Resting-state Functional Connectivity Maps Research Articles

Altered functional connectivity in preterm neonates with intraventricular hemorrhage assessed using functional near-infrared spectroscopy

Intraventricular hemorrhage (IVH) is a common neurological injury following very preterm birth. Resting-state functional connectivity (RSFC) using functional magnetic resonance imaging (fMRI) is associated with injury severity; yet, fMRI is impractical for use in intensive care settings. Functional near-infrared spectroscopy (fNIRS) measures RSFC through cerebral hemodynamics and has greater bedside accessibility than fMRI. We evaluated RSFC in preterm neonates with IVH using fNIRS and fMRI at term-equivalent age, and compared fNIRS connectivity between healthy newborns and those with IVH. Sixteen very preterm born neonates were scanned with fMRI and fNIRS. Additionally, fifteen healthy newborns were scanned with fNIRS. In preterms with IVH, fNIRS and fMRI connectivity maps were compared using Euclidean and Jaccard distances. The severity of IVH in relation to fNIRS-RSFC strength was examined using generalized linear models. fNIRS and fMRI RSFC maps showed good correspondence. Connectivity strength was significantly lower in healthy newborns (p-value = 0.023) and preterm infants with mild IVH (p-value = 0.026) compared to infants with moderate/severe IVH. fNIRS has potential to be a new bedside tool for assessing brain injury and monitoring cerebral hemodynamics, as well as a promising biomarker for IVH severity in very preterm born infants.

Network-targeted transcranial direct current stimulation of the hypothalamus appetite-control network: a feasibility study.

The hypothalamus is the key regulator for energy homeostasis and is functionally connected to striatal and cortical regions vital for the inhibitory control of appetite. Hence, the ability to non-invasively modulate the hypothalamus network could open new ways for the treatment of metabolic diseases. Here, we tested a novel method for network-targeted transcranial direct current stimulation (net-tDCS) to influence the excitability of brain regions involved in the control of appetite. Based on the resting-state functional connectivity map of the hypothalamus, a 12-channel net-tDCS protocol was generated (Neuroelectrics Starstim system), which included anodal, cathodal and sham stimulation. Ten participants with overweight or obesity were enrolled in a sham-controlled, crossover study. During stimulation or sham control, participants completed a stop-signal task to measure inhibitory control. Overall, stimulation was well tolerated. Anodal net-tDCS resulted in faster stop signal reaction time (SSRT) compared to sham (p = 0.039) and cathodal net-tDCS (p = 0.042). Baseline functional connectivity of the target network correlated with SSRT after anodal compared to sham stimulation (p = 0.016). These preliminary data indicate that modulating hypothalamus functional network connectivity via net-tDCS may result in improved inhibitory control. Further studies need to evaluate the effects on eating behavior and metabolism.

Large-scale functional network connectivity mediates the association between nigral neuromelanin hypopigmentation and motor impairment in Parkinson's disease.

Neuromelanin hypopigmentation within substantia nigra pars compacta (SNc) reflects the loss of pigmented neurons, which in turn contributes to the dysfunction of the nigrostriatal and striato-cortical pathways in Parkinson's disease (PD). Our study aims to investigate the relationships between SN degeneration manifested by neuromelanin reduction, functional connectivity (FC) among large-scale brain networks, and motor impairment in PD. This study included 68 idiopathic PD patients and 32 age-, sex- and education level-matched healthy controls who underwent neuromelanin-sensitive magnetic resonance imaging (MRI), functional MRI, and motor assessments. SN integrity was measured using the subregional contrast-to-noise ratio calculated from neuromelanin-sensitive MRI. Resting-state FC maps were obtained based on the independent component analysis. Subsequently, we performed partial correlation and mediation analyses in SN degeneration, network disruption, and motor impairment for PD patients. We found significantly decreased neuromelanin within SN and widely altered inter-network FCs, mainly involved in the basal ganglia (BG), sensorimotor and frontoparietal networks in PD. In addition, decreased neuromelanin content was negatively correlated with the dorsal sensorimotor network (dSMN)-medial visual network connection (P = 0.012) and dSMN-BG connection (P = 0.004). Importantly, the effect of SN neuromelanin hypopigmentation on motor symptom severity in PD is partially mediated by the increased connectivity strength between BG and dSMN (indirect effect = - 1.358, 95% CI: - 2.997, - 0.147). Our results advanced our understanding of the interactions between neuromelanin hypopigmentation in SN and altered FCs of functional networks in PD and suggested the potential of multimodal metrics for early diagnosis and monitoring the response to therapies.

Altered resting-state functional connectivity in newborns with hypoxic ischemic encephalopathy assessed using high-density functional near-infrared spectroscopy

Hypoxic-ischemic encephalopathy (HIE) results from a lack of oxygen to the brain during the perinatal period. HIE can lead to mortality and various acute and long-term morbidities. Improved bedside monitoring methods are needed to identify biomarkers of brain health. Functional near-infrared spectroscopy (fNIRS) can assess resting-state functional connectivity (RSFC) at the bedside. We acquired resting-state fNIRS data from 21 neonates with HIE (postmenstrual age [PMA] = 39.96), in 19 neonates the scans were acquired post-therapeutic hypothermia (TH), and from 20 term-born healthy newborns (PMA = 39.93). Twelve HIE neonates also underwent resting-state functional magnetic resonance imaging (fMRI) post-TH. RSFC was calculated as correlation coefficients amongst the time courses for fNIRS and fMRI data, respectively. The fNIRS and fMRI RSFC maps were comparable. RSFC patterns were then measured with graph theory metrics and compared between HIE infants and healthy controls. HIE newborns showed significantly increased clustering coefficients, network efficiency and modularity compared to controls. Using a support vector machine algorithm, RSFC features demonstrated good performance in classifying the HIE and healthy newborns in separate groups. Our results indicate the utility of fNIRS-connectivity patterns as potential biomarkers for HIE and fNIRS as a new bedside tool for newborns with HIE.

Common functional brain networks between attention deficit and disruptive behaviors in youth

Attention deficits (AD) and disruptive behavior (DB) are highly comorbid youth externalizing behaviors. This study aimed to study reliable functional brain networks shared by AD and DB in youth aged from 8 to 21 years from the Philadelphia Neurodevelopmental Cohort (PNC). The PNC study assessed AD and DB behaviors via Kiddie-Schedule for Affective Disorders and Schizophrenia (K-SADS). This study employed sparse canonical correlation analysis (SCCA) to examine the correlation of AD and DB behaviors with resting-state functional connectivity maps of the brain regions identified via activation likelihood estimation (ALE) meta-analyses on attention deficit/hyperactivity disorder (ADHD) and DB disorder (DBD). Our meta-analyses identified that the middle cingulate cortex, pre-supplementary motor area (pre-SMA), and striatum had a great consensus in existing ADHD studies and the amygdala and inferior parietal lobule were consistently found in existing DBD studies. Our SCCA analysis revealed that the AD and DB behavioral items relevant to inattention and delinquency were correlated with the functional connectivity of the pre-SMA with the ventral attentional and frontoparietal networks (FPN), and the striatum with the default mode (DMN) and dorsal attentional networks. The AD and DB behavioral items relevant to inattention and irritability were associated with the functional connectivity between the amygdala and the DMN and FPN. Our findings suggest that the functional organization of the ADHD- and DBD-related brain regions provides insights on the shared neural basis in AD and DB.

Analyzing the Effect of Resolution of Network Nodes on the Resting State Functional Connectivity Maps of Schizophrenic Human Brains.

Functional connectivity (FC) mapping from resting-state functional magnetic resonance imaging (rsfMRI) data is a widely used technique to characterize the brain abnormalities in mental health disorders. Using atlases for brain parcellation is an important intermediate step in calculation of FC maps. Atlases with varying resolution (number of nodes in an atlas) have been deployed by researchers to study the abnormal brain functions in Schizophrenia. In this work, we compared the variations in FC maps of Schizophrenic brains obtained from three different atlases: AAL atlas (2002), Dosenbach atlas (2010), and the Brainnetome atlas (2016). To evaluate the atlas-dependent variations in FC maps, we relied on the capability of the features of FC maps in accurately classifying a given data into healthy or Schizophrenia group. Our results indicate that the high-resolution Dosenbach and Brainnetome atlases perform better than AAL atlas in terms of the accuracy, sensitivity and specificity of the SVM classifier.

Failure of resting-state frontal–occipital connectivity in linking visual perception with reading fluency in Chinese children with developmental dyslexia

It is widely accepted that impairment in visual perception impedes children's reading development, and further studies have demonstrated significant enhancement in reading fluency after visual perceptual training. However, the mechanism of the neural linkage between visual perception and reading is unclear. The purpose of this study was to examine the intrinsic functional relationship between visual perception (indexed by the texture discrimination task,TDT) and reading ability (character reading and reading fluency) in Chinese children with developmental dyslexia (DD) and those with typical development (TD). The resting-state functional connectivity (RSFC) between the primary visual cortex (V1, BA17) and the entire brain was analyzed. In addition, how RSFC maps are associated with TDT performance and reading ability in the DD and TD groups was examined. The results demonstrated that the strength of the RSFC between V1 and the left middle frontal gyrus (LMFG, BA9/BA46) was significantly correlated with both the threshold (SOA) of the TDT and reading fluency in TD children but not in DD children. Moreover, LMFG-V1 resting-state connectivity played a mediating role in the association of visual texture discrimination and reading fluency, but not in character reading, in TD children. In contrast, this mediation was absent in DD children, albeit their strengths of RSFC between V1 and the left middle frontal gyrus (LMFG) were comparable to those for the TD group. These findings indicate that typically developing children use the linkage of the RSFC between the V1 and LMFG for visual perception skills, which in turn promote fluent reading; in contrast, children with dyslexia, who had higher TDT thresholds than TD children, could not take advantage of their frontal–occipital connectivity to improve reading fluency abilities. These findings suggest that visual perception plays an important role in reading skills and that children with developmental dyslexia lack the ability to use their frontal–occipital connectivity to link visual perception with reading fluency.

Dopaminergic pathways and resting-state functional connectivity in Parkinson’s disease with freezing of gait

Freezing of gait is a common phenomenon of advanced Parkinson’s disease. Besides locomotor function per se, a role of cognitive deficits has been suggested. Limited evidence of associated dopaminergic deficits points to caudatal denervation. Further, altered functional connectivity within resting-state networks with importance for cognitive functions has been described in freezers. A potential pathophysiological link between both imaging findings has not yet been addressed. The current study sought to investigate the association between dopaminergic pathway dysintegrity and functional dysconnectivity in relation to FOG severity and cognitive performance in a well-characterized PD cohort undergoing high-resolution 6-[18F]fluoro-L-Dopa PET and functional MRI. The freezing of gait questionnaire was applied to categorize patients (n = 59) into freezers and non-freezers. A voxel-wise group comparison of 6-[18F]fluoro-L-Dopa PET scans with focus on striatum was performed between both well-matched and neuropsychologically characterized patient groups. Seed-to-voxel resting-state functional connectivity maps of the resulting dopamine depleted structures and dopaminergic midbrain regions were created and compared between both groups. For a direct between-group comparison of dopaminergic pathway integrity, a molecular connectivity approach was conducted on 6-[18F]fluoro-L-Dopa scans. With respect to striatal regions, freezers showed significant dopaminergic deficits in the left caudate nucleus, which exhibited altered functional connectivity with regions of the visual network. Regarding midbrain structures, the bilateral ventral tegmental area showed altered functional coupling to regions of the default mode network. An explorative examination of the integrity of dopaminergic pathways by molecular connectivity analysis revealed freezing-associated impairments in mesolimbic and mesocortical pathways. This study represents the first characterization of a link between dopaminergic pathway dysintegrity and altered functional connectivity in Parkinson’s disease with freezing of gait and hints at a specific involvement of striatocortical and mesocorticolimbic pathways in freezers.

Structural and functional connectivity mapping of the human corpus callosum organization with white-matter functional networks

The corpus callosum serves as a crucial organization for understanding the information integration between the two hemispheres. Our previous study explored the functional connectivity between the corpus callosum and white-matter functional networks (WM-FNs), but the corresponding physical connectivity remains unknown. The current study uses the resting-state fMRI of Human Connectome Project data to identify ten WM-FNs in 108 healthy subjects, and then independently maps the structural and functional connectivity between the corpus callosum and above WM-FNs using the diffusion tensor images (DTI) tractography and resting-state functional connectivity (RSFC). Our results demonstrated that the structural and functional connectivity between the human corpus callosum and WM-FNs have the following high overall correspondence: orbitofrontal WM-FN, DTI map = 89% and RSFC map = 92%; sensorimotor middle WM-FN, DTI map = 47% and RSFC map = 77%; deep WM-FN, DTI map = 50% and RSFC map = 79%; posterior corona radiata WM-FN, DTI map = 82% and RSFC map = 73%. These findings reinforce the notion that the corpus callosum has unique spatial distribution patterns connecting to distinct WM-FNs. However, important differences between the structural and functional connectivity mapping results were also observed, which demonstrated a synergy between DTI tractography and RSFC toward better understanding the information integration of primary and higher-order functional systems in the human brain.

Altered amygdala-based functional connectivity in individuals with attenuated psychosis syndrome and first-episode schizophrenia

Altered resting-state functional connectivity (FC) of the amygdala (AMY) has been demonstrated to be implicated in schizophrenia (SZ) and attenuated psychosis syndrome (APS). Specifically, no prior work has investigated FC in individuals with APS using subregions of the AMY as seed regions of interest. The present study examined AMY subregion-based FC in individuals with APS and first-episode schizophrenia (FES) and healthy controls (HCs). The resting state FC maps of the three AMY subregions were computed and compared across the three groups. Correlation analysis was also performed to examine the relationship between the Z-values of regions showing significant group differences and symptom rating scores. Individuals with APS showed hyperconnectivity between the right centromedial AMY (CMA) and left frontal pole cortex (FPC) and between the laterobasal AMY and brain stem and right inferior lateral occipital cortex compared to HCs. Patients with FES showed hyperconnectivity between the right superficial AMY and left occipital pole cortex and between the left CMA and left thalamus compared to the APS and HCs respectively. A negative relationship was observed between the connectivity strength of the CMA with the FPC and negative-others score of the Brief Core Schema Scales in the APS group. We observed different altered FC with subregions of the AMY in individuals with APS and FES compared to HCs. These results shed light on the pathogenetic mechanisms underpinning the development of APS and SZ.

Neural connectivity biotypes: associations with internalizing problems throughout adolescence.

Neurophysiological patterns may distinguish which youth are at risk for the well-documented increase in internalizing symptoms during adolescence. Adolescents with internalizing problems exhibit altered resting-state functional connectivity (RSFC) of brain regions involved in socio-affective processing. Whether connectivity-based biotypes differentiate adolescents' levels of internalizing problems remains unknown. Sixty-eight adolescents (37 females) reported on their internalizing problems at ages 14, 16, and 18 years. A resting-state functional neuroimaging scan was collected at age 16. Time-series data of 15 internalizing-relevant brain regions were entered into the Subgroup-Group Iterative Multi-Model Estimation program to identify subgroups based on RSFC maps. Associations between internalizing problems and connectivity-based biotypes were tested with regression analyses. Two connectivity-based biotypes were found: a Diffusely-connected biotype (N = 46), with long-range fronto-parietal paths, and a Hyper-connected biotype (N = 22), with paths between subcortical and medial frontal areas (e.g. affective and default-mode network regions). Higher levels of past (age 14) internalizing problems predicted a greater likelihood of belonging to the Hyper-connected biotype at age 16. The Hyper-connected biotype showed higher levels of concurrent problems (age 16) and future (age 18) internalizing problems. Differential patterns of RSFC among socio-affective brain regions were predicted by earlier internalizing problems and predicted future internalizing problems in adolescence. Measuring connectivity-based biotypes in adolescence may offer insight into which youth face an elevated risk for internalizing disorders during this critical developmental period.

The Topography of Striatal Dopamine and Symptoms in Psychosis: An Integrative Positron Emission Tomography and Magnetic Resonance Imaging Study

BackgroundStriatal dopamine dysfunction is thought to underlie symptoms in psychosis, yet it remains unclear how a single neurotransmitter could cause the diverse presentations that are observed clinically. One hypothesis is that the consequences of aberrant dopamine signaling vary depending on where within the striatum the dysfunction occurs. Positron emission tomography allows for the quantification of dopamine function across the striatum. In the current study, we used a novel method to investigate the relationship between spatial variability in dopamine synthesis capacity and psychotic symptoms. MethodsWe used a multimodal imaging approach combining 18F-DOPA positron emission tomography and resting-state magnetic resonance imaging in 29 patients with first-episode psychosis and 21 healthy control subjects. In each participant, resting-state functional connectivity maps were used to quantify the functional connectivity of each striatal voxel to well-established cortical networks. Network-specific striatal dopamine synthesis capacity (Kicer) was then calculated for the resulting connectivity-defined parcellations. ResultsThe connectivity-defined parcellations generated Kicer values with equivalent reliability, and significantly greater orthogonality compared with standard anatomical parcellation methods. As a result, dopamine-symptom associations were significantly different from one another for different subdivisions, whereas no unique subdivision relationships were found when using an anatomical parcellation. In particular, dopamine function within striatal areas connected to the default mode network was strongly associated with negative symptoms (p < .001). ConclusionsThese findings suggest that individual differences in the topography of dopamine dysfunction within the striatum contribute to shaping psychotic symptomatology. Further validation of the novel approach in future studies is necessary.

Functional fractionation of default mode network in first episode schizophrenia

A disruption in the connectivity between brain regions may underlie the core pathology in schizophrenia. One of the most consistent observations in human functional imaging is a network of brain regions referred to as the default network (DMN) that contains core subsystem, the dorsomedial prefrontal cortex (dMPFC) subsystem and the medial temporal lobe (MTL) subsystem, with differential contributions. The goal of this study was to examine abnormalities of different DMN subsystems in first episode schizophrenia and associations between these abnormalities and individual psychopathology. We recruited 203 patients and 131 healthy controls. A seed-based resting-state functional connectivity (RSFC) analysis on the 2D surface was conducted. Individual DMN functional connectivity matrices were then obtained by calculating spatial correlations between pairs of RSFC maps, characterizing the functional fractionation of the DMN. Patients showed patterns similar to controls but markedly reduced strength of DMN fractionation, with the degree centrality of the MTL subsystem significantly reduced, including the posterior inferior parietal lobule (pIPL), parahippocampal cortex (PHC) and lateral temporal cortex (LTC). Patients also exhibited hypo-connectivity within the MTL subsystem and between the MTL and dMPFC subsystems. Clinical symptoms were negatively correlated with degree centrality of LTC, pIPL and PHC in patients. Hyper-fractionation of different DMN components implied that communication and coordination throughout the dissociated components of the DMN are functionally over-segregated in schizophrenia. The associations between the hyper-fractionation with clinical symptoms suggest a role of the high fractionation in the DMN in the abnormal neuropathology observed in schizophrenia.

Resting State Functional Connectivity of the Supplementary Motor Area to Motor and Language Networks in Patients with Brain Tumors.

We examined the resting-state functional connectivity (RSFC) of the supplementary motor area (SMA) in brain tumor patients. We compared the SMA subdivisions (pre-SMA, SMA proper, central SMA) in terms of RSFC projected from each region to the motor gyrus and language areas. We retrospectively identified 14 brain tumor patients who underwent task-based and resting-state fMRI, and who completed motor and language paradigms that activated the SMA proper and pre-SMA, respectively. Regions of interest (ROIs) obtained from task-based fMRI were generated in both areas and the central SMA to produce RSFC maps. Degree of RSFC was measured from each subdivision to the motor gyrus and Broca's area (BA). All patients showed RSFC between the pre-SMA and language centers and between the SMA proper and motor gyrus. Thirteen of 14 patients showed RSFC from the central SMA to both motor and language areas. There was no significant difference between subdivisions in degree of RSFC to BA (pre-SMA, r = .801; central SMA, r = .803; SMA proper; r = .760). The pre-SMA showed significantly less RSFC to the motor gyrus (r = .732) compared to the central SMA (r = .842) and SMA proper (r = .883) (P = .016, P = .001, respectively). The region between the pre-SMA and SMA proper produces reliable RSFC to the motor gyrus and language areas in brain tumor patients. This study is the first to examine RSFC of the central SMA in this population. Consequently, our results provide further validation to previous studies, supporting the existence of a central SMA with connectivity to both motor and language networks.

Nuclei-specific thalamic connectivity predicts seizure frequency in drug-resistant medial temporal lobe epilepsy.

Background and objectivesWe assessed correlations between the resting state functional connectivity (RSFC) of different thalamic nuclei and seizure frequency in patients with drug-resistant medial temporal lobe epilepsy (mTLE).MethodsSeventeen patients with mTLE and 17 sex-/age-/handedness-matched controls participated. A seed-based correlation method for the resting-state FMRI data was implemented to get RSFC maps of 70 thalamic nuclei seed masks. Group statistics for individual RSFC for subjects and seed masks were performed to obtain within-group characteristics and between-group differences with age covariates. A linear regression was applied to test whether seizure frequency correlated with thalamic nuclear RSFC with the whole brain in mTLE patients.ResultsRSFC of thalamic nuclei showed spatially distinguishable connectivity patterns that reflected principal inputs and outputs that were derived from priori anatomical knowledge. We found group differences between normal control and mTLE groups in RSFC for nuclei seeds located in various subdivisions of thalamus. The RSFCs in some of those nuclei were strongly correlated with seizure frequency.ConclusionsMediodorsal thalamic nuclei may play important roles in seizure activity or in the regulation of neuronal activity in the limbic system. The RSFC of motor- and sensory-relay nuclei may help elucidate sensory-motor deficits associated with chronic seizure activity. RSFC of the pulvinar nuclei of the thalamus could also be a key reflection of symptom-related functional deficits in mTLE.

Abnormal Global Functional Connectivity Patterns in Medication-Free Major Depressive Disorder.

Mounting studies have applied resting-state functional magnetic resonance imaging (rs-fMRI) to study major depressive disorder (MDD) and have identified abnormal functional activities. However, how the global functional connectivity patterns change in MDD is still unknown. Using rs-fMRI, we investigated the alterations of global resting-state functional connectivity (RSFC) patterns in MDD using weighted global brain connectivity (wGBC) method. First, a whole brain voxel-wise wGBC map was calculated for 23 MDD patients and 34 healthy controls. Two-sample t-tests were applied to compare the wGBC and RSFC maps and the significant level was set at p < 0.05, cluster-level correction with voxel-level p < 0.001. MDD patients showed significantly decreased wGBC in left temporal pole (TP) and increased wGBC in right parahippocampus (PHC). Subsequent RSFC analyses showed decreased functional interaction between TP and right posterior superior temporal cortex and increased functional interaction between PHC and right inferior frontal gyrus in MDD patients. These results revealed the abnormal global FC patterns and its corresponding disrupted functional connectivity in MDD. Our findings present new evidence for the functional interruption in MDD.

Intrinsic optical signal imaging of the blood volume changes is sufficient for mapping the resting state functional connectivity in the rodent cortex

Objective. Resting state functional connectivity (RSFC) allows the study of functional organization in normal and diseased brain by measuring the spontaneous brain activity generated under resting conditions. Intrinsic optical signal imaging (IOSI) based on multiple illumination wavelengths has been used successfully to compute RSFC maps in animal studies. The IOSI setup complexity would be greatly reduced if only a single wavelength can be used to obtain comparable RSFC maps. Approach. We used anesthetized mice and performed various comparisons between the RSFC maps based on single wavelength as well as oxy-, deoxy- and total hemoglobin concentration changes. Main results. The RSFC maps based on IOSI at a single wavelength selected for sensitivity to the blood volume changes are quantitatively comparable to the RSFC maps based on oxy- and total hemoglobin concentration changes obtained by the more complex IOSI setups. Moreover, RSFC maps do not require CCD cameras with very high frame acquisition rates, since our results demonstrate that they can be computed from the data obtained at frame rates as low as 5 Hz. Significance. Our results will have general utility for guiding future RSFC studies based on IOSI and making decisions about the IOSI system designs.

Value of Frequency Domain Resting-State Functional Magnetic Resonance Imaging Metrics Amplitude of Low-Frequency Fluctuation and Fractional Amplitude of Low-Frequency Fluctuation in the Assessment of Brain Tumor-Induced Neurovascular Uncoupling.

The aim of this study was to explore whether the phenomenon of brain tumor-related neurovascular uncoupling (NVU) in resting-state blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) (rsfMRI) may also affect the resting-state fMRI (rsfMRI) frequency domain metrics the amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF). Twelve de novo brain tumor patients, who underwent clinical fMRI examinations, including task-based fMRI (tbfMRI) and rsfMRI, were included in this Institutional Review Board-approved study. Each patient displayed decreased/absent tbfMRI activation in the primary ipsilesional (IL) sensorimotor cortex in the absence of a corresponding motor deficit or suboptimal task performance, consistent with NVU. Z-score maps for the motor tasks were obtained from general linear model analysis (reflecting motor activation vs. rest). Seed-based correlation analysis (SCA) maps of sensorimotor network, ALFF, and fALFF were calculated from rsfMRI data. Precentral and postcentral gyri in contralesional (CL) and IL hemispheres were parcellated using an automated anatomical labeling template for each patient. Region of interest (ROI) analysis was performed on four maps: tbfMRI, SCA, ALFF, and fALFF. Voxel values in the CL and IL ROIs of each map were divided by the corresponding global mean of ALFF and fALFF in the cortical brain tissue. Group analysis revealed significantly decreased IL ALFF (p = 0.02) and fALFF (p = 0.03) metrics compared with CL ROIs, consistent with similar findings of significantly decreased IL BOLD signal for tbfMRI (p = 0.0005) and SCA maps (p = 0.0004). The frequency domain metrics ALFF and fALFF may be markers of lesion-induced NVU in rsfMRI similar to previously reported alterations in tbfMRI activation and SCA-derived resting-state functional connectivity maps.

Altered Coupling between Motion-Related Activation and Resting-State Brain Activity in the Ipsilesional Sensorimotor Cortex after Cerebral Stroke.

Functional connectivity maps using resting-state functional magnetic resonance imaging (rs-fMRI) can closely resemble task fMRI activation patterns, suggesting that resting-state brain activity may predict task-evoked activation or behavioral performance. However, this conclusion was mostly drawn upon a healthy population. It remains unclear whether the predictive ability of resting-state brain activity for task-evoked activation would change under different pathological conditions. This study investigated dynamic changes of coupling between patterns of resting-state functional connectivity (RSFC) and motion-related activation in different stages of cerebral stroke. Twenty stroke patients with hand motor function impairment were involved. rs-fMRI and hand motion-related fMRI data were acquired in the acute, subacute, and early chronic stages of cerebral stroke on a 3-T magnetic resonance (MR) scanner. Sixteen healthy participants were enrolled as controls. For each subject, an activation map of the affected hand was first created using general linear model analysis on task fMRI data, and then an RSFC map was determined by seeding at the peak region of hand motion activation during the intact hand task. We then measured the extent of coupling between the RSFC maps and motion-related activation maps. Dynamic changes of the coupling between the two fMRI maps were estimated using one-way repeated measures analysis of variance across the three stages. Moreover, imaging parameters were correlated with motor performances. Data analysis showed that there were different coupling patterns between motion-related activation and RSFC maps associating with the affected motor regions during the acute, subacute, and early chronic stages of stroke. Coupling strengths increased as the recovery from stroke progressed. Coupling strengths were correlated with hand motion performance in the acute stage, while coupling recovery was negatively correlated with the recovery outcome of hand motion performance in the early chronic stages. Couplings between RSFC and motion-related activation were dynamically changed with stroke progression, which suggested changes in the prediction of resting-state brain activity for task-evoked brain activity in different pathological states. The changes in coupling strength between these two types of brain activity implicate a reparative mechanism of brain injury and may represent a biomarker for predicting motor recovery in cerebral stroke.

P106 Multimodal assessment of TMS-induced acute effects

Question Transcranial magnetic stimulation (TMS) has become a promising therapeutic treatment and neuroscientific research tool, yet how it works is not fully understood. We developed a dedicated MR coil array positioned beneath the TMS coil that allows for concurrent stimulation and imaging and flexible positioning while ensuring TMS efficiency, high MR sensitivity and the use of parallel/multiband imaging sequences. Here we aimed to explain acute effects of TMS over left DLPFC using a new online TMS/fMRI setup in combination with advanced imaging and neuronavigation methods. Resting State functional connectivity and DTI Tractography shall further explain resulting activation patterns at a network level. Methods The study was performed on a 3T Tim Trio scanner (Siemens, Erlangen, Germany). The TMS system used included a MagProX100 stimulator and MRi-B91 MR-compatible TMS coil (Magventure, Farum, Denmark). Five right-handed female subjects (age: 28.6 ± 4.3 years) were examined. Functional images were acquired using EPI (echo-planar imaging) sequence with TR/TE = 1000/33 ms, 28 slices, 1.5 × 1.5 × 3mm3. The experimental procedure is depicted in Fig. 1. FMRI data analyses were performed using SPM12. The design matrix comprised four regressors representing different stimulation amplitudes. DTI tractography was performed using DSI Studio. Figure options Download full-size image Download high-quality image (729 K) Download as PowerPoint slide Results TMS led to intensity-dependent activation increase in the left DLPFC and the contralateral DLPFC ( Figure options Download full-size image Download high-quality image (874 K) Download as PowerPoint slide Fig. 2): Higher stimulation intensities evoked higher bilateral activation. ACC showed a more complex response pattern. Resting-state functional connectivity maps using the stimulation target as seed-voxel showed a network very similar to the TMS-derived activation pattern (Fig. 2). DTI tractography provided additional information about the axonal connection between the left DLPFC stimulation site and the right DLPFC activation cluster. Conclusion This is the first study to assess the acute influence of TMS over DLPFC at an individual level, made possible by a dedicated concurrent TMS/fMRI coil array. Here we show a dose-dependent increase in activity not only underneath the stimulation site but also on the contralateral homologous area and apparent mediating responses in the ACC. This network is confirmed by additional resting-state and tractography data.