Motor-related Areas Research Articles

AAV9-mediated central nervous system–targeted gene delivery via cisterna magna route in mice

Current barriers to the use of adeno-associated virus serotype 9 (AAV9) in clinical trials for treating neurological disorders are its high expression in many off-target tissues such as liver and heart, and lack of cell specificity within the central nervous system (CNS) when using ubiquitous promoters such as human cytomegalovirus (CMV) or chicken-β-actin hybrid (CAG). To enhance targeting the transgene expression in CNS cells, self-complementary (sc) AAV9 vectors, scAAV9-GFP vectors carrying neuronal Hb9 and synapsin 1, and nonspecific CMV and CAG promoters were constructed. We demonstrate that synapsin 1 and Hb9 promoters exclusively targeted neurons in vitro, although their strengths were up to 10-fold lower than that of CMV. In vivo analyses of mouse tissue after scAAV9-GFP vector delivery via the cisterna magna revealed a significant advantage of synapsin 1 promoter over both Hb9 variants in targeting neurons throughout the brain, since Hb9 promoters were driving gene expression mainly within the motor-related areas of the brain stem. In summary, this study demonstrates that cisterna magna administration is a safe alternative to intracranial or intracerebroventricular vector delivery route using scAAV9, and introduces a novel utility of the Hb9 promoter for the targeted gene expression for both in vivo and in vitro applications.

Motor and sensory cortical reorganization after bilateral forearm transplantation: Four-year follow-up fMRI case study

The objective of this study was to characterize the cortical activity pattern of one patient who received bilateral forearm transplants.Using fMRI we acquired motor and sensory brain activity every year after surgery and during three consecutive years while the patient underwent physical rehabilitation.The motor related cortical activity evaluated during the first year showed a sparse pattern involving several brain regions. Over time, the analysis showed a progressive delimitation of the motor-related areas that had significant activity. The results also showed continuous size reductions of the activated cluster in the motor cortex. The activation in the sensory cortex showed significant increases in cluster size over time. The intensity of both motor and sensory cortical activations correlated with the Disabilities of the Arm, Shoulder and Hand questionnaire.Our results show significant cortical reorganization of motor and sensory cortices after transplantation of bilateral forearm transplantation over a four-year period.

Dose-dependent effects of isoflurane on regional activity and neural network function: A resting-state fMRI study of 14 rhesus monkeys: An observational study

The dose-dependent effect of isoflurane on cerebral regional activity and functional connectivity (FC) in 14 rhesus monkeys was investigated using resting-state functional MRI. Amplitude of low-frequency fluctuations (ALFF) decreased in the cerebellum, visual cortex, and cortico-subcortical network when the isoflurane dose changed from 1.0 to 1.3 MAC. ALFF decreased in the arousal system, cerebellum, sensory, visual areas, cortico-subcortical network and default mode network and increased in the bilateral dorsal prefrontal cortices, frontal eye fields and motor-related areas from 1.0 to 1.6 MAC. FC of the default mode network, frontal-parietal, cortico-subcortical, motor, sensory, auditory and visual areas was reduced when isoflurane increased from 1.0 to 1.3 MAC. FC decreased in more widespread areas, especially in regions of cortico-subcortical networks and limbic systems, when isoflurane further increased from 1.0 to 1.6 MAC. Both dose-dependent decreased and increased ALFF were separately observed, while FC deteriorated as the anesthesia deepened. These results suggest that changes continue to occur past the loss of consciousness, and the dose-dependent effects of isoflurane are different with regard to regional function and neural network integration.

Rhythm makes the world go round: An MEG-TMS study on the role of right TPJ theta oscillations in embodied perspective taking

While some aspects of social processing are shared between humans and other species, some aspects are not. The former seems to apply to merely tracking another's visual perspective in the world (i.e., what a conspecific can or cannot perceive), while the latter applies to perspective taking in form of mentally “embodying” another's viewpoint. Our previous behavioural research had indicated that only perspective taking, but not tracking, relies on simulating a body schema rotation into another's viewpoint. In the current study we employed Magnetoencephalography (MEG) and revealed that this mechanism of mental body schema rotation is primarily linked to theta oscillations in a wider brain network of body-schema, somatosensory and motor-related areas, with the right posterior temporo-parietal junction (pTPJ) at its core. The latter was reflected by a convergence of theta oscillatory power in right pTPJ obtained by overlapping the separately localised effects of rotation demands (angular disparity effect), cognitive embodiment (posture congruence effect), and basic body schema involvement (posture relevance effect) during perspective taking in contrast to perspective tracking. In a subsequent experiment we interfered with right pTPJ processing using dual pulse Transcranial Magnetic Stimulation (dpTMS) and observed a significant reduction of embodied processing. We conclude that right TPJ is the crucial network hub for transforming the embodied self into another's viewpoint, body and/or mind, thus, substantiating how conflicting representations between self and other may be resolved and potentially highlighting the embodied origins of high-level social cognition in general.

Voluntary Modulation of Hemodynamic Responses in Swallowing Related Motor Areas: A Near-Infrared Spectroscopy-Based Neurofeedback Study.

In the present study, we show for the first time that motor imagery of swallowing, which is defined as the mental imagination of a specific motor act without overt movements by muscular activity, can be successfully used as mental strategy in a neurofeedback training paradigm. Furthermore, we demonstrate its effects on cortical correlates of swallowing function. Therefore, N = 20 healthy young adults were trained to voluntarily increase their hemodynamic response in swallowing related brain areas as assessed with near-infrared spectroscopy (NIRS). During seven training sessions, participants received either feedback of concentration changes in oxygenated hemoglobin (oxy-Hb group, N = 10) or deoxygenated hemoglobin (deoxy-Hb group, N = 10) over the inferior frontal gyrus (IFG) during motor imagery of swallowing. Before and after the training, we assessed cortical activation patterns during motor execution and imagery of swallowing. The deoxy-Hb group was able to voluntarily increase deoxy-Hb over the IFG during imagery of swallowing. Furthermore, swallowing related cortical activation patterns were more pronounced during motor execution and imagery after the training compared to the pre-test, indicating cortical reorganization due to neurofeedback training. The oxy-Hb group could neither control oxy-Hb during neurofeedback training nor showed any cortical changes. Hence, successful modulation of deoxy-Hb over swallowing related brain areas led to cortical reorganization and might be useful for future treatments of swallowing dysfunction.

Increased spontaneous neuronal activity in structurally damaged cortex is correlated with early motor recovery in patients with subcortical infarction.

Secondary cortical thinning and volumetric atrophy in the motor-related cortex can inhibit early functional recovery after subcortical infarction. However, the relationship between the spontaneous neuronal activity in these cortices and motor recovery in patients with focal cerebral infarct remains unknown. Structural magnetic resonance imaging (MRI) and resting-state functional MRI were conducted 1, 4 and 12 weeks after onset in 22 patients with an acute subcortical infarct and in 22 normal subjects. Group differences in cortical thickness and in the amplitude of low-frequency fluctuation (ALFF) in motor-related areas were evaluated, and the relationships between ALFF, cortical thickness changes and changes in the Fugl-Meyer scores of physical performance were further analyzed. In patients with subcortical infarction, progressively decreasing cortical thickness was found over the observation period ipsilesionally in the primary motor cortex (PMC), supplementary motor cortex (SMC) and precuneus (all P < 0.05). Contralesionally, progressive increases in cortical thickness were detected in SMC and insula (all P < 0.05). Increases in ALFF were observed only in PMC (bilaterally) and only at 12 weeks after stroke (all P < 0.05). The cortical thickness changes in the contralesional SMC (rs = 0.483, P = 0.023) and the ALFF changes in bilateral PMC (ipsilesional, rs = 0.51, P = 0.015; contralesional, rs = 0.463, P = 0.03) were positively correlated with changes in the Fugl-Meyer scores. These results suggest that increased spontaneous neuronal activity of the PMC, a region structurally damaged secondarily to ischaemic lesion, may contribute to early motor recovery in patients with subcortical infarction.

Enhanced Neurobehavioral Outcomes of Action Observation Prosthesis Training

Background. Previous studies have demonstrated improved neurobehavioral outcomes when prosthesis users learn task-specific behaviors by imitating movements of prosthesis users (matched limb) compared with intact limbs (mismatched limb). Objective. This study is the first to use a unique combination of neurophysiological and task performance methods to investigate prosthetic device training strategies from a cognitive motor control perspective. Intact nonamputated prosthesis users (NAPUs) donned specially adapted prosthetic devices to simulate the wrist and forearm movement that persons with transradial limb loss experience. The hypothesis is that NAPUs trained with matched limb imitation would show greater engagement of parietofrontal regions and reduced movement variability compared with their counterparts trained with a mismatched limb. Methods. Training elapsed over 3 days comprised alternating periods of video demonstration observation followed by action imitation. At the beginning and end of the training protocol, participants performed a cued movement paradigm while electroencephalography and electrogoniometry data were collected to track changes in cortical activity and movement variability, respectively. Results. Matched limb participants showed greater engagement of motor-related areas while mismatched limb participants showed greater engagement of the parietooccipital system. Matched limb participants also showed lower movement variability. Conclusions. These results indicate that the type of limb imitated influences neural and behavioral strategies for novel prosthetic device usage. This finding is important, as customary prosthetic rehabilitation with intact therapists involves mismatched limb imitation that may exacerbate challenges in adapting to new motor patterns demanded by prosthesis use.

Transcranial direct current stimulation can enhance ability in motor imagery tasks.

Previous studies have shown that motor-related areas are activated when individuals perform the hand mental rotation task (HMRT), which is used as a motor imagery task. Transcranial direct current stimulation (tDCS) is a noninvasive method of cortical stimulation, and anodal tDCS enhances the excitability of target regions. The aim of this study was to investigate the effect of tDCS during the HMRT. Eighteen healthy, right-handed participants in this study performed the HMRT before (pre) and immediately after (post) anodal or sham tDCS. Both anodal and sham tDCS were applied to the left scalp over the hand-knob area for 10 min with a current intensity of 1 mA. Reaction times and error rates were analyzed and compared. As main results, reaction times were significantly shorter for postanodal tDCS than for preanodal tDCS (P<0.01) or postsham tDCS (P<0.05). No significant differences in reaction times were observed between presham and postsham tDCS. These findings indicate that anodal tDCS during the HMRT can enhance task performance.

Biological evidence of imagery abilities: intraindividual differences.

This study extended motor imagery theories by establishing specificity and verification of expected brain activation patterns during imagery. Eighteen female participants screened with the Movement Imagery Questionnaire-3 (MIQ-3) as having good imagery abilities were scanned to determine the neural networks active during an arm rotation task. Four experimental conditions (i.e., KINESTHETIC, INTERNAL Perspective, EXTERNAL Perspective, and REST) were randomly presented (counterbalanced for condition) during three brain scans. Behaviorally, moderate interscale correlations were found between the MIQ-3 and Vividness of Movement Imagery Questionnaire-2, indicating relatedness between the questionnaires. Partially confirming our hypotheses, common and distinct brain activity provides initial biological validation for imagery abilities delineated in the MIQ-3: kinesthetic imagery activated motor-related areas, internal visual imagery activated inferior parietal lobule, and external visual imagery activated temporal, but no occipital areas. Lastly, inconsistent neuroanatomical intraindividual differences per condition were found. These findings relative to recent biological evidence of imagery abilities are highlighted.

Use of functional near-infrared spectroscopy to evaluate the effects of anodal transcranial direct current stimulation on brain connectivity in motor-related cortex.

Transcranial direct current stimulation (tDCS) is a noninvasive, safe and convenient neuro-modulatory technique in neurological rehabilitation, treatment, and other aspects of brain disorders. However, evaluating the effects of tDCS is still difficult. We aimed to evaluate the effects of tDCS using hemodynamic changes using functional near-infrared spectroscopy (fNIRS). Five healthy participants were employed and anodal tDCS was applied to the left motor-related cortex, with cathodes positioned on the right dorsolateral supraorbital area. fNIRS data were collected from the right motor-related area at the same time. Functional connectivity (FC)between intracortical regions was calculated between fNIRS channels using a minimum variance distortion-less response magnitude squared coherence (MVDR-MSC) method. The levels of Oxy-HbO change and the FC between channels during the prestimulation, stimulation, and poststimulation stages were compared. Results showed no significant level difference, but the FC measured by MVDR-MSC significantly decreased during tDCS compared with pre-tDCS and post-tDCS, although the FC difference between pre-tDCS and post-tDCS was not significant. We conclude that coherence calculated from resting state fNIRS may be a useful tool for evaluating the effects of anodal tDCS and optimizing parameters for tDCS application.

Increased anxiety-like behavior and selective learning impairments are concomitant to loss of hippocampal interneurons in the presymptomatic SOD1(G93A) ALS mouse model.

Amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease primarily characterized by motor neuron death, causes damages beyond motor-related areas. In particular, cognitive impairments and hippocampal damage have been reported in ALS patients. We investigated spatial navigation learning and hippocampal interneurons in a mutant SOD1(G93A) mouse (mSOD1) model of ALS. Behavioral tests were performed by using presymptomatic mSOD1 mice. General motor activity was comparable to that of wild-type mice in the open-field test, in which, however mSOD1 exhibited increased anxiety-like behavior. In the Barnes maze test, mSOD1 mice displayed a delay in learning, outperformed wild-type mice during the first probe trial, and exhibited impaired long-term memory. Stereological counts of parvalbumin-positive interneurons, which are crucial for hippocampal physiology and known to be altered in other central nervous system regions of mSOD1 mice, were also performed. At postnatal day (P) 56, the population of parvalbumin-positive interneurons in mSOD1 mice was already reduced in CA1 and in CA3, and at P90 the reduction extended to the dentate gyrus. Loss of parvalbumin-positive hippocampal interneurons occurred mostly during the presymptomatic stage. Western blot analysis showed that hippocampal parvalbumin expression levels were already reduced in mSOD1 mice at P56. The hippocampal alterations in mSOD1 mice could at least partly account for the increased anxiety-like behavior and deficits in spatial navigation learning. Our study provides evidence for cognitive alterations and damage to the γ-aminobutyric acid (GABA)ergic system in the hippocampus of murine ALS, thereby revealing selective deficits antecedent to the onset of motor symptoms.

Interaction between affordance and handedness recognition: a chronometric study.

The visualization of tools and manipulable objects activates motor-related areas in the cortex, facilitating possible actions toward them. This pattern of activity may underlie the phenomenon of object affordance. Some cortical motor neurons are also covertly activated during the recognition of body parts such as hands. One hypothesis is that different subpopulations of motor neurons in the frontal cortex are activated in each motor program; for example, canonical neurons in the premotor cortex are responsible for the affordance of visual objects, while mirror neurons support motor imagery triggered during handedness recognition. However, the question remains whether these subpopulations work independently. This hypothesis can be tested with a manual reaction time (MRT) task with a priming paradigm to evaluate whether the view of a manipulable object interferes with the motor imagery of the subject's hand. The MRT provides a measure of the course of information processing in the brain and allows indirect evaluation of cognitive processes. Our results suggest that canonical and mirror neurons work together to create a motor plan involving hand movements to facilitate successful object manipulation.

Early lexico-semantic modulation of motor related areas during action and non-action verb processing

Although action verb processing deficits have been described in diseases affecting the motor system, research on temporal processing in this area has not been reported. In this study, action and non-action verb processing was contrasted in healthy volunteers using electro-encephalography. These data may serve as a control condition for further research in motor disorders. Latency and amplitude evaluations as well as source reconstruction were applied on event-related potentials. Action verbs evoked higher activation in bilateral sensorimotor areas from 155 to 174 ms and in bilateral dorsolateral prefrontal cortex (DLPFC) from 219 to 238 ms. Hand action verb processing activates the motor programmes of the actions the verbs refer to. This seems not restricted to the core (pre)motor cortical areas of the brain. A broad motor brain network is hypothesized to be involved. While sensorimotor activation seems essential for action verb understanding, this cannot be concluded for DLPFC activation. • Single verb processing evokes a peak in activity at 165 ms post-stimulus onset. • Bilateral sensorimotor cortex is activated by hand action verbs from 155 to 174 ms. • Sensorimotor activation is automatic and necessary for action verb understanding. • Bilateral dorsolateral prefrontal cortex contributes to hand action verb processing. • Embodied theories of cognition are confirmed.

Anticipating action effects with different attention foci is reflected in brain activation.

Anticipation is informed by experience. Having focused on action effects in the past will lead to differences when the focus is now on the effector. Boules-type throwing movements were presented as point-light displays of shoulder and arm-markers. Activation in motor-related areas measured with functional magnetic resonance imaging was compared between two tasks: Task A anticipating action effects and Task B judging the velocity of the hand marker. One group of participants performed a session of Task A followed by a session of Task B; the other group started with Task B followed by Task A. The group starting with Task A exhibited higher brain activation during Task A bilaterally in intraparietal areas and in right hemispheric frontal and premotor areas. These areas are known to be involved in effect estimation and action simulation. The second group showed higher activation during Task B in premotor cortex and human intraparietal area 3 of the right hemisphere. The results suggest that the instruction to focus on anticipating action effects facilitates the recruitment of core components of the simulation network during anticipation and when effect anticipation is not the primary intention.

Corticospinal excitability during imagined and observed dynamic force production tasks: Effortfulness matters

Research on motor imagery and action observation has become increasingly important in recent years particularly because of its potential benefits for movement rehabilitation and the optimization of athletic performance (Munzert et al., 2009). Motor execution, motor imagery, and action observation have been shown to rely largely on a similar neural network in motor and motor-related cortical areas (Jeannerod, 2001). Given that motor imagery is a covert stage of an action and its characteristics, it has been assumed that modifying the motor task in terms of, for example, effort will impact neural activity. With this background, the present study examined how different force requirements influence corticospinal excitability (CSE) and intracortical facilitation during motor imagery and action observation of a repetitive movement (dynamic force production). Participants were instructed to kinesthetically imagine or observe an abduction/adduction movement of the right index finger that differed in terms of force requirements. Trials were carried out with single- or paired-pulse transcranial magnetic stimulation. Surface electromyography was recorded from the first dorsal interosseous (FDI) and the abductor digiti minimi (ADM). As expected, results showed a significant main effect on mean peak-to-peak motor-evoked potential (MEP) amplitudes in FDI but no differences in MEP amplitudes in ADM muscle. Participants’ mean peak-to-peak MEPs increased when the force requirements (movement effort) of the imagined or observed action were increased. This reveals an impact of the imagined and observed force requirements of repetitive movements on CSE. It is concluded that this effect might be due to stronger motor neuron recruitment for motor imagery and action observation with an additional load. That would imply that the modification of motor parameters in movements such as force requirements modulates CSE.

Sensory–motor networks involved in speech production and motor control: An fMRI study

Speaking is one of the most complex motor behaviors developed to facilitate human communication. The underlying neural mechanisms of speech involve sensory–motor interactions that incorporate feedback information for online monitoring and control of produced speech sounds. In the present study, we adopted an auditory feedback pitch perturbation paradigm and combined it with functional magnetic resonance imaging (fMRI) recordings in order to identify brain areas involved in speech production and motor control. Subjects underwent fMRI scanning while they produced a steady vowel sound /a/ (speaking) or listened to the playback of their own vowel production (playback). During each condition, the auditory feedback from vowel production was either normal (no perturbation) or perturbed by an upward (+600 cents) pitch-shift stimulus randomly. Analysis of BOLD responses during speaking (with and without shift) vs. rest revealed activation of a complex network including bilateral superior temporal gyrus (STG), Heschl's gyrus, precentral gyrus, supplementary motor area (SMA), Rolandic operculum, postcentral gyrus and right inferior frontal gyrus (IFG). Performance correlation analysis showed that the subjects produced compensatory vocal responses that significantly correlated with BOLD response increases in bilateral STG and left precentral gyrus. However, during playback, the activation network was limited to cortical auditory areas including bilateral STG and Heschl's gyrus. Moreover, the contrast between speaking vs. playback highlighted a distinct functional network that included bilateral precentral gyrus, SMA, IFG, postcentral gyrus and insula. These findings suggest that speech motor control involves feedback error detection in sensory (e.g. auditory) cortices that subsequently activate motor-related areas for the adjustment of speech parameters during speaking.

Neural correlates of intentional switching from ternary to binary meter in a musical hemiola pattern.

Musical rhythms are often perceived and interpreted within a metrical framework that integrates timing information hierarchically based on interval ratios. Endogenous timing processes facilitate this metrical integration and allow us using the sensory context for predicting when an expected sensory event will happen (“predictive timing”). Previously, we showed that listening to metronomes and subjectively imagining the two different meters of march and waltz modulated the resulting auditory evoked responses in the temporal lobe and motor-related brain areas such as the motor cortex, basal ganglia, and cerebellum. Here we further explored the intentional transitions between the two metrical contexts, known as hemiola in the Western classical music dating back to the sixteenth century. We examined MEG from 12 musicians while they repeatedly listened to a sequence of 12 unaccented clicks with an interval of 390 ms, and tapped to them with the right hand according to a 3 + 3 + 2 + 2 + 2 hemiola accent pattern. While participants listened to the same metronome sequence and imagined the accents, their pattern of brain responses significantly changed just before the “pivot” point of metric transition from ternary to binary meter. Until 100 ms before the pivot point, brain activities were more similar to those in the simple ternary meter than those in the simple binary meter, but the pattern was reversed afterwards. A similar transition was also observed at the downbeat after the pivot. Brain areas related to the metric transition were identified from source reconstruction of the MEG using a beamformer and included auditory cortices, sensorimotor and premotor cortices, cerebellum, inferior/middle frontal gyrus, parahippocampal gyrus, inferior parietal lobule, cingulate cortex, and precuneus. The results strongly support that predictive timing processes related to auditory-motor, fronto-parietal, and medial limbic systems underlie metrical representation and its transitions.

Topographic pattern of cortical thinning with consideration of motor laterality in Parkinson disease.

The asymmetry of Parkinson's disease (PD) may contribute to the unilateral appearance of parkinsonism, as well as its cerebral morphological changes. However, previous studies have not considered that cerebral involvement would probably be asymmetric. Our study aimed to identify whether one-sided symptom dominance has an influence on cortical thinning patterns in early-stage, non-demented PD patients from cortical thickness analyses and cortical thinning patterns are associated with motor functions. We used cortical thickness analysis in 64 non-demented right-handed subjects: 21 PD patients with left-sided disease onset (LPD), 21 PD patients with right-sided disease onset (RPD) and 22 control subjects. We modeled local cortical thickness as a linear association with each motor symptom. We identified three clusters exhibiting significant cortical thinning (p<0.01 RFT corrected) in the LPD group compared with the control group: a cluster including the right primary sensory, motor cortex and paracentral lobule, as well as another two clusters in bilateral parahippocampal gyri. In the RPD group, there was only one cluster that exhibited significant cortical thinning compared with the control group, located in the left lingual gyrus. There were no significant correlations between cortical thinning clusters and motor severity, any of the motor subscales including tremor, rigidity, bradykinesia and axial impairment. Our right-handed PD population revealed that significant thinning of motor-related cortical areas in contralateral hemisphere to symptomatic side in LPD, but not in RPD group. Our results support that neuroprotective effect of enhanced physical activity by handedness on contralateral motor cortex.

Beta drives brain beats.

OPINION article Front. Syst. Neurosci., 27 August 2014 Volume 8 - 2014 | https://doi.org/10.3389/fnsys.2014.00155

Partially overlapping sensorimotor networks underlie speech praxis and verbal short-term memory: evidence from apraxia of speech following acute stroke.

We tested the hypothesis that motor planning and programming of speech articulation and verbal short-term memory (vSTM) depend on partially overlapping networks of neural regions. We evaluated this proposal by testing 76 individuals with acute ischemic stroke for impairment in motor planning of speech articulation (apraxia of speech, AOS) and vSTM in the first day of stroke, before the opportunity for recovery or reorganization of structure-function relationships. We also evaluated areas of both infarct and low blood flow that might have contributed to AOS or impaired vSTM in each person. We found that AOS was associated with tissue dysfunction in motor-related areas (posterior primary motor cortex, pars opercularis; premotor cortex, insula) and sensory-related areas (primary somatosensory cortex, secondary somatosensory cortex, parietal operculum/auditory cortex); while impaired vSTM was associated with primarily motor-related areas (pars opercularis and pars triangularis, premotor cortex, and primary motor cortex). These results are consistent with the hypothesis, also supported by functional imaging data, that both speech praxis and vSTM rely on partially overlapping networks of brain regions.