Most recent paper
Geroscience. 2022 Aug 11. doi: 10.1007/s11357-022-00632-1. Online ahead of print.
Declines in processing speed performance occur in aging and are a critical marker of functional independence in older adults. Numerous studies suggest that Useful Field of View (UFOV) training may ameliorate cognitive decline in older adults. Despite its efficacy, little is known about the neural correlates of this task. The current study is the first to investigate the coherence of functional connectivity during UFOV task completion. A total of 336 participants completed the UFOV task while undergoing task-based functional magnetic resonance imaging (fMRI). Ten spherical regions of interest (ROIs), selected a priori, were created based on regions with the greatest peak BOLD activation patterns in the UFOV fMRI task and regions that have been shown to significantly relate to UFOV fMRI task performance. We used a weighted ROI-to-ROI connectivity analysis to model task-specific functional connectivity strength between these a priori selected ROIs. We found that our UFOV fMRI network was functionally connected during task performance and was significantly associated to UFOV fMRI task performance. Within-network connectivity of the UFOV fMRI network showed comparable or better predictive power in accounting for UFOV accuracy compared to 7 resting state networks, delineated by Yeo and colleagues. Finally, we demonstrate that the within-network connectivity of UFOV fMRI task accounted for scores on a measure of "near transfer", the Double Decision task, better than the aforementioned resting state networks. Our data elucidate functional connectivity patterns of the UFOV fMRI task. This may assist in future targeted interventions that aim to improve synchronicity within the UFOV fMRI network.
Neurodegener Dis. 2022 Aug 9. doi: 10.1159/000526377. Online ahead of print.
BACKGROUND: While the hippocampus is not part of the nigrostriatal dopaminergic pathway, influence of Parkinson's Disease (PD) to the hippocampus has been consistently implicated. However, it is not clear how the hippocampal changes contribute to the pathology of PD.
OBJECTIVES: We aimed to elucidate the physiological changes of the hippocampus in its orchestration with the rest of the brain.
METHODS: Using the resting state fMRI data from Parkinson's Progression Markers Initiative (PPMI), functional connectivity of the hippocampus was analyzed in 93 individuals with PD and 18 individuals without PD.
RESULTS: A whole brain voxel-wise analysis showed that the bilateral paracingulate gyri were less connected to the hippocampus in the PD group compared to the control group. The hippocampus-paracingulate dysconnectivity did not show association with cognitive indices.
CONCLUSIONS: The hippocampus in PD shows dysconnectivity to the paracingulate gyri.
Contrasting the amygdala activity and functional connectivity profile between antidepressant-free participants with major depressive disorder and healthy controls: A systematic review of comparative fMRI studies
Psychiatry Res Neuroimaging. 2022 Jul 22;325:111517. doi: 10.1016/j.pscychresns.2022.111517. Online ahead of print.
Functional neuroimaging research suggests that the amygdala is implicated in the pathophysiology of major depressive disorder (MDD). This systematic review aimed to identify consistently reported amygdala activity and functional connectivity (FC) abnormalities in antidepressant-free participants with MDD as compared to healthy controls at baseline (i.e., before treatment initiation or experimental manipulation). A search for relevant published studies and registered clinical trials was conducted through OVID (MEDLINE, PsycINFO, and Embase) and ClinicalTrials.gov with an end date of March 7th, 2022. Fifty published studies and two registered clinical trials were included in this review. Participants with MDD frequently exhibited amygdala hyperactivity in response to negative stimuli, abnormal event-related amygdala-anterior cingulate cortex (ACC) FC, and abnormal resting-state amygdala FC with the insula and the prefrontal, temporal, and parietal cortices. Decreased resting-state FC was consistently found between the amygdala and the orbitofrontal cortex, striatum, cerebellum, and middle/inferior frontal gyri. Due to the limited number of studies examining resting-state amygdala activity and FC with specific subregions of interest, including those within the ACC, further investigation is warranted.
Altered dynamic functional connectivity of striatal-cortical circuits in Juvenile Myoclonic Epilepsy
Seizure. 2022 Jul 2;101:103-108. doi: 10.1016/j.seizure.2022.07.002. Online ahead of print.
OBJECTIVE: To investigate whether the dynamic functional connectivity (dFC) of striatal-cortical circuits changes in juvenile myoclonic epilepsy (JME).
METHODS: The resting-state EEG-fMRI and the sliding-window approach were adopted to explore the dynamic striatal-cortical circuitry in thirty JME patients compared with 30 well-matched health controls (HCs). Six pairs of striatal seeds were selected as regions of interests. The correlation analysis was performed to reveal the relationship between the altered dFC variability and clinical variables in JME group.
RESULTS: JME patients exhibited increased dFC variability mainly involved in fronto-striatal and striatal-thalamic networks; decreased dFC variability between striatum subdivisions and default mode network (DMN) regions compared with HCs (p<0.05, GRF corrected). In addition, the hypervariability between left ventral-rostral putamen and left medial superior frontal gyrus was positively (r= 0.493, p=0.008) correlated with the mean frequency score of myoclonic seizures in JME group.
CONCLUSION: JME presented altered dFC variability in striatal-cortical circuits. The pattern of altered circuits showed increased variability in fronto-striatal and striatal-thalamic networks and decreased variability in striatal-DMN. These results provide novel information about the dynamic neural striatal-cortical circuitry of JME.
Comparison of resting state and task-based functional MRI in preoperative mapping in patients with brain gliomas
Zh Vopr Neirokhir Im N N Burdenko. 2022;86(4):33-40. doi: 10.17116/neiro20228604133.
OBJECTIVE: To analyze and compare the results of cerebral cortex mapping with task-based (tb-fMRI) and resting-state functional MRI in patients with glioma of eloquent cortical areas.
MATERIAL AND METHODS: There were 55 patients (24 men and 31 women aged 24 - 74 years, median 39) with glial tumors. In 26 patients, the tumor was located in motor areas. Twenty-nine patients had lesions of Broca and Wernicke's areas. All patients underwent preoperative tb-fMRI and rs-fMRI. Then, resection of tumor was carried out in all cases.
RESULTS: Comparison of fMRI and rs-fMRI activation maps was assessed by calculating the Dice coefficient for inclusive speech and motor cortex masks and exclusive masks without brainstem, cerebellum, subcortical nuclei. Inclusive Dice coefficient for motor cortex ranged from 0.11 to 0.50, for speech cortex - from 0.006 to 0.240 (p<0.05). In case of exclusive masks, this value ranged from 0.15 to 0.55 for motor cortex and from 0.004 to 0.205 for speech cortex (p<0.05).
CONCLUSION: When comparing the results of cortical mapping in patients with glial tumors, the use of hemispheric exclusive and inclusive masks did not significantly increase activation maps matching. Probably, low degree of correspondence was associated with different genesis of activations, as well as with high variability of speech cortex.
Machine learning for resting state fMRI-based preoperative mapping: comparison with task-based fMRI and direct cortical stimulation
Zh Vopr Neirokhir Im N N Burdenko. 2022;86(4):25-32. doi: 10.17116/neiro20228604125.
OBJECTIVE: To develop a system for preoperative prediction of individual activations of motor and speech areas in patients with brain gliomas using resting state fMRI (rsfMRI), task-based fMRI (tb-fMRI), direct cortical stimulation and machine learning methods.
MATERIAL AND METHODS: Thirty-three patients with gliomas (19 females and 14 males aged 19 - 540) underwent DCS-assisted resection of tumor (19 ones with lesion of motor zones and 14 patients with lesions of speech areas). Awake craniotomy was performed in 14 cases. Preoperative mapping was performed according to special MRI protocol (T1, tb-fMRI, rs-fMRI).
Machine learning system was built on open source data from The Human Connectome Project. MR data of 200 healthy subjects from this database were used for system pre-training. Further, this system was trained on the data of our patients with gliomas.
RESULTS: In DCS, we obtained 332 stimulations including 173 with positive response. According to comparison of functional activations between rs-fMRI and tb-fMRI, there were more positive DCS responses predicted by rs-fMRI (132 vs 112). Non-response stimulation sites (negative) prevailed in tb-fMRI activations (69 vs 44).
CONCLUSION: The developed method with machine learning based on resting state fMRI showed greater sensitivity compared to classical task-based fMRI after verification with DCS: 0.72 versus 0.66 (p<0.05) for identifying the speech zones and 0.79 versus 0.62 (p<0.05) for motor areas.
Nat Sci Sleep. 2022 Aug 2;14:1341-1350. doi: 10.2147/NSS.S366234. eCollection 2022.
INTRODUCTION: In recent years, people have gained a profound understanding of chronic insomnia disorder (CID), but the pathophysiological mechanism of CID is still unclear. There is some evidence that the locus coeruleus (LC) is involved in the regulation of wakefulness in CID, but there have been few studies using brain functional imaging. The purpose of this study was to evaluate the resting-state functional connectivity (FC) between the LC and other brain voxels in CID and whether these abnormal FC are involved in the regulation of wakefulness.
METHODS: A total of 49 patients with chronic insomnia disorder and 47 healthy controls (HC) matched for gender, age, and education were examined with rs-fMRI in this study. The LC was selected as the region of interest, and then seed-based analysis was conducted on the LC and other voxels to obtain the brain regions with abnormal FC. The correlation between the FC value of the abnormal connection area and the clinical scale score was analyzed.
RESULTS: Compared with the HC, the FC between the LC and right precuneus, right posterior cingulate cortex, left middle temporal gyrus, left calcarine, and right superior orbitofrontal cortex was significantly enhanced (p < 0.05, FDR correction), and the functional connectivity signal value between the locus coeruleus and left middle temporal gyrus was positively correlated with the Self-Rating Depression Scale (p = 0.021).
CONCLUSION: The abnormal FC between the LC and multiple brain regions may contribute to a better understanding of the neurobiological mechanism of CID.
Effect of acupuncture on brain functional connectivity strength in patients with primary dysmenorrhea
Zhongguo Zhen Jiu. 2022 Aug 12;42(8):863-70. doi: 10.13703/j.0255-2930.20210826-k0004.
OBJECTIVE: To investigate the effect of acupuncture on the brain functional activities of the patients with primary dysmenorrhea based on the resting-state functional magnetic resonance imaging (rs-fMRI), and to provide visual evidence for the central mechanism of acupuncture in treatment of primary dysmenorrhea.
METHODS: Forty-two patients of primary dysmenorrhea were enrolled and randomly divided into an observation group (21 cases, 1 case dropped off) and a control group (21 cases, 2 cases dropped off, 3 cases withdrawal). In the observation group, acupuncture was exerted at Sanyinjiao (SP 6) and Guanyuan (CV 4), started 5-7 days before menstrual flow, once a day till menstrual onset, for a total of 3 menstrual cycles. No intervention was applied in the control group. The scores of visual analogue scale (VAS) and Cox menstrual symptom scale (CMSS) were observed in both groups before and after treatment. Based on rs-fMRI, the data of resting-state functional magnetic resonance were collected from two groups before and after treatment. Combined with functional connectivity strength (FCS) and functional connectivity (FC) analysis, the differences of brain regions before and after treatment were compared between the two groups and the correlation was analyzed between their functional connectivity changes and the improvements in VAS and CMSS scores of the patients in the observation group.
RESULTS: In the observation group, the scores of VAS and CMSS were all decreased after treatment (P<0.05), while the scores related to the symptom time in CMSS was reduced in comparison with that before treatment in the control group (P<0.05). The score reducing ranges of VAS and CMSS in the observation group were larger than the control group (P<0.05). Compared before treatment, FCS of the right middle cingulate cortex and the left cuneus was increased, while FCS of the left inferior parietal lobule was decreased after treatment in the observation group. In the control group, FCS of the left orbital frontal cortex was increased after treatment. Compared with the control group, FCS of the left anterior insula was increased in the observation group after treatment. FC analysis was performed using the left anterior insula as the seed point. In comparison with the control group, FC of the left anterior insula was increased either with the inferior temporal gyrus or with the right hippocampus; and was decreased either with the middle occipital lobe or with the right dorsolateral prefrontal cortex in the observation group after treatment. In the observation group, FC between the left anterior insula and the right hippocampus was positively correlated with the improvements in symptom severity (r =0.385, P<0.05) and symptom time (r =0.510, P<0.05) of CMSS, and FC between the right dorsolateral prefrontal cortex and the left anterior insula was negatively correlated with the improvement in symptom severity of CMSS after treatment (r =-0.373, P<0.05).
CONCLUSION: The anterior insula may be the key brain region in treatment of primary dysmenorrhea with acupuncture. Acupuncture may relieve dysmenorrhea and the related symptoms through strengthening the functional connectivity of anterior insula-limbic system and anterior insula-control network.
Reconfiguration of static and dynamic thalamo-cortical network functional connectivity of epileptic children with generalized tonic-clonic seizures
Front Neurosci. 2022 Jul 22;16:953356. doi: 10.3389/fnins.2022.953356. eCollection 2022.
OBJECTIVE: A number of studies in adults and children with generalized tonic-clonic seizure (GTCS) have reported the alterations in morphometry, functional activity, and functional connectivity (FC) in the thalamus. However, the neural mechanisms underlying the alterations in the thalamus of patients with GTCS are not well understood, particularly in children. The aim of the current study was to explore the temporal properties of functional pathways connecting thalamus in children with GTCS.
METHODS: Here, we recruited 24 children with GTCS and 36 age-matched healthy controls. Static and dynamic FC approaches were used to evaluate alterations in the temporal variability of thalamo-cortical networks in children with GTCS. The dynamic effective connectivity (dEC) method was also used to evaluate the directions of the fluctuations in effective connectivity. In addition, the relationships between the dynamic properties and clinical features were assessed.
RESULTS: The static FC analysis presented significantly decreased connectivity patterns between the bilateral thalamus and between the thalamus and right inferior temporal gyrus. The dynamic connectivity analysis found decreased FC variability in the thalamo-cortical network of children with epilepsy. Dynamic EC analyses identified increased connectivity variability from the frontal gyrus to the bilateral thalamus, and decreased connectivity variability from the right thalamus to the left thalamus and from the right thalamus to the right superior parietal lobe. In addition, correlation analysis revealed that both static FC and connectivity temporal variability in the thalamo-cortical network related to the clinical features (epilepsy duration and epilepsy onset time).
SIGNIFICANCE: Our findings of both increased and decreased connectivity variability in the thalamo-cortical network imply a dynamic restructuring of the functional pathways connecting the thalamus in children with GTCS. These alterations in static and temporal dynamic pathways connecting the bilateral thalamus may extend our understanding of the neural mechanisms underlying the GTCS in children.
Altered Regional Homogeneity in Patients With Diabetic Erectile Dysfunction: A Resting-State fMRI Study
Front Endocrinol (Lausanne). 2022 Jul 22;13:817523. doi: 10.3389/fendo.2022.817523. eCollection 2022.
INTRODUCTION: Erectile dysfunction (ED) is a common complication of Type-2 Diabetes Mellitus (T2DM) for male patients and it is considered to be associated with different causes including hyperglicemia-induced vascular endothelial cell damages. However, the possible central neural mechanisms shared by these two diseases remain unclear. This study aimed to explore the changes of brain activity and their relationships with the clinical characteristics in patients with diabetic ED.
METHODS: The data of resting-state functional magnetic resonance imaging were acquired in 31 T2DM patients with ED (DM-ED) and 31 matched healthy controls (HCs). The whole-brain regional homogeneity (ReHo) values were calculated and compared between groups. In addition, Pearson correlation analysis was performed to evaluate the relationships between brain regions with altered ReHo values and clinical characteristics in the patient group.
RESULTS: The DM-ED group exhibited increased ReHo values in the right middle frontal gyrus (orbital part) and decreased ReHo values in the left superior frontal gyrus (dorsolateral), paracentral lobule, precuneus and bilateral supplementary motor area when compared with the HCs group. Moreover, significantly negative correlations were found between ReHo values of the left superior frontal gyrus (dorsolateral) and IIEF-5 scores, as well as the level of HbA1c in the DM-ED group.
CONCLUSION: The altered spontaneous brain activity in cognitive-related regions revealed by ReHo values might provide new insights into the neurological pathophysiology underlying DM-ED and serve as potential neuroimaging biomarkers for detecting and evaluating ED in diabetes patients.
Alterations in Spontaneous Neuronal Activity and Microvascular Density of the Optic Nerve Head in Active Thyroid-Associated Ophthalmopathy
Front Endocrinol (Lausanne). 2022 Jul 22;13:895186. doi: 10.3389/fendo.2022.895186. eCollection 2022.
PURPOSE: To investigate changes in local spontaneous brain activity in patients with active thyroid-associated ophthalmopathy (TAO) and explore the relationship between such alterations and microvascular indices.
METHODS: Thirty-six active TAO patients with active phase and 39 healthy controls (HCs) were enrolled in this study. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI), neuropsychological tests, and ophthalmological examinations. The rs-fMRI-based fractional low-frequency fluctuation amplitude (fALFF) analysis methods were used to assess spontaneous brain activity in both groups. The structure (peripapillary retinal nerve fiber layer, pRNFL) and microvascular indices (the optic nerve head (ONH) whole image vessel density, ONH-wiVD, and peripapillary vessel density) were analyzed through optical coherence tomographic angiography imaging. The relationship between abnormal spontaneous brain activity and ophthalmological indices was analyzed using the Spearman's rank correlation analysis.
RESULTS: Compared with HCs, active TAO patients had increased fALFF in the right inferior temporal gyrus (R.ITG) and left posterior cingulate gyrus (L.PCC), but decreased fALFF in the right calcarine (R.CAL). The fALFF values in L.PCC were positively correlated with peripapillary vessel density, whereas fALFF values in R.CAL were negatively related to peripapillary vessel density.
CONCLUSIONS: This study demonstrates that changes in spontaneous brain activity of active TAO are accompanied by peripapillary microvascular variations. These results provide insights into the pathophysiological mechanisms of active TAO. In addition, the combination of fALFF values and peripapillary vessel density may be served as important references for better clinical decision making.
Inter-Network Brain Functional Connectivity in Adolescents Assigned Female at Birth Who Experience Gender Dysphoria
Front Endocrinol (Lausanne). 2022 Jul 22;13:903058. doi: 10.3389/fendo.2022.903058. eCollection 2022.
Gender dysphoria (GD) is characterized by distress due to an incongruence between experienced gender and sex assigned at birth. Brain functional connectivity in adolescents who experience GD may be associated with experienced gender (vs. assigned sex) and/or brain networks implicated in own-body perception. Furthermore, sexual orientation may be related to brain functional organization given commonalities in developmental mechanisms proposed to underpin GD and same-sex attractions. Here, we applied group independent component analysis to resting-state functional magnetic resonance imaging (rs-fMRI) BOLD timeseries data to estimate inter-network (i.e., between independent components) timeseries correlations, representing functional connectivity, in 17 GD adolescents assigned female at birth (AFAB) not receiving gender-affirming hormone therapy, 17 cisgender girls, and 15 cisgender boys (ages 12-17 years). Sexual orientation was represented by degree of androphilia-gynephilia and sexual attractions strength. Multivariate partial least squares analyses found that functional connectivity differed among cisgender boys, cisgender girls, and GD AFAB, with the largest difference between cisgender boys and GD AFAB. Regarding sexual orientation and age, the brain's intrinsic functional organization of GD AFAB was both similar to and different from cisgender girls, and both differed from cisgender boys. The pattern of group differences and the networks involved aligned with the hypothesis that brain functional organization is different among GD AFAB (vs. cisgender) adolescents, and certain aspects of this organization relate to brain areas implicated in own-body perception and self-referential thinking. Overall, brain functional organization of GD AFAB was generally more similar to that of cisgender girls than cisgender boys.
Front Psychiatry. 2022 Jul 22;13:929812. doi: 10.3389/fpsyt.2022.929812. eCollection 2022.
Major depressive disorder (MDD) is a common psychiatric condition associated with aberrant large-scale distributed brain networks. However, it is unclear how the network dysfunction in MDD patients is characterized by imbalance or derangement of network modular segregation. Fifty-one MDD patients and forty-three matched healthy controls (HC) were recruited in the present study. We analyzed intrinsic brain activity derived from resting-state functional magnetic resonance imaging (R-fMRI) and then examined brain network segregation by computing the participation coefficient (PC). Further intra- and inter-modular connections analysis were preformed to explain atypical PC. Besides, we explored the potential relationship between the above graph theory measures and symptom severity in MDD. Lower modular segregation of the frontal-parietal network (FPN) was found in MDD compared with the HC group. The MDD group exhibited increased inter-module connections between the FPN and cingulo-opercular network (CON), between the FPN and cerebellum (Cere), between the CON and Cere. At the nodal level, the PC of the anterior prefrontal cortex, anterior cingulate cortex, inferior parietal lobule (IPL), and intraparietal sulcus showed larger in MDD. Additionally, the inter-module connections between the FPN and CON and the PC values of the IPL were negatively correlated with depression symptom in the MDD group. These findings might give evidence about abnormal FPN in MDD from the perspective of modular segregation in brain networks.
Abnormal regional signal in the left cerebellum as a potential neuroimaging biomarker of sudden sensorineural hearing loss
Front Psychiatry. 2022 Jul 22;13:967391. doi: 10.3389/fpsyt.2022.967391. eCollection 2022.
OBJECTIVE: While prior reports have characterized visible changes in neuroimaging findings in individuals suffering from sudden sensorineural hearing loss (SSNHL), the utility of regional homogeneity (ReHo) as a means of diagnosing SSNHL has yet to be established. The present study was thus conducted to assess ReHo abnormalities in SSNHL patients and to establish whether these abnormalities offer value as a diagnostic neuroimaging biomarker of SSNHL through a support vector machine (SVM) analysis approach.
METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) analyses of 27 SSNHL patients and 27 normal controls were conducted, with the resultant imaging data then being analyzed based on a combination of ReHo and SVM approaches.
RESULTS: Relative to normal control individuals, patients diagnosed with SSNHL exhibited significant reductions in ReHo values in the left cerebellum, bilateral inferior temporal gyrus (ITG), left superior temporal pole (STP), right parahippocampal gyrus (PHG), left posterior cingulum cortex (PCC), and right superior frontal gyrus (SFG). SVM analyses suggested that reduced ReHo values in the left cerebellum were associated with high levels of diagnostic accuracy (96.30%, 52/54), sensitivity (92.59%, 25/27), and specificity (100.00%, 27/27) when distinguishing between SSNHL patients and control individuals.
CONCLUSION: These data suggest that SSNHL patients exhibit abnormal resting-state neurological activity, with changes in the ReHo of the left cerebellum offering value as a diagnostic neuroimaging biomarker associated with this condition.
Altered Brain Function in Treatment-Resistant and Non-treatment-resistant Depression Patients: A Resting-State Functional Magnetic Resonance Imaging Study
Front Psychiatry. 2022 Jul 22;13:904139. doi: 10.3389/fpsyt.2022.904139. eCollection 2022.
OBJECTIVE: In this study, we used amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) to observe differences in local brain functional activity and its characteristics in patients with treatment-resistant depression (TRD) and non-treatment-resistant depression (nTRD), and to explore the correlation between areas of abnormal brain functional activity and clinical symptoms.
METHOD: Thirty-seven patients with TRD, 36 patients with nTRD, and 35 healthy controls (HCs) were included in resting-state fMRI scans. ALFF and ReHo were used for image analysis and further correlation between abnormal brain regions and clinical symptoms were analyzed.
RESULTS: ANOVA revealed that the significantly different brain regions of ALFF and ReHo among the three groups were mainly concentrated in the frontal and temporal lobes. Compared with the nTRD group, the TRD group had decreased ALFF in the left/right inferior frontal triangular gyrus, left middle temporal gyrus, left cuneus and bilateral posterior lobes of the cerebellum, and increased ALFF in the left middle frontal gyrus and right superior temporal gyrus, and the TRD group had decreased ReHo in the left/right inferior frontal triangular gyrus, left middle temporal gyrus, and increased ReHo in the right superior frontal gyrus. Compared with the HC group, the TRD group had decreased ALFF/ReHo in both the right inferior frontal triangular gyrus and the left middle temporal gyrus. Pearson correlation analysis showed that both ALFF and ReHo values in these abnormal brain regions were positively correlated with HAMD-17 scores (P < 0.05).
CONCLUSION: Although the clinical symptoms were similar in the TRD and nTRD groups, abnormal neurological functional activity were present in some of the same brain regions. Compared with the nTRD group, ALFF and ReHo showed a wider range of brain area alterations and more complex neuropathological mechanisms in the TRD group, especially in the inferior frontal triangular gyrus of the frontal lobe and the middle temporal gyrus of the temporal lobe.
CNS Neurosci Ther. 2022 Aug 7. doi: 10.1111/cns.13933. Online ahead of print.
BACKGROUND: Neuroimaging studies have shown that the functional connectivity (FC) of corticostriatal circuits in nonmanifesting leucine-rich repeat kinase 2 (LRRK2) G2019S mutation carriers mirrors neural changes in idiopathic Parkinson's disease (PD). In contrast, neural network changes in LRRK2 G2385R and R1628P mutations are unclear. We aimed to investigate the FC of corticostriatal circuits in nonmanifesting LRRK2 G2385R and R1628P mutation carriers (NMCs).
METHODS: Twenty-three NMCs, 28 PD patients, and 29 nonmanifesting noncarriers (NMNCs) were recruited. LRRK2 mutation analysis was performed on all participants. Clinical evaluation included MDS-UPDRS.
RESULTS: When compared to NMNCs, NMCs showed significantly reduced FC between the caudate nucleus and superior frontal gyrus and cerebellum, and between the nucleus accumbens and parahippocampal gyrus, amygdala, and insula. We also found increased striatum-cortical FC in NMCs.
CONCLUSIONS: Although the corticostriatal circuits have characteristic changes similar to PD, the relatively intact function of the sensorimotor striatum-cortical loop may result in less possibility of developing parkinsonian motor symptoms for the NMCs. This study helps explain why LRRK2 G2385R and R1628P mutations are risk factors rather than pathogenic mutations for PD and suggests that various LRRK2 mutations have distinct effects on neural networks.
Magn Reson Imaging. 2022 Aug 4:S0730-725X(22)00138-2. doi: 10.1016/j.mri.2022.08.005. Online ahead of print.
Previous resting-state functional magnetic resonance imaging (fMRI) studies have revealed highly reproducible latency structures, reflecting the lead/lag relationship of BOLD fMRI signals in white matter (WM). With simultaneous electroencephalography and fMRI data from 35 healthy subjects who were instructed to sleep during imaging, we explored alterations of latency structures in the WM across wakefulness and nonrapid eye movement (NREM) sleep stages. Lagged cross-covariance was computed among voxelwise time series, followed by parabolic interpolation to determine the actual in-between latencies. WM regions, including the brainstem, internal capsule, optic radiation, genu of corpus callosum, and corona radiata, inconsistently changed temporal dynamics with respect to the rest of the WM across wakefulness and NREM sleep stages, as demonstrated when these regions were used as seeds for seed-based latency analysis. Latency analysis of resting-state networks, obtained by applying K-means clustering to a group-level functional connectivity matrix, identified a dominant direction of signaling, starting from the brainstem up to the internal capsule and then the corona radiata during wakefulness, which was reorganized according to stage transitions, e.g., the temporal organization of the internal capsule and corona radiata switched from unidirectional to bidirectional in the wakefulness to N3 transition. These findings suggest that WM BOLD signals are slow, dynamically modulated across wakefulness and NREM sleep stages and that they are involved in maintaining different levels of consciousness.
The neural effects of oxytocin administration in autism spectrum disorders studied by fMRI: A systematic review
J Psychiatr Res. 2022 Aug 4;154:80-90. doi: 10.1016/j.jpsychires.2022.06.033. Online ahead of print.
PURPOSE: Oxytocin (OXT) is a hypothalamic neuropeptide that is released from the posterior pituitary gland and at specific targets in the central nervous system (CNS). The prosocial effects of OXT acting in the CNS present it as a potential therapeutic agent for the treatment of aspects of autism spectrum disorder (ASD). In this article, we systematically review the functional MRI (fMRI) literature that reports task-state and resting-state fMRI (rsfMRI) studies of the neural effects of single or multiple dose intranasal OXT (IN-OXT) administration in individuals with ASD.
METHOD: We searched four databases for relevant documents (PubMed, Web of Science, Scopus, and Google Scholar) using the keywords "autism spectrum disorder", "Asperger Syndrome", "oxytocin", and "fMRI". Moreover, we made a manual search to assess the quality of our automatic search. The search was confined to English language articles published in the interval February 2013 until March 2021.
RESULTS: The search yielded 12 fMRI studies with OXT intervention, including 288 individuals with ASD (age 8-55 years) enrolled in randomized, double-blind, placebo-controlled, parallel designs, within-subject-crossover experimental OXT trials. Studies reporting activation task and rsfMRI were summarized with region of interest (ROI) or whole-brain voxel wise analysis. The systematic review of the 12 studies supported the proposition that IN-OXT administration alters brain activation in individuals with ASD. The effects of IN-OXT interacted with the type of the task and the overall results did not indicate restoration of normal brain activation in ASD signature regions albeit the lack of statistical evidence.
CONCLUSION: A large body of evidence consistently indicates that OXT alters activation to fMRI in brain networks of individuals with ASD, but with uncertain implications for alleviation of their social deficits.
Complement Ther Clin Pract. 2022 Jul 31;49:101653. doi: 10.1016/j.ctcp.2022.101653. Online ahead of print.
This clinical trial investigated the effect of an Emotional Freedom Techniques (EFT) intervention on brain activation in chronic pain sufferers using functional magnetic resonance imaging (fMRI). EFT is a brief stress reduction technique which combines stating a cognitive statement with somatic tapping on acupressure points. Twenty-four adults were allocated to a six-week online group EFT treatment and underwent resting-state fMRI pre and post the intervention. A repeated measures MANOVA indicated significant differences in the levels of pain severity (-21%), pain interference (-26%), quality of life (+7%), somatic symptoms (-28%), depression (-13.5%), anxiety (-37.1%), happiness (+17%), and satisfaction with life (+8.8%) from pre-to post-test. Cohen's effect sizes ranged from small (0.2) to large (0.75) values suggesting significance for the intervention. fMRI analysis showed post-EFT treatment significantly decreased connectivity between the medial prefrontal cortex (a pain modulating area) and bilateral grey matter areas in the posterior cingulate cortex and thalamus, both areas being related to modulating and catastrophizing of pain. There were no brain areas that showed significantly increased connectivity post-EFT treatment. Coupled with the psychological measures the findings support the effects of the EFT intervention in reducing chronic pain and its impacts. Recommendations for future research are discussed.
Associated factors and abnormal dorsal raphe nucleus connectivity patterns of freezing of gait in Parkinson's disease
J Neurol. 2022 Aug 6. doi: 10.1007/s00415-022-11294-6. Online ahead of print.
BACKGROUND: Freezing of gait (FOG) is a common, disabling symptom of Parkinson's disease (PD), and its exact pathophysiological mechanism is still poorly understood. The control of gait is a complex process that may be influenced by emotions modulated by serotonergic networks. Therefore, this study aimed to determine factors associated with FOG in PD patients and to evaluate the importance of the dorsal raphe nucleus (DRN; central node in the serotoninergic system) in FOG pathophysiology.
METHODS: We combined cross-sectional survey data from 453 PD patients. According to the Freezing of Gait Questionnaire (FOGQ), patients were divided into two groups: the "PD with frozen gait (PD-FOG)" and "PD without frozen gait (PD-nFOG)" groups. Demographic characteristics, clinical features, and motor and nonmotor symptoms (NMS) assessments of PD patients were recorded. Univariate statistical analysis was performed between the two groups, and then regression analysis was performed on related factors. We also acquired resting-state functional MRI (rs-fMRI) data from 20 PD-FOG, 21 PD-nFOG, and 22 healthy controls (HCs) who were randomly chosen. We defined seeds in the DRN to evaluate functional connectivity (FC) patterns.
RESULTS: The overall frequency of FOG was 11.9% patients in the PD-FOG group were older, had a longer disease duration, had a higher levodopa equivalent daily dose, had more severe motor symptoms and worse quality of life, had a higher proportion of dyskinesia, wearing-off and postural instability/gait difficulty (PIGD) clinical phenotype, and experienced more depression and impaired sleep function than those in the PD-nFOG group. Logistic regression analysis showed that H&Ystage ≥ 3, UPDRS-III scores, PIGD clinical phenotype and excessive daytime sleepiness were associated with FOG. In addition, there was significantly lower FC between the DRN and some cortical structures, including the supplementary motor area (SMA), left superior frontal gyrus (SFG), and left median cingulated cortex (MCC) in PD-FOG patients than HCs and PD-nFOG patients.
CONCLUSIONS: These results demonstrate that the severity of PD and PIGD clinical phenotype are associated factors for freezing and that DRN dysfunction may play a key role in PD-related NMS and FOG. An abnormal cortical and brainstem networks may contribute to the mechanisms underlying FOG.