Age-related alterations of the functional interactions within the basal ganglia and cerebellar motor loops in vivo

Aging may alter the motor functions of the basal ganglia and cerebellum; however, no previous neuroimaging study has investigated the effect of aging on the functional connectivity of the motor loops involving these structures. Recently, using fMRI with a parametric approach and structural equation modeling (SEM), we demonstrated a significant functional interaction within the basal ganglia-thalamo-motor (BGTM) loop during self-initiated (SI) finger movement in young normal subjects, whereas cerebro-cerebellar (CC) loop was mainly involved during externally triggered (ET) movement. We applied this method to 12 normal aged subjects (53-72 years old) in order to study the effect of age on BGTM and CC loops. Compared with the functional connectivity seen in young subjects, SEM showed decreased connectivity in BGTM loops during SI task, decreased interaction in the CC loop during ET task, and increased connectivity within motor cortices and between hemispheres during both types of tasks. These results suggest an age-related decline of cortico-subcortical connectivity with increased interactions between motor cortices. Aging effects on SI and ET movements are probably caused by functional alterations within BGTM and CC loops.     

The functional neuroanatomy of coordinated orofacial movements: sparse sampling fMRI of whistling

Whistling serves as a model for a skilful coordinated orofacial movement with sensorimotor integration of auditory and proprioceptive input. The neural substrate of whistling was investigated by sparse sampling functional MRI (fMRI) where the motor task occurred during a silent interval between successive image acquisitions to minimize task-related imaging artefacts. Whistling recruited a symmetrically represented neural network including primary motor and ventral premotor cortex (PMv), SMA, cingulate gyrus, basal ganglia, primary and secondary somatosensory cortex, amygdala, thalamus and cerebellum. A temporal analysis revealed higher activity of left sensory cortex, right PMv and cerebellum during late execution compared to initiation of whistling. Task-related signal changes in right PMv and right paravermal cerebellum were found to correlate with the amplitude of the whistle sound in a separate correlation analysis. The findings emphasize the role of ventral premotor cortex, cerebellum and somatosensory areas as integrators of afferent input within a distributed orofacial sensorimotor network.     

The musician's brain: functional imaging of amateurs and professionals during performance and imagery

We compared activation maps of professional and amateur violinists during actual and imagined performance of Mozart's violin concerto in G major (KV216). Execution and imagination of (left hand) fingering movements of the first 16 bars of the concerto were performed. Electromyography (EMG) feedback was used during imagery training to avoid actual movement execution and EMG recording was employed during the scanning of both executed and imagined musical performances. We observed that professional musicians generated higher EMG amplitudes during movement execution and showed focused cerebral activations in the contralateral primary sensorimotor cortex, the bilateral superior parietal lobes, and the ipsilateral anterior cerebellar hemisphere. The finding that professionals exhibited higher activity of the right primary auditory cortex during execution may reflect an increased strength of audio-motor associative connectivity. It appears that during execution of musical sequences in professionals, a higher economy of motor areas frees resources for increased connectivity between the finger sequences and auditory as well as somatosensory loops, which may account for the superior musical performance. Professionals also demonstrated more focused activation patterns during imagined musical performance. However, the auditory-motor loop was not involved during imagined performances in either musician group. It seems that the motor and auditory systems are coactivated as a consequence of musical training but only if one system (motor or auditory) becomes activated by actual movement execution or live musical auditory stimuli.     

Motor imagery of complex everyday movements. An fMRI study

The present study aimed to investigate the functional neuroanatomical correlates of motor imagery (MI) of complex everyday movements (also called everyday tasks or functional tasks). 15 participants imagined two different types of everyday movements, movements confined to the upper extremities (UE; e.g., eating a meal) and movements involving the whole body (WB; e.g., swimming), during fMRI scanning. Results showed that both movement types activated the lateral and medial premotor cortices bilaterally, the left parietal cortex, and the right basal ganglia. Direct comparison of WB and UE movements further revealed a homuncular organization in the primary sensorimotor cortices (SMC), with UE movements represented in inferior parts of the SMC and WB movements in superior and medial parts. These results demonstrate that MI of everyday movements drives a cortical network comparable to the one described for more simple movements such as finger opposition. The findings further are in accordance with the suggestion that motor imagery-based mental practice is effective because it activates a comparable cortical network as overt training. Since most people are familiar with everyday movements and therefore a practice of the movement prior to scanning is not necessarily required, the current paradigm seems particularly appealing for clinical research and application focusing on patients with low or no residual motor abilities.     

High frequency rTMS modulation of the sensorimotor networks: behavioral changes and fMRI correlates

Repetitive transcranial magnetic stimulation (rTMS) to the primary motor cortex (M1) may induce functional modulation of motor performance and sensory perception. To address the underlying neurophysiological modulation following 10 Hz rTMS applied over M1, we examined cortical activation using 3T functional magnetic resonance imaging (fMRI), as well as the associated motor and sensory behavioral changes. The motor performance measure involved a sequential finger motor task that was also used as an activation task during fMRI. For sensory assessment, current perception threshold was measured before and after rTMS outside the MR scanner, and noxious mechanical stimulation was used as an activation task during fMRI. We found that significant activation in the bilateral basal ganglia, left superior frontal gyrus, bilateral pre-SMA, right medial temporal lobe, right inferior parietal lobe, and right cerebellar hemisphere correlated with enhanced motor performance in subjects that received real rTMS compared with sham-stimulated controls. Conversely, significant deactivation in the right superior and middle frontal gyri, bilateral postcentral and bilateral cingulate gyri, left SMA, right insula, right basal ganglia, and right cerebellar hemisphere were associated with an increase in the sensory threshold. Our findings reveal that rTMS induced rapid changes in the sensorimotor networks associated with sensory perception and motor performance and demonstrate the complexity of such intervention.     

Differentiation between external and internal cuing: an fMRI study comparing tracing with drawing

Externally cued movement is thought to preferentially involve cerebellar and premotor circuits whereas internally generated movement recruits basal ganglia, pre-supplementary motor cortex (pre-SMA) and dorsolateral prefrontal cortex (DLPFC). Tracing and drawing are exemplar externally and internally guided actions and Parkinson's patients and cerebellar patients show deficits in tracking and drawing, respectively. In this study we aimed to examine this external/internal distinction in healthy subjects using functional imaging. Ten healthy subjects performed tracing and drawing of simple geometric shapes using pencil and paper while in a 3-T fMRI scanner. Results indicated that compared to tracing, drawing generated greater activation in the right cerebellar crus I, bilateral pre-SMA, right dorsal premotor cortex and right frontal eye field. Tracing did not recruit any additional activation compared to drawing except in striate and extrastriate visual areas. Therefore, drawing recruited areas more frequently associated with cognitively challenging tasks, attention and memory, but basal ganglia and cerebellar activity did not differentiate tracing from drawing in the hypothesised manner. As our paradigm was of a simple, repetitive and static design, these results suggest that the task familiarity and the temporal nature of visual feedback in tracking tasks, compared to tracing, may be important contributing factors towards the degree of cerebellar involvement. Future studies comparing dynamic with static external cues and visual feedback may clarify the role of the cerebellum and basal ganglia in the visual guidance of drawing actions.     

Hemispheric asymmetry in supplementary motor area connectivity during unilateral finger movements

Studies of unilateral finger movement in right-handed subjects have shown asymmetrical patterns of activation in primary motor cortex. Some studies have measured a similar asymmetry in the supplementary motor area (SMA), but others have not. To shed more light on the symmetry of function in the SMA, we used path analysis of functional MRI data to investigate effective connectivity during a unilateral finger movement task. We observed a slight asymmetry in task activation: left SMA was equally active during movement of either hand, while right SMA was more active for left-hand movement, suggesting a dominant role of left SMA. In addition, we tested for a corresponding asymmetry in the influence of SMA on sensorimotor cortex (SMC) using a path model based on the well-established principle that SMA is involved in motor control and SMC in execution. We observed that the influence of left SMA on left SMC increased during right-hand movement, and the influence of left SMA on right SMC increased during left-hand movement. However, there was no significant hand-dependent change in the influences of the right SMA. This asymmetry in connectivity implies that left SMA does play a dominant role in unilateral movements of either hand in right handers. The experiment also provides a basis for further studies of motor system connectivity in healthy or patient populations.     

Preservation of motor programs in paraplegics as demonstrated by attempted and imagined foot movements

Execution and imagination of movement activate distinct neural circuits, partially overlapping in premotor and parietal areas, basal ganglia and cerebellum. Can long-term deafferented/deefferented patients still differentiate attempted from imagined movements? The attempted execution and motor imagery network of foot movements have been investigated in nine chronic complete spinal cord-injured (SCI) patients using fMRI. Thorough behavioral assessment showed that these patients were able to differentiate between attempted execution and motor imagery. Supporting the outcome of the behavioral assessment, fMRI disclosed specific patterns of activation for movement attempt and for motor imagery. Compared with motor execution data of healthy controls, movement attempt in SCI patients revealed reduced primary motor cortex activation at the group level, although activation was found in all single subjects with a high variability. Further comparisons with healthy subjects revealed that during attempt and motor imagery, SCI patients show enhanced activation and recruitment of additional regions in the parietal lobe and cerebellum that are important in sensorimotor integration. These findings reflect central plastic changes due to altered input and output and suggest that SCI patients may require additional cognitive resources to perform these tasks that may be one and the same phenomenon, or two versions of the same phenomenon, with quantitative differences between the two. Nevertheless, the retained integrity of movement attempt and motor imagery networks in SCI patients demonstrates that chronic paraplegics can still dispose of the full motor programs for foot movements and that therefore, attempted and imagined movements should be integrated in rehabilitative strategies.     

预期性姿势调节的神经调控网络研究进展

预期性姿势调节(APAs)的产生和执行依赖于复杂的分布式神经网络系统,涉及大脑皮质(包括前运动皮质、初级运动区)、丘脑、基底节和小脑等多个结构,包括分层模式和平行模式两种神经环路模式。基底节与前运动皮质参与APAs相关的运动计划编码;辅助运动区与脑干的脚桥核共同调节APAs时序;初级运动区在APAs启动过程中投射皮质运动纤维至目标运动支配区;脑桥延髓网状结构进行纤维整合,并通过网状神经元投射到脊髓调节目标肌群;小脑与肌肉群的协调耦合相关。     

Role of hyperactive cerebellum and motor cortex in Parkinson's disease

Previous neuroimaging studies have found hyperactivation in the cerebellum and motor cortex and hypoactivation in the basal ganglia in patients with Parkinson's disease (PD) but the relationship between the two has not been established. This study examined whether cerebellar and motor cortex hyperactivation is a compensatory mechanism for hypoactivation in the basal ganglia or is a pathophysiological response that is related to the signs of the disease. Using a BOLD contrast fMRI paradigm PD patients and healthy controls performed automatic and cognitively controlled thumb pressing movements. Regions of interest analysis quantified the BOLD activation in motor areas, and correlations between the hyperactive and hypoactive regions were performed, along with correlations between the severity of upper limb rigidity and BOLD activation. There were three main findings. First, the putamen, supplementary motor area (SMA) and pre-SMA were hypoactive in PD patients. The left and right cerebellum and the contralateral motor cortex were hyperactive in PD patients. Second, PD patients had a significant negative correlation between the BOLD activation in the ipsilateral cerebellum and the contralateral putamen. The correlation between the putamen and motor cortex was not significant. Third, the BOLD activation in the motor cortex was positively correlated with the severity of upper limb rigidity, but the BOLD activation in the cerebellum was not correlated with rigidity. Further, the activation in the motor cortex was not correlated with upper extremity bradykinesia. These findings provide new evidence supporting the hypothesis that hyperactivation in the ipsilateral cerebellum is a compensatory mechanism for the defective basal ganglia. Our findings also provide the first evidence from neuroimaging that hyperactivation in the contralateral primary motor cortex is not a compensatory response but is directly related to upper limb rigidity.     

正常人三种运动任务的血氧水平依赖性磁共振脑功能成像定量分析

目的 利用全脑血氧水平依赖性磁共振脑功能成像(BOLD-fMRI)技术,探讨参与对指、握拳、被动运动的关键脑功能区.方法对10例健康右利手志愿者右手(利手)或左手(非利手)的对指、握拳、被动运动进行全脑BOLD-fMRI扫描,记录激活体积、激活强度,应用配对t检验进行定量分析.结果三种运动模式下,左手运动激活对侧感觉运动皮层(SMC)体积、强度大于右手运动(P<0.05).被动、时指运动激活对侧SMC体积、强度差异无统计学意义(P>0.05).被动、对指运动激活对侧SMC体积大于握拳运动(P<0.05).被动运动激活对侧SMC强度大于握拳运动(P<0.05).对指与握拳运动激活对侧SMC强度差异无统计学意义(P>0.05).结论脑功能区的激活情况与手运动复杂程度有关,体积、强度等定量指标进一步证实利手、非利手激活脑功能区的不对称性.恒定的被动运动(五指依次被动曲伸)任务用于BOLD-fMRI研究具有实用性、可靠性.     

正常人三种模式手指运动时脑激活区域的功能磁共振研究

目的　研究简单动作 (反复连续的手指对指动作 )、随意动作 (抓物体 )和假想动作三种运动模式时 ,脑功能区域的活动机制。方法　利用功能磁共振 (fMRI)影像技术分别摄取 1 0例正常人的利手和非利手在不同运动模式下的双侧脑激活区域 ,再进行机制分析。结果　随意动作时 ,脑同侧激活区的数目多于简单动作 (P <0 .0 5) ,而对侧无明显差异。在简单动作和随意动作中 ,无论利手或非利手 ,主要的激活区为对侧的初级感觉运动皮质 (SM1 ) ,但非利手也可激活同侧少量的SM1。另外 ,脑双侧辅助运动区 (SMA)、前运动区 (PMA) ,对侧顶上小叶 ,同侧小脑也有明显激活 ;偶见基底节激活。假想动作时主要激活额上回、额中回、顶上小叶 ,另见少量扣带回、小脑、脑干、中央旁小叶、基底节处激活。结论　利手的简单动作支配主要在对侧脑SM1 ,而双侧的SM1参与了非利手的简单动作。随意动作属于复杂动作 ,参与动作的区域多于简单动作 ,且双侧SMA均参与 ,可能与双手协调、记忆动作模式的选择、动作顺序的执行有关。假想动作时主要由SMA、PMA支配。该机制对脑卒中的运动训练具有指导意义     

The effect of verbal feedback on motor learning--a PET study. Positron emission tomography

The purpose of this study was to investigate brain mechanisms underlying feedback effects on motor learning. We measured human brain activity using positron emission tomography (PET) during length-of-line drawing tasks in the presence or absence of verbal feedback, i.e., information on the precision of motor performance. The average error in responses was significantly lower and the percentage of correct responses was significantly higher in the case of tasks with feedback than those in the absence of feedback. The contralateral sensorimotor, premotor, supplementary motor, the right prefrontal, bilateral parietal and temporal, and anterior cingulate cortices, and the left basal ganglia were activated during all the line-drawing tasks. The right lateral prefrontal and occipital cortices and the left basal ganglia exhibited marked increase in activity after learning. The right inferior parietal and the anterior cingulate cortices were activated in the presence of feedback which provided information on how the subjects should correct their performances. The results indicate that these brain areas may play an important role in representing knowledge of results during motor learning and that appropriate feedback may facilitate motor learning.     

The Effect of Verbal Feedback on Motor Learning—A PET Study

The purpose of this study was to investigate brain mechanisms underlying feedback effects on motor learning. We measured human brain activity using positron emission tomography (PET) during length-of-line drawing tasks in the presence or absence of verbal feedback, i.e., information on the precision of motor performance. The average error in responses was significantly lower and the percentage of correct responses was significantly higher in the case of tasks with feedback than those in the absence of feedback. The contralateral sensorimotor, premotor, supplementary motor, the right prefrontal, bilateral parietal and temporal, and anterior cingulate cortices, and the left basal ganglia were activated during all the line-drawing tasks. The right lateral prefrontal and occipital cortices and the left basal ganglia exhibited marked increase in activity after learning. The right inferior parietal and the anterior cingulate cortices were activated in the presence of feedback which provided information on how the subjects should correct their performances. The results indicate that these brain areas may play an important role in representing knowledge of results during motor learning and that appropriate feedback may facilitate motor learning.     

Principles of neurologic localization

Organic and nonorganic neurologic conditions can be differentiated by determining whether the symptoms can or cannot be feigned and whether the symptoms make neuroanatomic sense. For localization of organic disease, lower motor neuron signs and dermatome defects suggest peripheral nerves; sensory dissociation points to the spinal cord, and a cranial nerve deficit with a contralateral extremity deficit suggests a brainstem etiology. Higher level, organized dysfunction points to the cerebrum; ataxia during intentional movements indicates cerebellar involvement, and sudden, unintended movements suggest basal ganglia disorders.     

Cerebellar and premotor function in bimanual coordination: parametric neural responses to spatiotemporal complexity and cycling frequency

In the present functional magnetic resonance imaging (fMRI) study, we assessed the neural network governing bimanual coordination during manipulations of spatiotemporal complexity and cycling frequency. A parametric analysis was applied to determine the effects of each of both factors as well as their interaction. Subjects performed four different cyclical movement tasks of increasing spatiotemporal complexity (i.e., unimanual left-right hand movements, bimanual in-phase movements, bimanual anti-phase movements, and bimanual 90 degrees out-of-phase movements) across four frequency levels (0.9, 1.2, 1.5, and 1.8 Hz). Results showed that, within the network involved in bimanual coordination, functional subcircuits could be distinguished: Activation in the supplementary motor area, superior parietal cortex (SPS), and thalamic VPL Nc was mainly correlated with increasing spatiotemporal complexity of the limb movements, suggesting that these areas are involved in higher-order movement control. By contrast, activation within the primary motor cortex, cingulate motor cortex (CMC), globus pallidus, and thalamic VLo Nc correlated mainly with movement frequency, indicating that these areas play an important role during movement execution. Interestingly, the cerebellum and the dorsal premotor cortex were identified as the principal regions responding to manipulation of both parameters and exhibiting clear interaction effects. Therefore, it is concluded that both areas represent critical sites for the control of bimanual coordination.     

Passive somatosensory discrimination tasks in healthy volunteers: differential networks involved in familiar versus unfamiliar shape and length discrimination

Somatosensory discrimination of unseen objects relies on processing of proprioceptive and tactile information to detect spatial features, such as shape or length, as acquired by exploratory finger movements. This ability can be impaired after stroke, because of somatosensory-motor deficits. Passive somatosensory discrimination tasks are therefore used in therapy to improve motor function. Whereas the neural correlates of active discrimination have been addressed repeatedly, little is known about the neural networks activated during passive discrimination of somatosensory information. In the present study, we applied functional magnetic resonance imaging (fMRI) while the right index finger of ten healthy subjects was passively moved along various shapes and lengths by an fMRI compatible robot. Comparing discriminating versus non-discriminating passive movements, we identified a bilateral parieto-frontal network, including the precuneus, superior parietal gyrus, rostral intraparietal sulcus, and supramarginal gyrus as well as the supplementary motor area (SMA), dorsal premotor (PMd), and ventral premotor (PMv) areas. Additionally, we compared the discrimination of different spatial features, i.e., discrimination of length versus familiar (rectangles or triangles) and unfamiliar geometric shapes (arbitrary quadrilaterals). Length discrimination activated mainly medially located superior parietal and PMd circuits whereas discrimination of familiar geometric shapes activated more laterally located inferior parietal and PMv regions. These differential parieto-frontal circuits provide new insights into the neural basis of extracting spatial features from somatosensory input and suggest that different passive discrimination tasks could be used for lesion-specific training following stroke.     

Hand movement distribution in the motor cortex: the influence of a concurrent task and motor imagery

The aim of this work was to study the relevance of the primary motor cortex (M1) for motor functions different to the simple execution of motor orders. The M1 activity during the performance with individual fingers of a simple motor task (tonic flexion), a motor task that includes a complex motor computation but not motor execution (motor imagery), and a motor task that involves both the computation and execution of movements (phasic movement) was evaluated by functional magnetic resonance imaging (fMRI). The possible influence of other cortical tasks on the M1 activation induced by finger movements was assessed by evaluating the effect of a distracting concurrent task (numeric calculation). Data show that both the dimension of the area activated and the intensity of response were higher during motor planning than during motor execution. There is a mosaic-like distribution for motor-planning M1 functions, with the movement of individual fingers being controlled from several M1 loci. The concurrent mental-task induces a rapid functional reconfiguration of M1, adding M1 subsets to motor programming but excluding others. Present data support the involvement of the M1 in more than just simple motor execution, showing broader and more intense modifications during motor tasks not accompanied by movements (motor imagery) than during the execution of simple motor acts (tonic flexion).     

Distinct striatal regions for planning and executing novel and automated movement sequences

The basal ganglia-thalamo-cortical circuits are viewed as segregated parallel feed back loops crucially involved in motor control, cognition, and emotional processing. Their role in planning novel, as compared to overlearned movement patterns is as yet not well defined. We tested for the involvement of the associative striatum (caudate/anterior putamen) in the generation of novel movement patterns, which is a critical cognitive requirement for non-routine motor behavior. Using event related functional MRI in 14 right-handed male subjects, we analyzed brain activity in the planning phase of four digit finger sequences. Subjects either executed a single overlearned four digit sequence (RECALL), or self-determined four digit sequences of varying order (GENERATE). In both conditions, RECALL and GENERATE, planning was associated with activation in mesial/lateral premotor cortices, motor cingulate cortex, superior parietal cortex, basal ganglia, insula, thalamus, and midbrain nuclei. When contrasting the planning phase of GENERATE with the planning phase of RECALL, there was significantly higher activation within this distributed network. At the level of the basal ganglia, the planning phase of GENERATE was associated with differentially higher activation located specifically within the associative striatum bilaterally. On the other hand, the execution phase during both conditions was associated with a shift of activity towards the posterior part of the putamen. Our data show the specific involvement of the associative striatum during the planning of non-routine movement patterns and illustrate the propagation of activity from rostral to dorsal basal ganglia sites during different stages of motor processing.     

The cerebral control of speech tempo: opposite relationship between speaking rate and BOLD signal changes at striatal and cerebellar structures

So far, only sparse data on the cerebral organization of speech motor control are available. In order to further delineate the neural basis of articulatory functions, fMRI measurements were performed during self-paced syllable repetitions at six different frequencies (2-6 Hz). Bilateral hemodynamic main effects, calculated across all syllable rates considered, emerged within sensorimotor cortex, putamen, thalamus and cerebellum. At the level of the caudatum and the anterior insula, activation was found restricted to the left side. The computation of rate-to-response functions of the BOLD signal revealed a negative linear relationship between syllable frequency and response magnitude within the striatum whereas cortical areas and cerebellar hemispheres exhibited an opposite activation pattern. Dysarthric patients with basal ganglia disorders show unimpaired or even accelerated speaking rate whereas, in contrast, cerebellar dysfunctions give rise to slowed speech tempo which does not fall below a rate of about 3 Hz. The observed rate-to-response profiles of the BOLD signal thus might help to elucidate the pathophysiological mechanisms of dysarthric deficits in central motor disorders.