results:GWVI-HAP-DS group exhibited significantly (p &lt; 0.05) reduced FC compared to GWVI-HAP-DM between frontal lobe (medial (mPFC), and dorsolateral (dlPFC) prefrontal cortex) and the striatum. This indicates that malfunction of fronto-striatal circuits could be a source of the increased chronic pain and depression seen in veterans with GWVI- HAP-DS. Dysregulation of fronto-striatal networks has been implicated in major depressive disorder as well as many chronic pain conditions. In addition, FC between mPFC, and salience network (SN; anterior insula and dorsal anterior cingulate) and limbic (subgenual and ventral anterior cingulate) regions were also reduced in GWVI-HAP-DS. Similarly, mPFC and SN also exhibited reduced FC to pain processing regions (posterior insula, centromedian thalamus and cerebellum). These FC impairments could reflect greater deficits in regulation of and salience attribution to emotions and nociception in the GWVI-HAP-DS group. Finally, GWVI-HAP-DS also exhibited reduced FC between nodes of the default mode network. DMN impairments also have been observed in many depressive and chronic pain conditions.Conclusions:The results of this preliminary analysis implicate impairments in cognitive control of emotion and nociception as a mechanism underlying the enhanced chronic pain and depression observed in GWVI-HAP veterans, especially those with moderate to severe depression. A fuller picture of deficits in FC in brain function networks is expected to emerge as more GWI-HAP subjects of both groups along with age matched healthy controls are examined in this ongoing project. Better understanding of impairments in these networks in GWI-HAP will benefit the rehabilitation of veterans with GWI-HAP.

Enhanced brain functional connectivity and activation after 12-week Tai Chi-based action observation training in patients with Parkinson's disease.

Motor-cognitive interactive interventions, such as action observation training (AOT), have shown great potential in restoring cognitive function and motor behaviors. It is expected that an advanced AOT incorporating specific Tai Chi movements with continuous and spiral characteristics can facilitate the shift from automatic to intentional actions and thus enhance motor control ability for early-stage PD. Nonetheless, the underlying neural mechanisms remain unclear. The study aimed to investigate changes in brain functional connectivity (FC) and clinical improvement after 12 weeks of Tai Chi-based action observation training (TC-AOT) compared to traditional physical therapy (TPT). Thirty early-stage PD patients were recruited and randomly assigned to the TC-AOT group (N = 15) or TPT group (N = 15). All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans before and after 12 weeks of training and clinical assessments. The FCs were evaluated by seed-based correlation analysis based on the default mode network (DMN). The rehabilitation effects of the two training methods were compared while the correlations between significant FC changes and clinical improvement were investigated. The results showed that the TC-AOT group exhibited significantly increased FCs between the dorsal medial prefrontal cortex and cerebellum crus I, between the posterior inferior parietal lobe and supramarginal gyrus, and between the temporal parietal junction and clusters of middle occipital gyrus and superior temporal. Moreover, these FC changes had a positive relationship with patients' improved motor and cognitive performance. The finding supported that the TC-AOT promotes early-stage PD rehabilitation outcomes by promoting brain neuroplasticity where the FCs involved in the integration of sensorimotor processing and motor learning were strengthened.

Abnormal functional connectivity in radiologically isolated syndrome: A resting-state fMRI study

Background: Radiologically isolated syndrome (RIS) patients might have psychiatric and cognitive deficits, which suggests an involvement of major resting-state functional networks. Notwithstanding, very little is known about the neural networks involved in RIS. Objective: To examine functional connectivity differences between RIS and healthy controls using resting-state functional magnetic resonance imaging (fMRI). Methods: Resting-state fMRI data in 25 RIS patients and 28 healthy controls were analyzed using an independent component analysis; in addition, seed-based correlation analysis was used to obtain more information about specific differences in the functional connectivity of resting-state networks. Participants also underwent neuropsychological testing. Results: RIS patients did not differ from the healthy controls regarding age, sex, and years of education. However, in memory (verbal and visuospatial) and executive functions, RIS patients’ cognitive performance was significantly worse than the healthy controls. In addition, fluid intelligence was also affected. Twelve out of 25 (48%) RIS patients failed at least one cognitive test, and six (24.0%) had cognitive impairment. Compared to healthy controls, RIS patients showed higher functional connectivity between the default mode network and the right middle and superior frontal gyri and between the central executive network and the right thalamus (pFDR < 0.05; corrected). In addition, the seed-based correlation analysis revealed that RIS patients presented higher functional connectivity between the posterior cingulate cortex, an important hub in neural networks, and the right precuneus. Conclusion: RIS patients had abnormal brain connectivity in major resting-state neural networks and worse performance in neurocognitive tests. This entity should be considered not an “incidental finding” but an exclusively non-motor (neurocognitive) variant of multiple sclerosis.

Advancing (Neuro)Entrepreneurship Cognition Research Through Resting-State fMRI: A Methodological Brief

Despite many calls, functional brain magnetic resonance imaging (fMRI) studies are relatively rare in the domain of entrepreneurship research. This methodological brief presents the brain-imaging method of resting-state fMRI (rs-fMRI) and illustrates its application in neuroentrepreneurship for the first time. In contrast to the traditional task-based fMRI approach, rs-fMRI observes the brain in the absence of cognitive tasks or presentation of stimuli, which offers benefits for improving our understanding of the entrepreneurial mind. Here, we describe the method and provide methodological motivations for performing brain resting-state functional neuroimaging studies on entrepreneurs. In addition, we illustrate the use of seed-based correlation analysis, one of the most common analytical approaches for analyzing rs-fMRI data. In this illustration, we show that habitual entrepreneurs have increased functional connectivity between the insula (a region associated with cognitive flexibility) and the anterior prefrontal cortex (a key region for explorative choice) as compared to managers. This increased connectivity could help promote flexible behavior. Thus in brief, we provide an exemplar of a novel way to expand our understanding of the brain in the domain of entrepreneurship. We discuss possible directions for future research and challenges to be addressed to facilitate the inclusion of re-fMRI studies into neuroentrepreneurship.

Brain dysconnectivity with heart failure.

Structural brain damage associated with heart failure is well described; however, little is known about associated changes in various specific brain functions that bear immediate clinical relevance. A satisfactory pathophysiological link between heart failure and decline in cognitive function is still missing. In the present study, we aim to detect functional correlates of heart failure in terms of alterations in functional brain connectivity (quantified by functional magnetic resonance imaging) related to cognitive performance assessed by neuropsychological testing. Eighty patients were post hoc grouped into subjects with and without coronary artery disease. The coronary artery disease patients were further grouped as presenting with or without heart failure according to the guidelines of the European Society of Cardiology. On the basis of resting-state functional magnetic resonance imaging, brain connectivity was investigated using network centrality as well as seed-based correlation. Statistical analysis aimed at specifying centrality group differences and potential correlations between centrality and heart failure-related measures including left ventricular ejection fraction and serum concentrations of N-terminal fragment of the pro-hormone brain-type natriuretic peptide. The resulting correlation maps were then analysed using a flexible factorial model with the factors 'heart failure' and 'cognitive performance'. Our core findings are: (i) A statistically significant network centrality decrease was found to be associated with heart failure primarily in the precuneus, i.e. we show a positive correlation between centrality and left ventricular ejection fraction as well as a negative correlation between centrality and N-terminal fragment of the pro-hormone brain-type natriuretic peptide. (ii) Seed-based correlation analysis showed a significant interaction between heart failure and cognitive performance related to a significant decrease of precuneus connectivity to other brain regions. We obtained these results by different analysis approaches indicating the robustness of the findings we report here. Our results suggest that the precuneus is a brain region involved in connectivity decline in patients with heart failure, possibly primarily or already at an early stage. Current models of Alzheimer's disease-having pathophysiological risk factors in common with cerebrovascular disorders-also consider reduced precuneus connectivity as a marker of brain degeneration. Consequently, we propose that heart failure and Alzheimer's disease exhibit partly overlapping pathophysiological paths or have common endpoints associated with a more or less severe decrease in brain connectivity. This is further supported by specific functional connectivity alterations between the precuneus and widely distributed cortical regions, particularly in patients showing reduced cognitive performance.

Detecting residual brain networks in disorders of consciousness: A resting-state fNIRS study

Functional near infrared spectroscopy (fNIRS) is an emerging non-invasive technique that allows bedside measurement of blood oxygenation level-dependent hemodynamic signals. We aimed to examine the efficacy of resting-state fNIRS in detecting the residual functional networks in patients with disorders of consciousness (DOC). We performed resting-state fNIRS in 23 DOC patients of whom 12 were in minimally conscious state (MCS) and 11 were in unresponsive wakefulness state (UWS). Ten regions of interest (ROIs) in the prefrontal cortex (PFC) were selected: both sides of Brodmann area (BA) 9, BA10, BA44, BA45, and BA46. Graph-theoretical analysis and seed-based correlation analyses were used to investigate the network topology and the strength of pairwise connections between ROIs and channels. MCS and UWS exhibited varying degrees of the loss of topological architecture, and the regional nodal properties of BA10 were significantly different between them (Nodal degree, PLeft BA10 = 0.01, PRight BA10 < 0.01; nodal efficiency, PLeft BA10 = 0.03, PRight BA10 < 0.01). Compared to healthy controls, UWS had impaired functions in both short- and long-distance connectivity, however, MCS had significantly impaired functions only in long-distance connectivity. The functional connectivity of right BA10 (AUC = 0.88) and the connections between left BA46 and right BA10 (AUC = 0.86) had excellent performance in differentiating MCS and UWS. MCS and UWS have different patterns of topological architecture and short- and long-distance connectivity in PFC. Intraconnections within BA10 and interhemispheric connections between BA10 and 46 are excellent resting-state fNIRS classifiers for distinguishing between MCS and UWS.

Mindfulness meditation increases default mode, salience, and central executive network connectivity

Recent research has begun to identify the neural mechanisms underlying the beneficial impact of mindfulness meditation training (MMT) on health and cognition. However, little is known about the effects of MMT on the global interplay of large-scale networks (LSNs) in the brain. In the present study, healthy, meditation-naïve adults (N = 46) underwent resting state fMRI prior to and upon completing 31 days of MMT or an active control intervention. Independent component analysis, sliding time window, and seed-based correlation analyses were performed to assess training-related changes in functional connectivity (FC) within and between networks with relevance to mindfulness meditation. Across sliding time window analyses and seed-based correlation analyses, we found increased FC between nodes of the default mode network (DMN) and nodes of the salience network (SN) in participants of the MMT. Seed-based correlation analyses revealed further connectivity increases between the SN and key regions of the central executive network (CEN). These results indicate, that, among multiple LSNs, one month of mindfulness meditation effectively increases interconnectivity between networks of the triple network model (DMN, SN, CEN), hereby introducing a potential mechanistic concept underlying the beneficial impact of MMT.Clinical trial registration: This study is listed as a clinical trial on the ISRCTN registry with trial ID ISRCTN95197731 (date of first registration: 15/02/2022).

Covariance-based vs. correlation-based functional connectivity dissociates healthy aging from Alzheimer disease

Prior studies of aging and Alzheimer disease have evaluated resting state functional connectivity (FC) using either seed-based correlation (SBC) or independent component analysis (ICA), with a focus on particular functional systems. SBC and ICA both are insensitive to differences in signal amplitude. At the same time, accumulating evidence indicates that the amplitude of spontaneous BOLD signal fluctuations is physiologically meaningful. We systematically compared covariance-based FC, which is sensitive to amplitude, vs. correlation-based FC, which is not, in affected individuals and controls drawn from two cohorts of participants including autosomal dominant Alzheimer disease (ADAD), late onset Alzheimer disease (LOAD), and age-matched controls. Functional connectivity was computed over 222 regions of interest and group differences were evaluated in terms of components projected onto a space of lower dimension. Our principal observations are: (1) Aging is associated with global loss of resting state fMRI signal amplitude that is approximately uniform across resting state networks. (2) Thus, covariance FC measures decrease with age whereas correlation FC is relatively preserved in healthy aging. (3) In contrast, symptomatic ADAD and LOAD both lead to loss of spontaneous activity amplitude as well as severely degraded correlation structure. These results demonstrate a double dissociation between age vs. Alzheimer disease and the amplitude vs. correlation structure of resting state BOLD signals. Modeling results suggest that the AD-associated loss of correlation structure is attributable to a relative increase in the fraction of locally restricted as opposed to widely shared variance.

Resting-state functional connectivity of the amygdala in major depressive disorder with suicidal ideation

Suicide is a common issue among major depressive disorder (MDD) patients and suicidal ideation (SI) is the first step toward it. There are no definitive objective biomarkers of SI relative to MDD. In this study, a seed-based correlation analysis was performed among 36 MDD patients with SI, 66 MDD patients without SI (NSI), and 57 healthy controls (HCs) using amygdala resting-state functional connectivity (RSFC). Furthermore, the correlation between amygdala RSFC and clinical features was examined in the SI group. When compared to the NSI group, SI group exhibited increased RSFC between the left amygdala seed and left medial superior frontal gyrus (SFGmed) as well as left middle frontal gyrus (MFG). In turn, a decreased RSFC was observed between the left amygdala seed and the following brain regions including the left inferior parietal lobule (IPL), right precentral gyrus (PrCG), and left superior parietal lobule (SPL) in SI group compared to NSI group. Moreover, the SI group exhibited increased RSFC of the right amygdala with left middle temporal gyrus (MTG); In addition, the RSFC of the left amygdala with left MFG was negatively associated with learning and memory (VSM), speed of processing (SOP). The RSFC of the amygdala is distinct between MDD patients with SI and without SI. Our findings reveal the neurobiological characteristics of MDD with respect to SI and provide new clues regarding vulnerability to mental illness. It is necessary to carry out repeated and more longitudinal researches using multimodal approaches on SI in the future.

Subjective Well-Being and Bilateral Anterior Insula Functional Connectivity After Exercise Intervention in Older Adults With Mild Cognitive Impairment.

While it is well known that exercise training is associated with improvement in subjective well-being among older adults, it is unclear if individuals with cognitive impairment experience the same effects elicited by exercise on subjective well-being. We further explored whether the bilateral anterior insula network may be an underlying neural mechanism for the exercise training-related improvements in subjective well-being. We investigated the effects of exercise training on subjective well-being in older adults (78.4 ± 7.1 years) with mild cognitive impairment (MCI; n = 14) and a cognitively normal (CN; n = 14) control group. We specifically assessed the relationship between changes in subjective well-being and changes in functional connectivity (FC) with the bilateral anterior insula from before to after exercise training. Cardiorespiratory fitness, subjective well-being, and resting-state fMRI were measured before and after a 12-week moderate-intensity walking intervention. A seed-based correlation analysis was conducted using the bilateral anterior insula as a priori seed regions of interest. The associations between bilateral anterior insula FC with other brain regions and subjective well-being were computed before and after exercise training, respectively, and the statistical difference between the correlations (before vs after exercise training) was evaluated. There was a significant Group (MCI vs CN) × Time (before vs after exercise training) interaction for subjective well-being, such that while those with MCI demonstrated significantly increased subjective well-being after exercise training, no changes in subjective well-being were observed in CN. Participants with MCI also showed an exercise training-related increase in the bilateral anterior insula FC. While there was no significant correlation between subjective well-being and bilateral anterior insula FC before exercise training, a positive association between subjective well-being and bilateral anterior insula FC was found in the MCI group after exercise training. Our findings indicate that 12 weeks of exercise training may enhance subjective well-being in older adults diagnosed with MCI and, further, suggest that increased bilateral anterior insula FC with other cortical regions may reflect neural network plasticity associated with exercise training-related improvements in subjective well-being.

Early-Life Critical Windows of Susceptibility to Manganese Exposure and Sex-Specific Changes in Brain Connectivity in Late Adolescence

BackgroundEarly-life environmental exposures during critical windows (CWs) of development can impact life course health. Exposure to neuroactive metals such as manganese (Mn) during prenatal and early postnatal CWs may disrupt typical brain development, leading to persistent behavioral changes. Males and females may be differentially vulnerable to Mn, presenting distinctive CWs to Mn exposure. MethodsWe used magnetic resonance imaging to investigate sex-specific associations between early-life Mn uptake and intrinsic functional connectivity in adolescence. A total of 71 participants (15–23 years old; 53% female) from the Public Health Impact of Manganese Exposure study completed a resting-state functional magnetic resonance imaging scan. We estimated dentine Mn concentrations at prenatal, postnatal, and early childhood periods using laser ablation–inductively coupled plasma–mass spectrometry. We performed seed-based correlation analyses to investigate the moderating effect of sex on the associations between Mn and intrinsic functional connectivity adjusting for age and socioeconomic status. ResultsWe identified significant sex-specific associations between dentine Mn at all time points and intrinsic functional connectivity in brain regions involved in cognitive and motor function: 1) prenatal: dorsal striatum, occipital/frontal lobes, and middle frontal gyrus; 2) postnatal: right putamen and cerebellum; and 3) early childhood: putamen and occipital, frontal, and temporal lobes. Network associations differed depending on exposure timing, suggesting that different brain networks may present distinctive CWs to Mn. ConclusionsThese findings suggest that the developing brain is vulnerable to Mn exposure, with effects lasting through late adolescence, and that females and males are not equally vulnerable to these effects. Future studies should investigate cognitive and motor outcomes related to these associations.

The effects of nalmefene on the impulsive and reflective system in alcohol use disorder: A resting-state fMRI study

RationaleCentral aspects of alcohol use disorder (AUD) are the irresistible desire for alcohol and impaired control over its intake. According to the triadic neurocognitive model of addiction, this arises from aberrant functioning of different neural and cognitive systems: an impulsive system, a reflective system, and the abnormal dynamics between both systems based on an insular-dependent system.ObjectivesIn this study, we examined the effects of a single dose of nalmefene on resting-state functional connectivity (rsFC) patterns within and between these addiction-related neural systems in AUD.MethodsNon-treatment seeking participants with AUD (N = 17; 19–66 years, 6 female) took part in a randomized, placebo-controlled, double-blind, crossover study and received either a single dose of 18 mg nalmefene or a placebo. Using seed-based correlation analyses on resting‐state functional magnetic resonance imaging data, we examined the effects of nalmefene on key nodes related to the (1) impulsive system; (2) reflective system; (3) salience network; and (4) default mode network.ResultsUnder nalmefene, participants showed reduced rsFC between components of the impulsive system (Nucleus accumbens–putamen/pallidum/insula). Reduced rsFC was found between elements of the reflective system and impulsive system (orbitofrontal cortex–insula/putamen/pallidum), salience network (orbitofrontal cortex–insula/inferior frontal gyrus), and default mode network (lateral prefrontal cortex–precuneus/cuneus). Components of the salience network showed both increased (anterior cingulate cortex) and decreased (insular cortex) rsFC to elements of the reflective system.ConclusionA single dose of nalmefene impacts rsFC and alters the interaction between key nodes of addiction-related neural systems in non-treatment seeking participants with AUD. Nalmefene may normalize rsFC patterns by weakening the impulsive system while strengthening the reflective system.Trial registration: clinicaltrials.gov: NCT02372318.

Reducing the Effects of Motion Artifacts in fMRI: A Structured Matrix Completion Approach.

Functional MRI (fMRI) is widely used to study the functional organization of normal and pathological brains. However, the fMRI signal may be contaminated by subject motion artifacts that are only partially mitigated by motion correction strategies. These artifacts lead to distance-dependent biases in the inferred signal correlations. To mitigate these spurious effects, motion-corrupted volumes are censored from fMRI time series. Censoring can result in discontinuities in the fMRI signal, which may lead to substantial alterations in functional connectivity analysis. We propose a new approach to recover the missing entries from censoring based on structured low rank matrix completion. We formulated the artifact-reduction problem as the recovery of a super-resolved matrix from unprocessed fMRI measurements. We enforced a low rank prior on a large structured matrix, formed from the samples of the time series, to recover the missing entries. The recovered time series, in addition to being motion compensated, are also slice-time corrected at a fine temporal resolution. To achieve a fast and memory-efficient solution for our proposed optimization problem, we employed a variable splitting strategy. We validated the algorithm with simulations, data acquired under different motion conditions, and datasets from the ABCD study. Functional connectivity analysis showed that the proposed reconstruction resulted in connectivity matrices with lower errors in pair-wise correlation than non-censored and censored time series based on a standard processing pipeline. In addition, seed-based correlation analyses showed improved delineation of the default mode network. These demonstrate that the method can effectively reduce the adverse effects of motion in fMRI analysis.

Brain functional connectivity (FC) invariance and variability under timeseries editing (timeset operation)

Functional connectivity (FC) is defined by temporal correlations between pairwise timeseries signals, thus inheriting the correlation invariance property. In this report, we look into FC properties under versatile timeseries manipulations, as classified into cardinality-preserved or -reduced timeset operations. We show the effect of timeset operations on brain FC mapping by task-evoked and resting-state fMRI experiments through two data analysis methods: seed-based correlation analysis (SCA) and independent component analysis (ICA). The FC invariance and variability were numerically assessed by a spatial correlation (scorr) of a newly generated FC map after timeset operation against a reference of FC map with the original time setting. In the fingertapping task fMRI experiment, the FC invariance under cardinality-preserved timeset operation was verified with a fingertapping motor function (MOT) extracted by SCA (scorr = 1) and by ICA (scorr >0.98). Under timeset deletion editing, ICA yielded more FC variability (scorr <1) than SCA. Similar FC variability behavior was observed with resting-state fMRI experiments. In conclusion, brain FC mapping (networking) is theoretically invariant to arbitrary timepoint reordering during timeseries data preprocessing, and it is generally variant to timepoint reduction editing except for legitimate downsizing as governed by Nyquist sampling theorem and compressive sensing theory.