Cerebral Functional Connectivity Research Articles

The Physiological Mechanisms of Transcranial Direct Current Stimulation to Enhance Motor Performance: A Narrative Review

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that applies a stable, low-intensity (1–2 mA) direct current to modulate neuronal activity in the cerebral cortex. This technique is effective, simple to operate, affordable, and widely employed across various fields. tDCS has been extensively used in clinical and translational research, with growing applications in military and competitive sports domains. In recent years, the use of tDCS in sports science has garnered significant attention from researchers. Numerous studies have demonstrated that tDCS can enhance muscle strength, explosive power, and aerobic metabolism, reduce fatigue, and improve cognition, thereby serving as a valuable tool for enhancing athletic performance. Additionally, recent research has shed light on the physiological mechanisms underlying tDCS, including its modulation of neuronal resting membrane potential to alter cortical excitability, enhancement of synaptic plasticity to regulate long-term potentiation, modulation of neurovascular coupling to improve regional cerebral blood flow, and improvement of cerebral network functional connectivity, which activates and reinforces specific brain regions. tDCS also enhances the release of excitatory neurotransmitters, further regulating brain function. This article, after outlining the role of tDCS in improving physical performance, delves into its mechanisms of action to provide a deeper understanding of how tDCS enhances athletic performance and offers novel approaches and perspectives for physical performance enhancement.

Aberrant brain structural-functional connectivity coupling associated with cognitive dysfunction in different cerebral small vessel disease burdens.

Emerging evidence suggests that cerebral small vessel disease (CSVD) pathology changes brain structural connectivity (SC) and functional connectivity (FC) networks. Although network-level SC and FC are closely coupled in the healthy population, how SC-FC coupling correlates with neurocognitive outcomes in patients with different CSVD burdens remains largely unknown. Using multimodal MRI, we reconstructed whole-brain SC and FC networks for 54 patients with severe CSVD burden (CSVD-s), 106 patients with mild CSVD burden (CSVD-m), and 79 healthy controls. We then investigated the aberrant SC-FC coupling and functional network topology in CSVD and their correlations with cognitive dysfunction. Compared with controls, the CSVD-m patients showed no significant change in any SC-FC coupling, but the CSVD-s patients exhibited significantly decreased whole-brain (p = 0.014), auditory/motor (p = 0.033), and limbic modular (p = 0.011) SC-FC coupling. For functional network topology, despite no change in global efficiency, CSVD-s patients exhibited significantly reduced nodal efficiency of the bilateral amygdala (p = 0.024 and 0.035) and heschl gyrus (p = 0.001 and 0.005). Notably, for the CSVD-s patients, whole-brain SC-FC coupling showed a significantly positive correlation with MoCA (r = 0.327, p = 0.020) and SDMT (r = 0.373, p = 0.008) scores, limbic/subcortical modular SC-FC coupling showed a negative correlation (r = -0.316, p = 0.025) with SCWT score, and global/local efficiency (r = 0.367, p = 0.009 and r = 0.353, p = 0.012) showed a positive correlation with AVLT score. For the CSVD-m group, whole-brain and auditory/motor modular SC-FC couplings showed significantly positive correlations with SCWT (r = 0.217, p = 0.028 and r = 0.219, p = 0.027) and TMT (r = 0.324, p = 0.001 and r = 0.245, p = 0.013) scores, and global/local efficiency showed positive correlations with AVLT (r = 0.230, p = 0.020 and r = 0.248, p = 0.012) and SDMT (r = 0.263, p = 0.008 and r = 0.263, p = 0.007) scores. Our findings demonstrated that decreased whole-brain and module-dependent SC-FC coupling associated with reduced functional efficiency might underlie more severe burden and worse cognitive decline in CSVD. SC-FC coupling might serve as a more sensitive neuroimaging biomarker of CSVD burden and provided new insights into the pathophysiologic mechanisms of clinical development of CSVD.

Functional connectivity and cerebral cortex activation during the resting state and verbal fluency tasks for patients with mild cognitive impairment, Lewy body dementia, and Alzheimer's disease: A multi-channel fNIRS study

ObjectiveTo explore changes in cerebral cortex activation and functional connectivity during resting-state and verbal fluency tasks in patients with different types of dementia. MethodsWe recorded oxygenated hemoglobin concentration (HbO) signals detected by functional near-infrared spectroscopy (fNIRS) from the prefrontal cortex, partial parietal cortex, and cortex of the temporal lobe in four groups of participants: mild cognitive impairment (MCI), Lewy body dementia (LBD), Alzheimer's disease (AD), and cognitively normal (CN). ResultsThe study recruited 120 older adults with MCI (n = 30), LBD (n = 28), AD (n = 30), or CN (n = 32). The mean functional connectivity of the frontal and temporal lobe in resting state was significantly less in the AD (0.19 ± 0.11) group than in the MCI (0.23 ± 0.11), LBD (0.29 ± 0.12), and CN (0.40 ± 0.11) groups (p < 0.001). Further, the mean HbO concentrations in the brain regions and channels were significantly lower in the AD group than in the LBD and MCI groups (p < 0.001). Cognitive levels correlated significantly with the mean HbO concentrations in the resting state and verbal fluency task conditions. ConclusionThe fNIRS HbO signals significantly differed in the cerebral cortex regions in participants with different types of dementia. These findings suggest that fNIRS can effectively enhance the differential diagnosis and assessment of dementia.

A phase 2, open-label study of anti-inflammatory NE3107 in patients with dementias.

Alzheimer's disease (AD) is a progressive, multifactorial, neurodegenerative disorder affecting >6 million Americans. Chronic, low-grade neuroinflammation, and insulin resistance may drive AD pathogenesis. We explored the neurophysiological and neuropsychological effects of NE3107, an oral, anti-inflammatory, insulin-sensitizing molecule, in AD. In this phase 2, open-label study, 23 patients with mild cognitive impairment or mild dementia received 20-mg oral NE3107 twice daily for 3 months. Primary endpoints assessed changes from baseline in neurophysiological health and oxidative stress (glutathione level) using advanced neuroimaging analyses. Secondary endpoints evaluated changes from baseline in neuropsychological health using cognitive assessments, including the 11-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment, Clinical Dementia Rating, Quick Dementia Rating Scale, Alzheimer's Disease Composite Score, and Global Rating of Change (GRC). Exploratory endpoints assessed changes from baseline in neuroinflammation biomarkers (tumor necrosis factor alpha, TNF-α) and AD (amyloid beta and phosphorylated tau [P-tau]). NE3107 was associated with clinician-rated improvements in cerebral blood flow and functional connectivity within the brain. In patients with MMSE ≥ 20 (mild cognitive impairment to mild AD; n = 17), NE3107 was associated with directional, but statistically nonsignificant, changes in brain glutathione levels, along with statistically significant improvements in ADAS-Cog11 (P = .017), Clinical Dementia Rating (P = .042), Quick Dementia Rating Scale (P = .002), Alzheimer's Disease Composite Score (P = .0094), and clinician-rated GRC (P < .001), as well as in cerebrospinal fluid P-tau levels (P = .034) and P-tau:amyloid beta 42 ratio (P = .04). Biomarker analyses also demonstrated directional, but statistically non-significant, changes in plasma TNF-α, consistent with the expected mechanism of NE3107. Importantly, we observed a statistically significant correlation (r = 0.59) between improvements in TNF-α levels and ADAS-Cog11 scores (P = .026) in patients with baseline MMSE ≥ 20. Our results indicate that in this study NE3107 was associated with what appear to be positive neurophysiological and neuropsychological findings, as well as evidence of improvement in biomarkers associated with neuroinflammation and AD in patients diagnosed with dementia. Our findings are consistent with previous preclinical and clinical observations and highlight a central role of neuroinflammation in AD pathogenesis.

Phenomena of hypo- and hyperconnectivity in basal ganglia-thalamo-cortical circuits linked to major depression: a 7T fMRI study.

Major depressive disorder (MDD) typically manifests itself in depressed affect, anhedonia, low energy, and additional symptoms. Despite its high global prevalence, its pathophysiology still gives rise to questions. Current research places alterations in functional connectivity among MDD's most promising biomarkers. However, given the heterogeneity of previous findings, the use of higher-resolution imaging techniques, like ultra-high field (UHF) fMRI (≥7 Tesla, 7T), may offer greater specificity in delineating fundamental impairments. In this study, 7T UHF fMRI scans were conducted on 31 MDD patients and 27 age-gender matched healthy controls to exploratorily contrast cerebral resting-state functional connectivity patterns between both groups. The CONN toolbox was used to generate functional network connectivity (FNC) analysis based on the region of interest (ROI)-to-ROI correlations in order to enable the identification of clusters of significantly different connections. Correction for multiple comparisons was implemented at the cluster level using a false discovery rate (FDR). The analysis revealed three significant clusters differentiating MDD patients and healthy controls. In Clusters 1 and 2, MDD patients exhibited between-network hypoconnectivity in basal ganglia-cortical pathways as well as hyperconnectivity in thalamo-cortical pathways, including several individual ROI-to-ROI connections. In Cluster 3, they showed increased occipital interhemispheric within-network connectivity. These findings suggest that alterations in basal ganglia-thalamo-cortical circuits play a substantial role in the pathophysiology of MDD. Furthermore, they indicate potential MDD-related deficits relating to a combination of perception (vision, audition, and somatosensation) as well as more complex functions, especially social-emotional processing, modulation, and regulation. It is anticipated that these findings might further inform more accurate clinical procedures for addressing MDD.

Can transcranial photobiomodulation improve cognitive function in TBI patients? A systematic review.

Transcranial photobiomodulation (tPBM) is a non-invasive neuromodulation technology which has become a promising therapy for treating many brain diseases. Although it has been confirmed in studies targeting neurological diseases including Alzheimer's and Parkinson's that tPBM can improve cognitive function, the effectiveness of interventions targeting TBI patients remains to be determined. This systematic review examines the cognitive outcomes of clinical trials concerning tPBM in the treatment of traumatic brain injury (TBI). We conducted a systematic literature review, following the PRISMA guidelines. The PubMed, Web of Science, Scopus, EMBASE, and Cochrane Library databases were searched before October 31, 2023. The initial search retrieved 131 articles, and a total of 6 studies were finally included for full text-analysis after applying inclusion and exclusion criteria. Results showed improvements in cognition for patients with chronic TBI after tPBM intervention. The mechanism may be that tPBM increases the volume of total cortical gray matter (GM), subcortical GM, and thalamic, improves cerebral blood flow (CBF), functional connectivity (FC), and cerebral oxygenation, improving brain function. However, due to the significant heterogeneity in application, we cannot summarize the optimal parameters for tPBM treatment of TBI. In addition, there is currently a lack of RCT studies in this field. Therefore, given this encouraging but uncertain finding, it is necessary to conduct randomized controlled clinical trials to further determine the role of tPBM in cognitive rehabilitation of TBI patients.

Cerebral cortex activation and functional connectivity during low-load resistance training with blood flow restriction: An fNIRS study.

Despite accumulating evidence that blood flow restriction (BFR) training promotes muscle hypertrophy and strength gain, the underlying neurophysiological mechanisms have rarely been explored. The primary goal of this study is to investigate characteristics of cerebral cortex activity during BFR training under different pressure intensities. 24 males participated in 30% 1RM squat exercise, changes in oxygenated hemoglobin concentration (HbO) in the primary motor cortex (M1), pre-motor cortex (PMC), supplementary motor area (SMA), and dorsolateral prefrontal cortex (DLPFC), were measured by fNIRS. The results showed that HbO increased from 0 mmHg (non-BFR) to 250 mmHg but dropped sharply under 350 mmHg pressure intensity. In addition, HbO and functional connectivity were higher in M1 and PMC-SMA than in DLPFC. Moreover, the significant interaction effect between pressure intensity and ROI for HbO revealed that the regulation of cerebral cortex during BFR training was more pronounced in M1 and PMC-SMA than in DLPFC. In conclusion, low-load resistance training with BFR triggers acute responses in the cerebral cortex, and moderate pressure intensity achieves optimal neural benefits in enhancing cortical activation. M1 and PMC-SMA play crucial roles during BFR training through activation and functional connectivity regulation.

Aberrant cerebral blood flow and functional connectivity in patients with vestibular migraine: a resting-state ASL and fMRI study

BackgroundPrior neuroimaging studies on vestibular migraine (VM) have extensively certified the functional and structural alterations in multiple brain regions and networks. However, few studies have assessed the cerebral blood flow (CBF) in VM patients using arterial spin labeling (ASL). The present study aimed to investigate CBF and functional connectivity (FC) alterations in VM patients during interictal periods.MethodsWe evaluated 52 VM patients and 46 healthy controls (HC) who received resting-state pseudo-continuous ASL and functional magnetic resonance imaging (fMRI) scanning. Comparisons of voxel-based CBF and seed-based FC were performed between the two groups. Brain regions showed significant group differences in CBF analyses were chosen as seeds in FC analyses. Additionally, the associations between abnormal imaging results and clinical features were explored.ResultsCompared with HC, VM patients showed higher normalized CBF in the right precentral gyrus (PreCG), left postcentral gyrus (PostCG), left superior frontal gyrus and bilateral insular (p < 0.05, FDR corrected). Furthermore, VM patients exhibited increased FC between the right PreCG and areas of the left PostCG, left cuneus and right lingual gyrus (p < 0.05, FDR corrected). In addition, we observed decreased FC between the left insular and regions of the left thalamus and right anterior cingulate cortex, as well as increased FC between the left insular and right fusiform gyrus in VM patients (p < 0.05, FDR corrected). Moreover, these variations in brain perfusion and FC were significantly correlated with multiple clinical features including frequency of migraine symptoms, frequency of vestibular symptoms and disease duration of VM (all p < 0.05).ConclusionsPatients with VM during interictal period showed hyperperfusion and abnormal resting-state FC in brain regions potentially contributed to disrupted multi-sensory and autonomic processing, as well as impaired ocular motor control, pain modulation and emotional regulation. Our study provided novel insights into the complex neuropathology of VM from a CBF perspective.

Robot-assisted gait training improves walking and cerebral connectivity in children with unilateral cerebral palsy.

Robot-assisted gait training (RAGT) is promising to help walking rehabilitation in cerebral palsy, but training-induced neuroplastic effects have little been investigated. Forty unilateral cerebral palsy children aged 4-18 years were randomly allocated in a monocentric study to ten 20-minute RAGT sessions with the G-EO system, five days a week (n = 20) or to a control group (who continued conventional care with six 30-minute physiotherapy sessions, three days a week) (n = 20), two weeks running, from September 2020 to December 2021. Clinical and MRI outcomes were compared before and one month after therapy. The primary outcome was gait speed. Secondary outcomes were a 6-minute walking test distance, Gross Motor Function Measure-88 (GMFM-88) dimensions D and E, Patient Global Impression of Improvement, resting-state functional connectivity within the sensorimotor network, and structural connectivity in the corticospinal tracts. Gait speed and the 6-minute walking test distance improved more after RAGT. Resting-state functional connectivity increased after RAGT but decreased in controls between superior and lateral healthy or lateral injured sensorimotor networks. GMFM-88 and structural connectivity in corticospinal tracts were unchanged. Impression of improvement in children was better after RAGT. Short-term benefit of repetitive RAGT on walking abilities and functional cerebral connectivity was found in unilateral cerebral palsy children. Short-term repetitive robot-assisted gait training improves gait speed and walking resistance and increases cerebral functional connectivity in unilateral cerebral palsy. GMFM dimensions D and E were unchanged after short-term repetitive robot-assisted gait training in unilateral cerebral palsy.

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.

Disruption of Resting-State Functional Connectivity in Acute Ischemic Stroke: Comparisons Between Right and Left Hemispheric Insults.

Few resting-state functional magnetic resonance imaging (RS-fMRI) studies evaluated the impact of acute ischemic changes on cerebral functional connectivity (FC) and its relationship with functional outcomes after acute ischemic stroke (AIS), considering the side of lesions. To characterize alterations of FC of patients with AIS by analyzing 12 large-scale brain networks (NWs) with RS-fMRI. Additionally, we evaluated the impact of the side (right (RH) or left (LH) hemisphere) of insult on the disruption of brain NWs. 38 patients diagnosed with AIS (17 RH and 21 LH) who performed 3T MRI scans up to 72h after stroke were compared to 44 healthy controls. Images were processed and analyzed with the software toolbox UF2C with SPM12. For the first level, we generated individual matrices based on the time series extraction from 70 regions of interest (ROIs) from 12 functional NWs, constructing Pearson's cross-correlation; the second-level analysis included an analysis of covariance (ANCOVA) to investigate differences between groups. The statistical significance was determined with p < 0.05, after correction for multiple comparisons with false discovery rate (FDR) correction. Overall, individuals with LH insults developed poorer clinical outcomes after six months. A widespread pattern of lower FC was observed in the presence of LH insults, while a contralateral pattern of increased FC was identified in the group with RH insults. Our findings suggest that LH stroke causes a severe and widespread pattern of reduction of brain networks' FC, presumably related to the impairment in their long-term recovery.

Focal tDCS of auditory cortex in chronic tinnitus: A randomized controlled mechanistic trial

ObjectiveThe goal of this pilot study was to understand how focal transcranial direct current stimulation (tDCS) targeting auditory cortex changes brain function in chronic tinnitus using magnetic resonance imaging (MRI). MethodsPeople with chronic tinnitus were randomized to active or sham tDCS on five consecutive days in this mechanistic trial (n = 10/group). Focal 4x1 tDCS (central anode, surround cathodes) targeted left auditory cortex, with single-blind 2 mA current during twenty-minute sessions. Arterial spin-labeled and blood oxygenation level dependent MRI occurred immediately before and after the first tDCS session, and tinnitus symptoms were measured starting one week before the first tDCS session and through four weeks after the final session. ResultsAcute increases in cerebral blood flow and functional connectivity were noted in auditory cortex after the first active tDCS session. Reduced tinnitus loudness ratings after the final tDCS session correlated with acute change in functional connectivity between an auditory network and mediodorsal thalamus and prefrontal cortex. Reduced tinnitus intrusiveness also correlated with acute change in connectivity between precuneus and an auditory network. ConclusionsFocal auditory-cortex tDCS can influence function in thalamus, auditory, and prefrontal cortex, which may associate with improved tinnitus. SignificanceWith future refinement, tDCS targeting auditory cortex could become a viable intervention for tinnitus.

Stroke patients have lower blood levels of nutrients that are relevant for recovery: a systematic review and meta-analysis

BackgroundMalnutrition is common after stroke. Stroke patients often have a suboptimal energy intake, body weight and inadequate blood nutrient levels. Nutrient insufficiencies may not be detected, but their recognition is essential to provide adequate nutritional support after a stroke. This comprehensive summary of the literature is a collection of data on blood levels of a broad selection of nutrients involved in restoring cerebral blood flow and functional brain connectivity in stroke patients compared to controls.MethodsEmbase and MEDLINE were searched for studies published in English in the period 1980–2022. Studies including adult stroke subjects and controls whose blood samples were analyzed for docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), uridine, choline, folate, vitamin B6, vitamin B12, vitamin C, vitamin E, selenium, coenzyme Q10 (CoQ10), carnitine, arginine, or taurine were selected. If there were &amp;gt;3 reports (k) per nutrient, results were generated with an unadjusted and age-adjusted random-effects meta-analysis model. Risk of bias was evaluated for relevant domains from the ROBINS-I tool and with Egger's test.ResultsOne hundred five reports on blood nutrient levels were extracted from 56 eligible studies. Overall, meta-analyses showed lower blood levels of most nutrients in stroke patients compared to controls. The number of reports and the statistical significance for the unadjusted data were: folate (k = 27; p = 0.005), vitamin B12 (k = 23; p = 0.002), vitamin E (k = 11; p = 0.013), DHA (k = 7, p = 0.015), EPA (k = 7; p = 0.004), vitamin C (k = 6; p = 0.020), and selenium (k = 6; p = 0.018). No significant decreases were observed for vitamin B6 (k = 6; p = 0.52) and arginine (k = 4; p = 0.93). For other selected nutrients, there were insufficient reports to perform a meta-analysis. Available reports pointed toward lower (CoQ10, choline; k = 2), higher (taurine; k = 2), or unchanged (carnitine, uridine; k = 1) blood levels after stroke. In general, risk of bias was low.ConclusionOur findings indicate that nutrient insufficiencies occur for many nutrients that are involved in repair processes after stroke. The low blood levels of folate, vitamin B12, EPA, DHA, vitamin C, vitamin E, selenium, and possibly CoQ10 and choline, highlight the presence of a suboptimal nutritional status after stroke. The inclusion of targeted nutritional interventions to further support recovery should receive consideration in the multidisciplinary context of stroke rehabilitation.

Arterial spin labeling reveals disordered cerebral perfusion and cerebral blood flow-based functional connectivity in primary open-angle glaucoma

PurposePrimary open-angle glaucoma (POAG) is a widespread neurodegenerative condition affecting brain regions involved in visual processing, somatosensory processing, motor control, emotional regulation and cognitive functions. Cerebral hemodynamic dysfunction contributes to the pathogenesis of glaucomatous neurodegeneration. We aimed to investigate cerebral blood flow (CBF) redistributed patterns in visual and higher-order cognitive cortices and its relationship with clinical parameters in POAG, and we hypothesized that CBF changes together across regions within the same functional network.MethodsForty-five POAG patients and 23 normal controls underwent three-dimensional pseudocontinuous arterial spin labeling MRI to measure the resting-state CBF. Group comparisons of CBF and correlations between CBF changes and ophthalmological and neuropsychological indices were assessed. We determined CBF-based functional connectivity (CBFC) by calculating the correlations between specific regions and all other brain voxels and compared CBFC differences between groups.ResultsThe patients exhibited decreased CBF in visual cortices, postcentral gyrus, inferior parietal lobule and cerebellum and increased CBF in medial, middle, and superior frontal gyri, as well as the insula. The reduced CBF in the visual cortices positively correlated with visual field defect (r = 0.498, p = 0.001) in POAG patients, while the increased CBF in the right medial frontal gyrus was negatively associated with the visual field defect (r = −0.438, p = 0.004) and positively associated with the cup-to-disc ratio (r = 0.469, p = 0.002). POAG patients showed negative connections weakening or converting to mild positive connections, as well as positive connections converting to negative connections.ConclusionsRegional and interregional CBF properties confirmed that the aberrant brain regions extend beyond the visual pathway, including the somatosensory, emotional and cognitive networks, which highlights the importance of cerebral hemodynamic dysfunction in the pathophysiology of spreading neurodegeneration in POAG.

Functional Connectivity Change Associated With Apolipoprotein E Allotypes Precedes Structural Connectivity and Neurodegeneration in Cognitive Normal Older Adults Without Cerebral Aβ Deposition.

Apolipoprotein E (APOE) gene is known to influence cerebral functional connectivity (FC) in Alzheimer's disease continuum. We investigated association between APOE allotypes and FC, structural connectivity, and cortical thickness in amyloid-PET negative cognitive normal older adults (CN). A total of 188 CN (37 had ε2/ε2 or ε2/ε3 [ε2 group], 113 had ε3/ε3 [ε3 group], and 38 had ε3/ε4 or ε4/ε4 [ε4 group]) were recruited. Voxel-based morphometry and cortical thickness analysis were used to investigate differences in cortical thickness between three APOE allotypes. To investigate integrity of structural connectivity, we analyzed diffusion weighted imaging using fractional anisotropy and mean diffusivity. In terms of FC, differences of FC in default mode network (DMN) among APOE allotypes were measured using functional magnetic resonance imaging. There were no significant differences in age, sex, education, cerebral beta-amyloid (Aβ) deposition severity, or neuropsychological profiles. No significant differences were found in cortical thickness and structural connectivity among the APOE allotypes. However, FC within the DMN was significantly lower in ε4 and ε2 carriers compared to ε3 homozygotes. This study suggests that both ε4 and ε2 exhibit APOE-associated DMN FC changes before Aβ deposition, structural changes, and neurodegeneration.

Regional cerebral metabolism alterations and functional connectivity in individuals with opioid use disorder: An integrated resting-state PET/fMRI study

Individuals with opioid use disorder (OUD) have been reported to show abnormal brain metabolism and impaired coupling among brain networks such as the default mode network (DMN), salience network (SN), and executive control network (ECN). However, the characteristics of brain glucose metabolism and its related functions in the brain networks in individuals with OUD remain unknown. Thirty-six individuals with OUD and thirty matched healthy controls (HCs) were recruited in this integrated positron emission tomography/magnetic resonance imaging (PET/MRI) study. Differences in glucose metabolism were analyzed by using 18F-fluorodeoxyglucose (18F-FDG), and the corresponding coupling characteristics of the individuals with OUD were also analyzed. The individuals with OUD showed widespread bilateral hypometabolism in the middle temporal gyrus (MTG), superior temporal gyrus, angular gyrus, supramarginal gyrus, inferior parietal lobe, Rolandic operculum, and left insula, but obvious hypermetabolism in the brainstem and left cerebellum. Meanwhile, in individuals with OUD, the hypometabolism of right MTG which is included in the DMN was accompanied by decreased coupling with the left superior frontal gyrus and right superior parietal gyrus which are included in the ECN. Furthermore, individuals with OUD showed a positive correlation between the duration of heroin use and glucose metabolism of the left MTG. The individuals with OUD were characterized by widespread bilateral hypometabolism in the temporal and parietal regions but obvious hypermetabolism in the brainstem and left cerebellum. The results suggest that the hypometabolism in the temporal and parietal regions might be related to DMN dysfunction and the hypermetabolism in the brainstem and left cerebellum may be compensate for other brain regions showing hypometabolism. In particular, hypometabolism in the self-referential-related DMN regions in OUD might attenuate their relationships with the inhibitory-control-related ECN regions. These findings highlight the importance of evaluating the metabolic and functional profiles of the right MTG in future studies on the treatment of OUD.

Uncovering neural pathways underlying bulimia nervosa: resting-state neural connectivity disruptions correlate with maladaptive eating behaviors

PurposeBulimia nervosa (BN) is characterized by recurrent binge-eating episodes and inappropriate compensatory behaviors. This study investigated alterations in resting-state surface-based neural activity in BN patients and explored correlations between brain activity and eating behavior.MethodsA total of 26 BN patients and 28 healthy controls were enrolled. Indirect measurement of cerebral cortical activity and functional connectivity (FC) analyses were performed in Surfstat. A principal component analysis (PCA) model was used to capture the commonalities within the behavioral questionnaires from the BN group.ResultsCompared with the healthy control group, the BN group showed decreased surface-based two-dimensional regional homogeneity in the right superior parietal lobule (SPL). Additionally, the BN group showed decreased FC between the right SPL and the bilateral lingual gyrus and increased FC between the right SPL and the left caudate nucleus and right putamen. In the FC–behavior association analysis, the second principal component (PC2) was negatively correlated with FC between the right SPL and the left caudate nucleus. The third principal component (PC3) was negatively correlated with FC between the right SPL and the left lingual gyrus and positively correlated with FC between the right SPL and the right lingual gyrus.ConclusionWe revealed that the right SPL undergoes reorganization with respect to specific brain regions at the whole-brain level in BN. In addition, our results suggest a correlation between brain reorganization and maladaptive eating behavior. These findings may provide useful information to better understand the neural mechanisms of BN.Level of evidenceV, descriptive study.

Resting-state cerebral blood flow and functional connectivity abnormalities in depressed patients with childhood maltreatment: Potential biomarkers of vulnerability?

Childhood maltreatment (CM) is an important risk factor for major depressive disorder (MDD). This study aimed to explore the specific effect of CM on cerebral blood flow (CBF) and brain functional connectivity (FC) in MDD patients. A total of 150 subjects were collected including 55 MDD patients with CM, 34 MDD patients without CM, 19 healthy controls (HC) with CM, and 42 HC without CM. All subjects completed MRI scans and neuropsychological tests. Two-way analysis of covariance was used to detect the main and interactive effects of disease and CM on CBF and FC across subjects. Then, partial correlation analyses were conducted to explore the behavioral significance of altered CBF and FC in MDD patients. Finally, a support vector classifier model was applied to differentiate MDD patients. MDD patients represented increased CBF in bilateral temporal lobe and decreased CBF in right visual cortex. Importantly, significant depression-by-CM interactive effects on CBF were primarily located in the frontoparietal regions, including orbitofrontal cortex (OFC), lateral prefrontal cortex (PFC), and parietal cortex. Moreover, significant FC abnormalities were seen in OFC-PFC and frontoparietal-visual cortex. Notably, the abnormal CBF and FC were significantly associated with behavioral performance. Finally, a combination of altered CBF and FC behaved with a satisfactory classification ability to differentiate MDD patients. These results highlight the importance of frontoparietal and visual cortices for MDD with CM experience, proposing a potential neuroimaging biomarker for MDD identification.

Changes of cerebral functional connectivity induced by foot reflexology in a RCT

Non-Pharmacological Interventions (NPIs) are increasingly being introduced into healthcare, but their mechanisms are unclear. In this study, 30 healthy participants received foot reflexology (FR) and sham massage, and went through a resting-state functional magnetic resonance imaging (rs-fMRI) to evaluate NPIs effect on brain. Rs-fMRI revealed an effect of both NPIs on functional connectivity with changes occurring in the default-mode network, the sensorimotor network and a Neural Network Correlates of Pain (NNCP—a newly discovered network showing great robustness). Even if no differences were found between FR and SM, this study allowed to report brain biomarkers of well-being as well as the safety of NPIs. In further research, it could be relevant to study it in patients to look for a true reflexology induced-effect dependent of patient reported outcomes. Overall, these findings enrich the understanding of the neural correlates of well-being experienced with NPIs and provided insight into the basis of the mechanisms of NPIs.

Functional Near-Infrared Spectroscopy-Based Evidence of the Cerebral Oxygenation and Network Characteristics of Upper Limb Fatigue.

The objective of this research is to better understand the effects of upper limb fatigue on the cerebral cortex. The aim of this study was to investigate the characteristics of cerebral oxygenation and cortical functional connectivity in healthy adults after upper limb fatigue using functional near-infrared spectroscopy (fNIRS). Nineteen healthy adults participated in this study. The participants began exercising on an arm crank ergometer with no load, which was then increased by 0.2 kg per minute, maintaining a speed of at least 90 revolutions per minute during the exercise. Functional near-infrared spectroscopy covering the prefrontal cortex and motor area was used to monitor brain activity during rest and exercise. Heart rate and RPE were monitored during exercise to evaluate the degree of fatigue. Paired-sample t-tests were used to examine differences in the concentration of oxygenated hemoglobin (HbO2) and functional connectivity before and after fatigue. All participants completed the exercise test that induced fatigue. We observed a significant decrease in HbO2 levels in the prefrontal and motor areas after exercise. In addition, brain network features showed a significant decrease in functional connectivity between the left and right motor cortices, between the motor and prefrontal cortices, and between both prefrontal cortices after fatigue. This study demonstrates that, in healthy adults, exercise-induced fatigue in the upper limbs significantly affects brain function. In particular, it leads to reduced functional connectivity between the motor cortex and the prefrontal cortex.