Exploring manual asymmetries during grasping: a dynamic causal modeling approach

Recording of neural activity during grasping actions in macaques showed that grasp-related sensorimotor transformations are accomplished in a circuit constituted by the anterior part of the intraparietal sulcus (AIP), the ventral (F5) and the dorsal (F2) region of the premotor area. In humans, neuroimaging studies have revealed the existence of a similar circuit, involving the putative homolog of macaque areas AIP, F5 and F2. These studies have mainly considered grasping movements performed with the right dominant hand and only a few studies have measured brain activity associated with a movement performed with the left non-dominant hand. As a consequence of this gap, how the brain controls for grasping movement performed with the dominant and the non-dominant hand still represents an open question. A functional resonance imaging experiment (fMRI) has been conducted, and effective connectivity (Dynamic Causal Modelling, DCM) was used to assess how connectivity among grasping-related areas is modulated by hand (i.e., left and right) during the execution of grasping movements towards a small object requiring precision grasping. Results underlined boosted inter-hemispheric couplings between dorsal premotor cortices during the execution of movements performed with the left rather than the right dominant hand. More specifically, they suggest that the dorsal premotor cortices may play a fundamental role in monitoring the configuration of fingers when grasping movements are performed by either the right and the left hand. This role becomes particularly evident when the hand less-skilled (i.e., the left hand) to perform such action is utilized. The results are discussed in light of recent theories put forward to explain how parieto-frontal connectivity is modulated by the execution of prehensile movements

Visual feedback alters force control and functional activity in the visuomotor network after stroke.

Modulating visual feedback may be a viable option to improve motor function after stroke, but the neurophysiological basis for this improvement is not clear. Visual gain can be manipulated by increasing or decreasing the spatial amplitude of an error signal. Here, we combined a unilateral visually guided grip force task with functional MRI to understand how changes in the gain of visual feedback alter brain activity in the chronic phase after stroke. Analyses focused on brain activation when force was produced by the most impaired hand of the stroke group as compared to the non-dominant hand of the control group. Our experiment produced three novel results. First, gain-related improvements in force control were associated with an increase in activity in many regions within the visuomotor network in both the stroke and control groups. These regions include the extrastriate visual cortex, inferior parietal lobule, ventral premotor cortex, cerebellum, and supplementary motor area. Second, the stroke group showed gain-related increases in activity in additional regions of lobules VI and VIIb of the ipsilateral cerebellum. Third, relative to the control group, the stroke group showed increased activity in the ipsilateral primary motor cortex, and activity in this region did not vary as a function of visual feedback gain. The visuomotor network, cerebellum, and ipsilateral primary motor cortex have each been targeted in rehabilitation interventions after stroke. Our observations provide new insight into the role these regions play in processing visual gain during a precisely controlled visuomotor task in the chronic phase after stroke

The role of contralesional dorsal premotor cortex after stroke as studied with concurrent TMS-fMRI

Contralesional dorsal premotor cortex (cPMd) may support residual motor function following stroke. We performed two complementary experiments to explore how cPMd might perform this role in a group of chronic human stroke patients. First, we used paired-coil transcranial magnetic stimulation (TMS) to establish the physiological influence of cPMd on ipsilesional primary motor cortex (iM1) at rest. We found that this influence became less inhibitory/more facilitatory in patients with greater clinical impairment. Second, we applied TMS over cPMd during functional magnetic resonance imaging (fMRI) in these patients to examine the causal influence of cPMd TMS on the whole network of surviving cortical motor areas in either hemisphere and whether these influences changed during affected hand movement. We confirmed that hand grip-related activation in cPMd was greater in more impaired patients. Furthermore, the peak ipsilesional sensorimotor cortex activity shifted posteriorly in more impaired patients. Critical new findings were that concurrent TMS-fMRI results correlated with the level of both clinical impairment and neurophysiological impairment (i.e., less inhibitory/more facilitatory cPMd-iM1 measure at rest as assessed with paired-coil TMS). Specifically, greater clinical and neurophysiological impairment was associated with a stronger facilitatory influence of cPMd TMS on blood oxygenation level-dependent signal in posterior parts of ipsilesional sensorimotor cortex during hand grip, corresponding to the posteriorly shifted sensorimotor activity seen in more impaired patients. cPMd TMS was not found to influence activity in other brain regions in either hemisphere. This state-dependent influence on ipsilesional sensorimotor regions may provide a mechanism by which cPMd supports recovered function after stroke

Functional Imaging of Autonomic Regulation: Methods and Key Findings.

Central nervous system processing of autonomic function involves a network of regions throughout the brain which can be visualized and measured with neuroimaging techniques, notably functional magnetic resonance imaging (fMRI). The development of fMRI procedures has both confirmed and extended earlier findings from animal models, and human stroke and lesion studies. Assessments with fMRI can elucidate interactions between different central sites in regulating normal autonomic patterning, and demonstrate how disturbed systems can interact to produce aberrant regulation during autonomic challenges. Understanding autonomic dysfunction in various illnesses reveals mechanisms that potentially lead to interventions in the impairments. The objectives here are to: (1) describe the fMRI neuroimaging methodology for assessment of autonomic neural control, (2) outline the widespread, lateralized distribution of function in autonomic sites in the normal brain which includes structures from the neocortex through the medulla and cerebellum, (3) illustrate the importance of the time course of neural changes when coordinating responses, and how those patterns are impacted in conditions of sleep-disordered breathing, and (4) highlight opportunities for future research studies with emerging methodologies. Methodological considerations specific to autonomic testing include timing of challenges relative to the underlying fMRI signal, spatial resolution sufficient to identify autonomic brainstem nuclei, blood pressure, and blood oxygenation influences on the fMRI signal, and the sustained timing, often measured in minutes of challenge periods and recovery. Key findings include the lateralized nature of autonomic organization, which is reminiscent of asymmetric motor, sensory, and language pathways. Testing brain function during autonomic challenges demonstrate closely-integrated timing of responses in connected brain areas during autonomic challenges, and the involvement with brain regions mediating postural and motoric actions, including respiration, and cardiac output. The study of pathological processes associated with autonomic disruption shows susceptibilities of different brain structures to altered timing of neural function, notably in sleep disordered breathing, such as obstructive sleep apnea and congenital central hypoventilation syndrome. The cerebellum, in particular, serves coordination roles for vestibular stimuli and blood pressure changes, and shows both injury and substantially altered timing of responses to pressor challenges in sleep-disordered breathing conditions. The insights into central autonomic processing provided by neuroimaging have assisted understanding of such regulation, and may lead to new treatment options for conditions with disrupted autonomic function

Interregional compensatory mechanisms of motor functioning in progressing preclinical neurodegeneration.

Understanding brain reserve in preclinical stages of neurodegenerative disorders allows determination of which brain regions contribute to normal functioning despite accelerated neuronal loss. Besides the recruitment of additional regions, a reorganisation and shift of relevance between normally engaged regions are a suggested key mechanism. Thus, network analysis methods seem critical for investigation of changes in directed causal interactions between such candidate brain regions. To identify core compensatory regions, fifteen preclinical patients carrying the genetic mutation leading to Huntington's disease and twelve controls underwent fMRI scanning. They accomplished an auditory paced finger sequence tapping task, which challenged cognitive as well as executive aspects of motor functioning by varying speed and complexity of movements. To investigate causal interactions among brain regions a single Dynamic Causal Model (DCM) was constructed and fitted to the data from each subject. The DCM parameters were analysed using statistical methods to assess group differences in connectivity, and the relationship between connectivity patterns and predicted years to clinical onset was assessed in gene carriers. In preclinical patients, we found indications for neural reserve mechanisms predominantly driven by bilateral dorsal premotor cortex, which increasingly activated superior parietal cortices the closer individuals were to estimated clinical onset. This compensatory mechanism was restricted to complex movements characterised by high cognitive demand. Additionally, we identified task-induced connectivity changes in both groups of subjects towards pre- and caudal supplementary motor areas, which were linked to either faster or more complex task conditions. Interestingly, coupling of dorsal premotor cortex and supplementary motor area was more negative in controls compared to gene mutation carriers. Furthermore, changes in the connectivity pattern of gene carriers allowed prediction of the years to estimated disease onset in individuals. Our study characterises the connectivity pattern of core cortical regions maintaining motor function in relation to varying task demand. We identified connections of bilateral dorsal premotor cortex as critical for compensation as well as task-dependent recruitment of pre- and caudal supplementary motor area. The latter finding nicely mirrors a previously published general linear model-based analysis of the same data. Such knowledge about disease specific inter-regional effective connectivity may help identify foci for interventions based on transcranial magnetic stimulation designed to stimulate functioning and also to predict their impact on other regions in motor-associated networks

Complex interaction of sensory and motor signs and symptoms in chronic CRPS.

Spontaneous pain, hyperalgesia as well as sensory abnormalities, autonomic, trophic, and motor disturbances are key features of Complex Regional Pain Syndrome (CRPS). This study was conceived to comprehensively characterize the interaction of these symptoms in 118 patients with chronic upper limb CRPS (duration of disease: 43±23 months). Disease-related stress, depression, and the degree of accompanying motor disability were likewise assessed. Stress and depression were measured by Posttraumatic Stress Symptoms Score and Center for Epidemiological Studies Depression Test. Motor disability of the affected hand was determined by Sequential Occupational Dexterity Assessment and Michigan Hand Questionnaire. Sensory changes were assessed by Quantitative Sensory Testing according to the standards of the German Research Network on Neuropathic Pain. Almost two-thirds of all patients exhibited spontaneous pain at rest. Hand force as well as hand motor function were found to be substantially impaired. Results of Quantitative Sensory Testing revealed a distinct pattern of generalized bilateral sensory loss and hyperalgesia, most prominently to blunt pressure. Patients reported substantial motor complaints confirmed by the objective motor disability testings. Interestingly, patients displayed clinically relevant levels of stress and depression. We conclude that chronic CRPS is characterized by a combination of ongoing pain, pain-related disability, stress and depression, potentially triggered by peripheral nerve/tissue damage and ensuing sensory loss. In order to consolidate the different dimensions of disturbances in chronic CRPS, we developed a model based on interaction analysis suggesting a complex hierarchical interaction of peripheral (injury/sensory loss) and central factors (pain/disability/stress/depression) predicting motor dysfunction and hyperalgesia

The role of contralesional dorsal premotor cortex after stroke as studied with concurrent TMS-fMRI.

Contralesional dorsal premotor cortex (cPMd) may support residual motor function following stroke. We performed two complementary experiments to explore how cPMd might perform this role in a group of chronic human stroke patients. First, we used paired-coil transcranial magnetic stimulation (TMS) to establish the physiological influence of cPMd on ipsilesional primary motor cortex (iM1) at rest. We found that this influence became less inhibitory/more facilitatory in patients with greater clinical impairment. Second, we applied TMS over cPMd during functional magnetic resonance imaging (fMRI) in these patients to examine the causal influence of cPMd TMS on the whole network of surviving cortical motor areas in either hemisphere and whether these influences changed during affected hand movement. We confirmed that hand grip-related activation in cPMd was greater in more impaired patients. Furthermore, the peak ipsilesional sensorimotor cortex activity shifted posteriorly in more impaired patients. Critical new findings were that concurrent TMS-fMRI results correlated with the level of both clinical impairment and neurophysiological impairment (i.e., less inhibitory/more facilitatory cPMd-iM1 measure at rest as assessed with paired-coil TMS). Specifically, greater clinical and neurophysiological impairment was associated with a stronger facilitatory influence of cPMd TMS on blood oxygenation level-dependent signal in posterior parts of ipsilesional sensorimotor cortex during hand grip, corresponding to the posteriorly shifted sensorimotor activity seen in more impaired patients. cPMd TMS was not found to influence activity in other brain regions in either hemisphere. This state-dependent influence on ipsilesional sensorimotor regions may provide a mechanism by which cPMd supports recovered function after stroke

Role of the medial part of the intraparietal sulcus in implementing movement direction

The contribution of the posterior parietal cortex (PPC) to visually guided movements has been originally inferred from observations made in patients suffering from optic ataxia. Subsequent electrophysiological studies in monkeys and functional imaging data in humans have corroborated the key role played by the PPC in sensorimotor transformations underlying goal-directed movements, although the exact contribution of this structure remains debated. Here, we used transcranial magnetic stimulation (TMS) to interfere transiently with the function of the left or right medial part of the intraparietal sulcus (mIPS) in healthy volunteers performing visually guided movements with the right hand. We found that a "virtual lesion" of either mIPS increased the scattering in initial movement direction (DIR), leading to longer trajectory and prolonged movement time, but only when TMS was delivered 100-160 ms before movement onset and for movements directed toward contralateral targets. Control experiments showed that deficits in DIR consequent to mIPS virtual lesions resulted from an inappropriate implementation of the motor command underlying the forthcoming movement and not from an inaccurate computation of the target localization. The present study indicates that mIPS plays a causal role in implementing specifically the direction vector of visually guided movements toward objects situated in the contralateral hemifield

Imaging the spatial-temporal neuronal dynamics using dynamic causal modelling

Oscillatory brain activity is a ubiquitous feature of neuronal dynamics and the synchronous discharge of neurons is believed to facilitate integration both within functionally segregated brain areas and between areas engaged by the same task. There is growing interest in investigating the neural oscillatory networks in vivo. The aims of this thesis are to (1) develop an advanced method, Dynamic Causal Modelling for Induced Responses (DCM for IR), for modelling the brain network functions and (2) apply it to exploit the nonlinear coupling in the motor system during hand grips and the functional asymmetries during face perception. DCM for IR models the time-varying power over a range of frequencies of coupled electromagnetic sources. The model parameters encode coupling strength among areas and allows the differentiations between linear (within frequency) and nonlinear (between-frequency) coupling. I applied DCM for IR to show that, during hand grips, the nonlinear interactions among neuronal sources in motor system are essential while intrinsic coupling (within source) is very likely to be linear. Furthermore, the normal aging process alters both the network architecture and the frequency contents in the motor network. I then use the bilinear form of DCM for IR to model the experimental manipulations as the modulatory effects. I use MEG data to demonstrate functional asymmetries between forward and backward connections during face perception: Specifically, high (gamma) frequencies in higher cortical areas suppressed low (alpha) frequencies in lower areas. This finding provides direct evidence for functional asymmetries that is consistent with anatomical and physiological evidence from animal studies. Lastly, I generalize the bilinear form of DCM for IR to dissociate the induced responses from evoked ones in terms of their functional role. The backward modulatory effect is expressed as induced, but not evoked responses

Inhibition of left anterior intraparietal sulcus shows that mutual adjustment marks dyadic joint-actions in humans

Creating real-life dynamic contexts to study interactive behaviors is a fundamental challenge for the social neuroscience of interpersonal relations. Real synchronic interpersonal motor interactions involve online, inter-individual mutual adaptation (the ability to adapt one's movements to those of another in order to achieve a shared goal). In order to study the contribution of the left anterior Intra Parietal Sulcus (aIPS) (i.e. a region supporting motor functions) to mutual adaptation, here, we combined a behavioral grasping task where pairs of participants synchronized their actions when performing mutually adaptive imitative and complementary movements, with the inhibition of activity of aIPS via non-invasive brain stimulation. This approach allowed us to investigate whether aIPS supports online complementary and imitative interactions. Behavioral results showed that inhibition of aIPS selectively impairs pair performance during complementary compared to imitative interactions. Notably, this effect depended on pairs' mutual adaptation skills and was higher for pairs composed of participants who were less capable of adapting to each other. Thus, we provide the first causative evidence for a role of the left aIPS in supporting mutually adaptive interactions and show that the inhibition of the neural resources of one individual of a pair is compensated at the dyadic level