New resting-state fMRI related studies at PubMed

Regional skeletal muscle perfusion distribution in diabetic feet may differentiate short-term healed foot ulcers from non-healed ulcers

Tue, 01/31/2023 - 11:00

Eur Radiol. 2023 Jan 31. doi: 10.1007/s00330-023-09405-6. Online ahead of print.


OBJECTIVES: The purpose of this study was to leverage a magnetic resonance imaging (MRI) approach to characterize foot perfusion distribution in patients with diabetes, with or without foot ulcers, and determine the ability of the regional perfusion measurements to identify ulcer-healing status.

METHODS: Three groups of participants (n = 15 / group) were recruited: controls (without diabetes), type II diabetes, and type II diabetes with foot ulcers. All participants underwent MRI evaluating foot perfusion in three muscle layers (from plantar to dorsal) at rest and during a standardized toe-flexion exercise. The exercise perfusion and perfusion reserve values were analyzed around and away from ulcers. Participants with foot ulcers were followed up 3 months after the MRI exams to determine the foot healing status.

RESULTS: Foot plantar muscle perfusion reserves were progressively lower from controls to diabetes, and to diabetes with foot ulcers (e.g., 2.58 ± 0.67, 1.48 ± 0.71, 1.12 ± 0.35, p < 0.001). In controls, the plantar layer had significantly higher perfusion reserve than the dorsal layer, whereas in either diabetes group, there was no significant difference in perfusion reserve among muscle layers. Using the ratio of total exercise perfusion around ulcers to that away from ulcers, the sensitivity and specificity to differentiate healing from non-healed ulcers were 100% and 86%, respectively.

CONCLUSIONS: Our study reveals significantly different foot perfusion distribution among controls, diabetes, and diabetes with foot ulcers. The prognostic value of MRI regional perfusion assessments has the potential to monitor interventions to improve ulcer healing outcomes.

KEY POINTS: • Contrast-free MRI permits quantitative assessment of regional foot muscle perfusion at rest and during isometric exercise. • Patients with diabetes and foot ulcers, without clinical evidence of peripheral arterial disease, had significantly impaired foot muscle perfusion and perfusion reserve. • Regional foot perfusion distribution may be used to predict the short-term healing status of foot ulcers in diabetes.

PMID:36719497 | DOI:10.1007/s00330-023-09405-6

Sex based structural and functional MRI outcomes in the rat brain after soman (GD) exposure induced status epilepticus

Tue, 01/31/2023 - 11:00

Epilepsia Open. 2023 Jan 31. doi: 10.1002/epi4.12701. Online ahead of print.


OBJECTIVE: Exposure to the nerve agent, soman (GD), induces status epilepticus (SE), epileptogenesis and even death. Although rodent models studying the pathophysiological mechanisms show females to be more reactive to soman, no tangible sex differences in brains post-exposure have been reported. In this study, we used multimodal imaging using MRI in adult rats to determine potential sex-based biomarkers of soman effects.

METHODS: Male and female Sprague Dawley rats were challenged with 1.2xLD50 soman followed by medical countermeasures. Ten weeks later the brains were analyzed via structural and functional MRI.

RESULTS: Despite no significant sex differences in the initial SE severity after soman exposure, long-term MRI-based structural and functional differences were evident in the brains of both sexes. While T2 MRI showed lesser soman-induced neurodegeneration, large areas of T1 enhancements occurred in females than males, indicating a distinct pathophysiology unrelated to neurodegeneration. fMRI-based resting-state functional connectivity (RSFC), indicated greater reductions in soman-exposed females than males, associating with the T1 enhancements (unrelated to neurodegeneration) rather than T2-hyperintensity or T1-hypointensity (representing neurodegeneration). The wider T1 enhancements associating with the decreased spontaneous neuronal activity in multiple resting state networks in soman-exposed females than males suggest that neural changes unrelated to cellular atrophy impinge on brain function post-exposure. Taken together with lower spontaneous neural activity in soman exposed females, the results indicate some form of neuroprotective state that was not present in males.

SIGNIFICANCE: The results indicate that endpoints other than neurodegeneration may need to be considered to translate sex-based nerve agent effects in humans.

PMID:36718979 | DOI:10.1002/epi4.12701

Methylphenidate Enhances Spontaneous Fluctuations in Reward and Cognitive Control Networks in Children With Attention-Deficit/Hyperactivity Disorder

Mon, 01/30/2023 - 11:00

Biol Psychiatry Cogn Neurosci Neuroimaging. 2022 Oct 23:S2451-9022(22)00247-6. doi: 10.1016/j.bpsc.2022.10.001. Online ahead of print.


BACKGROUND: Methylphenidate, a first-line treatment for attention-deficit/hyperactivity disorder (ADHD), is thought to influence dopaminergic neurotransmission in the nucleus accumbens (NAc) and its associated brain circuitry, but this hypothesis has yet to be systematically tested.

METHODS: We conducted a randomized, placebo-controlled, double-blind crossover trial including 27 children with ADHD. Children with ADHD were scanned twice with resting-state functional magnetic resonance imaging under methylphenidate and placebo conditions, along with assessment of sustained attention. We examined spontaneous neural activity in the NAc and the salience, frontoparietal, and default mode networks and their links to behavioral changes. Replicability of methylphenidate effects on spontaneous neural activity was examined in a second independent cohort.

RESULTS: Methylphenidate increased spontaneous neural activity in the NAc and the salience and default mode networks. Methylphenidate-induced changes in spontaneous activity patterns in the default mode network were associated with improvements in intraindividual response variability during a sustained attention task. Critically, despite differences in clinical trial protocols and data acquisition parameters, the NAc and the salience and default mode networks showed replicable patterns of methylphenidate-induced changes in spontaneous activity across two independent cohorts.

CONCLUSIONS: We provide reproducible evidence demonstrating that methylphenidate enhances spontaneous neural activity in NAc and cognitive control networks in children with ADHD, resulting in more stable sustained attention. Our findings identified a novel neural mechanism underlying methylphenidate treatment in ADHD to inform the development of clinically useful biomarkers for evaluating treatment outcomes.

PMID:36717325 | DOI:10.1016/j.bpsc.2022.10.001

Development of the Functional Connectome Topology in Adolescence: Evidence from Topological Data Analysis

Mon, 01/30/2023 - 11:00

eNeuro. 2023 Jan 27:ENEURO.0296-21.2022. doi: 10.1523/ENEURO.0296-21.2022. Online ahead of print.


Adolescence is a crucial developmental period in terms of behavior and mental health. Therefore, understanding how the brain develops during this stage is a fundamental challenge for neuroscience. Recent studies have modeled the brain as a network or connectome, mainly applying measures from graph theory, showing a change in its functional organization, such as an increase in its segregation and integration. Topological Data Analysis (TDA) complements such modeling by extracting high-dimensional features across the whole range of connectivity values instead of exploring a fixed set of connections. This study inquires into the developmental trajectories of such properties using a longitudinal sample of typically developing human participants (N = 98; 53/45 female/male; 6.7-18.1 years), applying TDA to their functional connectomes. In addition, we explore the effect of puberty on individual developmental trajectories. Results showed that the adolescent brain has a more distributed topology structure compared with random networks but is more densely connected at the local level. Furthermore, developmental effects showed nonlinear trajectories for the topology of the whole brain and fronto-parietal networks, with an inflection point and increasing trajectories after puberty onset. These results add to the insights into the development of the functional organization of the adolescent brain.Significance StatementTopological Data Analysis (TDA) may be used to explore the topology of the brain along the whole range of connectivity values instead of selecting only a fixed set of connectivity thresholds. Here, we explored some properties of the topology of the brain's functional connectome and how they develop in adolescence. We show that developmental trajectories are nonlinear and better adjusted by puberty status than chronological age, with an inflection point around the onset of puberty. In particular, the results show that the topology of the fronto-parietal network is the one that drives the functional connectome changes in the adolescent period.

PMID:36717266 | DOI:10.1523/ENEURO.0296-21.2022

Verification of the brain network marker of major depressive disorder: Test-retest reliability and anterograde generalization performance for newly acquired data

Mon, 01/30/2023 - 11:00

J Affect Disord. 2023 Jan 27:S0165-0327(23)00105-2. doi: 10.1016/j.jad.2023.01.087. Online ahead of print.


BACKGROUND: Recently, we developed a generalizable brain network marker for the diagnosis of major depressive disorder (MDD) across multiple imaging sites using resting-state functional magnetic resonance imaging. Here, we applied this brain network marker to newly acquired data to verify its test-retest reliability and anterograde generalization performance for new patients.

METHODS: We tested the sensitivity and specificity of our brain network marker of MDD using data acquired from 43 new patients with MDD as well as new data from 33 healthy controls (HCs) who participated in our previous study. To examine the test-retest reliability of our brain network marker, we evaluated the intraclass correlation coefficients (ICCs) between the brain network marker-based classifier's output (probability of MDD) in two sets of HC data obtained at an interval of approximately 1 year.

RESULTS: Test-retest correlation between the two sets of the classifier's output (probability of MDD) from HCs exhibited moderate reliability with an ICC of 0.45 (95 % confidence interval,0.13-0.68). The classifier distinguished patients with MDD and HCs with an accuracy of 69.7 % (sensitivity, 72.1 %; specificity, 66.7 %).

LIMITATIONS: The data of patients with MDD in this study were cross-sectional, and the clinical significance of the marker, such as whether it is a state or trait marker of MDD and its association with treatment responsiveness, remains unclear.

CONCLUSIONS: The results of this study reaffirmed the test-retest reliability and generalization performance of our brain network marker for the diagnosis of MDD.

PMID:36717028 | DOI:10.1016/j.jad.2023.01.087

Functional connectivity changes between amygdala and prefrontal cortex after ECT are associated with improvement in distinct depressive symptoms

Mon, 01/30/2023 - 11:00

Eur Arch Psychiatry Clin Neurosci. 2023 Jan 30. doi: 10.1007/s00406-023-01552-7. Online ahead of print.


Electroconvulsive therapy (ECT) is one of the most effective treatments for treatment-resistant depression. However, the underlying mechanisms of action are not yet fully understood. The investigation of depression-specific networks using resting-state fMRI and the relation to differential symptom improvement might be an innovative approach providing new insights into the underlying processes. In this naturalistic study, we investigated the relationship between changes in resting-state functional connectivity (rsFC) and symptom improvement after ECT in 21 patients with treatment-resistant depression. We investigated rsFC before and after ECT and focused our analyses on FC changes directly related to symptom reduction and on FC at baseline to identify neural targets that might predict individual clinical responses to ECT. Additional analyses were performed to identify the direct relationship between rsFC change and symptom dimensions such as sadness, negative thoughts, detachment, and neurovegetative symptoms. An increase in rsFC between the left amygdala and left dorsolateral prefrontal cortex (DLPFC) after ECT was related to overall symptom reduction (Bonferroni-corrected p = 0.033) as well as to a reduction in specific symptoms such as sadness (r = 0.524, uncorrected p = 0.014), negative thoughts (r = 0.700, Bonferroni-corrected p = 0.002) and detachment (r = 0.663, p = 0.004), but not in neurovegetative symptoms. Furthermore, high baseline rsFC between the left amygdala and the right frontal pole (FP) predicted treatment outcome (uncorrected p = 0.039). We conclude that changes in FC in regions of the limbic-prefrontal network are associated with symptom improvement, particularly in affective and cognitive dimensions. Frontal-limbic connectivity has the potential to predict symptom improvement after ECT. Further research combining functional imaging biomarkers and a symptom-based approach might be promising.

PMID:36715751 | DOI:10.1007/s00406-023-01552-7

Altered brain activity and functional connectivity after MDMA-assisted therapy for post-traumatic stress disorder

Mon, 01/30/2023 - 11:00

Front Psychiatry. 2023 Jan 12;13:947622. doi: 10.3389/fpsyt.2022.947622. eCollection 2022.


INTRODUCTION: 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) for post-traumatic stress disorder (PTSD) has demonstrated promise in multiple clinical trials. MDMA is hypothesized to facilitate the therapeutic process, in part, by decreasing fear response during fear memory processing while increasing extinction learning. The acute administration of MDMA in healthy controls modifies recruitment of brain regions involved in the hyperactive fear response in PTSD such as the amygdala, hippocampus, and insula. However, to date there have been no neuroimaging studies aimed at directly elucidating the neural impact of MDMA-AT in PTSD patients.

METHODS: We analyzed brain activity and connectivity via functional MRI during both rest and autobiographical memory (trauma and neutral) response before and two-months after MDMA-AT in nine veterans and first-responders with chronic PTSD of 6 months or more.

RESULTS: We hypothesized that MDMA-AT would increase amygdala-hippocampus resting-state functional connectivity, however we only found evidence of a trend in the left amygdala-left hippocampus (t = -2.91, uncorrected p = 0.0225, corrected p = 0.0901). We also found reduced activation contrast (trauma > neutral) after MDMA-AT in the cuneus. Finally, the amount of recovery from PTSD after MDMA-AT correlated with changes in four functional connections during autobiographical memory recall: the left amygdala-left posterior cingulate cortex (PCC), left amygdala-right PCC, left amygdala-left insula, and left isthmus cingulate-left posterior hippocampus.

DISCUSSION: Amygdala-insular functional connectivity is reliably implicated in PTSD and anxiety, and both regions are impacted by MDMA administration. These findings compliment previous research indicating that amygdala, hippocampus, and insula functional connectivity is a potential target of MDMA-AT, and highlights other regions of interest related to memory processes. More research is necessary to determine if these findings are specific to MDMA-AT compared to other types of treatment for PTSD.


PMID:36713926 | PMC:PMC9879604 | DOI:10.3389/fpsyt.2022.947622

Desynchronized white matter function and structure in drug-naive first-episode major depressive disorder patients

Mon, 01/30/2023 - 11:00

Front Psychiatry. 2023 Jan 11;13:1082052. doi: 10.3389/fpsyt.2022.1082052. eCollection 2022.


BACKGROUND: Major depressive disorder (MDD) is a highly prevalent mental disease. Using magnetic resonance imaging (MRI), although numerous studies have revealed the alterations in structure and function of grey matter (GM), few studies focused on the synchronization of white matter (WM) structure and function in MDD. The aim of this study was to investigate whether functional and structural abnormalities of WM play an essential role in the neurobiological mechanisms of MDD.

METHODS: Gradient-echo imaging sequences at 3.0T were used to gather resting state functional MRI (rsfMRI) data, which were performed on 33 drug-naive first-episode MDD patients and 34 healthy controls (HCs). After data preprocessed, amplitude of low frequency fluctuation (ALFF) of WM was calculated. ALFF values in different frequency bands were analyzed, including typical (0.01-0.15 Hz) band, slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz) bands. In addition, the fractional anisotropy (FA) values in WM in 23 patients and 26 HCs were examined using tract-based spatial statistics (TBSS) and tractography based on diffusion tensor imaging (DTI). Pearson correlation analysis was applied to analyze the relationships between ALFF values and Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA).

RESULTS: Compared with the HCs, MDD patients showed decreased ALFF values in posterior thalamic radiation (PTR) and superior longitudinal fasciculus (SLF) in slow-5 frequency band, no significant differences of ALFF values were found in typical and slow-4 frequency bands. In addition, there were no significant differences in FA values with TBSS analysis as well as the number of fibers in PTR and SLF with tractography analysis between two groups. Further correlation analysis showed that the ALFF value in SLF was negatively correlated with HAMA-2 score (r = -0.548, p FDR = 0.037) in patients.

CONCLUSION: Our results indicated that WM dysfunction may be associated with the pathophysiological mechanism of depression. Our study also suggested that the functional damage of the WM may precedes the structural damage in first-episode MDD patients. Furthermore, for mental disorders, slow-5 frequency band may be a more sensitive functional indicator for early detection of abnormal spontaneous brain activity in WM.

PMID:36713909 | PMC:PMC9874158 | DOI:10.3389/fpsyt.2022.1082052

A method for reconstruction of interpretable brain networks from transient synchronization in resting-state BOLD fluctuations

Mon, 01/30/2023 - 11:00

Front Neuroinform. 2023 Jan 12;16:960607. doi: 10.3389/fninf.2022.960607. eCollection 2022.


Resting-state (rs) fMRI has been widely used to examine brain-wide large-scale spatiotemporal architectures, known as resting-state networks (RSNs). Recent studies have focused on the temporally evolving characteristics of RSNs, but it is unclear what temporal characteristics are reflected in the networks. To address this issue, we devised a novel method for voxel-based visualization of spatiotemporal characteristics of rs-fMRI with a time scale of tens of seconds. We first extracted clusters of dominant activity-patterns using a region-of-interest approach and then used these temporal patterns of the clusters to obtain voxel-based activation patterns related to the clusters. We found that activation patterns related to the clusters temporally evolved with a characteristic temporal structure and showed mutual temporal alternations over minutes. The voxel-based representation allowed the decoding of activation patterns of the clusters in rs-fMRI using a meta-analysis of functional activations. The activation patterns of the clusters were correlated with behavioral measures. Taken together, our analysis highlights a novel approach to examine brain activity dynamics during rest.

PMID:36713290 | PMC:PMC9878402 | DOI:10.3389/fninf.2022.960607

Resting state network mapping in individuals using deep learning

Mon, 01/30/2023 - 11:00

Front Neurol. 2023 Jan 12;13:1055437. doi: 10.3389/fneur.2022.1055437. eCollection 2022.


INTRODUCTION: Resting state functional MRI (RS-fMRI) is currently used in numerous clinical and research settings. The localization of resting state networks (RSNs) has been utilized in applications ranging from group analysis of neurodegenerative diseases to individual network mapping for pre-surgical planning of tumor resections. Reproducibility of these results has been shown to require a substantial amount of high-quality data, which is not often available in clinical or research settings.

METHODS: In this work, we report voxelwise mapping of a standard set of RSNs using a novel deep 3D convolutional neural network (3DCNN). The 3DCNN was trained on publicly available functional MRI data acquired in n = 2010 healthy participants. After training, maps that represent the probability of a voxel belonging to a particular RSN were generated for each participant, and then used to calculate mean and standard deviation (STD) probability maps, which are made publicly available. Further, we compared our results to previously published resting state and task-based functional mappings.

RESULTS: Our results indicate this method can be applied in individual subjects and is highly resistant to both noisy data and fewer RS-fMRI time points than are typically acquired. Further, our results show core regions within each network that exhibit high average probability and low STD.

DISCUSSION: The 3DCNN algorithm can generate individual RSN localization maps, which are necessary for clinical applications. The similarity between 3DCNN mapping results and task-based fMRI responses supports the association of specific functional tasks with RSNs.

PMID:36712434 | PMC:PMC9878609 | DOI:10.3389/fneur.2022.1055437

Preoperative functional connectivity by magnetic resonance imaging for refractory neocortical epilepsy

Mon, 01/30/2023 - 11:00

medRxiv. 2023 Jan 11:2023.01.10.23284374. doi: 10.1101/2023.01.10.23284374. Preprint.


OBJECTIVE: Patients with refractory epilepsy experience extensive and invasive clinical testing for seizure onset zones treatable by surgical resection. However, surgical resection can fail to provide therapeutic benefit, and patients with neocortical epilepsy have the poorest therapeutic outcomes. This case series studied patients with neocortical epilepsy who were referred for surgical treatment. Prior to surgery, patients volunteered for resting-state functional magnetic resonance imaging (rs-fMRI) in addition to imaging for the clinical standard of care. This work examined the variability of functional connectivity in patients, estimated from rs-fMRI, for associations with surgical outcomes.

METHODS: This work examined pre-operative structural imaging, pre-operative rs-fMRI, and post-operative structural imaging from seven epilepsy patients. Review of the clinical record provided Engel classifications for surgical outcomes. A novel method assessed pre-operative rs-fMRI from patients using comparative rs-fMRI from a large cohort of healthy control subjects and estimated Gibbs distributions for functional connectivity in patients compared to healthy controls.

RESULTS: Three patients had Engel classification Ia, one patient had Engel classification IIa, and three patients had Engel classification IV. Metrics for variability of functional connectivity, including absolute differences of the functional connectivity of each patient from healthy control averages and probabilistic scores for absolute differences, were higher for patients classified as Engel IV, for whom epilepsy surgery provided no meaningful improvement.

SIGNIFICANCE: This work continues on-going efforts to use rs-fMRI to characterize abnormal functional connectivity in the brain. Preliminary evidence indicates that the topography of variant functional connectivity in epilepsy patients may be clinically relevant for identifying patients unlikely to have favorable outcomes after epilepsy surgery. Widespread topographic variations of functional connectivity also support the hypothesis that epilepsy is a disease of brain resting-state networks.

PMID:36712003 | PMC:PMC9882436 | DOI:10.1101/2023.01.10.23284374

Real-time feedback reduces participant motion during task-based fMRI

Mon, 01/30/2023 - 11:00

bioRxiv. 2023 Jan 24:2023.01.12.523791. doi: 10.1101/2023.01.12.523791. Preprint.


The potential negative impact of head movement during fMRI has long been appreciated. Although a variety of prospective and retrospective approaches have been developed to help mitigate these effects, reducing head movement in the first place remains the most appealing strategy for optimizing data quality. Real-time interventions, in which participants are provided feedback regarding their scan-to-scan motion, have recently shown promise in reducing motion during resting state fMRI. However, whether feedback might similarly reduce motion during task-based fMRI is an open question. In particular, it is unclear whether participants can effectively monitor motion feedback while attending to task-related demands. Here we assessed whether a combination of real-time and between-run feedback could reduce head motion during task-based fMRI. During an auditory word repetition task, 78 adult participants (aged 18â€"81) were pseudorandomly assigned to receive feedback, implemented in FIRMM software, or not. We quantified movement using framewise displacement (FD). We found that motion feedback resulted in a statistically significant reduction in participant head motion, with a small-to-moderate effect size (reducing average FD from 0.347 to 0.282). There was some evidence for a change of effect over the course of six runs, but no clear evidence for practice effects based on motion feedback. We conclude that under some circumstances real-time feedback may reduce head motion during task-based fMRI, although its effectiveness may depend on the specific participant population and task demands of a given study.

PMID:36711722 | PMC:PMC9882243 | DOI:10.1101/2023.01.12.523791

Resting state networks of awake adolescent and adult squirrel monkeys using ultra-high field (9.4T) functional magnetic resonance imaging

Mon, 01/30/2023 - 11:00

bioRxiv. 2023 Jan 9:2023.01.08.523000. doi: 10.1101/2023.01.08.523000. Preprint.


Resting state networks (RSNs) are increasingly forwarded as candidate biomarkers for neuropsychiatric disorders. Such biomarkers may provide objective measures for evaluating novel therapeutic interventions in nonhuman primates often used in translational neuroimaging research. This study aimed to characterize the RSNs of awake squirrel monkeys and compare the characteristics of those networks in adolescent and adult subjects. Twenty-seven squirrel monkeys ( n =12 adolescents [6 male/6 female] ∼2.5 years and n =15 adults [7 male/8 female] ∼9.5 years) were gradually acclimated to awake scanning procedures; whole-brain fMRI images were acquired with a 9.4 Tesla scanner. Group level independent component (IC) analysis (30 ICs) with dual regression was used to detect and compare RSNs. Twenty ICs corresponding to physiologically meaningful networks representing a range of neural functions, including motor, sensory, reward (e.g., basal ganglia), and cognitive processes were identified in both adolescent and adult monkeys. Significant age-related differences between the adult and adolescent subjects (adult > adolescent) were found in two networks of interest: (1) the right upper occipital region with an OFC IC and (2) the left temporal cortex, bilateral visual areas, and cerebellum with the cingulate IC. These results demonstrate that squirrel monkey RSNs are stable and consistent with RSNs previously identified in humans, rodents, and other nonhuman primate species. These data also identify several networks in adolescence that are conserved and others that may change into adulthood.

SIGNIFICANCE STATEMENT: Functional magnetic resonance imaging procedures have revealed important information about how the brain is modified by experimental manipulations, disease states, and aging throughout the lifespan. Preclinical neuroimaging, especially in nonhuman primates, has become a frequently used means to answer targeted questions related to brain resting-state functional connectivity. The present study characterized resting state networks (RSNs) in adult and adolescent squirrel monkeys; twenty RSNs corresponding to networks representing a range of neural functions were identified. The RSNs identified here can be utilized in future studies examining the effects of experimental manipulations on brain connectivity in squirrel monkeys. These data also may be useful for comparative analysis with other primate species to provide an evolutionary perspective for understanding brain function and organization.

PMID:36711620 | PMC:PMC9881954 | DOI:10.1101/2023.01.08.523000

Subcortical Functional Connectivity Gradients in Temporal Lobe Epilepsy

Mon, 01/30/2023 - 11:00

medRxiv. 2023 Jan 9:2023.01.08.23284313. doi: 10.1101/2023.01.08.23284313. Preprint.


BACKGROUND AND MOTIVATION: Functional gradients have been used to study differences in connectivity between healthy and diseased brain states, however this work has largely focused on the cortex. Because the subcortex plays a key role in seizure initiation in temporal lobe epilepsy (TLE), subcortical functional-connectivity gradients may help further elucidate differences between healthy brains and TLE, as well as differences between left (L)-TLE and right (R)-TLE.

METHODS: In this work, we calculated subcortical functional-connectivity gradients (SFGs) from resting-state functional MRI (rs-fMRI) by measuring the similarity in connectivity profiles of subcortical voxels to cortical gray matter voxels. We performed this analysis in 23 R-TLE patients and 32 L-TLE patients (who were otherwise matched for age, gender, disease specific characteristics, and other clinical variables), and 16 controls. To measure differences in SFGs between L-TLE and R-TLE, we quantified deviations in the average functional gradient distributions, as well as their variance, across subcortical structures.

RESULTS: We found an expansion, measured by increased variance, in the principal SFG of TLE relative to controls. When comparing the gradient across subcortical structures between L-TLE and R-TLE, we found that abnormalities in the ipsilateral hippocampal gradient distributions were significantly different between L-TLE and R-TLE.

CONCLUSION: Our results suggest that expansion of the SFG is characteristic of TLE. Subcortical functional gradient differences exist between left and right TLE and are driven by connectivity changes in the hippocampus ipsilateral to the seizure onset zone.

PMID:36711498 | PMC:PMC9882434 | DOI:10.1101/2023.01.08.23284313

Spontaneous brain activity in healthy aging: An overview through fluctuations and regional homogeneity

Mon, 01/30/2023 - 11:00

Front Aging Neurosci. 2023 Jan 12;14:1002811. doi: 10.3389/fnagi.2022.1002811. eCollection 2022.


INTRODUCTION: This study aims to explore whole-brain resting-state spontaneous brain activity using fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) strategies to find differences among age groups within a population ranging from middle age to older adults.

METHODS: The sample comprised 112 healthy persons (M = 68.80, SD = 7.99) aged 48-89 who were split into six age groups (< 60, 60-64, 65-69, 70-74, 75-79, and ≥ 80). Fractional amplitude of low-frequency fluctuation and ReHo analyses were performed and were compared among the six age groups, and the significant results commonly found across groups were correlated with the gray matter volume of the areas and the age variable.

RESULTS: Increased activity was found using fALFF in the superior temporal gyrus and inferior frontal gyrus when comparing the first group and the fifth. Regarding ReHo analysis, Group 6 showed increased ReHo in the temporal lobe (hippocampus), right and left precuneus, right caudate, and right and left thalamus depending on the age group. Moreover, significant correlations between age and fALFF and ReHo clusters, as well as with their gray matter volume were found, meaning that the higher the age, the higher the regional synchronization, the lower the fALFF activation, and the lower gray matter of the right thalamus.

CONCLUSION: Both techniques have been shown to be valuable and usable tools for disentangling brain changes in activation in a very low interval of years in healthy aging.

PMID:36711210 | PMC:PMC9877451 | DOI:10.3389/fnagi.2022.1002811

Hippocampal functional connectivity across age in an <em>App</em> knock-in mouse model of Alzheimer's disease

Mon, 01/30/2023 - 11:00

Front Aging Neurosci. 2023 Jan 12;14:1085989. doi: 10.3389/fnagi.2022.1085989. eCollection 2022.


INTRODUCTION: Alzheimer's disease (AD) is a progressive neurodegenerative disease. The early processes of AD, however, are not fully understood and likely begin years before symptoms manifest. Importantly, disruption of the default mode network, including the hippocampus, has been implicated in AD.

METHODS: To examine the role of functional network connectivity changes in the early stages of AD, we performed resting-state functional magnetic resonance imaging (rs-fMRI) using a mouse model harboring three familial AD mutations (App NL-G-F/NL-G-F knock-in, APPKI) in female mice in early, middle, and late age groups. The interhemispheric and intrahemispheric functional connectivity (FC) of the hippocampus was modeled across age.

RESULTS: We observed higher interhemispheric functional connectivity (FC) in the hippocampus across age. This was reduced, however, in APPKI mice in later age. Further, we observed loss of hemispheric asymmetry in FC in APPKI mice.

DISCUSSION: Together, this suggests that there are early changes in hippocampal FC prior to heavy onset of amyloid β plaques, and which may be clinically relevant as an early biomarker of AD.

PMID:36711209 | PMC:PMC9878347 | DOI:10.3389/fnagi.2022.1085989

Continuous theta burst stimulation-induced suppression of the right fronto-thalamic-cerebellar circuit accompanies improvement in language performance in poststroke aphasia: A resting-state fMRI study

Mon, 01/30/2023 - 11:00

Front Aging Neurosci. 2023 Jan 12;14:1079023. doi: 10.3389/fnagi.2022.1079023. eCollection 2022.


BACKGROUND: Continuous theta burst stimulation (cTBS) is a specific paradigm of repetitive transcranial magnetic stimulation (rTMS) with an inhibitory effect on cortical excitability for up to 60 min after less than 1 min of stimulation. The right posterior superior temporal gyrus (pSTG), homotopic to Wernicke's area in the left hemisphere, may be a potential stimulation target based on its critical role in semantic processing. The objective of this study was to explore whether cTBS over the right pSTG can promote language improvements in aphasic patients and the underlying mechanism.

METHODS: A total of 34 subjects with aphasia were randomly assigned to undergo 15 sessions of either 40-s inhibitory cTBS over the right pSTG (the cTBS group) or sham stimulation (the sham group), followed by 30 min of speech and language therapy. Subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI), and the aphasia quotient (AQ) of the Chinese version of the Western Aphasia Battery (WAB) was calculated before and after the intervention. This randomized controlled trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR210052962).

RESULTS: After treatment, the language performance of the cTBS group was higher than that of the sham group in terms of the WAB-AQ score (p = 0.010) and the WAB scores for auditory comprehension (p = 0.022) and repetition (p = 0.035). The fractional amplitude of low-frequency fluctuations (fALFF) was significantly decreased in the pars triangularis of the inferior frontal gyrus (IFG), right middle frontal gyrus, right thalamus, and left cerebellar crus I. Clusters in the left orbitofrontal cortex exhibited increased fALFF. The change in WAB comprehension scores were significantly correlated with the change in the fALFF of the right IFG pars triangularis in both groups. Greatly increased functional connectivity was observed between the right pars triangularis and left paracingulate gyrus and between the right pSTG and right angular gyrus and the posterior cingulate gyrus with pre-and post-treatment between the two groups.

CONCLUSION: Our findings indicate that cTBS of the right pSTG may improve language production by suppressing intrinsic activity of the right fronto-thalamic-cerebellar circuit and enhancing the involvement of the right temporoparietal region.

PMID:36711202 | PMC:PMC9877515 | DOI:10.3389/fnagi.2022.1079023

Associations between abnormal spontaneous neural activity and clinical variables, eye movements, and event-related potential indicators in major depressive disorder

Mon, 01/30/2023 - 11:00

Front Neurosci. 2023 Jan 11;16:1056868. doi: 10.3389/fnins.2022.1056868. eCollection 2022.


BACKGROUND: This study aimed to investigate the correlations between abnormal spontaneous neural activity measured with fractional amplitude of low-frequency fluctuations (fALFF) and clinical variables, eye movements, and event-related potential indicators in patients with major depressive disorder (MDD).

METHODS: We recruited 42 patients with MDD and 42 healthy controls (HCs) and collected their clinical variables, eye movement, event-related potential, and resting-state functional magnetic resonance imaging (rs-fMRI) data. The fALFF, support vector machine (SVM), and correlation analysis were used to analyze the data.

RESULTS: The results of the study showed that the fALFF values of the sensorimotor network, including the right middle temporal gyrus, right cerebellar Crus2, left occipital gyrus, and left middle temporal gyrus, were significantly higher compared to HCs. Correlation analysis showed that the abnormal fALFF value of the right cerebellar Crus2 was inversely correlated with the active coping scores of the Simplified Coping Style Questionnaire in the patients (r = -0.307, p = 0.048). No correlation was observed between abnormal fALFF values and other clinical symptoms, neuropsychological tests, eye movements, and event-related potential-related indicators in patients with MDD. fALFF values in the left middle temporal gyrus could be used to distinguish patients with MDD from HCs with an accuracy of 78.57%.

CONCLUSIONS: Patients with MDD exhibited enhanced spontaneous neural activity in the sensorimotor network. No associations were found between abnormal spontaneous neural activity and clinical variables, eye movements, and event-related potential related indicators in MDD.

PMID:36711124 | PMC:PMC9875062 | DOI:10.3389/fnins.2022.1056868

Associations Between Insulin-Like Growth Factor-1 and Resting-State Functional Connectivity in Cognitively Unimpaired Midlife Adults

Mon, 01/30/2023 - 11:00

J Alzheimers Dis. 2023 Jan 23. doi: 10.3233/JAD-220608. Online ahead of print.


BACKGROUND: Insulin-like growth factor (IGF)-1 plays an important role in Alzheimer's disease (AD) pathogenesis and increases disease risk. However, prior research examining IGF-1 levels and brain neural network activity is mixed.

OBJECTIVE: The present study investigated the relationship between IGF-1 levels and 21 neural networks, as measured by functional magnetic resonance imaging (fMRI) in 13,235 UK Biobank participants.

METHODS: Linear mixed models were used to regress IGF-1 against the intrinsic functional connectivity (i.e., degree of network activity) for each neural network. Interactions between IGF-1 and AD risk factors such as Apolipoprotein E4 (APOE4) genotype, sex, AD family history, and age were also tested.

RESULTS: Higher IGF-1 was associated with more network activity in the right Executive Function neural network. IGF-1 interactions with APOE4 or sex implicated motor, primary/extrastriate visual, and executive function related neural networks. Neural network activity trends with increasing IGF-1 were different in different age groups. Higher IGF-1 levels relate to much more network activity in the Sensorimotor Network and Cerebellum Network in early-life participants (40-52 years old), compared with mid-life (52-59 years old) and late-life (59-70 years old) participants.

CONCLUSION: These findings suggest that sex and APOE4 genotype may modify the relationship between IGF-1 and brain network activities related to visual, motor, and cognitive processing. Additionally, IGF-1 may have an age-dependent effect on neural network connectivity.

PMID:36710671 | DOI:10.3233/JAD-220608

The human functional connectome in neurodegenerative diseases: relationship to pathology and clinical progression

Mon, 01/30/2023 - 11:00

Expert Rev Neurother. 2023 Jan 29. doi: 10.1080/14737175.2023.2174016. Online ahead of print.


INTRODUCTION: Neurodegenerative diseases can be considered as 'disconnection syndromes', in which a communication breakdown prompts cognitive or motor dysfunction. Mathematical models applied to functional resting-state MRI allow for the organization of the brain into nodes and edges, which interact to form the functional brain connectome.

AREAS COVERED: The authors discuss the recent applications of functional connectomics to neurodegenerative diseases, from preclinical diagnosis, to follow up along with the progressive changes in network organization, to the prediction of the progressive spread of neurodegeneration, to stratification of patients into prognostic groups, and to record responses to treatment. The authors searched PubMed using the terms 'neurodegenerative diseases' AND 'fMRI' AND 'functional connectome' OR 'functional connectivity' AND 'connectomics' OR 'graph metrics' OR 'graph analysis'. The time range covered the past 20 years.

EXPERT OPINION: Considering the great pathological and phenotypical heterogeneity of neurodegenerative diseases, the identification of a common framework to diagnose, monitor and elaborate prognostic models is challenging. Graph analysis can describe the complexity of brain architectural rearrangements supporting the network-based hypothesis as a unifying pathogenetic mechanism. Although a multidisciplinary team is needed to overcome the limit of methodologic complexity in clinical application, advanced methodologies are valuable tools to better characterize the functional disconnection in neurodegeneration.

PMID:36710600 | DOI:10.1080/14737175.2023.2174016