Related Functional Connectivity Research Articles

Exploring potential working mechanisms of accelerated HF-rTMS in refractory major depression with a focus on locus coeruleus connectivity.

This study investigates the effects of accelerated high-frequency repetitive transcranial magnetic stimulation (aHF-rTMS), applied to the left dorsolateral prefrontal cortex (DLPFC), on locus coeruleus (LC) functional connectivity in the treatment of refractory medication-resistant major depression (MRD). We studied 12 antidepressant-free refractory MRD patients, focusing on how aHF-rTMS affects the LC, a central component of the brain's noradrenergic system and key to mood regulation and stress response. A stronger decrease in LC functional connectivity following aHF-rTMS treatment resulted in better clinical improvement. We observed such LC functional connectivity decreases with several brain regions, including the superior frontal gyrus, precentral gyrus, middle occipital gyrus, and cerebellum. Moreover, our exploratory analyses hint at a possible role for E-field modeling in forecasting clinical outcomes. Additional analyses suggest potential genetic and dopaminergic factors influencing changes in LC functional connectivity in relation to clinical response. The findings of this study underscore the pivotal role of the LC in orchestrating higher cognitive functions through its extensive connections with the prefrontal cortices, facilitating decision-making, influencing attention, and addressing depressive rumination. Additionally, the observed enhancement in LC-(posterior) cerebellar connectivity not only highlights the cerebellum's role in moderating clinical outcomes through noradrenergic system modulation but also suggests its potential as a predictive marker for aHF-rTMS efficacy. These results reveal new insights into the neural mechanisms of refractory depression and suggest therapeutic targets for enhancing noradrenergic activity, thereby addressing both cognitive and psychomotor symptoms associated with the disorder.

Structural and functional connectivity in relation to executive functions in antipsychotic-naïve patients with first episode schizophrenia

Patients with schizophrenia exhibit structural and functional dysconnectivity but the relationship to the well-documented cognitive impairments is less clear. This study investigates associations between structural and functional connectivity and executive functions in antipsychotic-naïve patients experiencing schizophrenia. Sixty-four patients with schizophrenia and 95 matched controls underwent cognitive testing, diffusion weighted imaging and resting state functional magnetic resonance imaging. In the primary analyses, groupwise interactions between structural connectivity as measured by fixel-based analyses and executive functions were investigated using multivariate linear regression analyses. For significant structural connections, secondary analyses examined whether functional connectivity and associations with executive functions also differed for the two groups. In group comparisons, patients exhibited cognitive impairments across all executive functions compared to controls (p < 0.001), but no group difference were observed in the fixel-based measures. Primary analyses revealed a groupwise interaction between planning abilities and fixel-based measures in the left anterior thalamic radiation (p = 0.004), as well as interactions between cognitive flexibility and fixel-based measures in the isthmus of corpus callosum and cingulum (p = 0.049). Secondary analyses revealed increased functional connectivity between grey matter regions connected by the left anterior thalamic radiation (left thalamus with pars opercularis p = 0.018, and pars orbitalis p = 0.003) in patients compared to controls. Moreover, a groupwise interaction was observed between cognitive flexibility and functional connectivity between contralateral regions connected by the isthmus (precuneus p = 0.028, postcentral p = 0.012), all p-values corrected for multiple comparisons. We conclude that structural and functional connectivity appear to associate with executive functions differently in antipsychotic-naïve patients with schizophrenia compared to controls.

Functional Connectivity of the Auditory Cortex in Women With Trauma-Related Disorders Who Hear Voices

BackgroundVoice hearing (VH) is a transdiagnostic experience that is common in trauma-related disorders. However, the neural substrates that underlie trauma-related VH remain largely unexplored. While auditory perceptual dysfunction is among the abnormalities implicated in VH in schizophrenia, whether VH in trauma-related disorders also involves auditory perceptual alterations is unknown. MethodsWe investigated auditory cortex (AC)–related functional connectivity (FC) in 65 women with trauma-related disorders stemming from childhood abuse with varying severities of VH. Using a novel, computationally driven and individual-specific method of functionally parcellating the brain, we calculated the FC of 2 distinct AC subregions—Heschl’s gyrus (corresponding to the primary AC) and lateral superior temporal gyrus (in the nonprimary AC)—with both the cerebrum and cerebellum. Then, we measured the association between VH severity and FC using leave-one-out cross-validation in the cerebrum and voxelwise multiple regression analyses in the cerebellum. ResultsWe found that VH severity was positively correlated with left lateral superior temporal gyrus–frontoparietal network FC, while it was negatively correlated with FC between the left lateral superior temporal gyrus and both cerebral and cerebellar representations of the default mode network. VH severity was not predicted by FC of the left Heschl’s gyrus or right AC subregions. ConclusionsOur findings point to altered interactions between auditory perceptual processing and higher-level processes related to self-reference and executive functioning. This is the first study to show alterations in auditory cortical connectivity in trauma-related VH. While VH in trauma-related disorders appears to be mediated by brain networks that are also implicated in VH in schizophrenia, the results suggest a unique mechanism that could distinguish VH in trauma-related disorders.

Resting-state functional connectivity and cognitive performance in aging adults with cognitive decline: A data-driven multivariate pattern analysis

BackgroundCognitive impairments occur on a continuous spectrum in multiple cognitive domains showing individual variability of the deteriorating patterns; however, often, cognitive domains are studied separately. MethodsThe present study investigated aging individual variations of cognitive abilities and related resting-state functional connectivity (rsFC) using data-driven approach. Cognitive and neuroimaging data were obtained from 62 elderly outpatients with cognitive decline. Principal component analysis (PCA) was conducted on the cognitive data to determine patterns of cognitive performance, then data-driven whole-brain connectome multivariate pattern analysis (MVPA) was applied on the neuroimaging data to discover neural regions associated with the cognitive characteristic. ResultsThe first component (PC1) delineated an overall decline in all domains of cognition, and the second component (PC2) represented a compensatory relationship within basic cognitive functions. MVPA indicated rsFC of the cerebellum lobule VIII and insula with the default-mode network, frontoparietal network, and salience network inversely correlated with PC1 scores. Additionally, PC2 score was related to rsFC patterns with temporal pole and occipital cortex. ConclusionsThe featured primary cognitive characteristic depicted the importance of the cerebellum and insula connectivity patterns in of the general cognitive decline. The findings also discovered a secondary characteristic that communicated impaired interactions within the basic cognitive function, which was independent from the impairment severity.

Heightened neural activity and functional connectivity responses to social rejection in female adolescents at risk for depression: Testing the Social Signal Transduction Theory of Depression

BackgroundAlthough social rejection is among the strongest proximal precipitants of major depressive disorder (MDD), little is known about the underlying neurobiological mechanisms and whether neural sensitivity to social rejection may help explain differences in MDD risk. To address this issue, we tested whether neural responses to social threat differed in female adolescents at high vs. low maternal risk for MDD. MethodFemale adolescents with (high-risk; n = 22, Mage = 14.68) and without (low-risk; n = 30, Mage = 15.07) a maternal history of depression were experimentally exposed to negative and neutral social evaluation while undergoing an fMRI scan. Neural responses were assessed by event-related activity and functional connectivity, as well as multivoxel pattern analysis. Activity and functional connectivity analyses focused on a priori-selected regions of interest implicated in self-referential processing and emotion regulation. ResultsCompared to low-risk female adolescents, high-risk female adolescents exhibited greater increases in self-reported depression and social disconnection following social evaluation. Moreover, compared to low-risk female adolescents, high-risk female adolescents exhibited greater amygdala responses to negative social evaluation and a differential pattern of functional connectivity in brain regions related to emotion regulation, self-referential processing, and negative affect. Additionally, these markers of neural threat reactivity were related to depressive symptoms. LimitationsA cross-sectional study design and relatively small, Western sample. ConclusionsThese results suggest that exaggerated neural reactivity to social threat—and an atypical pattern of related functional connectivity—is evident in individuals with a preclinical risk factor for depression. Targeting such responding may thus be a fruitful strategy for preventing depression in at-risk youth.

Resting-State Functional Magnetic Resonance Imaging as an Indicator of Neuropsychological Changes in Type 1 Narcolepsy

To explore indicators of neuropsychological changes in patients with type 1 narcolepsy (NT1) using resting-state functional magnetic resonance imaging (rs-fMRI). Thirty-four NT1 patients and 34 age- and sex-matched healthy volunteers were recruited for neuropsychiatric assessments and rs-fMRI data acquisition. Fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and related brain functional connectivity (FC) were calculated for the two groups and compared using a two-sample t test with cluster-level FDR correction. Moreover, partial correlation analysis was performed between these functional values of changed brain regions and clinical scales. Compared to those of healthy controls, spontaneous functional activities were significantly weakened in patients with NT1 in regions such as the left/right posterior cerebellum lobe, left inferior temporal gyrus, and left dorsolateral superior frontal gyrus, whereas those in regions such as the left middle occipital gyrus, right inferior occipital gyrus, and left/right lingual gyrus were significantly strengthened. Furthermore, NT1 patients displayed significantly changed FCs between the left/right anterior cingulate gyrus (ACG) and regions such as the left/right cerebellum, left middle occipital gyrus, and left inferior frontal gyrus in the operculum. In partial correlation analysis, the functions in the left dorsolateral superior frontal gyrus were significantly related to the Trail Making Tests (TMT) score. Moreover, the FC between the left ACG and left inferior frontal gyrus in the operculum washighly correlated with anxiety and depression features, including the Hamilton Anxiety Scale (HAMA) score and Hamilton Depression Rating Scale (HAMD-17) score. Patients with NT1 exhibited abnormalities in the anterior cingulate cortex, frontal-parietal cortex, hippocampus, and left/right posterior cerebellum lobe. The deactivation of the left frontal-temporal cortex is stronger, which is involved in the cognitive decline and mental disorders in these patients. Damage to the ACG may affect its FC with other regions and cause cognition and emotion dysregulation, perhaps by impairing patients' visual pathways and frontal-temporal-parietal networks. Hence, these could be important biomarkers for their neuropsychological changes.

Intrinsic Dynamics of Brain Functional Connectivity in Relation to Women’s Menstrual Cyclic Phases and its Impact on Their Stress, Life Satisfaction, and Social Distress

Research has reported that the fluctuations of sex hormones like estrogen and progesterone lead to neurological changes in the different brain regions across the menstrual cycle and its phases: menses, follicular, and luteal. Although some psychological changes have also been reported for women across their menstrual cycle, not enough studies have approached this topic from a neuropsychological perspective. For this reason, I am investigating brain connectivity fluctuations across a 32-day menstruation cycle and its impact on women’s life satisfaction (LS), perceived stress (PS), and emotional support (ES). For this study, I am using the data (n=406) that has been collected by the Human Connectome Project. I am using an experimental research methodology looking at correlations (connectivity) between brain regions and associated variables of menstrual cycle phases (menses, follicular, and luteal) across a 32-day menstrual cycle, and what this tells us about the participants’ LS, PS, and ES total scores. In neuroscience, artificial intelligence (AI) techniques are applied to understand complex brain functions, brain and behaviour relationships, and shows potential to diagnose neurological disorders and interventions. AI, and elastic net regression, which is a type of statistical technique for neuroimaging data, will be used to analyse the brain activity relationships that I am investigating. In my presentation, I aim to discuss whether functional connectivity in brain regions is linked to women’s LS, PS, and ES, and the implications of this for menstrual health. This pilot study, by using a big data set of relatively healthy participants to further our understanding of this topic, will help to open doors for future research with similar investigating aims for more impactful menstrual related health conditions like Premenstrual Syndrome and Premenstrual Dysphoric Disorder.

Reduced loss aversion in value-based decision-making and edge-centric functional connectivity in patients with internet gaming disorder.

Impaired value-based decision-making is a feature of substance and behavioral addictions. Loss aversion is a core of value-based decision-making and its alteration plays an important role in addiction. However, few studies explored it in internet gaming disorder patients (IGD). In this study, IGD patients (PIGD) and healthy controls (Con-PIGD) performed the Iowa gambling task (IGT), under functional magnetic resonance imaging (fMRI). We investigated group differences in loss aversion, brain functional networks of node-centric functional connectivity (nFC) and the overlapping community features of edge-centric functional connectivity (eFC) in IGT. PIGD performed worse with lower average net score in IGT. The computational model results showed that PIGD significantly reduced loss aversion. There was no group difference in nFC. However, there were significant group differences in the overlapping community features of eFC1. Furthermore, in Con-PIGD, loss aversion was positively correlated with the edge community profile similarity of the edge2 between left IFG and right hippocampus at right caudate. This relationship was suppressed by response consistency3 in PIGD. In addition, reduced loss aversion was negatively correlated with the promoted bottom-to-up neuromodulation from the right hippocampus to the left IFG in PIGD. The reduced loss aversion in value-based decision making and their related edge-centric functional connectivity support that the IGD showed the same value-based decision-making deficit as the substance use and other behavioral addictive disorders. These findings may have important significance for understanding the definition and mechanism of IGD in the future.

Amygdala subdivisions exhibit aberrant whole-brain functional connectivity in relation to stress intolerance and psychotic symptoms in 22q11.2DS

The amygdala is a key region in emotional regulation, which is often impaired in psychosis. However, it is unclear if amygdala dysfunction directly contributes to psychosis, or whether it contributes to psychosis through symptoms of emotional dysregulation. We studied the functional connectivity of amygdala subdivisions in patients with 22q11.2DS, a known genetic model for psychosis susceptibility. We investigated how dysmaturation of each subdivision’s connectivity contributes to positive psychotic symptoms and impaired tolerance to stress in deletion carriers. Longitudinally-repeated MRI scans from 105 patients with 22q11.2DS (64 at high-risk for psychosis and 37 with impaired tolerance to stress) and 120 healthy controls between the ages of 5 to 30 years were included. We calculated seed-based whole-brain functional connectivity for amygdalar subdivisions and employed a longitudinal multivariate approach to evaluate the developmental trajectory of functional connectivity across groups. Patients with 22q11.2DS presented a multivariate pattern of decreased basolateral amygdala (BLA)-frontal connectivity alongside increased BLA-hippocampal connectivity. Moreover, associations between developmental drops in centro-medial amygdala (CMA)-frontal connectivity to both impaired tolerance to stress and positive psychotic symptoms in deletion carriers were detected. Superficial amygdala hyperconnectivity to the striatum was revealed as a specific pattern arising in patients who develop mild to moderate positive psychotic symptoms. Overall, CMA-frontal dysconnectivity was found as a mutual neurobiological substrate in both impaired tolerance to stress and psychosis, suggesting a role in prodromal dysregulation of emotions in psychosis. While BLA dysconnectivity was found to be an early finding in patients with 22q11.2DS, which contributes to impaired tolerance to stress.

Neuro-imaging characteristics of sensory impairment in cerebral palsy; a systematic review.

Objective: To identify and examine neural reorganization of the sensory network in terms of lesion type, somatotopic organization of the primary somatosensory area, and functional connectivity in relation to sensory function in children and young adults with cerebral palsy (CP). Design: systematic review, Prospero registration ID 342570. Data sources: PubMed; Cochrane; Web of Science; Embase; CINAHL and PEDro from inception to March 13, 2021. Eligibility criteria: All types of original studies, concerning sensory connectivity in relation to sensory outcome in patients with spastic CP, <30 years of age. No publication status or date restrictions were applied. Data extraction and synthesis: Two authors independently determined the eligibility of studies. Quality assessment was performed by a third author. Neuro-imaging/neurophysiological techniques, sensory outcomes and patient characteristics were extracted. Children and young adults with periventricular leucomalacia (PVL) lesions have significantly better hand function and sensation scores than patients with cortical-subcortical/middle cerebral artery (MCA) lesions. Ipsilesional reorganization of the S1 (primary somatosensory cortex) area appears to be the primary compensation mechanism after a unilateral early brain lesion, regardless of the timing of the lesion. Interhemispheric reorganization of the sensory system after early brain lesions is rare and, when it occurs, poorly effective. Diffusion tractography shows a positive correlation between the ascending sensory tract (AST) diffusivity metrics of the more affected hemisphere and sensory test outcomes. Because of the large variability in study design, patient characteristics, neuroimaging/neurophysiological techniques and parameters as well as sensory assessment methods used, it is difficult to draw definite inferences on the relationship between the reorganization of the sensory network following early brain damage and sensory function in children and young adults with CP. In general, sensory function seems to be worse in cortical as opposed to white matter tract (PVL) lesions. International consensus on a clinically relevant sensory test battery is needed to enhance understanding of the intriguing compensatory mechanisms of sensory network following early brain damage and potential consequences for rehabilitation strategies. https://www.crd.york.ac.uk/prospero/.

Lifespan differences in visual short-term memory load-modulated functional connectivity

Working memory is critical to higher-order executive processes and declines throughout the adult lifespan. However, our understanding of the neural mechanisms underlying this decline is limited. Recent work suggests that functional connectivity between frontal control and posterior visual regions may be critical, but examinations of age differences therein have been limited to a small set of brain regions and extreme group designs (i.e., comparing young and older adults). In this study, we build on previous research by using a lifespan cohort and a whole-brain approach to investigate working memory load-modulated functional connectivity in relation to age and performance. The article reports on analysis of the Cambridge center for Ageing and Neuroscience (Cam-CAN) data. Participants from a population-based lifespan cohort (N = 101, age 23–86) performed a visual short-term memory task during functional magnetic resonance imaging. Visual short-term memory was measured with a delayed recall task for visual motion with three different loads. Whole-brain load-modulated functional connectivity was estimated using psychophysiological interactions in a hundred regions of interest, sorted into seven networks (Schaefer et al., 2018, Yeo et al., 2011). Results showed that load-modulated functional connectivity was strongest within the dorsal attention and visual networks during encoding and maintenance. With increasing age, load-modulated functional connectivity strength decreased throughout the cortex. Whole-brain analyses for the relation between connectivity and behavior were non-significant. Our results give additional support to the sensory recruitment model of working memory. We also demonstrate the widespread negative impact of age on the modulation of functional connectivity by working memory load. Older adults might already be close to ceiling in terms of their neural resources at the lowest load and therefore less able to further increase connectivity with increasing task demands.

Changes in brain structure and related functional connectivity during menstruation in women with primary dysmenorrhea.

Neuroimaging studies have identified altered brain structures and functions in women with primary dysmenorrhea (PDM). However, previous studies focused on either structural or functional changes in specific brain regions rather than combining structural and functional analysis. Therefore, this prospective cross-sectional study aimed to investigate the changes in whole brain structure, and functional variation along with structural abnormalities in women with PDM during menstruation. In all, 31 patients with PDM (PTs) and 31 healthy controls (HCs) were recruited. Voxel-based morphometry (VBM) and surface-based morphometry (SBM) analyses were applied to investigate structural changes based on high-resolution T1-weighted magnetic resonance images. Functional connectivity (FC) analysis was performed to evaluate functional variations related to the brain regions that showed structural group differences. Pearson correlation analysis was performed to assess the relationship between neuroimaging changes and clinical measures. Compared to HCs, PTs had reduced gray matter volume (GMV) in the right superior temporal gyrus (STG) and reduced thickness in the bilateral orbitofrontal cortex (OFC), left postcentral gyrus (PoCG), and left superior occipital gyrus (SOG). Among these areas, the STG and PoCG are responsible for altered resting-state FC patterns in PTs. Results showed decreased FC between the STG and the left cerebellar posterior lobe (poCb), the right dorsolateral prefrontal cortex (DLPFC), and the left precentral gyrus (PrCG). Results also showed decreased FC between the PoCG and the right precuneus and the right DLPFC. We also found greater FCs between the PoCG and the bilateral poCb, the left middle temporal gyrus (MTG), and the left angular gyrus. In addition, the FCs between the STG and poCb, and DLPFC in PTs were positively correlated with history and Cox menstrual symptom scale (CMSS) scores, respectively, while the FCs between STG and PrCG were negatively correlated with the onset age of PDM. Our research found structural abnormalities and related FC changes in several brain regions that were mainly involved in the emotional and sensory aspects of menstrual pain in PDM. These findings could help us understand the occurrence of PDM from a neuroimaging perspective.

Interictal Gamma Event Connectivity Differentiates the Seizure Network and Outcome in Patients after Temporal Lobe Epilepsy Surgery.

Studies of interictal EEG functional connectivity in the epileptic brain seek to identify abnormal interactions between brain regions involved in generating seizures, which clinically often is defined by the seizure onset zone (SOZ). However, there is evidence for abnormal connectivity outside the SOZ (NSOZ), and removal of the SOZ does not always result in seizure control, suggesting, in some cases, that the extent of abnormal connectivity indicates a larger seizure network than the SOZ. To better understand the potential differences in interictal functional connectivity in relation to the seizure network and outcome, we computed event connectivity in the theta (4-8 Hz, ThEC), low-gamma (30-55 Hz, LGEC), and high-gamma (65-95 Hz, HGEC) bands from interictal depth EEG recorded in surgical patients with medication-resistant seizures suspected to begin in the temporal lobe. Analysis finds stronger LGEC and HGEC in SOZ than NSOZ of seizure-free (SF) patients (p = 1.10e-9, 0.0217), but no difference in not seizure-free (NSF) patients. There were stronger LGEC and HGEC between mesial and lateral temporal SOZ of SF than NSF patients (p = 0.00114, 0.00205), and stronger LGEC and ThEC in NSOZ of NSF than SF patients (p = 0.0089, 0.0111). These results show that event connectivity is sensitive to differences in the interactions between regions in SOZ and NSOZ and SF and NSF patients. Patients with differential strengths in event connectivity could represent a well-localized seizure network, whereas an absence of differences could indicate a larger seizure network than the one localized by the SOZ and higher likelihood for seizure recurrence.

Is frontoparietal electroencephalogram activity related to the level of functional disability in patients emerging from a minimally conscious state? A preliminary study.

ObjectiveWhen regaining consciousness, patients who emerge from a minimally conscious state (EMCS) present with different levels of functional disability, which pose great challenges for treatment. This study investigated the frontoparietal activity in EMCS patients and its effects on functional disability.Materials and methodsIn this preliminary study, 12 EMCS patients and 12 healthy controls were recruited. We recorded a resting-state scalp electroencephalogram (EEG) for at least 5 min for each participant. Each patient was assessed using the disability rating scale (DRS) to determine the level of functional disability. We analyzed the EEG power spectral density and sensor-level functional connectivity in relation to the patient’s functional disability.ResultsIn the frontoparietal region, EMCS patients demonstrated lower relative beta power (P < 0.01) and higher weighted phase lag index (wPLI) values in the theta (P < 0.01) and gamma (P < 0.01) bands than healthy controls. The frontoparietal theta wPLI values of EMCS patients were positively correlated with the DRS scores (rs = 0.629, P = 0.029). At the whole-brain level, EMCS patients only had higher wPLI values in the theta band (P < 0.01) than healthy controls. The whole-brain theta wPLI values of EMCS patients were also positively correlated with the DRS scores (rs = 0.650, P = 0.022). No significant difference in the power and connectivity between the frontoparietal region and the whole brain in EMCS patients was observed.ConclusionEMCS patients still experience neural dysfunction, especially in the frontoparietal region. However, the theta connectivity in the frontoparietal region did not increase specifically. At the level of the whole brain, the same shift could also be seen. Theta functional connectivity in the whole brain may underlie different levels of functional disability.

Disrupted Spontaneous Neural Activity and Its Interaction With Pain and Emotion in Temporomandibular Disorders.

Background and PurposeTemporomandibular disorders (TMD), especially pain-related TMD, are closely related to social and psychological factors. We aimed to measure changes in spontaneous brain activity and its related functional connectivity (FC), as well as FC characteristics within the mood-regulating circuits (MRC) in TMD patients by resting-state functional magnetic resonance imaging (RS-fMRI), and to analyze the relationship between these parameters and emotional symptoms.Materials and MethodsTwenty-one adult TMD patients and thirty demographically matched healthy controls (HCs) underwent clinical scale evaluation and RS-fMRI scanning. After processing RS-fMRI data, the values of the amplitude of low-frequency fluctuation (ALFF) between the two groups were compared. Regions with abnormal ALFF values were selected as areas of interest (ROIs) to compare the differences of whole-brain seed-based FC between groups. The FCs between regions within MRC were also analyzed and compared. In addition, the relationships between RS-fMRI characteristics and pain and mood were explored by correlation and mediation analyses.ResultsCompared with HCs, TMD patients showed increased ALFF in the right parahippocampal gyrus (PHG), the right supplementary motor area, and the bilateral precentral gyrus, with decreased ALFF in the right cerebelum_crus2. Patients showed enhanced right PHG-related FC in the vermis and posterior cingulate cortex, orbitofrontal cortex (OFC)-related FC in the striatal-frontal regions, while decreased dorsolateral prefrontal cortex-related FC in the amygdala. In TMD patients, ALFF values in the right PHG and FC values between the right PHG and the vermis were positively correlated with depressive symptoms. Abnormal FCs in the left striatal-orbitofrontal pathway were correlated with pain and depressive symptoms. More importantly, mediation analysis revealed that chronic pain mediates the relationship between FC of right PHG with vermis and depressive symptoms, and abnormal FC in the left striatal-orbitofrontal pathway can mediate the association between pain and depressive symptoms.ConclusionTMD patients have dysregulated spontaneous activity and FC in the default mode network, sensorimotor network and pain-related regions, as well as dysfunction of the fronto-striatal-limbic circuits. The development of negative emotions in TMD may be related to the dysfunction of components within the reward system (especially hippocampus complex, OFC, striatum) due to chronic pain.

Functional Connectivity Alterations Based on Hypometabolic Region May Predict Clinical Prognosis of Temporal Lobe Epilepsy: A Simultaneous 18F-FDG PET/fMRI Study.

Simple SummaryAccurate localization of the epileptogenic zone and understanding the related whole-brain functional alteration patterns are critical for the prediction of postsurgical outcomes in patients with temporal lobe epilepsy (TLE). Previous studies suggested that functional connectivity (FC) alterations based on structurally abnormal lesion on MRI could indicate the clinical prognosis. However, hypometabolic regions localized by 18F-FDG PET precedes the appearance of structural abnormalities in lesion localization. By using hybrid 18F-FDG PET/fMRI, we aim to obtain spatially and temporally matched structural, functional, and metabolic information of TLE patients, localize their hypometabolic regions, compare the differences of FC alteration patterns based on hypometabolic region and structural lesion, respectively, and further explore their relationships with disease progression and postsurgical outcome. The results showed that hypometabolic region could be used for detecting a more extensive long-range functional alteration pattern, which correlated with disease progression (epilepsy duration) and surgical outcome (seizure-free or not in follow-up). In this way, we conclude that FC alterations based on hypometabolic region constructed by 18F-FDG PET/fMRI may provide additional value in the prediction of clinical prognosis in TLE patients.(1) Background: Accurate localization of the epileptogenic zone and understanding the related functional connectivity (FC) alterations are critical for the prediction of clinical prognosis in patients with temporal lobe epilepsy (TLE). We aim to localize the hypometabolic region in TLE patients, compare the differences in FC alterations based on hypometabolic region and structural lesion, respectively, and explore their relationships with clinical prognosis. (2) Methods: Thirty-two TLE patients and 26 controls were recruited. Patients underwent 18F-FDG PET/MR scan, surgical treatment, and a 2–3-year follow-up. Visual assessment and voxel-wise analyses were performed to identify hypometabolic regions. ROI-based FC analyses were performed. Relationships between clinical prognosis and FC values were performed by using Pearson correlation analyses and receiver operating characteristic (ROC) analysis. (3) Results: Hypometabolic regions in TLE patients were found in the ipsilateral hippocampus, parahippocampal gyrus, and temporal lobe (p < 0.001). Functional alterations based on hypometabolic regions showed a more extensive whole-brain FC reduction. FC values of these regions negatively correlated with epilepsy duration (p < 0.05), and the ROC curve of them showed significant accuracy in predicting postsurgical outcome. (4) Conclusions: In TLE patients, FC related with hypometabolic region obtained by PET/fMRI may provide value in the prediction of disease progression and seizure-free outcome.

The functional connectivity of basal forebrain is associated with superior memory performance in older adults: a case-control study

BackgroundAging is related with memory deterioration. However, some older adults demonstrate superior performance compared to age- and education-matched adults, who are referred to as superagers. To explore the neural mechanisms that mediate their unusually successful memory is important not only for the ameliorate the effects of aging in brain, but also for the prevention of neurodegenerative diseases, including Alzheimer’s disease. This case-control study is aimed to investigate the effects of volume and function of basal forebrain cholinergic neurons on the cognition of superagers.MethodsThe morphometric and resting-state functional MRI analysis, including 34 superagers and 48 typical older adults, were conducted. We compared the basal forebrain gray matter density and related resting-state functional connectivity (FC) in the two groups. To investigate the relationship of FC with cognition, we measure the correlation of significant altered FC and individual cognitive domain.ResultsNo significant differences of gray matter density was observed between superagers and typical older adults. The superagers had stronger cortical FC of Ch1-3 with left putamen and insular cortex. The strength of FC positively correlated with global cognition, memory and executive function.ConclusionsThese findings demonstrated that the stronger FC of basal forebrain correlated with specific cognitive difference in global cognition and domains of memory and executive function in superagers.

Estrogen, Cognitive Performance, and Functional Imaging Studies: What Are We Missing About Neuroprotection?

Menopause transition can be interpreted as a vulnerable state characterized by estrogen deficiency with detrimental systemic effects as the low-grade chronic inflammation that appears with aging and partly explains age-related disorders as cancer, diabetes mellitus and increased risk of cognitive impairment. Over the course of a lifetime, estrogen produces several beneficial effects in healthy neurological tissues as well as cardioprotective effects, and anti-inflammatory effects. However, clinical evidence on the efficacy of hormone treatment in menopausal women has failed to confirm the benefit reported in observational studies. Unambiguously, enhanced verbal memory is the most robust finding from longitudinal and cross-sectional studies, what merits consideration for future studies aiming to determine estrogen neuroprotective efficacy. Estrogen related brain activity and functional connectivity remain, however, unexplored. In this context, the resting state paradigm may provide valuable information about reproductive aging and hormonal treatment effects, and their relationship with brain imaging of functional connectivity may be key to understand and anticipate estrogen cognitive protective effects. To go in-depth into the molecular and cellular mechanisms underlying rapid-to-long lasting protective effects of estrogen, we will provide a comprehensive review of cognitive tasks used in animal studies to evaluate the effect of hormone treatment on cognitive performance and discuss about the tasks best suited to the demonstration of clinically significant differences in cognitive performance to be applied in human studies. Eventually, we will focus on studies evaluating the DMN activity and responsiveness to pharmacological stimulation in humans.

Resting-state functional connectivity indicators of risk and resilience for self-harm in adolescent bipolar disorder.

Suicide is the second leading cause of death in all youth and among adults with bipolar disorder (BD). The risk of suicide in BD is among the highest of all psychiatric conditions. Self-harm, including suicide attempts and non-suicidal self-injury, is a leading risk factor for suicide. Neuroimaging studies suggest reward circuits are implicated in both BD and self-harm; however, studies have yet to examine self-harm related resting-state functional connectivity (rsFC) phenotypes within adolescent BD. Resting-state fMRI data were analyzed for 141 adolescents, ages 13-20 years, including 38 with BD and lifetime self-harm (BDSH+), 33 with BD and no self-harm (BDSH-), and 70 healthy controls (HC). The dorsolateral prefrontal cortex (dlPFC), orbitofrontal cortex (OFC) and amygdala were examined as regions of interest in seed-to-voxel analyses. A general linear model was used to explore the bivariate correlations for each seed. BDSH- had increased positive rsFC between the left amygdala and left lateral occipital cortex, and between the right dlPFC and right frontal pole, and increased negative rsFC between the left amygdala and left superior frontal gyrus compared to BDSH+ and HC. BDSH+ had increased positive rsFC of the right OFC with the precuneus and left paracingulate gyrus compared to BDSH- and HC. This study provides preliminary evidence of altered reward-related rsFC in relation to self-harm in adolescents with BD. Between-group differences conveyed a combination of putative risk and resilience connectivity patterns. Future studies are warranted to evaluate changes in rsFC in response to treatment and related changes in self-harm.

Intracranial recordings in humans reveal specific hippocampal spectral and dorsal vs. ventral connectivity signatures during visual, attention and memory tasks

Invasive brain recordings using many electrodes across a wide range of tasks provide a unique opportunity to study the role of oscillatory patterning and functional connectivity. We used large-scale recordings (stereo EEG) within and beyond the human hippocampus to investigate the role of distinct frequency oscillations during real-time execution of visual, attention and memory tasks in eight epileptic patients. We found that activity patterns in the hippocampus showed task and frequency dependent properties. Importantly, we found distinct connectivity signatures, in particular concerning parietal-hippocampal connectivity, thus revealing large scale synchronization of networks involved in memory tasks. Comparing the power per frequency band, across tasks and hippocampal regions (anterior/posterior) we confirmed a main effect of frequency band (p = 0.002). Gamma band activity was higher for visuo-spatial memory tasks in the anterior hippocampus. Further, we found that alpha and beta band activity in posterior hippocampus had larger modulation for high memory load visual tasks (p = 0.004). Three functional connectivity task related networks were identified: (dorsal) parietal-hippocampus (visual attention and memory), ventral stream- hippocampus and hippocampal-frontal connections (mainly tasks involving face recognition or object based search). These findings support the critical role of oscillatory patterning in the hippocampus during visual and memory tasks and suggests the presence of task related spectral and functional connectivity signatures. These results show that the use of large scale human intracranial recordings can validate the role of oscillatory and functional connectivity patterns across a broad range of cognitive domains.