Oxytocin enhances the triangular association among behavior, resting-state, and task-state functional connectivity.

<bold>Objective</bold> To observe the differences in brain network activation and functional connectivity of patients with post-stroke cognitive impairment (PSCI) of different severity using functional near-infrared spectroscopy (fNIRS). <bold>Methods</bold> A total of 40 stroke patients in the outpatient and inpatient Rehabilitation Department in the Pudong District of Huashan Hospital, Fudan University from April to November 2020 were recruited and divided into normal group (<italic>n</italic>=14), mild to moderate group (<italic>n</italic>=11) and severe group (<italic>n</italic>=15) according to the mini-mental state examination (MMSE) score. Fugl-Meyer assessment scale (FMA) and functional comprehensive assessment (FCA) were used to evaluate the motor function of upper and lower limbs; 64-channel fNIRS functional imaging device was used to collect the resting-state brain network data of patients. The whole brain functional connectivity was analyzed based on oxyhemoglobin (HbO₂) and deoxyhemoglobin (HbR). Differences in functional connectivity strengths between homologous and heterologous brain networks in dorsal attention network (DAN), sensorimotor network (SEN), ventral attention network (VAN), frontoparietal network (FPN), default mode network (DMN) and visual network (VIS) regions were analyzed. <bold>Results</bold> (1) Motor function: there was no significant difference in FMA and FCA scores in three groups (<italic>P</italic>&gt;0.05). (2) Whole brain functional connectivity and strength of homologous brain network functional connectivity: there was no significant difference in whole brain functional connectivity based on HbO₂ and HbR in three groups (<italic>P</italic>&gt;0.05). Compared with the normal group, there were significant differences in the strength of functional connectivity of the in the SEN and FPN regions of the HbO₂-based homologous brain network in the severe group (<italic>P</italic>&lt;0.05), but there were no significant differences in the regions of interest of the HbR-based homologous brain network in the three groups (<italic>P</italic>&gt;0.05). (3) Functional connectivity strength of heterologous brain networks: compared with the normal group, the functional connectivity of SEN-VAN, SEN-DMN, SEN-FPN, VAN-FPN and DMN-FPN in the severe group decreased significantly, and the differences were statistically significant (<italic>P</italic>&lt;0.05). Compared with the mild to moderate group, the functional connectivity of SEN-DAN and SEN-FPN in the severe group decreased significantly, and the differences were statistically significant (<italic>P</italic>&lt;0.05). There was no significant difference of strength of functional connectivity based on HbR in the three groups (<italic>P</italic>&gt;0.05). (4) Correlation analysis between SEN-FPN heterologous functional connectivity and MMSE, FCA scores: MMSE score (<italic>r</italic>=0.32, <italic>P</italic>&lt;0.05) and FCA score (<italic>r</italic>=0.38, <italic>P</italic>&lt;0.05) were positively correlated with SEN-FPN functional connectivity. <bold>Conclusion</bold> The SEN-FPN functional connectivity may play an important role in the cognitive function of stroke patients. Altered functional connectivity patterns of SEN-FPN may be closely related to the occurrence and progression of PSCI, and changes in functional connectivity strength of SEN-FPN may be a potential imaging indicator of PSCI.

Developmental changes in large-scale network connectivity in autism

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.

The current study examined the effects of a 16-week creative expression program on brain activity during a story creating task and resting-state functional network connectivity in mild cognitive impairment (MCI) adults. Thirty-six MCI adults were allocated to either the creative expression program (CrExp, n = 18) or control group (CG,n = 18). Before and after intervention, all participants were scanned with functional magnetic resonance imaging (fMRI) during story creating task performance and a resting state. The two-group comparison was calculated between the blood oxygenation level-dependent (BOLD) signal changes for each cluster to investigate the differences in fMRI activation and functional connectivity (FC) between two groups. Task activation analyses showed an increase in the right anterior cingulate gyrus (ACG), right medial frontal gyrus (MFG), right lentiform nucleus (LN), left hippocampus(HIP), left middle occipital gyrus (MOG), and left cerebellum posterior lobe (CPL) (p < 0.05). Story creating performance improvements were associated with greater activation in the left HIPregion. Resting-state functional connectivity (FC) between left HIP and certain other brain areas shown a significant interaction of creative expression group versus control group. Moreover, connectivity between the right angular gyrus (ANG), right inferior temporal gyrus (ITG), right superior occipital gyrus (SOG), left ANG, and left MFGwere related to improved cognitive performance (p < 0.05). These data extend current knowledge by indicating that the creative expression program can improve cognitive activation in MCI, and these enhancements may be related to the neurocognitive network plasticity changes induced by creative expression training.

A wealth of neuroscience evidence demonstrates that diet and nutrition play an important role in structural brain plasticity, promoting the development of gray matter volume and maintenance of white matter integrity across the lifespan. However, the role of nutrition in shaping individual differences in the functional brain connectome remains to be well established. We therefore investigated whether nutrient biomarkers known to have beneficial effects on brain structure (i.e., the omega-3 polyunsaturated fatty acids; ω-3 PUFAs), explain individual differences in functional brain connectivity within healthy older adults (N = 96). Our findings demonstrate that ω-3 PUFAs are associated with individual differences in functional connectivity within regions that support executive function (prefrontal cortex), memory (hippocampus), and emotion (amygdala), and provide key evidence that the influence of these regions on global network connectivity reliably predict general, fluid, and crystallized intelligence. The observed findings not only elucidate the role of ω-3 PUFAs in functional brain plasticity and intelligence, but also motivate future studies to examine their impact on psychological health, aging, and disease.

Mainero C, Boshyan J, Hadjikhani N. Altered functional magnetic resonance imaging resting-state connectivity in periaqueductal gray networks in migraine. Annals of Neurology 2011;70:838-845. Objective: The periaqueductal gray matter (PAG), a known modulator of somatic pain transmission, shows evidence of interictal functional and structural abnormalities in migraineurs, which may contribute to hyperexcitability along spinal and trigeminal nociceptive pathways, and lead to the migraine attack. The aim of this study was to examine functional connectivity of the PAG in migraine. Methods: Using resting-state functional MRI, we compared functional connectivity between PAG and a subset of brain areas involved in nociceptive/somatosensory processing and pain modulation in 17 subjects with migraine, during a pain-free state, versus 17 genderand age-matched controls. We also assessed the relation between intrinsic resting-state correlations within PAG networks and the average monthly frequency of migraine attacks, as well as allodynia. Results: Our findings show stronger connectivity between the PAG and several brain areas within nociceptive and somatosensory processing pathways in migraineurs versus controls. In addition, as the monthly frequency of migraine attacks worsens, the strength of the connectivity in some areas within these pathways increases, whereas a significant decrease in functional resting-state connectivity between the PAG and brain regions with a predominant role in pain modulation (prefrontal cortex, anterior cingulate, amygdala) can be evidenced. Finally, migraineurs with a history of allodynia exhibit significantly reduced connectivity between PAG, prefrontal regions, and anterior cingulate compared to migraineurs without allodynia. Interpretation: These data reveal interictal dysfunctional dynamics within pain pathways in migraine manifested as an impairment of the descending pain modulatory circuits, likely leading to loss of pain inhibition, and hyperexcitability primarily in nociceptive areas. Comments: Functional neuroimaging techniques have helped elucidate the underlying physiology of migraines. Unlike traditional functional magnetic resonance imaging scans done during a task, resting state functional connectivity is a relatively new neuroimaging technique in which participants are scanned at rest, and the lowfrequency spontaneous fluctuations found to be highly correlated are thought to represent brain areas that are functionally connected at baseline. Mainero et al recently conducted this study to assess the functional connectivity of the periaqueductal gray (PAG) (a region previously implicated in the pathogenesis of migraine) to other brain regions in 17 migraineurs interictally compared with 17 age-/gendermatched controls. They found that compared with the controls, the migraineurs had increased resting state functional connectivity between the PAG, and somatosensory and nociceptive processing pathways. The connections between the PAG and the supramarginal gyrus, anterior insula, and hypothalamus were increased in migraineurs with more frequent attacks, while the connections between PAG and the prefrontal cortex, anterior cingulate, amygdala, and medial thalamus were decreased in migraineurs with more frequent attacks. The 5 migraineurs with allodynia also had significantly reduced connectivity between the PAG and the anterior insula, anterior cingulate, and prefrontal cortex vs genderand age-matched migraineurs without allodynia. This study is one of the first to use resting state functional connectivity analyses to compare the intrinsic neural connections in migraineurs vs controls. As expected, many of the connections between the PAG, and nociceptive and sensory processing pathways were increased in the migraineurs, and some of those connections were stronger in those with more frequent attacks. However, unexpectedly, those with more frequent migraines and those with allodynia had decreased connections between the PAG and areas involved in the cognitive modulation of pain. This suggests that From the Graham Headache Center, Faulkner/Brigham and Women’s Hospital, Boston, MA,

Fatigue is commonly observed in pediatric multiple sclerosis (pedMS) patients, but its underlying mechanisms remain largely unexplored. We evaluated whether resting-state (RS) functional connectivity (FC) abnormalities in monoaminergic networks contributed to explain fatigue in pedMS. Fifty-five pedMS and twenty-three matched healthy controls (HC) underwent clinical and RS functional MRI assessment. Patients with Fatigue Severity Scale (FSS) score ≥ 4 were classified as fatigued (F). Patterns of dopamine-, noradrenaline- and serotonin-related RS FC were derived by constrained independent component analysis, using PET atlases for dopamine, noradrenaline, and serotonin transporters obtained in HCs' brain. Compared to non-fatigued (NF)-pedMS patients and HC, F-pedMS patients (15/55, 27.3%) showed decreased dopamine-related RS FC in the right postcentral gyrus. They also showed decreased dopamine-related RS FC in the left insula vs. HC and increased dopamine-related RS FC in the left middle temporal gyrus and cerebellum (lobule VI) vs. NF patients. In the noradrenaline-related network, F-pedMS patients showed decreased RS FC in the left superior parietal lobule and increased RS FC in the right thalamus vs. HC and NF-pedMS. Compared to HC, F-pedMS patients also showed decreased RS FC in the right calcarine cortex and increased RS FC in the right middle frontal gyrus. In the serotonin-related network, F-pedMS patients showed decreased RS FC in the right angular gyrus and increased RS FC in the right postcentral gyrus vs. NF-pedMS patients. In pedMS, fatigue is associated with specific monoaminergic network abnormalities, providing pathological markers for this bothersome symptom and putative targets for its treatment.

Resting-state functional MRI (rs-fMRI) has emerged as a powerful tool for investigating brain functional connectivity (FC). Research in recent years has focused on assessing the reliability of FC across younger subjects within and between scan-sessions. Test-retest reliability in resting-state functional connectivity (RSFC) has not yet been examined in older adults. In this study, we investigated age-related differences in reliability and stability of RSFC across scans. In addition, we examined how global signal regression (GSR) affects RSFC reliability and stability. Three separate resting-state scans from 29 younger adults (18–35 yrs) and 26 older adults (55–85 yrs) were obtained from the International Consortium for Brain Mapping (ICBM) dataset made publically available as part of the 1000 Functional Connectomes project www.nitrc.org/projects/fcon_1000. 92 regions of interest (ROIs) with 5 cubic mm radius, derived from the default, cingulo-opercular, fronto-parietal and sensorimotor networks, were previously defined based on a recent study. Mean time series were extracted from each of the 92 ROIs from each scan and three matrices of z-transformed correlation coefficients were created for each subject, which were then used for evaluation of multi-scan reliability and stability. The young group showed higher reliability of RSFC than the old group with GSR (p-value = 0.028) and without GSR (p-value <0.001). Both groups showed a high degree of multi-scan stability of RSFC and no significant differences were found between groups. By comparing the test-retest reliability of RSFC with and without GSR across scans, we found significantly higher proportion of reliable connections in both groups without GSR, but decreased stability. Our results suggest that aging is associated with reduced reliability of RSFC which itself is highly stable within-subject across scans for both groups, and that GSR reduces the overall reliability but increases the stability in both age groups and could potentially alter group differences of RSFC.

How is psychological stress linked to sleep quality? The mediating role of functional connectivity between the sensory/somatomotor network and the cingulo-opercular control network

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

ObjectiveNumerous studies suggest that hypnosis has significant potential in mental health and cognitive disorder treatments. However, the mechanisms by which hypnosis influences brain activity and functional network connectivity remain unclear. This study employed functional near-infrared spectroscopy (fNIRS) to investigate resting-state functional connectivity (rsFC) under hypnosis.MethodsTwenty-six healthy college students participated in the study. Resting-state oxygenated hemoglobin (HbO) data were collected from the prefrontal cortex (PFC) during both control aware and hypnotic states. Functional connectivity strengths between these states were analyzed to assess changes in brain activity associated with deep hypnosis.ResultsA total of 55 paired samples t-tests were conducted across 11 regions of interest (ROIs), revealing statistically significant differences (p < 0.05) in functional connectivity strength between the control state and hypnotic state in 10 paired comparisons. Increased connectivity during hypnosis (6 pairs): LBA9-RBA10 (t = −2.672, p = 0.013), LBA6-RBA46 (t = −2.948, p = 0.007), LBA46-RBA46 (t = −2.516, p = 0.019), RBA8-RBA46 (t = −2.689, p = 0.013), RBA9-RBA46 (t = −2.090, p = 0.047), LBA10-RBA10 (t = −2.315, p = 0.029); Decreased connectivity during hypnosis (4 pairs): LBA9-LBA45 (t = 2.064, p = 0.049), LBA6-LBA45 (t = 3.151, p = 0.004), LBA8-LBA45 (t = 2.438, p = 0.022), LBA8-RBA9 (t = 2.085, p = 0.047). No significant differences were observed in connectivity strength between other ROI pairs.ConclusionHypnosis appears to modulate the function of the DLPFC, PFC, and related regions, enhancing specific brain network functional connectivity. This preliminary study demonstrates that resting-state functional connectivity analysis using fNIRS is a valuable approach for studying brain activity during hypnosis.

Intranasal oxytocin alters amygdala-temporal resting-state functional connectivity in body dysmorphic disorder: A double-blind placebo-controlled randomized trial

Altered gray matter morphometry and resting-state functional and structural connectivity in social anxiety disorder

Sensory processing dysfunction not only affects most individuals with autism spectrum disorder (ASD), but at least 5% of children without ASD also experience dysfunctional sensory processing. Our understanding of the relationship between sensory dysfunction and resting state brain activity is still emerging. This study compared long-range resting state functional connectivity of neural oscillatory behavior in children aged 8–12 years with autism spectrum disorder (ASD; N=18), those with sensory processing dysfunction (SPD; N=18) who do not meet ASD criteria, and typically developing control participants (TDC; N=24) using magnetoencephalography (MEG). Functional connectivity analyses were performed in the alpha and beta frequency bands, which are known to be implicated in sensory information processing. Group differences in functional connectivity and associations between sensory abilities and functional connectivity were examined. Distinct patterns of functional connectivity differences between ASD and SPD groups were found only in the beta band, but not in the alpha band. In both alpha and beta bands, ASD and SPD cohorts differed from the TDC cohort. Somatosensory cortical beta-band functional connectivity was associated with tactile processing abilities, while higher-order auditory cortical alpha-band functional connectivity was associated with auditory processing abilities. These findings demonstrate distinct long-range neural synchrony alterations in SPD and ASD that are associated with sensory processing abilities. Neural synchrony measures could serve as potential sensitive biomarkers for ASD and SPD.

Introduction: Stuttering is defined as speech characterized by verbal dysfluencies, but should not be seen as an isolated speech disorder, but as a generalized sensorimotor timing deficit due to impaired communication between speech related brain areas. Therefore we focused on resting state brain activity and functional connectivity.Method: We included 11 patients with developmental stuttering and 11 age matched controls. To objectify stuttering severity and the impact on quality of life (QoL), we used the Dutch validated Test for Stuttering Severity-Readers (TSS-R) and the Overall Assessment of the Speaker’s Experience of Stuttering (OASES), respectively. Furthermore, we used standardized low resolution brain electromagnetic tomography (sLORETA) analyses to look at resting state activity and functional connectivity differences and their correlations with the TSS-R and OASES.Results: No significant results could be obtained when looking at neural activity, however significant alterations in resting state functional connectivity could be demonstrated between persons who stutter (PWS) and fluently speaking controls, predominantly interhemispheric, i.e., a decreased functional connectivity for high frequency oscillations (beta and gamma) between motor speech areas (BA44 and 45) and the contralateral premotor (BA6) and motor (BA4) areas. Moreover, a positive correlation was found between functional connectivity at low frequency oscillations (theta and alpha) and stuttering severity, while a mixed increased and decreased functional connectivity at low and high frequency oscillations correlated with QoL.Discussion: PWS are characterized by decreased high frequency interhemispheric functional connectivity between motor speech, premotor and motor areas in the resting state, while higher functional connectivity in the low frequency bands indicates more severe speech disturbances, suggesting that increased interhemispheric and right sided functional connectivity is maladaptive.