Most recent paper

Hippocampal connectivity and memory decline in cognitively intact APOE ε4 carriers

Sun, 03/12/2023 - 18:00

Alzheimers Dement. 2023 Mar 12. doi: 10.1002/alz.13023. Online ahead of print.


INTRODUCTION: Resting-state functional magnetic resonance imaging (fMRI) graph theory may help detect subtle functional connectivity changes affecting memory prior to impairment.

METHODS: Cognitively normal apolipoprotein E (APOE) ε4 carriers/noncarriers underwent longitudinal cognitive assessment and one-time MRI. The relationship of left/right hippocampal connectivity and memory trajectory were compared between carriers/noncarriers.

RESULTS: Steepness of verbal memory decline correlated with decreased connectivity in the left hippocampus, only among APOE ε4 carriers. Right hippocampal metrics were not correlated with memory and there were no significant correlations in the noncarriers. Verbal memory decline correlated with left hippocampal volume loss for both carriers and noncarriers, with no other significant volumetric findings.

DISCUSSION: Findings support early hippocampal dysfunction in intact carriers, the AD disconnection hypothesis, and left hippocampal dysfunction earlier than the right. Combining lateralized graph theoretical metrics with a sensitive measure of memory trajectory allowed for detection of early-stage changes in APOE ε4 carriers before symptoms of mild cognitive impairment are present.

HIGHLIGHTS: Graph theory connectivity detects preclinical hippocampal changes in APOE ε4 carriers. The AD disconnection hypothesis was supported in unimpaired APOE ε4 carriers. Hippocampal dysfunction starts asymmetrically on the left.

PMID:36906845 | DOI:10.1002/alz.13023

Association of aberrant dynamic brain network and gut microbial composition uncovers the disrupted brain-gut-microbiome interactions in irritable bowel syndrome : preliminary findings

Sat, 03/11/2023 - 19:00

Eur J Neurol. 2023 Mar 11. doi: 10.1111/ene.15776. Online ahead of print.


BACKGROUND: Growing evidences support that abnormalities in brain-gut-microbiome (BGM) interactions have been implicated in the pathogenesis of irritable bowel syndrome (IBS). Our study aimed to explore the alterations in dynamic functional connectivity (DFC), gut microbiome and the bidirectional interaction in the BGM.

METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI), fecal samples and clinical measures were collected from 33 IBS patients and 32 healthy controls. We performed a systematical DFC analysis on rs-fMRI. The gut microbiome were analyzed by 16S rRNA gene sequencing. Associations between DFC characteristics and microbial alterations were explored.

RESULTS: In DFC analysis, four dynamic functional states were identified. IBS patients exhibited increased mean dwell and fraction time in State 4, and reduced transitions from State 3 to State 1. The aberrant temporal properties in State 4 were only evident when choosing a short window (36s or 44s). Decreased functional connectivity (FC) variability was found in State 1 and State 3 of IBS patients, two of which showed significant correlations with clinical characteristics. Additionally, we identified 9 significantly differential abundances in microbial composition. We also found that IBS-related microbiota was associated with aberrant FC variability, albeit these exploratory results obtained at an uncorrected threshold of significance.

CONCLUSIONS: Although future studies are needed to confirm these findings, our findings not only provide a new insight for the dysconnectivity hypothesis in IBS from a dynamic perspective, but also established a possible link between the DFC and gut microbiome, which laid the foundation for future research on the disrupted BGM interactions.

PMID:36905309 | DOI:10.1111/ene.15776

Physical Activity Alters Functional Connectivity of Orbitofrontal Cortex Subdivisions in Healthy Young Adults: A Longitudinal fMRI Study

Sat, 03/11/2023 - 19:00

Healthcare (Basel). 2023 Feb 26;11(5):689. doi: 10.3390/healthcare11050689.


Physical activity (PA) plays an important role in affect processing. Studies describe the orbitofrontal cortex (OFC) as a major hub for emotion processing and the pathophysiology of affective disorders. Subregions of the OFC show diverse functional connectivity (FC) topographies, but the effect of chronic PA on subregional OFC FC still lacks scientific understanding. Therefore, we aimed at investigating the effects of regular PA on the FC topographies of OFC subregions in healthy individuals within a longitudinal randomized controlled exercise study. Participants (age: 18-35 years) were randomly assigned to either an intervention group (IG; N = 18) or a control group (CG; N = 10). Fitness assessments, mood questionnaires, and resting state functional magnetic resonance imaging (rsfMRI) were performed four times over the duration of 6 months. Using a detailed parcellation of the OFC, we created subregional FC topography maps at each time point and applied a linear mixed model to assess the effects of regular PA. The posterior-lateral right OFC showed a group and time interaction, revealing decreased FC with the left dorsolateral prefrontal cortex in the IG, while FC in the CG increased. Group and time interaction in the anterior-lateral right OFC with the right middle frontal gyrus was driven by increased FC in the IG. The posterior-lateral left OFC showed a group and time interaction based on differential change in FC to the left postcentral gyrus and the right occipital gyrus. This study emphasized regionally distinctive FC changes induced by PA within the lateral OFC territory, while providing aspects for further research.

PMID:36900693 | DOI:10.3390/healthcare11050689

Functional Deficiency of Interneurons and Negative BOLD fMRI Response

Sat, 03/11/2023 - 19:00

Cells. 2023 Mar 6;12(5):811. doi: 10.3390/cells12050811.


The functional deficiency of the inhibitory system typically appears during development and can progress to psychiatric disorders or epilepsy, depending on its severity, in later years. It is known that interneurons, the major source of GABAergic inhibition in the cerebral cortex, can make direct connections with arterioles and participate in the regulation of vasomotion. The goal of this study was to mimic the functional deficiency of interneurons through the use of localized microinjections of the GABA antagonist, picrotoxin, in such a concentration that it did not elicit epileptiform neuronal activity. First, we recorded the dynamics of resting-state neuronal activity in response to picrotoxin injections in the somatosensory cortex of an awake rabbit; second, we assessed the altered neuronal and hemodynamic responses to whisker stimulation using BOLD fMRI and electrophysiology recordings; third, we evaluated brain tissue oxygen levels before and after picrotoxin injection. Our results showed that neuronal activity typically increased after picrotoxin administration, the BOLD responses to stimulation became negative, and the oxygen response was nearly abolished. Vasoconstriction during the resting baseline was not observed. These results indicate that picrotoxin provoked imbalanced hemodynamics either due to increased neuronal activity, decreased vascular response, or a combination of both.

PMID:36899947 | DOI:10.3390/cells12050811

Atypical functional connectivity of temporal cortex with precuneus and visual regions may be an early-age signature of ASD

Fri, 03/10/2023 - 19:00

Mol Autism. 2023 Mar 10;14(1):11. doi: 10.1186/s13229-023-00543-8.


BACKGROUND: Social and language abilities are closely intertwined during early typical development. In autism spectrum disorder (ASD), however, deficits in social and language development are early-age core symptoms. We previously reported that superior temporal cortex, a well-established social and language region, shows reduced activation to social affective speech in ASD toddlers; however, the atypical cortical connectivity that accompanies this deviance remains unknown.

METHODS: We collected clinical, eye tracking, and resting-state fMRI data from 86 ASD and non-ASD subjects (mean age 2.3 ± 0.7 years). Functional connectivity of left and right superior temporal regions with other cortical regions and correlations between this connectivity and each child's social and language abilities were examined.

RESULTS: While there was no group difference in functional connectivity, the connectivity between superior temporal cortex and frontal and parietal regions was significantly correlated with language, communication, and social abilities in non-ASD subjects, but these effects were absent in ASD subjects. Instead, ASD subjects, regardless of different social or nonsocial visual preferences, showed atypical correlations between temporal-visual region connectivity and communication ability (r(49) = 0.55, p < 0.001) and between temporal-precuneus connectivity and expressive language ability (r(49) = 0.58, p < 0.001).

LIMITATIONS: The distinct connectivity-behavior correlation patterns may be related to different developmental stages in ASD and non-ASD subjects. The use of a prior 2-year-old template for spatial normalization may not be optimal for a few subjects beyond this age range.

CONCLUSIONS: Superior temporal cortex is known to have reduced activation to social affective speech in ASD at early ages, and here we find in ASD toddlers that it also has atypical connectivity with visual and precuneus cortices that is correlated with communication and language ability, a pattern not seen in non-ASD toddlers. This atypicality may be an early-age signature of ASD that also explains why the disorder has deviant early language and social development. Given that these atypical connectivity patterns are also present in older individuals with ASD, we conclude these atypical connectivity patterns persist across age and may explain why successful interventions targeting language and social skills at all ages in ASD are so difficult to achieve.

PMID:36899425 | DOI:10.1186/s13229-023-00543-8

Disruption of periaqueductal gray-default mode network functional connectivity in patients with Crohn's disease with abdominal pain

Fri, 03/10/2023 - 19:00

Neuroscience. 2023 Mar 8:S0306-4522(23)00118-5. doi: 10.1016/j.neuroscience.2023.03.002. Online ahead of print.


Abdominal pain in Crohn's disease (CD) has been known to be associated with changes in the central nervous system. The periaqueductal gray (PAG) plays a well-established role in pain processing. However, the role of PAG-related network and the effect of pain on the network in CD remain unclear.Resting-state functional magnetic imaging (fMRI) data were collected from 24 CD patients in remission with abdominal pain, 24 CD patients without abdominal pain and 28 healthy controls (HCs). Using the subregions of PAG (dorsomedial (dmPAG), dorsolateral (dlPAG), lateral (lPAG) and ventrolateral (vlPAG)) as seeds, the seed-based FC maps were calculated and one-way analysis of variance (ANOVA) was performed to investigate the differences among the three groups.Results showed that the group differences were mainly involved in the FC of the vlPAG with the precuneus, medial prefrontal cortex (mPFC) as well as orbitofrontal cortex (OFC), and the FC of the right lateral PAG (lPAG) with the precuneus, inferior parietal lobule (IPL), angular gyrus and premotor cortex. The FC values of all these regions decreased successively in the order of HCs, CD without abdominal pain and CD with abdominal pain. The pain score was negatively correlated with the FC of the l/vlPAG with the precuneus, angular gyrus and mPFC in CD patients with abdominal pain.This study implicated the disrupt communication between the PAG and the default mode network (DMN). These findings complemented neuroimaging evidence for the pathophysiology of visceral pain in CD patients.

PMID:36898497 | DOI:10.1016/j.neuroscience.2023.03.002

Differential Brain Structural and Functional Patterns in Crohn's Disease Patients are Associated with Different Disease Stages

Fri, 03/10/2023 - 19:00

Inflamm Bowel Dis. 2023 Mar 10:izad029. doi: 10.1093/ibd/izad029. Online ahead of print.


BACKGROUND: Crohn's disease (CD) is an inflammatory, chronic disorder that alternates between a quiescent phase and inflammatory flare-ups. Research has begun to elucidate the impact of CD in modulating brain structure and function. The previous neuroimaging studies mainly involved CD patients in remission (CD-R); therefore, little is known about how inflammation influences brain-related features in different stages of the disease. We carried out a magnetic resonance imaging (MRI) study to explore whether the different levels of disease activity may differentially affect brain structure and function.

METHODS: Fourteen CD-R patients, 19 patients with mild to moderate inflammatory activity (CD-A), and 18 healthy controls (HCs) underwent an MRI scan including structural and functional sequences.

RESULTS: Between-group comparisons showed morphological and functional brain differences distinctively associated with the stage of disease activity. The CD-A patients had reduced gray matter within the posterior cingulate cortex (PCC) relative to CD-R patients. Analysis on resting fMRI data showed the following patterns: (1) increased connectivity within the left fronto-parietal network (in the superior parietal lobe) in CD-R patients relative to CD-A patients; (2) decreased connectivity in the motor network (in parietal and motor areas) in the CD-A group relative to the HC group; (3) reduced connectivity in the motor network and (4) in the language network (in parietal areas and in the PCC) in CD-R patients relative to HC.

CONCLUSIONS: The present findings represent a further step towards understanding brain morphological and functional changes in the active vs remission stages of CD patients.

PMID:36897213 | DOI:10.1093/ibd/izad029

Accumulation of network redundancy marks the early stage of Alzheimer's disease

Fri, 03/10/2023 - 19:00

Hum Brain Mapp. 2023 Mar 10. doi: 10.1002/hbm.26257. Online ahead of print.


Brain wiring redundancy counteracts aging-related cognitive decline by reserving additional communication channels as a neuroprotective mechanism. Such a mechanism plays a potentially important role in maintaining cognitive function during the early stages of neurodegenerative disorders such as Alzheimer's disease (AD). AD is characterized by severe cognitive decline and involves a long prodromal stage of mild cognitive impairment (MCI). Since MCI subjects are at high risk of converting to AD, identifying MCI individuals is essential for early intervention. To delineate the redundancy profile during AD progression and enable better MCI diagnosis, we define a metric that reflects redundant disjoint connections between brain regions and extract redundancy features in three high-order brain networks-medial frontal, frontoparietal, and default mode networks-based on dynamic functional connectivity (dFC) captured by resting-state functional magnetic resonance imaging (rs-fMRI). We show that redundancy increases significantly from normal control (NC) to MCI individuals and decreases slightly from MCI to AD individuals. We further demonstrate that statistical features of redundancy are highly discriminative and yield state-of-the-art accuracy of up to 96.8 ± 1.0% in support vector machine (SVM) classification between NC and MCI individuals. This study provides evidence supporting the notion that redundancy serves as a crucial neuroprotective mechanism in MCI.

PMID:36896755 | DOI:10.1002/hbm.26257

The involvement of spontaneous brain activity in natural recovery from internet gaming disorder: A resting-state fMRI study

Fri, 03/10/2023 - 19:00

Front Psychiatry. 2023 Feb 21;14:1093784. doi: 10.3389/fpsyt.2023.1093784. eCollection 2023.


OBJECTIVE: Internet gaming disorder (IGD) can seriously impair an individual's physical and mental health. However, unlike the majority of those suffering from substance addiction, individuals with IGD may recover without any professional intervention. Understanding the brain mechanisms of natural recovery from IGD may provide new insight into how to prevent addiction and implement more targeted interventions.

METHODS: Sixty individuals with IGD were scanned by using a resting-state fMRI to assess brain region changes associated with IGD. After 1 year, 19 individuals with IGD no longer met the IGD criteria and were considered recovered (RE-IGD), 23 individuals still met the IGD criteria (PER-IGD), and 18 individuals left the study. The brain activity in resting state between 19 RE-IGD individuals and 23 PER-IGD individuals was compared by using regional homogeneity (ReHo). Additionally, brain structure and cue-craving functional MRIs were collected to further support the results in the resting-state.

RESULTS: The resting-state fMRI results revealed that activity in brain regions responsible for reward and inhibitory control [including the orbitofrontal cortex (OFC), the precuneus and the dorsolateral prefrontal cortex (DLPFC)] was decreased in the PER-IGD individuals compared to RE-IGD individuals. In addition, significant positive correlations were found between mean ReHo values in the precuneus and self-reported craving scores for gaming, whether among the PER-IGD individuals or the RE-IGD individuals. Furthermore, we found similar results in that brain structure and cue-craving differences exist between the PER-IGD individuals and RE-IGD individuals, specifically in the brain regions associated with reward processing and inhibitory control (including the DLPFC, anterior cingulate gyrus, insula, OFC, precuneus, and superior frontal gyrus).

CONCLUSION: These findings indicate that the brain regions responsible for reward processing and inhibitory control are different in PER-IGD individuals, which may have consequences on natural recovery. Our present study provides neuroimaging evidence that spontaneous brain activity may influence natural recovery from IGD.

PMID:36896348 | PMC:PMC9990821 | DOI:10.3389/fpsyt.2023.1093784

Environmental effects on brain functional networks in a juvenile twin population

Thu, 03/09/2023 - 19:00

Sci Rep. 2023 Mar 9;13(1):3921. doi: 10.1038/s41598-023-30672-2.


The brain's intrinsic organization into large-scale functional networks, the resting state networks (RSN), shows complex inter-individual variability, consolidated during development. Nevertheless, the role of gene and environment on developmental brain functional connectivity (FC) remains largely unknown. Twin design represents an optimal platform to shed light on these effects acting on RSN characteristics. In this study, we applied statistical twin methods to resting-state functional magnetic resonance imaging (rs-fMRI) scans from 50 young twin pairs (aged 10-30 years) to preliminarily explore developmental determinants of brain FC. Multi-scale FC features were extracted and tested for applicability of classical ACE and ADE twin designs. Epistatic genetic effects were also assessed. In our sample, genetic and environmental effects on the brain functional connections largely varied between brain regions and FC features, showing good consistency at multiple spatial scales. Although we found selective contributions of common environment on temporo-occipital connections and of genetics on frontotemporal connections, the unique environment showed a predominant effect on FC link- and node-level features. Despite the lack of accurate genetic modeling, our preliminary results showed complex relationships between genes, environment, and functional brain connections during development. A predominant role of the unique environment on multi-scale RSN characteristics was suggested, which needs replications on independent samples. Future investigations should especially focus on nonadditive genetic effects, which remain largely unexplored.

PMID:36894644 | DOI:10.1038/s41598-023-30672-2

Detecting type 2 diabetes mellitus cognitive impairment using whole-brain functional connectivity

Thu, 03/09/2023 - 19:00

Sci Rep. 2023 Mar 9;13(1):3940. doi: 10.1038/s41598-023-28163-5.


Type 2 diabetes mellitus (T2DM) is closely linked to cognitive decline and alterations in brain structure and function. Resting-state functional magnetic resonance imaging (rs-fMRI) is used to diagnose neurodegenerative diseases, such as cognitive impairment (CI), Alzheimer's disease (AD), and vascular dementia (VaD). However, whether the functional connectivity (FC) of patients with T2DM and mild cognitive impairment (T2DM-MCI) is conducive to early diagnosis remains unclear. To answer this question, we analyzed the rs-fMRI data of 37 patients with T2DM and mild cognitive impairment (T2DM-MCI), 93 patients with T2DM but no cognitive impairment (T2DM-NCI), and 69 normal controls (NC). We achieved an accuracy of 87.91% in T2DM-MCI versus T2DM-NCI classification and 80% in T2DM-NCI versus NC classification using the XGBoost model. The thalamus, angular, caudate nucleus, and paracentral lobule contributed most to the classification outcome. Our findings provide valuable knowledge to classify and predict T2DM-related CI, can help with early clinical diagnosis of T2DM-MCI, and provide a basis for future studies.

PMID:36894561 | DOI:10.1038/s41598-023-28163-5

Altered static and dynamic indices of intrinsic brain activity in patients with subcortical ischemic vascular disease: a resting-state functional magnetic resonance imaging analysis

Thu, 03/09/2023 - 19:00

Neuroradiology. 2023 Mar 9. doi: 10.1007/s00234-023-03135-8. Online ahead of print.


PURPOSE: To explore the static and dynamic characteristics of intrinsic brain activity (IBA) in subcortical ischemic vascular disease (SIVD) patients with or without cognitive impairment.

METHODS: In total, 90 participants were recruited, including 32 SIVD patients with cognitive impairment (SIVD-CI, N = 32), 26 SIVD patients with no cognitive impairment (SIVD-NCI, N = 26), and 32 healthy controls (HC, N = 32) matched for age, gender, and education. All subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning and neuropsychological tests. Amplitude of low-frequency fluctuation (ALFF) was calculated to reflect static alterations of regional IBA. Sliding window analysis was conducted in order to explore the dynamic characteristics.

RESULTS: Both SIVD-CI and SIVD-NCI group showed significantly decreased ALFF in left angular gyrus (ANG), whereas SIVD-CI group showed increased ALFF in right superior frontal gyrus (SFG), compared with HCs. Furthermore, SIVD-CI group showed significantly decreased ALFF dynamics (dALFF) in right precuneus (PreCu) and left dorsal anterior cingulate cortex (dACC), compared with HC and SIVD-NCI groups (Gaussian random field-corrected, voxel-level P < 0.001, cluster-level P < 0.05). No dynamic changes were detected between SIVD-NCI group and HC group. The mean ALFF value in left ANG of SIVD-CI group was correlated with the score of delayed memory scale.

CONCLUSION: ANG may be a vulnerable brain region in SIVD patients. Temporal dynamic analysis could serve as a sensitive and promising method to investigate IBA alterations in SIVD patients.

PMID:36892613 | DOI:10.1007/s00234-023-03135-8

Functional connectivity between pre-supplementary motor area and inferior parietal lobule associated with impaired motor response inhibition in first-degree relatives of patients with obsessive-compulsive disorder

Thu, 03/09/2023 - 19:00

Cereb Cortex. 2023 Mar 9:bhad058. doi: 10.1093/cercor/bhad058. Online ahead of print.


Previous studies have suggested that specific fronto-striatal circuits are associated with impaired motor response inhibition in patients with obsessive-compulsive disorder (OCD) and their relatives. However, no study has investigated the underlying resting-state network associated with motor response inhibition in the unaffected first-degree relatives of patients with OCD. We measured motor response inhibition using stop-signal task, and obtained resting-state fMRI in 23 first-degree relatives and 52 healthy control participants. We explored the group differences in the functional network from seed regions-of-interest (ROIs) associated with motor response inhibition abilities. We used the inferior frontal gyrus (IFG) and pre-supplementary motor area (pre-SMA) as seed-ROIs. A significant group difference was observed in functional connectivity between the pre-SMA and inferior parietal lobule. In the relative group, reduced functional connectivity between these areas was associated with a longer stop-signal reaction time. Additionally, relatives showed significantly greater functional connectivity between the IFG and SMA, precentral, and postcentral areas. Our results could provide new insights into the resting-state neural activity of the pre-SMA underlying impaired motor response inhibition of unaffected first-degree relatives. In addition, our results suggested that relatives have an altered connectivity of the sensorimotor region, similar to that of patients with OCD shown in previous literature.

PMID:36892216 | DOI:10.1093/cercor/bhad058

Modulation effects of different treatments on periaqueductal gray resting state functional connectivity in knee osteoarthritis knee pain patients

Thu, 03/09/2023 - 19:00

CNS Neurosci Ther. 2023 Mar 8. doi: 10.1111/cns.14153. Online ahead of print.


BACKGROUND: The analgesic effect of acupuncture is widely recognized, but the mechanical characteristics of acupuncture for pain relief, compared to non-steroidal anti-inflammatory (NSAIDs) and placebo medication, remain unknown.

AIMS: To compare the modulation effects of acupuncture treatment with NSAIDs and placebo medication on descending pain modulation system (DPMS) in knee osteoarthritis (KOA) patients.

METHODS: This study recruited 180 KOA patients with knee pain and 41 healthy controls (HCs). Individuals with KOA knee pain were divided randomly into groups of verum acupuncture (VA), sham acupuncture (SA), celecoxib (SC), placebo (PB), and waiting list (WT), with 36 patients in each group. VA and SA groups included ten sessions of puncturing acupoints or puncturing non-acupoints acupuncture treatment for two successive weeks. Celecoxib capsules were continuously given orally to patients in the SC group at a dosage of 200 mg daily for 2 weeks. In the PB group, patients received a placebo capsule once a day for 2 weeks at the same dosage as celecoxib capsules. In the WL group, patients did not receive any treatment. Patients underwent a resting-state BOLD-fMRI scan pre- and post-receiving the therapy, whereas HCs only underwent a baseline scan. Seed (ventrolateral periaqueductal gray, vlPAG, a key node in DPMS) based resting-state functional connectivity (rs-FC) was applied in the data analysis.

RESULTS: All groups demonstrated improved knee pain scores relative to the initial state. There was no statistical difference between the VA and SA groups in all clinical outcomes, and vlPAG rs-FC alterations. KOA knee pain individuals reported higher vlPAG rs-FC in the bilateral thalamus than HCs. KOA knee pain patients in the acupuncture group (verum + sham, AG) exhibited increased vlPAG rs-FC with the right dorsolateral prefrontal cortex (DLPFC) and the right angular, which is associated with knee pain improvement. In contrast with the SC and PB group, the AG exhibited significantly increased vlPAG rs-FC with the right DLPFC and angular. Contrary to the WT group, the AG showed greater vlPAG rs-FC with the right DLPFC and precuneus.

CONCLUSIONS: Acupuncture treatment, celecoxib, and placebo medication have different modulation effects on vlPAG DPMS in KOA knee pain patients. Acupuncture could modulate vlPAG rs-FC with brain regions associated with cognitive control, attention, and reappraisal for knee pain relief in KOA patients, compared with celecoxib and placebo medication.

PMID:36890655 | DOI:10.1111/cns.14153

Establishing language laterality: does resting-state functional MRI help?

Wed, 03/08/2023 - 19:00

J Neurosurg Pediatr. 2023 Mar 3:1-7. doi: 10.3171/2023.1.PEDS22497. Online ahead of print.


OBJECTIVE: Task-based functional MRI (tb-fMRI) is now considered the standard, noninvasive technique in establishing language laterality in children for surgical planning. The evaluation can be limited due to several factors such as age, language barriers, and developmental and cognitive delays. Resting-state functional MRI (rs-fMRI) offers a potential path to establish language dominance without active task participation. The authors sought to compare the ability of rs-fMRI for language lateralization in the pediatric population with conventional tb-fMRI used as the gold standard.

METHODS: The authors performed a retrospective evaluation of all pediatric patients at a dedicated quaternary pediatric hospital who underwent tb-fMRI and rs-fMRI from 2019 to 2021 as part of the surgical workup for patients with seizures and brain tumors. Task-based fMRI language laterality was based on a patient's adequate performance on one or more of the following: sentence completion, verb generation, antonym generation, or passive listening tasks. Resting-state fMRI data were postprocessed using statistical parametric mapping, FMRIB Software Library, and FreeSurfer as described in the literature. The laterality index (LI) was calculated from the independent component (IC) with the highest Jaccard Index (JI) for the language mask. Additionally, the authors visually inspected the activation maps for two ICs with the highest JIs. The rs-fMRI LI of IC1 and the authors' image-based subjective interpretation of language lateralization were compared with tb-fMRI, which was considered the gold standard for this study.

RESULTS: A retrospective search yielded 33 patients with language fMRI data. Eight patients were excluded (5 with suboptimal tb-fMRI and 3 with suboptimal rs-fMRI data). Twenty-five patients (age range 7-19 years, male/female ratio 15:10) were included in the study. The language laterality concordance between tb-fMRI and rs-fMRI ranged from 68% to 80% for assessment based on LI of independent component analysis with highest JI and for subjective evaluation by visual inspection of activation maps, respectively.

CONCLUSIONS: The concordance rates between tb-fMRI and rs-fMRI of 68% to 80% show the limitation of rs-fMRI in determining language dominance. Resting-state fMRI should not be used as the sole method for language lateralization in clinical practice.

PMID:36883636 | DOI:10.3171/2023.1.PEDS22497

BOLD frequency-dependent alterations in resting-state functional connectivity by pallidal deep brain stimulation in patients with Parkinson's disease

Wed, 03/08/2023 - 19:00

J Neurosurg. 2023 Mar 3:1-12. doi: 10.3171/2023.1.JNS221858. Online ahead of print.


OBJECTIVE: Functional MRI (fMRI) has been used to investigate the therapeutic mechanisms underlying deep brain stimulation (DBS) for Parkinson's disease (PD). However, the alterations in stimulation site-seeded functional connectivity induced by DBS at the internal globus pallidus (GPi) remain unclear. Furthermore, whether DBS-modulated functional connectivity is differentially affected within particular frequency bands remains unknown. The present study aimed to reveal the alterations in stimulation site-seeded functional connectivity induced by GPi-DBS and to examine whether there exists a frequency band effect in blood oxygen level-dependent (BOLD) signals related to DBS.

METHODS: Patients with PD receiving GPi-DBS (n = 28) were recruited for resting-state fMRI with DBS on and DBS off under a 1.5-T MR scanner. Age- and sex-matched healthy controls (n = 16) and DBS-naïve PD patients (n = 24) also received fMRI scanning. The alterations in stimulation site-seeded functional connectivity in the stimulation-on state versus stimulation-off state, as well as the relationship between alterations in connectivity and improvement in motor function induced by GPi-DBS, were examined. Furthermore, the modulatory effect of GPi-DBS on the BOLD signals within the 4 frequency subbands (slow-2 to slow-5) was investigated. Finally, the functional connectivity of the motor-related network, consisting of multiple cortical and subcortical regions, was also examined among the groups. In this study, p < 0.05 with Gaussian random field correction indicates statistical significance.

RESULTS: Functional connectivity seeding from the stimulation site (i.e., the volume of tissue activated [VTA]) increased in the cortical sensorimotor areas and decreased in the prefrontal regions with GPi-DBS. Alterations in connectivity between the VTA and the cortical motor areas were correlated with motor improvement by pallidal stimulation. The alterations in connectivity were dissociable between the frequency subbands in the occipital and cerebellar areas. The motor network analysis indicated decreased connectivity among most cortical and subcortical regions but increased connectivity between the motor thalamus and the cortical motor area in patients with GPi-DBS compared with those in DBS-naïve patients. The DBS-induced decrease in several cortical-subcortical connectivities within the slow-5 band correlated with motor improvement with GPi-DBS.

CONCLUSIONS: These findings indicate that the alterations in functional connectivity from the stimulation site to the cortical motor areas, as well as multiple connectivities among the motor-related network, were associated with the efficacy of GPi-DBS for PD. Furthermore, the changing pattern of functional connectivity within the 4 BOLD frequency subbands is partially dissociable.

PMID:36883631 | DOI:10.3171/2023.1.JNS221858

Aberrant olfactory network functional connectivity in people with olfactory dysfunction following COVID-19 infection: an exploratory, observational study

Wed, 03/08/2023 - 19:00

EClinicalMedicine. 2023 Apr;58:101883. doi: 10.1016/j.eclinm.2023.101883. Epub 2023 Mar 2.


BACKGROUND: Olfactory impairments and anosmia from COVID-19 infection typically resolve within 2-4 weeks, although in some cases, symptoms persist longer. COVID-19-related anosmia is associated with olfactory bulb atrophy, however, the impact on cortical structures is relatively unknown, particularly in those with long-term symptoms.

METHODS: In this exploratory, observational study, we studied individuals who experienced COVID-19-related anosmia, with or without recovered sense of smell, and compared against individuals with no prior COVID-19 infection (confirmed by antibody testing, all vaccine naïve). MRI Imaging was carried out between the 15th July and 17th November 2020 at the Queen Square House Clinical Scanning Facility, UCL, United Kingdom. Using functional magnetic resonance imaging (fMRI) and structural imaging, we assessed differences in functional connectivity (FC) between olfactory regions, whole brain grey matter (GM) cerebral blood flow (CBF) and GM density.

FINDINGS: Individuals with anosmia showed increased FC between the left orbitofrontal cortex (OFC), visual association cortex and cerebellum and FC reductions between the right OFC and dorsal anterior cingulate cortex compared to those with no prior COVID-19 infection (p < 0.05, from whole brain statistical parametric map analysis). Individuals with anosmia also showed greater CBF in the left insula, hippocampus and ventral posterior cingulate when compared to those with resolved anosmia (p < 0.05, from whole brain statistical parametric map analysis).

INTERPRETATION: This work describes, for the first time to our knowledge, functional differences within olfactory areas and regions involved in sensory processing and cognitive functioning. This work identifies key areas for further research and potential target sites for therapeutic strategies.

FUNDING: This study was funded by the National Institute for Health and Care Research and supported by the Queen Square Scanner business case.

PMID:36883140 | PMC:PMC9980836 | DOI:10.1016/j.eclinm.2023.101883

Tensorial independent component analysis reveals social and reward networks associated with major depressive disorder

Tue, 03/07/2023 - 19:00

Hum Brain Mapp. 2023 Mar 7. doi: 10.1002/hbm.26254. Online ahead of print.


Major depressive disorder (MDD) has been associated with changes in functional brain connectivity. Yet, typical analyses of functional connectivity, such as spatial independent components analysis (ICA) for resting-state data, often ignore sources of between-subject variability, which may be crucial for identifying functional connectivity patterns associated with MDD. Typically, methods like spatial ICA will identify a single component to represent a network like the default mode network (DMN), even if groups within the data show differential DMN coactivation. To address this gap, this project applies a tensorial extension of ICA (tensorial ICA)-which explicitly incorporates between-subject variability-to identify functionally connected networks using functional MRI data from the Human Connectome Project (HCP). Data from the HCP included individuals with a diagnosis of MDD, a family history of MDD, and healthy controls performing a gambling and social cognition task. Based on evidence associating MDD with blunted neural activation to rewards and social stimuli, we predicted that tensorial ICA would identify networks associated with reduced spatiotemporal coherence and blunted social and reward-based network activity in MDD. Across both tasks, tensorial ICA identified three networks showing decreased coherence in MDD. All three networks included ventromedial prefrontal cortex, striatum, and cerebellum and showed different activation across the conditions of their respective tasks. However, MDD was only associated with differences in task-based activation in one network from the social task. Additionally, these results suggest that tensorial ICA could be a valuable tool for understanding clinical differences in relation to network activation and connectivity.

PMID:36880638 | DOI:10.1002/hbm.26254

Resting-state functional connectivity of the raphe nuclei in major depressive Disorder: A Multi-site study

Mon, 03/06/2023 - 19:00

Neuroimage Clin. 2023 Feb 24;37:103359. doi: 10.1016/j.nicl.2023.103359. Online ahead of print.


Accumulating evidence showed that major depressive disorder (MDD) is characterized by a dysfunction of serotonin neurotransmission. Raphe nuclei are the sources of most serotonergic neurons that project throughout the brain. Incorporating measurements of activity within the raphe nuclei into the analysis of connectivity characteristics may contribute to understanding how neurotransmitter synthesized centers are involved in thepathogenesisof MDD. Here, we analyzed the resting-state functional magnetic resonance imaging (RS-fMRI) dataset from 1,148 MDD patients and 1,079 healthy individuals recruited across nine centers. A seed-based analysis with the dorsal raphe and median raphe nuclei was performed to explore the functional connectivity (FC) alterations. Compared to controls, for dorsal raphe, the significantly decreased FC linking with the right precuneus and median cingulate cortex were found; for median raphe, the increased FC linking with right superior cerebellum (lobules V/VI) was found in MDD patients. In further exploratory analyzes, MDD-related connectivity alterations in dorsal and median raphe nuclei in different clinical factors remained highly similar to the main findings, indicating these abnormal connectivities are a disease-related alteration. Our study highlights a functional dysconnection pattern of raphe nuclei in MDD with multi-site big data. These findings help improve our understanding of the pathophysiology of depression and provide evidence of the theoretical foundation for the development of novel pharmacotherapies.

PMID:36878150 | DOI:10.1016/j.nicl.2023.103359

Macroscopic resting state model predicts theta burst stimulation response: A randomized trial

Mon, 03/06/2023 - 19:00

PLoS Comput Biol. 2023 Mar 6;19(3):e1010958. doi: 10.1371/journal.pcbi.1010958. Online ahead of print.


Repetitive transcranial magnetic stimulation (rTMS) is a promising alternative therapy for treatment-resistant depression, although its limited remission rate indicates room for improvement. As depression is a phenomenological construction, the biological heterogeneity within this syndrome needs to be considered to improve the existing therapies. Whole-brain modeling provides an integrative multi-modal framework for capturing disease heterogeneity in a holistic manner. Computational modelling combined with a probabilistic nonparametric fitting was applied to the resting-state fMRI data from 42 patients (21 women), to parametrize baseline brain dynamics in depression. All patients were randomly assigned to two treatment groups, namely active (i.e., rTMS, n = 22) or sham (n = 20). The active treatment group received rTMS treatment with an accelerated intermittent theta burst protocol over the dorsomedial prefrontal cortex. The sham treatment group underwent the identical procedure but with the magnetically shielded side of the coil. We stratified the depression sample into distinct covert subtypes based on their baseline attractor dynamics captured by different model parameters. Notably, the two detected depression subtypes exhibited different phenotypic behaviors at baseline. Our stratification could predict the diverse response to the active treatment that could not be explained by the sham treatment. Critically, we further found that one group exhibited more distinct improvement in certain affective and negative symptoms. The subgroup of patients with higher responsiveness to treatment exhibited blunted frequency dynamics for intrinsic activity at baseline, as indexed by lower global metastability and synchrony. Our findings suggested that whole-brain modeling of intrinsic dynamics may constitute a determinant for stratifying patients into treatment groups and bringing us closer towards precision medicine.

PMID:36877733 | DOI:10.1371/journal.pcbi.1010958