Task demand modulation of steady-state functional connectivity to primary motor cortex

Correlations in blood oxygen level-dependent (BOLD) MRI signals from separate areas within the human brain have been used as a measure of functional connectivity. Steady-state measures of interregional correlations are particularly useful because they do not depend on the specific design of a task nor on subtracting conditions in a blocked design task. However, the conditions under which such correlations are measured may influence these indices of functional connectivity. The aim of this study was to investigate the influence of task demand on interregional correlations within the motor system. Specifically, tapping rates in audibly paced finger-tapping tasks were controlled and varied between runs in order to observe their effects on interregional correlations to contralateral primary motor cortex (PM). Regions of interest included the supplementary motor area, ipsilateral cerebellum, ipsilateral auditory cortex, and a control region. It was found that tapping rate was a significant factor in determining the mean correlation of some regions to PM, and that correlations measured during tapping in general increased relative to resting state. Furthermore, analysis of the percent of voxels in each region significantly correlated to PM suggested that changes in the mean correlation of that region to PM could be accounted for by changes in the fraction of significantly correlated voxels within a region. This provides insight into the manner in which steady-state correlations are modified in response to different task demands and further evidence that low-frequency fluctuations in BOLD signals reflect functional connectivity.     

The cortical rhythms of chronic back pain

Chronic pain is maladaptive and influences brain function and behavior by altering the flow and integration of information across brain regions. Here we use a power spectral analysis to investigate impact of presence of chronic pain on brain oscillatory activity in humans. We examine changes in BOLD fluctuations, across different frequencies, in chronic back pain (CBP) patients (n = 15) as compared to healthy controls (n = 15) during resting-state fMRI. While healthy subjects exhibited a specific, frequency band-dependent, large-scale neural organization, patients showed increased high-frequency BOLD oscillations (0.12-0.20 Hz) circumscribed mainly to medial prefrontal cortex (mPFC) and parts of the default mode network. In the patients a correlation analysis related the mPFC aberrant BOLD high-frequency dynamics to altered functional connectivity to pain signaling/modulating brain regions, thus linking BOLD frequency changes to function. We also found that increased frequency fluctuations within the mPFC were temporally synchronous with spontaneous pain changes in patients during a pain-rating task. These observations provide novel insights about the nature of CBP, identifying how it disturbs the resting brain, and link high-frequency BOLD oscillations to perception.     

静息态下复发抑郁症患者海马的功能连接

目的:利用功能性磁共振成像(fMRI)技术,观察静息态下复发抑郁症患者海马的功能连接。方法:16例复发重性抑郁症患者与16名年龄、性别、受教育程度均匹配的健康者参与了静息态fMRI扫描。通过分析海马与大脑其他区域的低频fMRI信号波动的相关性,观察海马的功能连接。结果:抑郁症患者左海马与右前额背侧、左前额中部、左楔前叶、左顶下小叶、左后扣带回、左脑岛、左海马旁回、左屏状核及左豆状核的功能连接减低;抑郁症患者右海马与左前额中部、右后扣带回、右脑岛及双侧海马旁回的功能连接减低,而与右前扣带回BA25区的功能连接增高。结论:本研究证实了静息态下抑郁症患者海马与广泛的皮质、皮质下结构的功能连接存在异常,这可能与抑郁症患者一系列认知与情绪功能的损伤有关,从而初步描绘了静息态下复发抑郁症患者海马的功能连接模式。     

Reductions in interhemispheric motor cortex functional connectivity after muscle fatigue

Muscle fatigue has been known to differentially affect the activation level of the primary motor cortices (MIs) of the brain's two hemispheres. Whether this fatigue-related decoupling influence on the motor cortical signals extends beyond the motor action to the after-fatigue-task resting state is unknown. This question can be addressed by analyzing functional connectivity (FC) of low-frequency oscillations of resting-state functional MRI (fMRI) signals of the MIs. Low-frequency oscillations (<0.08 Hz) have been detected in many fMRI studies and appear to be synchronized between functionally related areas. These patterns of FC have been shown to differ between normal and various pathological states. The purpose of this study was to examine muscle fatigue-induced resting-state interhemispheric motor cortex FC changes in healthy subjects. We hypothesized that muscle fatigue would create a temporary "disrupted state" in the brain, and would decrease resting state interhemispheric motor cortical FC. Ten healthy subjects performed repetitive unilateral handgrip contractions that induced significant muscle fatigue, with resting state fMRI data collected before and after the task. After excluding two subjects due to gross head motion, interhemispheric motor cortex FC was assessed by cross-correlating the MI fMRI signal time courses. We found that the number of significant interhemispheric correlations in the MI fMRI signals decreased significantly after the performance of the fatigue task. These results suggest that resting state interhemispheric motor cortex FC may be used as an index of recovery from fatigue.     

Brain alterations in low-frequency fluctuations across multiple bands in obsessive compulsive disorder

The extent of functional abnormalities in frontal-subcortical circuits in obsessive-compulsive disorder (OCD) is still unclear. Although neuroimaging studies, in general, and resting-state functional Magnetic Resonance Imaging (rs-fMRI), in particular, have provided relevant information regarding such alterations, rs-fMRI studies have been typically limited to the analysis of between-region functional connectivity alterations at low-frequency signal fluctuations (i.e., <0.08 Hz). Conversely, the local attributes of Blood Oxygen Level Dependent (BOLD) signal across different frequency bands have been seldom studied, although they may provide valuable information. Here, we evaluated local alterations in low-frequency fluctuations across different oscillation bands in OCD. Sixty-five OCD patients and 50 healthy controls underwent an rs-fMRI assessment. Alterations in the fractional amplitude of low-frequency fluctuations (fALFF) were evaluated, voxel-wise, across four different bands (from 0.01 Hz to 0.25 Hz). OCD patients showed decreased fALFF values in medial orbitofrontal regions and increased fALFF values in the dorsal-medial prefrontal cortex (DMPFC) at frequency bands <0.08 Hz. This pattern was reversed at higher frequencies, where increased fALFF values also appeared in medial temporal lobe structures and medial thalamus. Clinical variables (i.e., symptom-specific severities) were associated with fALFF values across the different frequency bands. Our findings provide novel evidence about the nature and regional distribution of functional alterations in OCD, which should contribute to refine neurobiological models of the disorder. We suggest that the evaluation of the local attributes of BOLD signal across different frequency bands may be a sensitive approach to further characterize brain functional alterations in psychiatric disorders.     

Spontaneous low-frequency fluctuations in the BOLD signal in schizophrenic patients: anomalies in the default network

Spontaneous low-frequency fluctuations in the blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (MRI) signal have been shown to reflect neural synchrony between brain regions. A "default network" of spontaneous low-frequency fluctuations has been described in healthy volunteers during stimulus-independent thought. Negatively correlated with this network are regions activated during attention-demanding tasks. Both these networks involve brain regions and functions that have been linked with schizophrenia in previous research. The present study examined spontaneous slow fluctuations in the BOLD signal at rest, as measured by correlation with low-frequency oscillations in the posterior cingulate, in 17 schizophrenic patients, and 17 comparable healthy volunteers. Healthy volunteers demonstrated correlation between spontaneous low-frequency fluctuations of the BOLD signal in the posterior cingulate and fluctuations in the lateral parietal, medial prefrontal, and cerebellar regions, similar to previous reports. Schizophrenic patients had significantly less correlation between spontaneous slow activity in the posterior cingulate and that in the lateral parietal, medial prefrontal, and cerebellar regions. Connectivity of the posterior cingulate was found to vary with both positive and negative symptoms in schizophrenic patients. Because these data suggest significant abnormalities in resting-state neural networks in schizophrenia, further investigations of spontaneous slow fluctuations of the BOLD signal seem warranted in this population.     

静息状态功能磁共振成像观察轻度阿尔茨海默病后扣带回功能连通性的变化

目的 利用静息状态功能磁共振成像(fMRI)研究阿尔茨海默病(AD)早期后扣带回相关的静息脑网络连通性是如何变化的.方法 运用fMRI研究了16例轻度AD患者和16名健康对照者在静息状态后扣带回的功能连通性.与后扣带回有功能连通性的脑区是通过检测低频波动信号的时程相关性获得的.应用通用的SPM2图像统计软件计算组间和组内连通性差异,激活区阈值设置:P<0.01(校正),像素范围>5.利用SPM2软件随机效应分析t检验(经校正P<0.01,t=2.47,像素范围>5),比较患者组和对照组连通性激活的脑区.结果 与后扣带回有功能连通性减弱的脑区包括前额叶中线区、楔前叶、双侧视皮质、双侧颞下回、左侧海马、右侧丘脑、右侧额叶背外侧区;偏左侧化的连通性增高的脑区包括前额叶中线区、左侧颞下回、左侧基底节区、双侧额叶背外侧区及左侧中央前区.结论 与后扣带回相关的静息状态脑网络连通性减低与AD早期情节记忆损害和高级视觉功能损害有关系,轻度AD保留着功能连接的重塑性以便维持脑功能.静息fMRI是一种探索AD脑功能机制的适宜方法.     

Predicting conceptual processing capacity from spontaneous neuronal activity of the left middle temporal gyrus

Conceptual processing is a crucial brain function for humans. Past research using neuropsychological and task-based functional brain-imaging paradigms indicates that widely distributed brain regions are related to conceptual processing. Here, we explore the potential contribution of intrinsic or spontaneous brain activity to conceptual processing by examining whether resting-state functional magnetic resonance imaging (rs-fMRI) signals can account for individual differences in the conceptual processing efficiencies of healthy individuals. We acquired rs-fMRI and behavioral data on object conceptual processing tasks. We found that the regional amplitude of spontaneous low-frequency fluctuations in the blood oxygen level-dependent signal in the left (posterior) middle temporal gyrus (LMTG) was highly correlated with participants' semantic processing efficiency. Furthermore, the strength of the functional connectivity between the LMTG and a series of brain regions-the left inferior frontal gyrus, bilateral anterior temporal lobe, bilateral medial temporal lobe, posterior cingulate gyrus, and ventromedial and dorsomedial prefrontal cortices-also significantly predicted conceptual behavior. The regional amplitude of low-frequency fluctuations and functionally relevant connectivity strengths of LMTG together accounted for 74% of individual variance in object conceptual performance. This semantic network, with the LMTG as its core component, largely overlaps with the regions reported in previous conceptual/semantic task-based fMRI studies. We conclude that the intrinsic or spontaneous activity of the human brain reflects the processing efficiency of the semantic system.     

Detection of PCC functional connectivity characteristics in resting-state fMRI in mild Alzheimer's disease

Resting-state networks dissociate in the early stage of Alzheimer's disease (AD). The posterior cingulate cortex (PCC) in AD brain is vulnerable to isolation from the rest of brain. However, it remains unclear how this functional connectivity is related to PCC changes. We employed resting-state functional MRI (fMRI) to examine brain regions with a functional connection to PCC in a mild AD group compared with matched control subjects. PCC connectivity was gathered by investigating synchronic low frequency fMRI signal fluctuations with a temporal correlation method. We found asymmetric PCC-left hippocampus, right dorsal-lateral prefrontal cortex and right thalamus connectivity disruption. In addition, some other regions such as the bilateral visual cortex, the infero-temporal cortex, the posterior orbital frontal cortex, the ventral medial prefrontal cortex and the precuneus showed decreased functional connectivity to the PCC. There were also some regions, primarily in the left frontal-parietal cortices, that showed increased connectivity. These regions included the medial prefrontal cortex, bilateral dorsal-lateral prefrontal cortex, the left basal ganglia and the left primary motor cortex. Impairments to memory, high vision-related functions and olfaction in AD can be explained by a disruption to the functional connection of resting-state networks. The results of increased connectivity may support the compensatory-recruitment hypothesis. Our findings suggest that the characteristics of resting-state functional connectivity could plausibly provide an early imaging biomarker for AD.     

Altered functional connectivity in early Alzheimer's disease: a resting-state fMRI study

Previous studies have led to the proposal that patients with Alzheimer's disease (AD) may have disturbed functional connectivity between different brain regions. Furthermore, recent resting-state functional magnetic resonance imaging (fMRI) studies have also shown that low-frequency (<0.08 Hz) fluctuations (LFF) of the blood oxygenation level-dependent signals were abnormal in several brain areas of AD patients. However, few studies have investigated disturbed LFF connectivity in AD patients. By using resting-state fMRI, this study sought to investigate the abnormal functional connectivities throughout the entire brain of early AD patients, and analyze the global distribution of these abnormalities. For this purpose, the authors divided the whole brain into 116 regions and identified abnormal connectivities by comparing the correlation coefficients of each pair. Compared with healthy controls, AD patients had decreased positive correlations between the prefrontal and parietal lobes, but increased positive correlations within the prefrontal lobe, parietal lobe, and occipital lobe. The AD patients also had decreased negative correlations (closer to zero) between two intrinsically anti-correlated networks that had previously been found in the resting brain. By using resting-state fMRI, our results supported previous studies that have reported an anterior-posterior disconnection phenomenon and increased within-lobe functional connectivity in AD patients. In addition, the results also suggest that AD may disturb the correlation/anti-correlation effect in the two intrinsically anti-correlated networks.     

An improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state fMRI: fractional ALFF

Most of the resting-state functional magnetic resonance imaging (fMRI) studies demonstrated the correlations between spatially distinct brain areas from the perspective of functional connectivity or functional integration. The functional connectivity approaches do not directly provide information of the amplitude of brain activity of each brain region within a network. Alternatively, an index named amplitude of low-frequency fluctuation (ALFF) of the resting-state fMRI signal has been suggested to reflect the intensity of regional spontaneous brain activity. However, it has been indicated that the ALFF is also sensitive to the physiological noise. The current study proposed a fractional ALFF (fALFF) approach, i.e., the ratio of power spectrum of low-frequency (0.01-0.08 Hz) to that of the entire frequency range and this approach was tested in two groups of resting-state fMRI data. The results showed that the brain areas within the default mode network including posterior cingulate cortex, precuneus, medial prefrontal cortex and bilateral inferior parietal lobule had significantly higher fALFF than the other brain areas. This pattern was consistent with previous neuroimaging results. The non-specific signal components in the cistern areas in resting-state fMRI were significantly suppressed, indicating that the fALFF approach improved the sensitivity and specificity in detecting spontaneous brain activities. Its mechanism and sensitivity to abnormal brain activity should be evaluated in the future studies.     

Detection of functional connectivity using temporal correlations in MR images

Functional connectivity among brain regions has been investigated via an analysis of correlations between regional signal fluctuations recorded in magnetic resonance (MR) images obtained in a steady state. In comparison with studies of functional connectivity that utilize task manipulations, the analysis of correlations in steady state data is less susceptible to confounds arising when functionally unrelated brain regions respond in similar ways to changes in task. A new approach to identifying interregional correlations in steady state data makes use of two independent data sets. Regions of interest (ROIs) are defined and hypotheses regarding their connectivity are generated in one data set. The connectivity hypotheses are then evaluated in the remaining (independent) data set by analyzing low frequency temporal correlations between regions. The roles of the two data sets are then reversed and the process repeated, perhaps multiple times. This method was illustrated by application to the language system. The existence of a functional connection between Broca's area and Wernicke's area was confirmed in healthy subjects at rest. An increase in this functional connection when the language system was actively engaged (when subjects were continuously listening to narrative text) was also confirmed. In a second iteration of analyses, a correlation between Broca's area and a region in left premotor cortex was found to be significant at rest and to increase during continuous listening. These findings suggest that the proposed methodology can reveal the presence and strength of functional connections in high-level cognitive systems.     

Multi-modal investigation of transcranial ultrasound-induced neuroplasticity of the human motor cortex

IntroductionThere is currently a gap in accessibility to neuromodulation tools that can approximate the efficacy and spatial resolution of invasive methods. Low intensity transcranial focused ultrasound stimulation (TUS) is an emerging technology for non-invasive brain stimulation (NIBS) that can penetrate cortical and deep brain structures with more focal stimulation compared to existing NIBS modalities. Theta burst TUS (tbTUS, TUS delivered in a theta burst pattern) is a novel repetitive TUS protocol that can induce durable changes in motor cortex excitability, thereby holding promise as a novel neuromodulation tool with durable effects.ObjectiveThe aim of the present study was to elucidate the neurophysiologic effects of tbTUS motor cortical excitability, as well on local and global neural oscillations and network connectivity.MethodsAn 80-s train of active or sham tbTUS was delivered to the left motor cortex in 15 healthy subjects. Motor cortical excitability was investigated through transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) using paired-pulse TMS. Magnetoencephalography (MEG) recordings during resting state and an index finger abduction-adduction task were used to assess oscillatory brain responses and network connectivity. The correlations between the changes in neural oscillations and motor cortical excitability were also evaluated.ResultstbTUS to the motor cortex results in a sustained increase in MEP amplitude and decreased SICI, but no change in ICF. MEG spectral power analysis revealed TUS-mediated desynchronization in alpha and beta spectral power. Significant changes in alpha power were detected within the supplementary motor cortex (Right > Left) and changes in beta power within bilateral supplementary motor cortices, right basal ganglia and parietal regions. Coherence analysis revealed increased local connectivity in motor areas. MEP and SICI changes correlated with both local and inter-regional coherence.ConclusionThe findings from this study provide novel insights into the neurophysiologic basis of TUS-mediated neuroplasticity and point to the involvement of regions within the motor network in mediating this sustained response. Future studies may further characterize the durability of TUS-mediated neuroplasticity and its clinical applications as a neuromodulation strategy for neurological and psychiatric disorders.     

Low-frequency BOLD fluctuations demonstrate altered thalamocortical connectivity in schizophrenia

The thalamus plays a central and dynamic role in information transmission and processing in the brain. Multiple studies reveal increasing association between schizophrenia and dysfunction of the thalamus, in particular the medial dorsal nucleus (MDN), and its projection targets. The medial dorsal thalamic connections to the prefrontal cortex are of particular interest, and explicit in vivo evidence of this connection in healthy humans is sparse. Additionally, recent neuroimaging evidence has demonstrated disconnection among a variety of cortical regions in schizophrenia, though the MDN thalamic prefrontal cortex network has not been extensively probed in schizophrenia. To this end, we have examined thalamo-anterior cingulate cortex connectivity using detection of low-frequency blood oxygen level dependence fluctuations (LFBF) during a resting-state paradigm. Eleven schizophrenic patients and 12 healthy control participants were enrolled in a study of brain thalamocortical connectivity. Resting-state data were collected, and seed-based connectivity analysis was performed to identify the thalamocortical network. First, we have shown there is MDN thalamocortical connectivity in healthy controls, thus demonstrating that LFBF analysis is a manner to probe the thalamocortical network. Additionally, we have found there is statistically significantly reduced thalamocortical connectivity in schizophrenics compared with matched healthy controls. We did not observe any significant difference in motor networks between groups. We have shown that the thalamocortical network is observable using resting-state connectivity in healthy controls and that this network is altered in schizophrenia. These data support a disruption model of the thalamocortical network and are consistent with a disconnection hypothesis of schizophrenia.     

Functional networks underlying freezing of gait: a resting-state electroencephalographic study

IntroductionThe pathophysiology of freezing of gait in people with Parkinson's disease (PD) remains unclear, despite its association with motor, cognitive, limbic and sensory-perceptual impairments. Resting-state electroencephalography (EEG) may provide functional information for a better understanding of freezing of gait by studying spectral power and connectivity between brain regions in different frequency bands.MethodsHigh-resolution EEG was recorded in 36 patients with PD (18 freezers, 18 non-freezers), and 18 healthy controls during a 5-min resting-state protocol with eyes open, followed by a basic spectral analysis in the sensor space and a more advanced analysis of functional connectivity at the source level.ResultsFreezers showed a diffusely higher theta-band relative spectral power than controls. This increased power was correlated with a deficit in executive control. Concerning resting-state functional connectivity, connectivity strength within a left fronto-parietal network appeared to be higher in freezers than in controls in the theta band, and to be correlated with freezing severity and a history of falls.ConclusionWe have shown that spectral power and connectivity analyses of resting-state EEG provide useful and complementary information to better understand freezing of gait in PD. The higher connectivity strength seen within the left ventral attention network in freezers is in keeping with an excessive guidance of behavior by external cues, due to executive dysfunction, and spectral analysis also found changes in freezers that was closely correlated with executive control deficits. This exaggerated influence of the external environment might result in behavioral consequences that contribute to freezing of gait episodes. These findings should be further investigated with a longitudinal study.     

Effects of morphine and alcohol on functional brain connectivity during "resting state": a placebo-controlled crossover study in healthy young men

A major challenge in central nervous system (CNS) drug research is to develop a generally applicable methodology for repeated measurements of drug effects on the entire CNS, without task-related interactions and a priori models. For this reason, data-driven resting-state fMRI methods are promising for pharmacological research. This study aimed to investigate whether different psychoactive substances cause drug-specific effects in functional brain connectivity during resting-state. In this double blind placebo-controlled (double dummy) crossover study, seven resting-state fMRI scans were obtained in 12 healthy young men in three different drug sessions (placebo, morphine and alcohol; randomized). Drugs were administered intravenously based on validated pharmacokinetic protocols to minimize the inter- and intra-subject variance in plasma drug concentrations. Dual-regression was used to estimate whole-brain resting-state connectivity in relation to eight well-characterized resting-state networks, for each data set. A mixed effects analysis of drug by time interactions revealed dissociable changes in both pharmacodynamics and functional connectivity resulting from alcohol and morphine. Post hoc analysis of regions of interest revealed adaptive network interactions in relation to pharmacokinetic and pharmacodynamic curves. Our results illustrate the applicability of resting-state functional brain connectivity in CNS drug research.     

Evaluation and tracking of Alzheimer's disease severity using resting-state magnetoencephalography

We have conducted multicenter clinical studies in which brain function was evaluated with brief, resting-state magnetoencephalography (MEG) scans. A study cohort of 117 AD patients and 123 elderly cognitively normal volunteers was recruited from community neurology clinics in Denver, Colorado and Minneapolis, Minnesota. Each subject was evaluated through neurological examination, medical history, and a modest battery of standard neuropsychological tests. Brain function was measured by a one-minute, resting-state, eyes-open MEG scan. Cross-sectional analysis of MEG scans revealed global changes in the distribution of relative spectral power (centroid frequency of healthy subjects = 8.24 ± 0.2 Hz and AD patients = 6.78 ± 0.25 Hz) indicative of generalized slowing of brain signaling. Functional connectivity patterns were measured using the synchronous neural interactions (SNI) test, which showed a global increase in the strength of functional connectivity (cO2 value of healthy subjects = 0.059 ± 0.0007 versus AD patients = 0.066 ± 0.001) associated with AD. The largest magnitude disease-associated changes were localized to sensors near posterior and lateral cortical regions. Part of the cohort (31 AD and 46 cognitively normal) was evaluated in an identical fashion approximately 10 months after the first assessments. Follow-up scans revealed multiple MEG scan features that correlated significantly with changes in neuropsychological test scores. Linear combinations of these MEG scan features generated an accurate multivariate model of disease progression over 10 months. Our results demonstrate the utility of brief resting-state tests based on MEG. The non-invasive, rapid and convenient nature of these scans offers a new tool for translational AD research and early phase development of novel treatments for AD.     

Altered regional homogeneity and connectivity in cerebellum and visual-motor relevant cortex in Parkinson's disease with rapid eye movement sleep behavior disorder

ObjectiveRapid eye movement sleep behavior disorder (RBD) frequently occurs in Parkinson's disease (PD), however, the exact pathophysiological mechanism underlying its occurrence is not clear. In this study, we explored whether there is abnormal spontaneous neuronal activities and connectivity maps in some brain areas under resting-state in PD patients with RBD.MethodsWe recruited 38 PD patients (19 PD with RBD and 19 PD without RBD), and 20 age- and gender-matched normal controls. We used resting-state functional magnetic resonance imaging (RS-fMRI) to analyze regional homogeneity (ReHo) and functional connectivity (FC), and further to reveal the neuronal activity in all subjects.ResultsCompared with the PD without RBD patients, the PD with RBD patients showed a significant increase in regional homogeneity in the left cerebellum, the right middle occipital region and the left middle temporal region, and decreased regional homogeneity in the left middle frontal region. The REM sleep behavioral disorders questionnaire scores were significantly positively correlated with the ReHo values of the left cerebellum. The functional connectivity analysis in which the four regions described above were used as regions of interest revealed increased functional activity between the left cerebellum and bilateral occipital regions, bilateral temporal regions and bilateral supplementary motor area.ConclusionThe pathophysiological mechanism of PD with RBD may be related to abnormal spontaneous neuronal activity patterns with strong synchronization of cerebellar and visual-motor relevant cortex, and the increased connectivity of the cerebellum with the occipital and motor regions.     

Dopaminergic modulation of cortico-cortical functional connectivity in Parkinson's disease: an MEG study

Recent studies have demonstrated increased resting-state cortico-cortical functional connectivity in untreated Parkinson's disease (PD). We set out to determine whether this connectivity can be modulated by dopamine replacement therapy (DRT) and explore the relationship of therapy-induced changes in connectivity with motor improvement in the relatively early stages of DRT in PD. Whole-head magnetoencephalography was performed in an eyes-closed resting-state condition in 37 patients with levodopa-treated PD (Hoehn and Yahr stages 1–3) both in a practically defined “OFF” and in the “ON” medication state. Data analysis involved calculation of three synchronisation likelihood (SL; a general measure of linear and non-linear temporal correlations between time series) measures which reflect functional coupling within and between ten major cortical areas in five frequency bands. The transition from the “OFF” to the “ON” state led to increases of SL in the 4–30 Hz range, most conspicuously with regard to local SL, in tandem with motor improvement. We found a negative correlation between the change in local beta SL and the reduction of parkinsonism after DRT. Patients presenting with relatively large motor responses (41% or better) actually showed decreases in local beta SL. The present study shows that the already elevated levels of resting-state cortico-cortical functional connectivity in the 4–30 Hz range in mild to moderate PD are on average increased even further by DRT. However, a strong motor response appears to be associated with decreases in local beta-band coupling, which may constitute a risk factor for the development of motor response fluctuations or dyskinesias.     

The relationship between glucose metabolism,resting-state fMRI BOLD signal,and GABAA-binding potential: a preliminary study in healthy subjects and those with temporal lobe epilepsy

Glucose metabolism has been associated with magnitude of blood oxygen level-dependent (BOLD) signal and connectivity across subjects within the default mode and dorsal attention networks. Similar correlations within subjects across the entire brain remain unexplored. [¹⁸F]-fluorodeoxyglucose positron emission tomography ([¹⁸F]-FDG PET), [¹¹C]-flumazenil PET, and resting-state functional magnetic resonance imaging (fMRI) scans were acquired in eight healthy individuals and nine with temporal lobe epilepsy (TLE). Regional metabolic rate of glucose (rMRGlu) was correlated with amplitude of low frequency fluctuations (ALFFs) in the fMRI signal, global fMRI connectivity (GC), regional homogeneity (ReHo), and gamma-aminobutyric acid A–binding potential (GABA_A BP_ND) across the brain. Partial correlations for ALFFs, GC, and ReHo with GABA_A BP_ND were calculated, controlling for rMRGlu. In healthy subjects, significant positive correlations were observed across the brain between rMRGlu and ALFF, ReHo and GABA_A BP_ND, and between ALFFs and GABA_A BP_ND, controlling for rMRGlu. Brain-wide correlations between rMRGlu and ALFFs were significantly lower in TLE patients, and correlations between rMRGlu and GC were significantly greater in TLE than healthy subjects. These results indicate that the glutamatergic and GABAergic systems are coupled across the healthy human brain, and that ALFF is related to glutamate use throughout the healthy human brain. TLE may be a disorder of altered long-range connectivity in association with glutamate function.