The neural correlates of gait improvement by rhythmic sound stimulation in adults with Parkinson's disease - A functional magnetic resonance imaging study.

INTRODUCTION: Adults with Parkinson's disease (PD) experience gait disturbances that can sometimes be improved with rhythmic auditory stimulation (RAS); however, the underlying physiological mechanism for this improvement is not well understood. We investigated brain activation patterns in adults with PD and healthy controls (HC) using functional magnetic resonance imaging (fMRI) while participants imagined gait with or without RAS. METHODS: Twenty-seven adults with PD who could walk independently and walked more smoothly with rhythmic auditory cueing than without it, and 25 age-matched HC participated in this study. Participants imagined gait in the presence of RAS or white noise (WN) during fMRI. RESULTS: In the PD group, gait imagery with RAS activated cortical motor areas, including supplementary motor areas and the cerebellum, while gait imagery with WN additionally recruited the left parietal operculum. In HC, the induced activation was limited to cortical motor areas and the cerebellum for both the RAS and WN conditions. Within- and between-group analyses demonstrated that RAS reduced the activity of the left parietal operculum in the PD group but not in the HC group (condition-by-group interaction by repeated measures analysis of variance, p < 0.05). CONCLUSION: During gait imagery in adults with PD, the left parietal operculum was less activated by RAS than by WN, while no change was observed in HC, suggesting that rhythmic auditory stimulation may support the sensory-motor networks involved in gait, thus alleviating the overload of the parietal operculum and compensating for its dysfunction in these patients.

Sensorimotor Connectivity after Motor Exercise with Neurofeedback in Post-Stroke Patients with Hemiplegia.

Impaired finger motor function in post-stroke hemiplegia is a debilitating condition with no evidence-based or accessible treatments. Here, we evaluated the neurophysiological effectiveness of direct brain control of robotic exoskeleton that provides movement support contingent with brain activity. To elucidate the mechanisms underlying the neurofeedback intervention, we assessed resting-state functional connectivity with functional magnetic resonance imaging (rsfcMRI) between the ipsilesional sensory and motor cortices before and after a single 1-h intervention. Eighteen stroke patients were randomly assigned to crossover interventions in a double-blind and sham-controlled design. One patient dropped out midway through the study, and 17 patients were included in this analysis. Interventions involved motor imagery, robotic assistance, and neuromuscular electrical stimulation administered to a paretic finger. The neurofeedback intervention delivered stimulations contingent on desynchronized ipsilesional electroencephalographic (EEG) oscillations during imagined movement, and the control intervention delivered sensorimotor stimulations that were independent of EEG oscillations. There was a significant time × intervention interaction in rsfcMRI in the ipsilesional sensorimotor cortex. Post-hoc analysis showed a larger gain in increased functional connectivity during the neurofeedback intervention. Although the neurofeedback intervention delivered fewer total sensorimotor stimulations compared to the sham-control, rsfcMRI in the ipsilesional sensorimotor cortices was increased during the neurofeedback intervention compared to the sham-control. Higher coactivation of the sensory and motor cortices during neurofeedback intervention enhanced rsfcMRI in the ipsilesional sensorimotor cortices. This study showed neurophysiological evidence that EEG-contingent neurofeedback is a promising strategy to induce intrinsic ipsilesional sensorimotor reorganization, supporting the importance of integrating closed-loop sensorimotor processing at a neurophysiological level.

Ventral striatum links motivational and motor networks during operant-conditioned movement in rats.

Voluntary actions require motives. It is already known that the medial prefrontal cortex (MPFC) assess the motivational values. However, it remains unclear how the motivational process gains access to the motor execution system in the brain. Here we present evidence that the ventral striatum (VS) plays a hub-like role in mediating motivational and motor processing in operant behavior. We used positron emission tomography (PET) to detect the neural activation areas associated with motivational action. Using obtained regions, partial correlation analysis was performed to examine how the motivational signals propagate to the motor system. The results revealed that VS activity propagated to both MPFC and primary motor cortex through the thalamus. Moreover, muscimol injection into the VS suppressed the motivational behavior, supporting the idea of representations of motivational signals in VS that trigger motivational behavior. These results suggest that the VS-thalamic pathway plays a pivotal role for both motivational processing through interactions with the MPFC and for motor processing through interactions with the motor BG circuits.

The Neural Correlates of Shoulder Apprehension: A Functional MRI Study.

Although shoulder apprehension is an established clinical finding and is important for the prevention of shoulder dislocation, how this subjective perception is evoked remains unclear. We elucidated the functional neuroplasticity associated with apprehension in patients with recurrent anterior shoulder instability (RSI) using functional magnetic resonance imaging (fMRI). Twelve healthy volunteers and 14 patients with right-sided RSI performed a motor imagery task and a passive shoulder motion task. Brain activity was compared between healthy participants and those with RSI and was correlated with the apprehension intensity reported by participants after each task. Compared to healthy volunteers, participants with RSI exhibited decreased brain activity in the motor network, but increased activity in the hippocampus and amygdala. During the passive motion task, participants with RSI exhibited decreased activity in the left premotor and primary motor/somatosensory areas. Furthermore, brain activity was correlated with apprehension intensity in the left amygdala and left thalamus during the motor imagery task (memory-induced), while a correlation between apprehension intensity and brain activity was found in the left prefrontal cortex during the passive motion task (instability-induced). Our findings provide insight into the pathophysiology of RSI by identifying its associated neural alterations. We elucidated that shoulder apprehension was induced by two different factors, namely instability and memory.

Abacus in the brain: a longitudinal functional MRI study of a skilled abacus user with a right hemispheric lesion.

The abacus, a traditional physical calculation device, is still widely used in Asian countries. Previous behavioral work has shown that skilled abacus users perform rapid and precise mental arithmetic by manipulating a mental representation of an abacus, which is based on visual imagery. However, its neurophysiological basis remains unclear. Here, we report the case of a patient who was a good abacus user, but transiently lost her "mental abacus" and superior arithmetic performance after a stroke owing to a right hemispheric lesion including the dorsal premotor cortex (PMd) and inferior parietal lobule (IPL). Functional magnetic resonance imaging experiments were conducted 6 and 13 months after her stroke. In the mental calculation task, her brain activity was shifted from the language-related areas, including Broca's area and the left dorsolateral prefrontal and IPLs, to the visuospatial-related brain areas including the left superior parietal lobule (SPL), according to the recovery of her arithmetic abilities. In the digit memory task, activities in the bilateral SPL, and right visual association cortex were also observed after recovery. The shift of brain activities was consistent with her subjective report that she was able to shift the calculation strategy from linguistic to visuospatial as her mental abacus became stable again. In a behavioral experiment using an interference paradigm, a visual presentation of an abacus picture, but not a human face picture, interfered with the performance of her digit memory, confirming her use of the mental abacus after recovery. This is the first case report on the impairment of the mental abacus by a brain lesion and on recovery-related brain activity. We named this rare case "abacus-based acalculia." Together with previous neuroimaging studies, the present result suggests an important role for the PMd and parietal cortex in the superior arithmetic ability of abacus users.

Event related desynchronization-modulated functional electrical stimulation system for stroke rehabilitation: a feasibility study.

BACKGROUND: We developed an electroencephalogram-based brain computer interface system to modulate functional electrical stimulation (FES) to the affected tibialis anterior muscle in a stroke patient. The intensity of FES current increased in a stepwise manner when the event-related desynchronization (ERD) reflecting motor intent was continuously detected from the primary cortical motor area. METHODS: We tested the feasibility of the ERD-modulated FES system in comparison with FES without ERD modulation. The stroke patient who presented with severe hemiparesis attempted to perform dorsiflexion of the paralyzed ankle during which FES was applied either with or without ERD modulation. RESULTS: After 20 minutes of training, the range of movement at the ankle joint and the electromyography amplitude of the affected tibialis anterior muscle were significantly increased following the ERD-modulated FES compared with the FES alone. CONCLUSIONS: The proposed rehabilitation technique using ERD-modulated FES for stroke patients was feasible. The system holds potentials to improve the limb function and to benefit stroke patients.

Single session of transcranial direct current stimulation transiently increases knee extensor force in patients with hemiparetic stroke.

BACKGROUND: Transcranial direct current stimulation (tDCS) of the motor cortex can enhance the performance of a paretic upper extremity after stroke. Reported effects on lower limb (LL) function are sparse. OBJECTIVE: The authors examined whether tDCS can increase the force production of the paretic quadriceps. METHODS: In this double-blind, crossover, sham-controlled experimental design, 8 participants with chronic subcortical stroke performed knee extension using their hemiparetic leg before, during, and after anodal or sham tDCS of the LL motor cortex representation in the affected hemisphere. Affected hand-grip force was also recorded. RESULTS: The maximal knee-extension force increased by 21 N (13.2%, P < .01) during anodal tDCS compared with baseline and sham stimulation. The increase persisted less than 30 minutes. Maximal hand-grip force did not change. CONCLUSIONS: Anodal tDCS transiently enhanced knee extensor strength. The modest increase was specific to the LL. Thus, tDCS might augment the rehabilitation of stroke patients when combined with lower extremity strengthening or functional training.

[The functional significance of the basal ganglia-thalamo-cortical loop in gait control in humans: a neuroimaging approach].

The basic locomotor modules located in the brainstem and the spinal cord can control elements of gait movement independently from other structures. Although these locomotor modules are considered to be acquired innately, their higher-level control is important in primates, especially in humans, who employ bipedal gait to adapt to the external environment. The basal ganglia-thalamo-cortical loops are involved in higher-leveled gait control. These loops are composed of several parallel, segregated, and functionally distinct, but homologous, neural circuits. The motor loop originates from the motor cortices, namely, the primary motor cortex, supplementary motor area (SMA), and lateral premotor cortex, and projects to the somatomotor region of the basal ganglia, thereby controlling voluntary movement. Dysfunction of the basal ganglia-thalamo-SMA loop results in gait disturbance in Parkinson disease and vascular parkinsonism. The dysfunction of the SMA loop could be compensated for by the activation of the lateral premotor cortex, the function of which appears to be preserved under appropriate external stimuli in parkinsonian patients.

Neural mechanisms involved in mental imagery and observation of gait.

Brain activity during observation and imagery of gait was investigated. Sixteen subjects were scanned with a 3-Tesla MRI scanner while viewing six types of video clips: observation of gait movement (GO) from the third-person perspective, observation of stepping movement, observation of standing posture, "virtual walking" (VW) that was observation of visual scenes mimicking the visual afferent during walking, and the scrambled version of the GO and VW stimuli. In the VW condition, moving scenes provided a virtual visual environment in which subjects easily imagined as if they were actually walking from the first-person perspective. A behavioral experiment revealed a correlation of cadence during actual walking with that during imaginary walking under the influence of the VW stimuli, indicating that a gait planning mechanism was shared by actual walking and gait imagery. The VW condition activated the dorsal premotor cortex (PMd), supplementary motor area/cingulate motor area (SMA/CMA), parahippocampal gyrus, and subcortical nuclei. The GO stimuli yielded activation of the SMA, PMd, inferior frontal gyrus, and inferior parietal lobule. Moreover, the conjunction null test of GO and VW revealed common activity in the SMA/CMA and PMd, which were reportedly active during actual gait movement, in addition to visual areas. Detailed analyses of activity during stepping or standing observation supported the specificity of the SMA and PMd to GO. These findings suggest that motor planning centers of gait, including the SMA and PMd, are activated during both imagination (first-person perspective) and observation (third-person perspective) of gait behaviors.

Motor planning, imagery, and execution in the distributed motor network: a time-course study with functional MRI.

Activation of motor-related areas has consistently been found during various motor imagery tasks and is regarded as the central mechanism generating motor imagery. However, the extent to which motor execution and imagery share neural substrates remains controversial. We examined brain activity during preparation for and execution of physical or mental finger tapping. During a functional magnetic resonance imaging at 3 T, 13 healthy volunteers performed an instructed delay finger-tapping task either in a physical mode or mental mode. Number stimuli instructed subjects about a finger-tapping sequence. After an instructed delay period, cue stimuli prompted them either to execute the tapping movement or to imagine it. Two types of planning/preparatory activity common for movement and imagery were found: instruction stimulus-related activity represented widely in multiple motor-related areas and delay period activity in the medial frontal areas. Although brain activity during movement execution and imagery was largely shared in the distributed motor network, imagery-related activity was in general more closely related to instruction-related activity than to the motor execution-related activity. Specifically, activity in the medial superior frontal gyrus, anterior cingulate cortex, precentral sulcus, supramarginal gyrus, fusiform gyrus, and posterolateral cerebellum likely reflects willed generation of virtual motor commands and analysis of virtual sensory signals.

Finger and face representations in the ipsilateral precentral motor areas in humans.

Several human neuroimaging studies have reported activity in the precentral gyrus (PcG) ipsilateral to the side of hand movements. This activity has been interpreted as the part of the primary motor cortex (M1) that controls bilateral or ipsilateral hand movements. To better understand hand ipsilateral-PcG activity, we performed a functional MRI experiment in eight healthy right-handed adults. Behavioral tasks involved hand or lower face movements on each side or motor imagery of the same movements. Consistent with the known M1 organization, the hand contralateral-PcG activity was centered at the "hand-knob" portion of the PcG; face contralateral-PcG activity was localized ventrolateral to it. Hand ipsilateral-PcG activity was identified in most subjects. However, converging results indicated that this ipsilateral PcG activity was situated in Brodmann's area 6 in both hemispheres. The hand ipsilateral-PcG zones were active not only during hand movements but also face movements. Moreover, the hand ipsilateral-PcG zones revealed substantial imagery-related activity, which also failed to differentiate the hand and face. Statistical analyses confirmed poor effector selectivity of the hand ipsilateral PcG activity during both movement and imagery tasks. From these results, we conclude that the hand ipsilateral-PcG activity in healthy adults probably corresponds to a part of the ventral premotor cortex. In contrast, available evidence suggests that M1 contributes to controlling the ipsilateral hand in children and patients after stroke recovery. It appears that within the human PcG, there are two parallel systems potentially capable of controlling ipsilateral hand movements: ventral premotor cortex and M1. These two systems may be differentially influenced by developmental or pathologic changes.

Neural correlates of cross-modal binding.

Little is known about how the brain binds together signals from multiple sensory modalities to produce unified percepts of objects and events in the external world. Using event-related functional magnetic resonance imaging (fMRI) in humans, we measured transient brain responses to auditory/visual binding, as evidenced by a sound-induced change in visual motion perception. Identical auditory and visual stimuli were presented in all trials, but in some trials they were perceived to be bound together and in others they were perceived as unbound unimodal events. Cross-modal binding was associated with higher activity in multimodal areas, but lower activity in predominantly unimodal areas. This activation pattern suggests that a reciprocal and 'competitive' interaction between multimodal and unimodal areas underlies the perceptual interpretation of simultaneous signals from multiple sensory modalities.

Modulation of the visual word retrieval system in writing: a functional MRI study on the Japanese orthographies.

We used functional magnetic resonance imaging (fMRI) to examine whether the act of writing involves different neuropsychological mechanisms between the two script systems of the Japanese language: kanji (ideogram) and kana (phonogram). The main experiments employed a 2 x 2 factorial design that comprised writing-to-dictation and visual mental recall for kanji and kana. For both scripts, the actual writing produced a widespread fronto-parietal activation in the left hemisphere. Especially, writing of kanji activated the left posteroinferior temporal cortex (lPITC), whereas that of kana also yielded a trend of activation in the same area. Mental recall for both scripts activated similarly the left parietotemporal regions including the lPITC. The writing versus mental recall comparison revealed greater activations in the left sensorimotor areas and right cerebellum. The kanji versus kana comparison showed increased responses in the left prefrontal and anterior cingulate areas. Especially, the lPITC showed a significant task-by-script interaction. Two additional control tasks, repetition (REP) and semantic judgment (SJ), activated the bilateral perisylvian areas, but enhanced the lPITC response only weakly. These results suggest that writing of the ideographic and phonographic scripts, although using the largely same cortical regions, each modulates the visual word-retrieval system according to their graphic features. Furthermore, comparisons with two additional tasks indicate that the activity of the lPITC increases especially in expressive language operations regardless of sensory modalities of the input stimulus.