Motor Network Connectivity Research Articles

Motor versus Psychomotor? Deciphering the Neural Source of Psychomotor Retardation in Depression.

Major depressive disorder (MDD) is characterized by psychomotor retardation whose underlying neural source remains unclear. Psychomotor retardation may either be related to a motor source like the motor cortex or, alternatively, to a psychomotor source with neural changes outside motor regions, like input regions such as visual cortex. These two alternative hypotheses in main (n = 41) and replication (n = 18) MDD samples using 7 Tesla MRI are investigated. Analyzing both global and local connectivity in primary motor cortex (BA4), motor network and middle temporal visual cortex complex (MT+), the main findings in MDD are: 1) Reduced local and global synchronization and increased local-to-global output in motor regions, which do not correlate with psychomotor retardation, though. 2) Reduced local-to-local BA4 - MT+ functional connectivity (FC) which correlates with psychomotor retardation. 3) Reduced global synchronization and increased local-to-global output in MT+ which relate to psychomotor retardation. 4) Reduced variability in the psychophysical measures of MT+ based motion perception which relates to psychomotor retardation. Together, it is shown that visual cortex MT+ and its relation to motor cortex play a key role in mediating psychomotor retardation. This supports psychomotor over motor hypothesis about the neural source of psychomotor retardation in MDD.

Mendelian randomization analyses reveal causal relationships between brain functional networks and risk of psychiatric disorders.

Dysfunction of brain resting-state functional networks has been widely reported in psychiatric disorders. However, the causal relationships between brain resting-state functional networks and psychiatric disorders remain largely unclear. Here we perform bidirectional two-sample Mendelian randomization (MR) analyses to investigate the causalities between 191 resting-state functional magnetic resonance imaging (rsfMRI) phenotypes (n = 34,691 individuals) and 12 psychiatric disorders (n = 14,307 to 698,672 individuals). Forward MR identified 8 rsfMRI phenotypes causally associated with the risk of psychiatric disorders. For example, the increase in the connectivity of motor, subcortical-cerebellum and limbic network was associated with lower risk of autism spectrum disorder. In adddition, increased connectivity in the default mode and central executive network was associated with lower risk of post-traumatic stress disorder and depression. Reverse MR analysis revealed significant associations between 4 psychiatric disorders and 6 rsfMRI phenotypes. For instance, the risk of attention-deficit/hyperactivity disorder increases the connectivity of the attention, salience, motor and subcortical-cerebellum network. The risk of schizophrenia mainly increases the connectivity of the default mode and central executive network and decreases the connectivity of the attention network. In summary, our findings reveal causal relationships between brain functional networks and psychiatric disorders, providing important interventional and therapeutic targets for psychiatric disorders at the brain functional network level.

Exercise intervention in middle-aged and elderly individuals with insomnia improves sleep and restores connectivity in the motor network

Exercise is a potential treatment to improve sleep quality in middle-aged and elderly individuals. Understanding exercise-induced changes in functional plasticity of brain circuits that underlie improvements in sleep among middle-aged and older adults can inform treatment of sleep problems. The aim of the study is to identify the effects of a 12-week exercise program on sleep quality and brain functional connectivity in middle-aged and older adults with insomnia. The trial was registered with Chinese Clinical Trial Register (ChiCTR2000033652). We recruited 84 healthy sleepers and 85 individuals with insomnia. Participants with insomnia were assigned to receive either a 12-week exercise intervention or were placed in a 12-week waitlist control condition. Thirty-seven middle-aged and older adults in the exercise group and 30 in the waitlist group completed both baseline and week 12 assessments. We found that middle-aged and older adults with insomnia showed significantly worse sleep quality than healthy sleepers. At the brain circuit level, insomnia patients showed decreased connectivity in the widespread motor network. After exercise intervention, self-reported sleep was increased in the exercise group (P < 0.001) compared to that in the waitlist group. We also found increased functional connectivity of the motor network with the cerebellum in the exercise group (P < 0.001). Moreover, we observed significant correlations between improvement in subjective sleep indices and connectivity changes within the motor network. We highlight exercise-induced improvement in sleep quality and functional plasticity of the aging brain.

Sustained connectivity correlates of motor function in Alzheimer’s disease

AbstractBackgroundIn addition to cognitive deficits, issues with motor control are present across the dementia spectrum. Traditional functional connectivity measures synchrony of intrinsic activity between brain regions and is altered in patients with Alzheimer’s disease in regions supporting motor function; however, less is known regarding the temporal stability of that synchrony. Sustained connectivity uses the width of cross correlation curves of BOLD time series to reflect the relative duration of synchronous activity between brain regions. This study investigates sustained connectivity across the dementia spectrum in motor regions.Method109 participants were included in this analysis and included 32 individuals with mild cognitive impairment (MCI) (18 F, 73.84 ± 5.14), 30 with Alzheimer’s disease (AD) (19 F, 77.37 ± 6.45), and 47 control individuals (29 F, mean age 72.13 ± 4.68). All study participants completed MP2RAGE structural imaging and two 15‐minute resting fMRI scans. Preprocessing steps included segmentation, motion realignment, registration to MNI space, and regression of motion parameters. Sustained connectivity values were averaged across both scans and only participants with more than 50% volumes remaining after censoring were included in analysis. A 17 resting‐state network parcellation was used to evaluate sustained connectivity across the brain with each network treated as a single ROI. A linear regression analysis was used to compare sustained connectivity across groups controlling for mean head motion, age, and sex. T statistics and p‐values are reported for across group sustained connectivity values.ResultAcross all three groups, sustained connectivity with the dorsal and ventral somatomotor networks was significantly increased across a number of resting‐state networks including the central visual, anterior ventral attention, and lateral temporal default mode network (DMN; all dorsal) and the somatomotor association, anterior ventral attention, medial frontoparietal, lateral temporal and lateral DMN (all ventral; Figure 1; pFDR &lt; .05).ConclusionThese data suggest sustained connectivity may be a potential metric for assessing progressive cognitive decline in dementia. Our results indicate that sustained connectivity may be used to track changes in the temporal duration of functional connectivity in motor networks in individuals with intact cognition, mild cognitive impairment, and Alzheimer’s disease.

Sex-Related Variations in the Brain Motor-Network Connectivity at Rest during Puberty

The development of functional neuroimaging technologies has resulted in a flood of mathematical models that investigate functional brain connections in health and disease. Motor network activity in the resting state and its response to puberty remains to be investigated. Variations between sexes in puberty may appear not just in brain regions involved in sexual and emotional activities, but also in cognitive and motor abilities that are active even when the individual is resting. The aim of this study was to investigate the interactions of the motor subnetwork in the resting state of healthy males and females aged 12 and 16. This study used the OpenNeuro Dataset ds004169:1.0.7, Queensland Twin IMaging. The MRI signals were preprocessed to get adjacency matrices from the sensory/somatomotor and cerebellar networks in the Power atlas. Network topology was analyzed using the centrality measures of strength, hubness, and leverage. The strength of the nodes increases with age in both sex groups. Both sexes had right hemisphere dominance in the cerebellar-mouth subnetwork and left dominance in the cerebellar-hand subnetwork. Eleven leverage centrality regions were common to all groups, the most relevant were the Precuneus, the cingulum postcentral and the supplementary motor area. In both sexes, hubs at age 12 were detected only in the right hemisphere. This dominance was reduced at age 16. Understanding connectivity changes in the brain during rest may enable the identification of neurophysiological mechanisms of cognitive and behavioral development that may contribute to long-term psychological well-being in adolescents.

Task-residual effective connectivity of motor network in transient ischemic attack

Transient ischemic attack (TIA) is a temporary episode of neurological dysfunction that results from focal brain ischemia. Although TIA symptoms are quickly resolved, patients with TIA have a high risk of stroke and persistent impairments in multiple domains of cognitive and motor functions. In this study, using spectral dynamic causal modeling, we investigate the changes in task-residual effective connectivity of patients with TIA during fist-closing movements. 28 healthy participants and 15 age-matched patients with TIA undergo functional magnetic resonance imaging at 7T. Here we show that during visually cued motor movement, patients with TIA have significantly higher effective connectivity toward the ipsilateral primary motor cortex and lower connectivity to the supplementary motor area than healthy controls. Our results imply that TIA patients have aberrant connections among motor regions, and these changes may reflect the decreased efficiency of primary motor function and disrupted control of voluntary movement in patients with TIA.

Functional Correlates of Intelligence Quotient and Cognitive Abilities Vary According to Maturation in Pediatric MS (P9-3.013)

<h3>Objective:</h3> To test maturation effects on neuropsychological profiles and resting state (RS) functional connectivity (FC) in cognitive and motor networks of pediatric patients with multiple sclerosis (MS). <h3>Background:</h3> Clinical and cognitive features of pediatric MS patients differ from adults. The effect of brain maturation on RS FC and its possible interaction with cognitive features has never been studied. <h3>Design/Methods:</h3> Seventy-six pediatric MS patients underwent a neuropsychological assessment of Wechsler-Intelligence-Scales for Intelligent Quotient (IQ), Semantic/Phonemic Verbal Fluency Test (SVFT/PVFT), Symbol Digit Modalities Test (SDMT), Coding Design (CD) and Block Design (BD) subtests, Trial Making Test (TMT-A/B). In 58 right-handed MS patients and 22 matched healthy controls (HC), RS FC within basal ganglia, executive, language, sensorimotor, and default-mode networks was estimated. Maturation effects were tested by splitting pediatric MS in those below the age of 16 years (B16) (n=46) and those above or equal 16 years (A16) (n=30). <h3>Results:</h3> Most patients (81.6%) achieved IQ scores within or above average values (median IQ=97.5). The highest rate of failure was observed in CD (21.1%), TMT-B (15.8%), TMT-A (10.5%), and SDMT (9.2%). Compared to HC, pediatric MS patients showed reduced RS FC in all networks, mainly involving the caudate nucleus and its connections with cingulate, prefrontal, and sensorimotor cortices. This effect was particularly relevant in younger patients (B16), where reduced basal ganglia, language and executive RS FC was associated with poorer cognitive performances (r range=0.37/0.48), while reduced cingulate RS FC was associated with a lower IQ (r=0.36). In older patients (A16), reduced language and executive RS FC was correlated with lower IQ and CD, BD and PVFT/SVFT scores (r range=0.42–0.67). However, A16 patients also presented increased executive, default-mode and language RS FC <i>vs</i> HC, which was detrimental on performance at the same tests (r range=−0.39/−0.62). <h3>Conclusions:</h3> Maturation significantly impacts on RS FC abnormalities and on their association with cognitive performances. <b>Disclosure:</b> Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva. The institution of Maria Assunta Rocca has received research support from Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BMS Celgene. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BIOMEDIA. Dr. Curatoli has nothing to disclose. Carmen Vizzino has nothing to disclose. Monica Margoni has received research support from MAGNIMS. Paola Valsasina has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ACCMED. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

Patient-tailored transcranial direct current stimulation to improve stroke rehabilitation: study protocol of a randomized sham-controlled trial

BackgroundMany patients do not fully regain motor function after ischemic stroke. Transcranial direct current stimulation (TDCS) targeting the motor cortex may improve motor outcome as an add-on intervention to physical rehabilitation. However, beneficial effects on motor function vary largely among patients within and across TDCS trials. In addition to a large heterogeneity of study designs, this variability may be caused by the fact that TDCS was given as a one-size-fits-all protocol without accounting for anatomical differences between subjects. The efficacy and consistency of TDCS might be improved by a patient-tailored design that ensures precise targeting of a physiologically relevant area with an appropriate current strength.MethodsIn a randomized, double-blinded, sham-controlled trial, patients with subacute ischemic stroke and residual upper-extremity paresis will receive two times 20 min of focal TDCS of ipsilesional primary motor hand area (M1-HAND) during supervised rehabilitation training three times weekly for 4 weeks. Anticipated 60 patients will be randomly assigned to active or sham TDCS of ipsilesional M1-HAND, using a central anode and four equidistant cathodes. The placement of the electrode grid on the scalp and current strength at each cathode will be personalized based on individual electrical field models to induce an electrical current of 0.2 V/m in the cortical target region resulting in current strengths between 1 and 4 mA. Primary endpoint will be the difference in change of Fugl-Meyer Assessment of Upper Extremity (FMA-UE) score between active TDCS and sham at the end of the intervention. Exploratory endpoints will include UE-FMA at 12 weeks. Effects of TDCS on motor network connectivity and interhemispheric inhibition will be assessed with functional MRI and transcranial magnetic stimulation.DiscussionThe study will show the feasibility and test the efficacy of personalized, multi-electrode anodal TDCS of M1-HAND in patients with subacute stroke patients with upper-extremity paresis. Concurrent multimodal brain mapping will shed light into the mechanisms of action of therapeutic personalized TDCS of M1-HAND. Together, the results from this trial may inform future personalized TDCS studies in patients with focal neurological deficits after stroke.

Changes in Distributed Motor Network Connectivity Correlates With Functional Outcome After Surgical Resection of Brain Tumors

BACKGROUND: In patients with brain tumors around the motor cortices, deterioration of motor performance may be observed even if the integrity of the cortical output is maintained. Especially, resection of medial premotor area (PM) can cause postoperative deterioration called supplementary motor area syndrome. OBJECTIVE: To clarify the neuronal mechanisms underlying postsurgical deterioration with a case-control study. METHODS: Twelve patients with brain tumors underwent preoperative and postoperative sessions consisting of motor performance evaluation and 3T-magnetic resonance imaging data acquisition. Based on additional postsurgical motor deficits, 6 patients were classified into “deficit group,” and 6 others were into “no deficit group.” Using resting-state functional magnetic resonance imaging (fMRI), the integrity of functional connectivity was evaluated by placing a seed in the ipsilesional primary motor area (M1). With motor task fMRI, hand and foot representations were identified in the M1 and lateral and medial PMs. Probabilistic tractography assessed anatomic connectivity in the cortico-cortical and corticofugal networks. RESULTS: Functional connectivity among M1 and lateral and medial PMs during resting-state fMRI was reduced postoperatively in the deficit group (P &lt; .05, corrected) and preserved in the no deficit group. The deficit was unlikely to be attributable to surgical resection of specific anatomic connectivity. The amplitude of motor-evoked potential was maintained in available cases. These intraoperative observations agree with imaging findings suggesting preserved anatomic connectivity of the estimated corticofugal pathway. CONCLUSION: The present findings suggest that supplementary motor area syndrome is caused by disorganization of functional connectivity among cortical motor networks rather than resection of anatomic connectivity of corticofugal pathway.

Enhancing the connectivity in a 2-node motor network using reinforcement learning-based closed-loop rTMS

Abstract TMS has been extensively used to investigate the physiology of the central nervous system in health and disease. However, there is a strong need for a personalized, multi-locus, real-time stimulation procedure, which can be adaptively fine-tuned based on case-specific feedback. Here, we modulate the effective connectivity of the 2-node brain network from supplementary motor area (SMA) to primary motor cortex (M1) by closed-loop stimulation, optimized by application of an online reinforcement learning algorithm. This algorithm learns to identify the individually optimal phase of the ongoing μ-rhythm to be targeted by paired SMA-M1 TMS for maximized long-term enhancement of facilitatory effective connectivity between SMA and M1. This is one of the first demonstrations of true closed-loop stimulation, a crucially important step towards individualized highly-effective brain stimulation for therapeutic modulation of dysfunctional brain networks, e.g., the deficient SMA-M1 connection in motor stroke. Research Category and Technology and Methods Translational Research: 7. Responsive (Closed-Loop) Stimulation Keywords: EEG-TMS, Machine Learning, Closed-loop stimulation, Motor cortex

Longitudinal changes in functional connectivity in speech motor networks in apraxia of speech after stroke.

The cerebral substrates of apraxia of speech (AOS) recovery remain unclear. Resting state fMRI post stroke can inform on altered functional connectivity (FC) within cortical language networks. Some initial studies report reduced FC between bilateral premotor cortices in patients with AOS, with lowest FC in patients with the most severe AOS. However, longitudinal FC studies in stroke are lacking. The aims of the present longitudinal study in early post stroke patients with AOS were (i) to compare connectivity strength in AOS patients to that in left hemisphere (LH) lesioned stroke patients without a speech-language impairment, (ii) to investigate the relation between FC and severity of AOS, aphasia and non-verbal oral apraxia (NVOA) and (iii) to investigate longitudinal changes in FC, from the subacute phase to the chronic phase to identify predictors of AOS recovery. Functional connectivity measures and comprehensive speech-language assessments were obtained at 4 weeks and 6 months after stroke in nine patients with AOS after a LH stroke and in six LH lesioned stroke patients without speech-language impairment. Functional connectivity was investigated in a network for speech production: inferior frontal gyrus (IFG), anterior insula (aINS), and ventral premotor cortex (vPMC), all bilaterally to investigate signs of adaptive or maladaptive changes in both hemispheres. Interhemispheric vPMC connectivity was significantly reduced in patients with AOS compared to LH lesioned patients without speech-language impairment. At 6 months, the AOS severity was associated with interhemispheric aINS and vPMC connectivity. Longitudinal changes in FC were found in individuals, whereas no significant longitudinal change in FC was found at the group level. Degree of longitudinal AOS recovery was strongly associated with interhemispheric IFG connectivity strength at 4 weeks. Early interhemispheric IFG connectivity may be a strong predictor of AOS recovery. The results support the importance of interhemispheric vPMC connection in speech motor planning and severity of AOS and suggest that also bilateral aINS connectivity may have an impact on AOS severity. These findings need to be validated in larger cohorts.

Precise motor rhythmicity relies on motor network responsivity.

Rhythmic movements are the building blocks of human behavior. However, given that rhythmic movements are achieved through complex interactions between neural modules, it remains difficult to clarify how the central nervous system controls motor rhythmicity. Here, using a novel tempo-precision trade-off paradigm, we first modeled interindividual behavioral differences in tempo-dependent rhythmicity for various external tempi. We identified 2 behavioral extremes: conventional and paradoxical tempo-precision trade-off types. We then explored the neural substrates of these behavioral differences using task and resting-state functional magnetic resonance imaging. We found that the responsibility of interhemispheric motor network connectivity to tempi was a key to the behavioral repertoire. In the paradoxical trade-off type, interhemispheric connectivity was low at baseline but increased in response to increasing tempo; in the conventional trade-off type, strong baseline connectivity was coupled with low responsivity. These findings suggest that tunable interhemispheric connectivity underlies tempo-dependent rhythmicity control.

A 90-channel triaxial magnetoencephalography system using optically pumped magnetometers.

Magnetoencephalography (MEG) measures the small magnetic fields generated by current flow in neural networks, providing a noninvasive metric of brain function. MEG is well established as a powerful neuroscientific and clinical tool. However, current instrumentation is hampered by cumbersome cryogenic field-sensing technologies. In contrast, MEG using optically pumped magnetometers (OPM-MEG) employs small, lightweight, noncryogenic sensors that provide data with higher sensitivity and spatial resolution, a natural scanning environment (including participant movement), and adaptability to any age. However, OPM-MEG is new and the optimum way to design a system is unknown. Here, we construct a novel, 90-channel triaxial OPM-MEG system and use it to map motor function during a naturalistic handwriting task. Results show that high-precision magnetic field control reduced background fields to ∼200 pT, enabling free participant movement. Our triaxial array offered twice the total measured signal and better interference rejection compared to a conventional (single-axis) design. We mapped neural oscillatory activity to the sensorimotor network, demonstrating significant differences in motor network activity and connectivity for left-handed versus right-handed handwriting. Repeatability across scans showed that we can map electrophysiological activity with an accuracy ∼4mm. Overall, our study introduces a novel triaxial OPM-MEG design and confirms its potential for high-performance functional neuroimaging.

The hand motor hotspot for seed-based functional connectivity of hand motor networks at rest.

In the seed-based method for studying functional connectivity (FC), seed selection is relevant. Here, we propose a new methodological approach for resting-state FC analysis of hand motor networks using the individual hand motor hotspot (hMHS) as seed. Nineteen right-handed healthy volunteers underwent a transcranial magnetic stimulation (TMS) session and resting-state fMRI. For each subject, the hMHS in both hemispheres was identified by TMS with the contralateral abductor pollicis brevis muscle as the target, the site eliciting the highest and most reliable motor-evoked potentials. Seed regions were built on coordinates on the cortex corresponding to the individual left and right hMHSs. For comparison, the left and right Brodmann’s area 4 (BA4) masks extracted from a standard atlas were used as seed. The left and right hMHSs showed FC patterns at rest mainly including sensorimotor regions, with a bilateral connectivity only for the left hMHS. The statistical contrast BA4 > hMHS for both hemispheres showed different extension and lateralization of the functionally connected cortical regions. On the contrary, no voxels survived the opposite contrast (hMHS > BA4). This suggests that detection of individual hand motor seeds by TMS allows to identify functionally connected motor networks that are more specific with respect to those obtained starting from the a priori atlas-based identification of the primary motor cortex.

Is Resting State Functional MRI Effective Connectivity in Movement Disorders Helpful? A Focused Review Across Lifespan and Disease.

In the evolving modern era of neuromodulation for movement disorders in adults and children, much progress has been made recently characterizing the human motor network (MN) with potentially important treatment implications. Herein is a focused review of relevant resting state fMRI functional and effective connectivity of the human motor network across the lifespan in health and disease. The goal is to examine how the transition from functional connectivity to dynamic effective connectivity may be especially informative of network-targeted movement disorder therapies, with hopeful implications for children.

FV 25 Interhemispheric connectivity of frontoparietal motor regions aids grasping performance after stroke

Introduction: After a stroke, increased neural activation in the contralesional primary motor cortex (M1) and the anterior intraparietal sulcus (aIPS) has been discussed to indicate supporting or disturbing roles for motor function, depending on patients‘ impairment and motor network connectivity (Di Pino et al., 2014). Prior studies have focused on interfering with M1 during the execution of simple motor tasks to test this hypothesis using online-rTMS. However, parietal areas are typically engaged in more demanding tasks. We hence combined task and resting-state fMRI, followed by neuronavigated online-rTMS to assess the roles of M1 and aIPS for complex upper limb movements in relation to interhemispheric resting-state functional connectivity (RSFC) with their ipsilesional counterparts. Methods: Resting fMRI and task fMRI were acquired from 18 chronic stroke patients and 18 age-matched controls. Task-related activation peaks in bilateral aIPS as well as the electrophysiological hotspot in contralesional M1 were identified in each participant and targeted by online-rTMS (10 Hz trains, 90% of resting motor threshold) during (i) index finger-tapping, (ii) reach-to-point, and (iii) reach-to-grasp movements. For sham rTMS, the coil was tilted over the parieto-occipital vertex. We analyzed 3D hand kinematics (smoothness, efficiency, accuracy, speed) in each task and clustered well and poorly recovered patients using K means. Additionally, we extracted performance across all kinematic data by multiple factor analysis. Kinematics during real online rTMS were normalized to the sham condition and correlated with RSFC between bilateral M1, aIPS, and dorsal premotor cortex (dPMC; Rehme et al., 2012). Results: Clustering of kinematics yielded one cluster with healthy controls and recovered patients as opposed to a second cluster with impaired patients. RSFC between bilateral aIPS and between ipsilesional aIPS and dorsal premotor cortex was higher in recovered compared to impaired patients. Interhemispheric connectivity between bilateral M1 and ipsilesional aIPS with contralesional M1 correlated with better motor performance. Online rTMS revealed that patients with increased RSFC between bilateral M1 were impaired in grasping speed when interfering with contralesional M1, whereas patients with increased RSFC between bilateral aIPS deteriorated in grasping accuracy when interfering with contralesional aIPS. Conclusion: The present findings suggest a link between stroke impairment and interhemispheric RSFC between bilateral M1 and aIPS. Interfering with contralesional M1 and aIPS further showed a supportive role of M1 and aIPS in patients with higher interhemispheric connectivity. This finding may indicate that resources from the contralesional M1 and aIPS are accessed via transcallosal connections, aiding different aspects of complex hand movements in chronic stroke. References Di Pino G et al. Nat Rev Neurol 2014. Rehme AK et al. NeuroImage 2012.

FV 11 Physical activity at youth is associated with the strength of connectivity in subcortical locomotor and motor networks: A resting-state fMRI study

Background: In the face of aging and neurological disease some people show better motor function than others despite similar structural preconditions of the nervous system, suggesting the existence of a reserve that enables them to compensate for damages. Previous work in stroke patients has identified connections between regions of the subcortical locomotor and motor networks that are strongly linked to better motor outcome. Objective: To identify associations between resting-state functional connectivity (rs-FC) between regions of the subcortical locomotor and motor networks, performance in a visuomotor adaptation task, and current as well as past physical activity. Methods: In this preliminary study, 11 neurologically healthy individuals (mean age: 43 [21-63]; 55% female) were included. High-resolution T1-weighted MRI was acquired to quantify brain atrophy, and resting-state functional connectivity (rsFC) of the motor network was assessed. A visuomotor adaptation task (VAT) was used as a measure of current adaptive performance. The main measure of adaptive performance were the rates of adaptation and deadaptation. This was measured as the rate of change in error between the start of the adaptation/deadaptation phase and the plateau. The plateau range was determined as the mean ± standard deviation of the last 32 trials. Plateaus were defined as the trial in which subsequent 5 trials fell within the plateau range. Additionally, subjects reported their current and past physical activity. Relationships between regional brain volumes, rsFC values, VAT measures, and reported physical activity were evaluated using Spearman’s partial correlations with age as a covariate. Results: Physical activity between ages 14 and 21 was strongly correlated with connectivity between right premotor area (PMA) and left supplementary motor area (SMA) (r=0.89, p=0.001), right PMA and left M1 (r=0.85, p=0.004), left SMA and left PMA (r=0.85, p<0.001), and pedunculopontine nucleus (PPN) and right superior frontal gyrus (SFG) (r=0.85, p<0.001). The rate of deadaptation positively correlated with the volume of the right M1 and right SMA (r=0.70, p=0.023; r=0.69, p=0.027). Conclusion: The present pilot study indicates that physical activity at ages 14-21 may turn out to be an important determinant of individual motor network efficiency. Further steps of analysis will be done to investigate the link between locomotor adaptation rates and motor adaptive capacity. This may ultimately enable us to assess quantitative aspects of the individual motor reserve and to further understand its contribution to successful adaptation to ageing and disease.

Depression and Psychosis Risk Shared Vulnerability for Motor Signs Across Development, Symptom Dimensions, and Familial Risk.

Motor abnormalities are strong transdiagnostic indicators of psychopathology risk that reflect emerging neural network abnormalities. Indeed, motor signs, such as motor slowing and agitation, are widely recognized as core features of both psychosis and depression. However, it is unclear whether these reflect shared or distinct etiology. A sample of 11 878 adolescents completed self-reported clinical measures of rated psychotic-like experiences (PLEs) and depression. Familial risk for psychopathology and the presence of motor signs were drawn from parental reports, including developmental motor delays (eg, sitting, walking), and adolescent motor signs (eg, dyscoordination, psychomotor retardation, and psychomotor agitation). Finally, motor network connectivity in theoretically relevant networks (cortico-striatal, cortico-thalamic, and cortico-cerebellar) were related to symptoms and familial risk for psychopathology. Developmental motor delays related to increased PLEs, increased depression symptoms, and greater familial risk. Familial risk for both PLEs and depression showed higher rates of developmental motor delays than all other groups. Adolescent motor signs, however, showed unique patterns of relationships to symptoms and familial risk such that dyscoordination reflected risk for PLEs, both psychomotor agitation and retardation reflected depression risk, and psychomotor agitation reflected transdiagnostic risk. Cortico-striatal connectivity was related to depression and PLEs, but cortico-cerebellar connectivity was linked to PLEs only. Motor signs may be a transdiagnostic marker of vulnerability for psychopathology. Early developmental motor delays could belie pluripotent, familial risk features. Unique items, eg, dyscoordination specifically related to PLEs, possibly reflecting processes inherent in distinct emerging forms of psychopathology.

Translational Model of Cortical Premotor-Motor Networks.

Deciphering the physiological patterns of motor network connectivity is a prerequisite to elucidate aberrant oscillatory transformations and elaborate robust translational models of movement disorders. In the proposed translational approach, we studied the connectivity between premotor (PMC) and primary motor cortex (M1) by recording high-density electroencephalography in humans and between caudal (CFA) and rostral forelimb (RFA) areas by recording multi-site extracellular activity in mice to obtain spectral power, functional and effective connectivity. We identified a significantly higher spectral power in β- and γ-bands in M1compared to PMC and similarly in mice CFA layers (L) 2/3 and 5 compared to RFA. We found a strong functional β-band connectivity between PMC and M1 in humans and between CFA L6 and RFA L5 in mice. We observed that in both humans and mice the direction of information flow mediated by β- and γ-band oscillations was predominantly from PMC toward M1 and from RFA to CFA, respectively. Combining spectral power, functional and effective connectivity, we revealed clear similarities between human PMC-M1 connections and mice RFA-CFA network. We propose that reciprocal connectivity of mice RFA-CFA circuitry presents a suitable model for analysis of motor control and physiological PMC-M1 functioning or pathological transformations within this network.

Early motor network connectivity after stroke: An interplay of general reorganization and state-specific compensation.

Motor recovery after stroke relies on functional reorganization of the motor network, which is commonly assessed via functional magnetic resonance imaging (fMRI)‐based resting‐state functional connectivity (rsFC) or task‐related effective connectivity (trEC). Measures of either connectivity mode have been shown to successfully explain motor impairment post‐stroke, posing the question whether motor impairment is more closely reflected by rsFC or trEC. Moreover, highly similar changes in ipsilesional and interhemispheric motor network connectivity have been reported for both rsFC and trEC after stroke, suggesting that altered rsFC and trEC may capture similar aspects of information integration in the motor network reflecting principle, state‐independent mechanisms of network reorganization rather than state‐specific compensation strategies. To address this question, we conducted the first direct comparison of rsFC and trEC in a sample of early subacute stroke patients (n = 26, included on average 7.3 days post‐stroke). We found that both rsFC and trEC explained motor impairment across patients, stressing the clinical potential of fMRI‐based connectivity. Importantly, intrahemispheric connectivity between ipsilesional M1 and premotor areas depended on the activation state, whereas interhemispheric connectivity between homologs was state‐independent. From a mechanistic perspective, our results may thus arise from two distinct aspects of motor network plasticity: task‐specific compensation within the ipsilesional hemisphere and a more fundamental form of reorganization between hemispheres.