Simple and complex movement-associated functional MRI changes in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis

Using functional magnetic resonance imaging (fMRI), we investigated whether movement-associated functional changes of the brain are present in patients who are, most likely, at the earliest stage of multiple sclerosis (MS). Functional MRI exams were obtained from 16 patients at presentation with clinically isolated syndromes (CIS) suggestive of MS and 15 sex- and age-matched healthy volunteers during the performance of three simple and one more complex motor tasks with fully normal functioning extremities. fMRI analysis was performed using statistical parametric mapping (SPM99). Compared to healthy volunteers, CIS patients had increased activations of the contralateral primary sensorimotor cortex (SMC), secondary somatosensory cortex (SII), and inferior frontal gyrus (IFG), when performing a simple motor task with the dominant hand. The increased recruitment of the contralateral primary SMC was also found during the performance of the same motor task with the non-dominant hand and with the dominant foot. In this latter case, an anterior shift of the center of activation of this region was detected. During the performance of a complex motor task with the dominant upper and lower limbs, CIS patients had an increased recruitment of a widespread network (including the frontal lobe, the insula, the thalamus), usually considered to function in motor, sensory, and multimodal integration processing. The comparison of brain activations during the performance of simple vs. complex motor tasks showed that the movement-associated somatotopic organization of the cerebral and cerebellar cortices was retained in patients with CIS. Cortical reorganization occurs in patients at presentation with CIS highly suggestive of MS. Local synaptic reorganization, recruitment of parallel existing pathways, and reorganization of distant sites are all likely to contribute to the observed functional changes. Hum. Brain Mapping 21:106-115, 2004.     

Altered fMRI-derived functional connectivity in patients with high-tension glaucoma

BackgroundHigh-tension glaucoma (HTG) is associated with functional changes in the brain, and elevated intraocular pressure (IOP) is one of the major causes.PurposeTo evaluate the effects of high IOP on the brain in patients with HTG by using resting-state functional magnetic resonance imaging (rs-fMRI).Materials and methodsThirty-six patients with HTG and 20 age- and gender-matched healthy controls (HCs) were recruited and underwent IOP examination and rs-fMRI scan. Voxel-wise functional connectivity (FC) values were obtained between the Brodmann Area (BA) 17 (primary visual cortex) and the rest of the brain, two-sample t test was performed between HTG group and HCs. Correlation analysis was performed between FC and clinical information.ResultsCompared with HCs, HTG patients demonstrated decreased FC between BA 17 and the right precuneus gyrus, decreased FC between BA 17 and the right superior frontal gyrus (SFG) (GRF corrected at voxel level P < 0.001 and cluster level P < 0.05, two-tailed). FC between BA 17 and the right SFG showed significantly negative correlation with right eyes’ IOP and mean IOP.ConclusionHTG patients had abnormal FC changes between the visual cortex and multiple functional brain regions related to visual sense, memory consolidation and cognitive processing, which provided image support for the pathophysiology research of HTG, and revealed new targets for the accurate treatment of HTG.     

Linking structural, metabolic and functional changes in multiple sclerosis

In patients with multiple sclerosis (MS), conventional magnetic resonance imaging (MRI) has markedly improved our ability to detect the macroscopic abnormalities of the brain and spinal cord. New quantitative magnetic resonance (MR) approaches with increased sensitivity to subtle normal-appearing white matter (NAWM) and grey matter changes and increased specificity to the heterogeneous pathological substrates of MS may give information complementary to conventional MRI. Magnetization transfer imaging (MTI) and diffusion-weighted imaging (DWI) have the potential to provide important information on the structural changes occurring within and outside T2-visible lesions. Magnetic resonance spectroscopy (MRS) adds information on the biochemical nature of such changes. Functional MRI might quantify the efficiency of brain plasticity in response to MS injury and improve our understanding of the link between structural damage and clinical manifestations. The present review summarizes how the application of these MR techniques to the study of MS is dramatically changing our understanding of how MS causes irreversible neurological deficits.     

Correlation between structural and functional connectivity impairment in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, characterized by progressive loss of motor function. While the pathogenesis of ALS remains largely unknown, imaging studies of the brain should lead to more insight into structural and functional disease effects on the brain network, which may provide valuable information on the underlying disease process. This study investigates the correlation between changes in structural connectivity (SC) and functional connectivity (FC) of the brain network in ALS. Structural reconstructions of the brain network, derived from diffusion weighted imaging (DWI), were obtained from 64 patients and 27 healthy controls. Functional interactions between brain regions were derived from resting‐state fMRI. Our results show that (i) the most structurally affected connections considerably overlap with the most functionally impaired connections, (ii) direct connections of the motor cortex are both structurally and functionally more affected than connections at greater topological distance from the motor cortex, and (iii) there is a strong positive correlation between changes in SC and FC averaged per brain region (r = 0.44, P < 0.0001). Our findings indicate that structural and functional network degeneration in ALS is coupled, suggesting the pathogenic process affects both SC and FC of the brain, with the most prominent effects in SC. Hum Brain Mapp 35:4386–4395, 2014. © 2014 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.     

Abnormal connectivity of the sensorimotor network in patients with MS: A multicenter fMRI study

In this multicenter study, we used dynamic causal modeling to characterize the abnormalities of effective connectivity of the sensorimotor network in 61 patients with multiple sclerosis (MS) compared with 74 age‐matched healthy subjects. We also investigated the correlation of such abnormalities with findings derived from structural MRI. In a subgroup of subjects, diffusion tensor (DT) MRI metrics of the corpus callosum and the left corticospinal tract (CST) were also assessed. MS patients showed increased effective connectivity relative to controls between: (a) the left primary SMC and the left dorsal premotor cortex (PMd), (b) the left PMd and the supplementary motor areas (SMA), (c) the left secondary sensorimotor cortex (SII) and the SMA, (d) the right SII and the SMA, (e) the left SII and the right SII, and (f) the right SMC and the SMA. MS patients had relatively reduced effective connectivity between the left SMC and the right cerebellum. No interaction was found between disease group and center. Coefficients of altered connectivity were weakly correlated with brain T2 LV, but moderately correlated with DT MRI‐measured damage of the left CST. In conclusion, large multicenter fMRI studies of effective connectivity changes in diseased people are feasible and can facilitate studies with sample size large enough for robust outcomes. Increased effective connectivity in the patients for the simple motor task suggests local network modulation contributing to enhanced long‐distance effective connectivity in MS patients. This extends and generalizes previous evidence that enhancement of effective connectivity may provide an important compensatory mechanism in MS. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.     

抑郁症患者眶额叶皮层功能连接偏离的研究

目的 通过功能磁共振成像技术,研究抑郁症患者和健康对照组在情感处理时眶额叶皮层的功能连接偏离,为抑郁症的早期诊断和疗效评估提供影像学依据.方法 对25例重度抑郁症患者和15名健康对照组在执行面貌一致性任务时进行功能性磁共振成像.结果 和健康对照组相比重度抑郁症患者的背侧前扣带回皮层、楔前叶、小脑与眶额叶的活动连接减少;抑郁症患者的眶额叶皮层和背外侧前额叶皮层、右额叶岛盖部、左运动区之间的功能连接比健康对照组有所增加.结论 眶额叶皮层在抑郁症的病理生理学机制中发挥着关键作用.眶额叶皮层连接的失衡似乎代表加工偏离的神经机制.从神经生物学的角度来看,楔前叶和扣带回的连接解离活动与眶额叶皮层的自我架构规则的问题相关,而背外侧前额叶皮层到眶额叶的连接增加可能代表更高消极刺激的神经反应.     

难治性癫痫患者楔前叶功能连接的静息态功能磁共振成像研究

目的应用静息态功能磁共振成像(rs-f MRI)探讨难治性癫痫患者楔前叶与全脑功能连接的改变及其意义。方法对23例难治性癫痫患者(癫痫组)及23名健康人(对照组)进行rs-f MRI检查,采集数据后采用功能连接的方法,分别计算以左侧楔前叶和右侧楔前叶为感兴趣区与全脑的功能连接,运用双样本t检验的统计学方法发现两组的显著性差异并进行分析。结果癫痫组左侧楔前叶与双侧顶下小叶、双侧岛叶、右侧缘上回、右侧额中回和双侧额下回的功能连接较对照组减弱(均P0.05);癫痫组左侧楔前叶与双侧海马旁回、双侧额上回、左侧后扣带回的功能连接较对照组增强(均P0.05)。癫痫组右侧楔前叶与左侧顶下小叶、右侧缘上回、右侧额中回、右侧额下回的功能连接较对照组减弱(均P0.05);癫痫组右侧楔前叶与双侧楔叶、左侧后扣带回的功能连接较对照组增强(均P0.05)。结论难治性癫痫患者静息状态下楔前叶与全脑的功能连接存在异常,"默认网络"功能的抑制可能是癫痫患者意识及认知等功能损害的重要原因。     

Spatial and temporal functional connectivity changes between resting and attentive states

Remote brain regions show correlated spontaneous activity at rest within well described intrinsic connectivity networks (ICNs). Meta‐analytic coactivation studies have uncovered networks similar to resting ICNs, suggesting that in task states connectivity modulations may occur principally within ICNs. However, it has also been suggested that specific “hub” regions dynamically link networks under different task conditions. Here, we used functional magnetic resonance imaging at rest and a continuous visual attention task in 16 participants to investigate whether a shift from rest to attention was reflected by within‐network connectivity modulation, or changes in network topography. Our analyses revealed evidence for both modulation of connectivity within the default‐mode (DMN) and dorsal attention networks (DAN) between conditions, and identified a set of regions including the temporoparietal junction (TPJ) and posterior middle frontal gyrus (MFG) that switched between the DMN and DAN depending on the task. We further investigated the temporal nonstationarity of flexible (TPJ and MFG) regions during both attention and rest. This showed that moment‐to‐moment differences in connectivity at rest mirrored the variation in connectivity between tasks. Task‐dependent changes in functional connectivity of flexible regions may, therefore, be understood as shifts in the proportion of time specific connections are engaged, rather than a switch between networks per se. This ability of specific regions to dynamically link ICNs under different task conditions may play an important role in behavioral flexibility. Hum Brain Mapp 36:549–565, 2015. © 2014 Wiley Periodicals, Inc.     

Corticostriatal functional connectivity in non-medicated patients with obsessive-compulsive disorder

The basal ganglia represents a key component of the pathophysiological model for obsessive-compulsive disorder (OCD). This brain region is part of several neural circuits, including the orbitofronto-striatal circuit and dorsolateral prefronto-striatal circuit. There are, however, no published studies investigating those circuits at a network level in non-medicated patients with OCD. Resting state functional magnetic resonance imaging scans were obtained from 20 non-medicated patients with OCD and 23 matched healthy volunteers. Voxelwise statistical parametric maps testing strength of functional connectivity of three striatal seed regions of interest (ROIs) with remaining brain regions were calculated and compared between groups. We performed additional correlation analyses between strength of connectivity and the severity scores for obsessive-compulsive symptoms, depression, and anxiety in the OCD group. Positive functional connectivity with the ventral striatum was significantly increased (P_corrected <.05) in the orbitofrontal cortex, ventral medial prefrontal cortex and dorsal lateral prefrontal cortex of subjects with OCD. There was no significant correlation between measures of symptom severity and the strength of connectivity (P_uncorrected <.001). This is the first study to investigate the corticostriatal connectivity in non-medicated patients with OCD. These findings provide the first direct evidence supporting a pathophysiological model involving basal ganglia circuitry in OCD.     

Altered interhemispheric functional connectivity in patients with obsessive-compulsive disorder and its potential in therapeutic response prediction

The trajectory of voxel-mirrored homotopic connectivity (VMHC) after medical treatment in obsessive-compulsive disorder (OCD) and its value in prediction of treatment response remains unclear. This study aimed to investigate the pathophysiological mechanism of OCD, as well as biomarkers for prediction of pharmacological efficacy. Medication-free patients with OCD and healthy controls (HCs) underwent magnetic resonance imaging. The patients were scanned again after a 4-week treatment with paroxetine. The acquired data were subjected to VMHC, support vector regression (SVR), and correlation analyses. Compared with HCs (36 subjects), patients with OCD (34 subjects after excluding two subjects with excessive head movement) exhibited significantly lower VMHC in the bilateral superior parietal lobule (SPL), postcentral gyrus, and calcarine cortex, and VMHC in the postcentral gyrus was positively correlated with cognitive function. After treatment, the patients showed increased VMHC in the bilateral posterior cingulate cortex/precuneus (PCC/PCu) with the improvement of symptoms. SVR results showed that VMHC in the postcentral gyrus at baseline could aid to predict a change in the scores of OCD scales. This study revealed that SPL, postcentral gyrus, and calcarine cortex participate in the pathophysiological mechanism of OCD while PCC/PCu participate in the pharmacological mechanism. VMHC in the postcentral gyrus is a potential predictive biomarker of the treatment effects in OCD.     

Partially enhanced thalamocortical functional connectivity in autism

Based on evidence for thalamic abnormalities in autism, impairments of thalamocortical pathways have been suspected. We examined the functional connectivity between thalamus and cerebral cortex in terms of blood oxygen level dependent (BOLD) signal cross-correlation in 8 male participants with high-functioning autism and matched normal controls, using functional MRI during simple visuomotor coordination. Both groups exhibited widespread connectivity, consistent with known extensive thalamocortical connectivity. In a direct group comparison, overall more extensive connectivity was observed in the autism group, especially in the left insula and in right postcentral and middle frontal regions. Our findings are inconsistent with the hypothesis of general underconnectivity in autism and instead suggest that subcortico-cortical connectivity may be hyperfunctional, potentially compensating for reduced cortico-cortical connectivity.     

Right‐hemispheric language reorganization in patients with brain arteriovenous malformations: A functional magnetic resonance imaging study

Brain arteriovenous malformation (AVM), a presumed congenital lesion, may involve traditional language areas but usually does not lead to language dysfunction unless it ruptures. The objective of this research was to study right‐hemispheric language reorganization patterns in patients with brain AVMs using functional magnetic resonance imaging (fMRI). We prospectively enrolled 30 AVM patients with lesions involving language areas and 32 age‐ and sex‐matched healthy controls. Each subject underwent fMRI during three language tasks: visual synonym judgment, oral word reading, and auditory sentence comprehension. The activation differences between the AVM and control groups were investigated by voxelwise analysis. Lateralization indices (LIs) for the frontal lobe, temporal lobe, and cerebellum were compared between the two groups, respectively. Results suggested that the language functions of AVM patients and controls were all normal. Voxelwise analysis showed no significantly different activations between the two groups in visual synonym judgment and oral word reading tasks. In auditory sentence comprehension task, AVM patients had significantly more activations in the right precentral gyrus (BA 6) and right cerebellar lobule VI (AAL 9042). According to the LI results, the frontal lobe in oral word reading task and the temporal lobe in auditory sentence comprehension task were significantly more right‐lateralized in the AVM group. These findings suggest that for patients with AVMs involving language cortex, different language reorganization patterns may develop for different language functions. The recruitment of brain areas in the right cerebral and cerebellar hemispheres may play a compensatory role in the reorganized language network of AVM patients.     

Disrupted functional connectivity of default mode and salience networks in chronic pancreatitis patients

ObjectiveThe functional connectivity of the brain in chronic pancreatitis (CP) remains unknown. This study aimed to investigate functional connectivity in CP patients using resting state functional magnetic resonance imaging (fMRI) and explore the associations to clinical parameters and altered cerebral metabolites.MethodsSeed-based and ROI-to-ROI analyses were performed to assess connectivity within and between the default mode network (DMN) and salience network (SN). Additionally, functional connectivity in these networks were investigated in relation to clinical parameters (CP etiology, pain, medication, etc.) and cerebral glutamate/creatine level in the anterior cingulate cortex.ResultsThirty CP patients and 23 healthy controls were analyzed. CP patients showed hyper-connectivity in DMN and SN as compared to healthy controls. Furthermore, CP patients had reduced anti-correlated functional connectivity between DMN and SN (all P ≤ 0.009). The altered DMN connectivity correlated to glutamate/creatine level (r = 0.503, P = 0.020) in patients with pain, but not to the clinical parameters.ConclusionsCP patients had altered functional connectivity within and between brain networks. Altered DMN functional connectivity had an association to cerebral metabolic changes.SignificanceAltered functional connectivity in CP share similarities with other chronic pain conditions, and support our understanding of altered brain circuitry associated with the CP disease.     

A network-based cognitive training induces cognitive improvements and neuroplastic changes in patients with relapsing-remitting multiple sclerosis: an exploratory case-control study

Cognitive impairments are commonly observed in patients with multiple sclerosis and are associated with lower levels of quality of life. No consensus has been reached on how to tackle effectively cognitive decline in this clinical population non-pharmacologically. This exploratory case-control study aims to investigate the effectiveness of a hypothesis-based cognitive training designed to target multiple domains by promoting the synchronous co-activation of different brain areas and thereby improve cognition and induce changes in functional connectivity in patients with relapsing-remitting multiple sclerosis. Forty-five patients(36 females and 9 males, mean age 44.62 ± 8.80 years) with clinically stable relapsing-remitting multiple sclerosis were assigned to either a standard cognitive training or to control groups(sham training and nonactive control). The standard training included twenty sessions of computerized exercises involving various cognitive functions supported by distinct brain networks. The sham training was a modified version of the standard training that comprised the same exercises and number of sessions but with increased processing speed load. The non-active control group received no cognitive training. All patients underwent comprehensive neuropsychological and magnetic resonance imaging assessments at baseline and after 5 weeks. Cognitive and resting-state magnetic resonance imaging data were analyzed using repeated measures models. At reassessment, the standard training group showed significant cognitive improvements compared to both control groups in memory tasks not specifically targeted by the training: the Buschke Selective Reminding Test and the Semantic Fluency test. The standard training group showed reductions in functional connectivity of the salience network, in the anterior cingulate cortex, associated with improvements on the Buschke Selective Reminding Test. No changes were observed in the sham training group. These findings suggest that multi-domain training that stimulates multiple brain areas synchronously may improve cognition in people with relapsing-remitting multiple sclerosis if sufficient time to process training material is allowed. The associated reduction in functional connectivity of the salience network suggests that training-induced neuroplastic functional reorganization may be the mechanism supporting performance gains. This study was approved by the Regional Ethics Committee of Yorkshire and Humber(approval No. 12/YH/0474) on November 20, 2013.     

Preserved network functional connectivity underlies cognitive reserve in multiple sclerosis

Cognitive reserve is one's mental resilience or resistance to the effects of structural brain damage. Reserve effects are well established in people with multiple sclerosis (PwMS) and Alzheimer's disease, but the neural basis of this phenomenon is unclear. We aimed to investigate whether preservation of functional connectivity explains cognitive reserve. Seventy‐four PwMS and 29 HCs underwent neuropsychological assessment and 3 T MRI. Structural damage measures included gray matter (GM) atrophy and network white matter (WM) tract disruption between pairs of GM regions. Resting‐state functional connectivity was also assessed. PwMS exhibited significantly impaired cognitive processing speed (t = 2.14, p = .037) and visual/spatial memory (t = 2.72, p = .008), and had significantly greater variance in functional connectivity relative to HCs within relevant networks (p < .001, p < .001, p = .016). Higher premorbid verbal intelligence, a proxy for cognitive reserve, predicted relative preservation of functional connectivity despite accumulation of GM atrophy (standardized‐β = .301, p = .021). Furthermore, preservation of functional connectivity attenuated the impact of structural network WM tract disruption on cognition (β = ?.513, p = .001, for cognitive processing speed; β = ?.209, p = .066, for visual/spatial memory). The data suggests that preserved functional connectivity explains cognitive reserve in PwMS, helping to maintain cognitive capacity despite structural damage.     

Altered functional connectivity networks of hippocampal subregions in remitted late-onset depression:a longitudinal resting-state study

The regional specifi city of hippocampal abnormalities in late-life depression(LLD) has been demonstrated in previous studies. In this study,we sought to examine the functional connectivity(FC) patterns of hippocampal subregions in remitted late-onset depression(r LOD),a special subtype of LLD. Fourteen r LOD patients and 18 healthy controls underwent clinical and cognitive evaluations as well as resting-state functional magnetic resonance imaging scans at baseline and at ~21 months of follow-up. Each hippocampus was divided into three parts,the cornu ammonis(CA),the dentate gyrus,and the subicular complex,and then six seed-based hippocampal subregional networks were established.Longitudinal changes of the six networks over time were directly compared between the rL OD and control groups. From baseline to follow-up,the r LOD group showed a greater decline in connectivity of the left CA to the bilateral posterior cingulate cortex/precuneus(PCC/PCUN),but showed increased connectivity of the right hippocampal subregional networks with the frontal cortex(bilateral medial prefrontal cortex/anterior cingulate cortex and supplementary motor area). Further correlative analyses revealed thatthe longitudinal changes in FC between the left CA and PCC/PCUN were positively correlated with longitudinal changes in the Symbol Digit Modalities Test(r = 0.624,P = 0.017) and the Digit Span Test(r = 0.545,P = 0.044) scores in the r LOD group. These results may provide insights into the neurobiological mechanism underlying the cognitive dysfunction in r LOD patients.