Premotor cortex and preparation for movement

Summary Many cells in premotor cortex change their activity while a monkey waits before responding. In the present experiment lesions were placed in premotor cortex in order to investigate the information carried by this neuronal activity. The monkeys were trained to make one of two movements depending on the colour of a cue. There were two conditions: in one they could respond when the cue was presented, in the other they had to wait three seconds before responding. The monkeys were then retested after the bilateral removal of premotor cortex. Animals with premotor lesions performed very poorly under both conditions. It is concluded that premotor cortex is concerned with retrieving the response that is appropriate given a particular cue.     

Motor areas beyond motor performance: deficits in serial prediction following ventrolateral premotor lesions

Previous functional MRI findings have indicated that a premotor-parietal network is involved in the perceptual processing of sequential information. Given that premotor functions have traditionally been restricted to behaviors requiring motor or sensorimotor computations, the goal of the present patient study was to further investigate whether the lateral premotor cortex is critical in purely perceptual sequencing. Patients with either ventral premotor or inferior parietal lesions, in addition to patients with prefrontal lesions and age- and gender-matched healthy controls, were tested during the processing of temporal, object-specific, and spatial sequences. Results revealed that premotor patients as well as parietal patients showed significantly higher error rates than did healthy controls on all sequence tasks. In contrast, prefrontal patients showed no behavioral deficits. These findings support the significance of the ventrolateral premotor cortex, in addition to parietal areas, in nonmotor (attentional) functions.     

Globus Pallidus and motor initiation: the bilateral effects of unilateral quisqualic acid-induced lesion on reaction times in monkeys

The results of many experimental studies have shown that the globus pallidus (GP) is involved in the control of motor activities, particularly during motor execution. Whether or not the GP is involved in the initiation phase is still a matter of controversy, however. This question was investigated in the present study in Papio papio monkeys after GP lesion using a simple reaction time (RT) task, focusing particularly on the initiation phase. The monkeys were trained to perform this task, which consisted of raising their hand as quickly as possible in response to a visual signal. The RT and its premotor and motor components were measured. In addition, the distribution of the RTs was analyzed in order to assess the number of long latency responses. After making unilateral GP cell lesions by locally injecting small amounts of the excitatory amino acid quisqualic acid, a bilateral increase was observed in RT. This lengthening involved both the premotor and the motor phases of the RT when the task was performed with the contralateral limb and only the premotor phase when it was performed with the ipsilateral one. A significant increase was observed in the percentage of long latency responses recorded in the contralateral limb after the GP lesion but not in the ipsilateral one. Increases in the RT and in the percentage of long latency responses are thought to constitute two indices of the akinesia observed in our task involving speed constraints, which suggests that the GP may participate in motor initiation. A complete recovery of the RT was observed within one month, whereas the increase in the percentage of long latency responses persisted. These two indices of akinesia seemed therefore to result from an impairment involving both motor and nonmotor processes. These data suggest that the GP may be involved in the control of postural adjustment, motivation, and/or the control of the initial isometric part of movements. The time course of the recovery from the deficits observed after GP lesion shows the existence of mechanisms which seem to have been operative particularly in the case of impairments affecting motor processes.     

Sensorimotor nucleus NIf is necessary for auditory processing but not vocal motor output in the avian song system

Sensorimotor integration in the avian song system is crucial for both learning and maintenance of song, a vocal motor behavior. Although a number of song system areas demonstrate both sensory and motor characteristics, their exact roles in auditory and premotor processing are unclear. In particular, it is unknown whether input from the forebrain nucleus interface of the nidopallium (NIf), which exhibits both sensory and premotor activity, is necessary for both auditory and premotor processing in its target, HVC. Here we show that bilateral NIf lesions result in long-term loss of HVC auditory activity but do not impair song production. NIf is thus a major source of auditory input to HVC, but an intact NIf is not necessary for motor output in adult zebra finches.     

An improved approach to the evaluation of the deep motor branch of the ulnar nerve

The detection of ulnar nerve lesions at Guyon's canal requires evaluation of the distal ulnar sensory and distal motor latency to the abductor digiti minimi (ADM). In addition precision in the measurement of distal motor latencies (DL) to the first dorsal interosseous (1DI) muscle and response amplitude is necessary. This study examines a standardized technique assessing distal ulnar nerve conduction aimed to provide a more sensitive evaluation of these lesions. Fifty normals and eighteen subjects with hand symptoms were assessed to determine DL to the ADM and 1DI and response amplitudes. These standard values were then compared to values obtained from clinically proven cases of distal ulnar lesions over the previous 2 years. The main outcome measures were elimination of premotor potentials and prolongation of 1DI DL. The results revealed that the standardized technique consistently eliminates premotor potentials (PMP) and provides a significantly narrowed range of normal DL values. This enhanced precision allows for more accurate normative values, making recognition of more subtle lesions possible. Normative data compared to values from a 2 year chart review of distal ulnar lesions shows predictive trends toward prolonged 1DI DL and diminution of 1DI amplitudes (AMP).     

A Neural Basis for the Retrieval of Words for Actions

Although much has been learned in recent years about the neural basis for retrieving words denoting concrete entities, the neural basis for retrieving words denoting actions remains poorly understood. We addressed this issue by testing two specific anatomical hypotheses. (1) Naming of actions depends not only on the classical implementation structures of the left frontal operculum, but also on mediational structures located in left premotor/prefrontal areas. (2) The neural systems subserving naming of actions and naming of concrete entities are segregated. The study used the lesion method and involved 75 subjects with focal, stable lesions in the left or right hemispheres, whose magnetic resonance data were analysed with a three-dimensional reconstruction method. The experimental tasks were standardised procedures for measuring action and object naming. The findings offered partial support for the hypotheses, in that: (1) lesions related to impaired action naming overlapped maximally in the left frontal operculum and in the underlying white matter and anterior insula; and (2) lesions of the left anterior temporal and inferotemporal regions, which produce impairments in naming of concrete entities, did not cause action naming deficits. A follow-up analysis indicated that action naming impairments, especially when they were disproportionate relative to concrete entity naming impairments, were not only associated with premotor/prefrontal lesions, but also with lesions of the left mesial occipital cortex and of the paraventricular white matter underneath the supramarginal and posterior temporal regions.     

A neural basis for the retrieval of words for actions

Although much has been learned in recent years about the neural basis for retrieving words denoting concrete entities, the neural basis for retrieving words denoting actions remains poorly understood. We addressed this issue by testing two specific anatomical hypotheses. (1) Naming of actions depends not only on the classical implementation structures of the left frontal operculum, but also on mediational structures located in left premotor/prefrontal areas. (2) The neural systems subserving naming of actions and naming of concrete entities are segregated. The study used the lesion method and involved 75 subjects with focal, stable lesions in the left or right hemispheres, whose magnetic resonance data were analysed with a three-dimensional reconstruction method. The experimental tasks were standardised procedures for measuring action and object naming. The findings offered partial support for the hypotheses, in that: (1) lesions related to impaired action naming overlapped maximally in the left frontal operculum and in the underlying white matter and anterior insula; and (2) lesions of the left anterior temporal and inferotemporal regions, which produce impairments in naming of concrete entities, did not cause action naming deficits. A follow-up analysis indicated that action naming impairments, especially when they were disproportionate relative to concrete entity naming impairments, were not only associated with premotor/prefrontal lesions, but also with lesions of the left mesial occipital cortex and of the paraventricular white matter underneath the supramarginal and posterior temporal regions.     

小鼠脑干交感运动前区前阿黑皮素能神经传入投射的实验研究

目的:研究脑干交感运动前区的前阿黑皮素能神经纤维的分布及其传入投射。方法:以免疫组化法检测前阿黑皮素能神经纤维在脑干交感运动前区的分布;将霍乱毒素B微量注入小鼠脑干交感运动前区进行逆行追踪。结果:α-MSH(α-melanocyte-stimulating hormone)能神经终末密集分布于交感运动前区内,同时则未见AgRP(agouti-related protein)能神经终末,显示交感运动前区仅接受前阿黑皮素(POMC)能神经的单向调节。逆行追踪实验显示脑干交感运动前区的POMC能纤维投射来自于下丘脑弓状核/视交叉后区,而非孤束核尾侧部;统计结果表明下丘脑弓状核/视交叉后区向脑干交感运动前区的神经投射中有近一半为POMC能投射。结论:小鼠下丘脑的POMC能神经元可直接投射到脑干交感运动前区,该神经通路在能量平衡的调节中可能发挥重要的作用。     

Distribution of mu-opioid receptors in rat visceral premotor neurons

Agonists of the mu-opioid receptor (MOR) can modulate the activity of visceral premotor neurons, including cardiac premotor neurons. Neurons in brainstem regions containing these premotor neurons also contain dense concentrations of the MOR1. This study examined the distribution of MOR1 within two populations of visceral premotor neurons: one located in the dorsal motor nucleus of the vagus and the other in the nucleus ambiguus. Visceral premotor neurons contained the retrograde tracer Fluoro-Gold following injections of the tracer into the pericardiac region of the thoracic cavity. MOR1 was localized using immunogold detection of an anti-peptide antibody. Visceral premotor neurons in both regions contained MOR1 at somatic and dendritic sites, although smaller dendrites were less likely to contain the receptor than larger dendrites, suggesting there may be selective trafficking of MOR1 within these neurons. MOR1 labeling in nucleus ambiguus neurons was more likely to be localized to plasma membrane sites, suggesting that ambiguus neurons may be more responsive to opioid ligands than neurons in the dorsal motor nucleus of the vagus. In addition, many of the dendrites of visceral premotor neurons were in direct apposition to other dendrites. MOR1 was often detected at these dendro-dendritic appositions that may be gap junctions. Together these findings indicate that the activity of individual visceral premotor neurons, as well as the coupling between neurons, may be regulated by ligands of the MOR.     

Cues for movement in monkeys (Macaca mulatta) with lesions in premotor cortex

It has been shown previously that after removal of premotor cortex, monkeys are poor at selecting movements on the basis of a visual contextual cue. In those experiments, the monkeys had to pull or turn a handle depending on the color of a cue presented in the foreground or background. In the present experiments, it is shown that animals with lesions that include premotor cortex can select movements correctly if the cue is given by information about the handle itself. In the first experiment, the cue was provided by the direction in which the monkey had last moved the handle; the monkeys had been required to squeeze a handle if they had been forced to squeeze it 5 s earlier, and they were required to turn it if they had been forced to turn it. In the second experiment, the cue was provided by the identity of the handle itself: When presented with a blue handle, they had to pull the handle; when presented with a yellow handle, they had to turn it. It is argued that the animals are impaired only when the task is a true conditional task.     

Motor areas in the frontal lobe of the primate

There has been a substantial change in our concepts about the cortical motor areas. It is now clear that the frontal lobe of primates contains at least six premotor areas that project directly to the primary motor cortex (M1). Two premotor areas, the ventral premotor area (PMv) and the dorsal premotor area (PMd), are located on the lateral surface of the hemisphere. Four premotor areas are located on the medial wall of the hemisphere and include the supplementary motor area (SMA) and three cingulate motor areas. Each of these premotor areas has substantial direct projections to the spinal cord. Corticospinal axons from the premotor areas terminate in the intermediate zone of the spinal cord, and some also terminate in the ventral horn around motoneurons. In this respect, the premotor areas are like M1 and appear to have direct connections with spinal motoneurons, particularly those innervating hand muscles. Furthermore, it is possible to evoke movements of the distal and proximal forelimb using intracortical stimulation at relatively low currents in the premotor areas. Thus, the premotor areas appear to have the potential to influence the control of movement not only at the level of M1, but also more directly at the level of the spinal cord. For these reasons, we have suggested that the premotor areas may operate at a hierarchical level comparable to M1. We propose that each premotor area is a functionally distinct efferent system that differentially generates and/or controls specific aspects of motor behavior.     

Primate models of dystonia

Several models of dystonia have emerged from clinical studies providing a comprehensive explanation for the pathophysiology of this movement disorder. However, several points remain unclear notably concerning the specific role of brainstem, basal ganglia nuclei and premotor cortex. We review data collected in sub-human primate to see whether they might provide new insights into the pathophysiology of dystonia. As in human patients, lesions of the putamen induce dystonia, as well as pharmacological manipulations of the dopaminergic system. In addition, primate studies revealed that lesions in brain stem areas involved in the control of muscular tone and GABAergic manipulations in various basal ganglia nuclei or thalamus also lead to dystonia. Moreover, there is a dramatic disruption in the processing of proprioceptive information with abnormal large receptive fields in the basal ganglia, thalamus, primary somesthetic cortex and premotor cortex of dystonic monkeys. These data highlight the idea that dystonia is associated with aberrant sensory representations interfering with motor control. Considering that the supplementary motor area (SMAp) is the target of basal ganglia projections within the motor loop, we propose a model of dystonia in which abnormal excitability, associated with alteration in sensory receptive fields within the SMAp, leads to an abnormal synchronization between primary motor cortex columns. Such a phenomenon might account for the co-contractions of antagonist muscles favored by action and the abnormal postures observed in dystonia.     

Functional connectivity between secondary and primary motor areas underlying hand-foot coordination

Coincident hand and foot movements are more reliably performed in the same direction than in opposite directions. Using transcranial magnetic stimulation (TMS) to assess motor cortex function, we examined the physiological basis of these movements across three novel experiments. Experiment 1 demonstrated that upper limb corticomotor excitability changed in a way that facilitated isodirectional movements of the hand and foot, during phasic and isometric muscle activation conditions. Experiment 2 demonstrated that motor cortex inhibition was modified with active, but not passive, foot movement in a manner that facilitated hand movement in the direction of foot movement. Together, these findings demonstrate that the coupling between motor representations within motor cortex is activity dependent. Because there are no known connections between hand and foot areas within primary motor cortex, experiment 3 used a dual-coil paired-pulse TMS protocol to examine functional connectivity between secondary and primary motor areas during active ankle dorsiflexion and plantarflexion. Dorsal premotor cortex (PMd) and supplementary motor area (SMA) conditioning, but not ventral premotor cortex (PMv) conditioning, produced distinct phases of task-dependent modulation of excitability of forearm representations within primary motor cortex (M1). Networks involving PMd–M1 facilitate isodirectional movements of hand and foot, whereas networks involving SMA–M1 facilitate corticomotor pathways nonspecifically, which may help to stabilize posture during interlimb coordination. These results may have implications for targeted neurorehabilitation after stroke.     

Where language meets meaningful action: a combined behavior and lesion analysis of aphasia and apraxia

It is debated how language and praxis are co-represented in the left hemisphere (LH). As voxel-based lesion-symptom mapping in LH stroke patients with aphasia and/or apraxia may contribute to this debate, we here investigated the relationship between language and praxis deficits at the behavioral and lesion levels in 50 sub-acute stroke patients. We hypothesized that language and (meaningful) action are linked via semantic processing in Broca’s region. Behaviorally, half of the patients suffered from co-morbid aphasia and apraxia. While 24 % (n = 12) of all patients exhibited aphasia without apraxia, apraxia without aphasia was rare (n = 2, 4 %). Left inferior frontal, insular, inferior parietal, and superior temporal lesions were specifically associated with deficits in naming, reading, writing, or auditory comprehension. In contrast, lesions affecting the left inferior frontal gyrus, premotor cortex, and the central region as well as the inferior parietal lobe were associated with apraxic deficits (i.e., pantomime, imitation of meaningful and meaningless gestures). Thus, contrary to the predictions of the embodied cognition theory, lesions to sensorimotor and premotor areas were associated with the severity of praxis but not language deficits. Lesions of Brodmann area (BA) 44 led to combined apraxic and aphasic deficits. Data suggest that BA 44 acts as an interface between language and (meaningful) action thereby supporting parcellation schemes (based on connectivity and receptor mapping) which revealed a BA 44 sub-area involved in semantic processing.     

Mu-opioid receptors are located postsynaptically and endomorphin-1 inhibits voltage-gated calcium currents in premotor cardiac parasympathetic neurons in the rat nucleus ambiguus

Activation of opioid receptors in the CNS evokes a dramatic decrease in heart rate which is mediated by increases in inhibitory parasympathetic activity to the heart. Injection of opiates into the nucleus ambiguus, where premotor cardiac parasympathetic nucleus ambiguus neurons are located elicits an increase in parasympathetic cardiac activity and bradycardia. However, the mechanisms responsible for altering the activity of premotor cardiac parasympathetic nucleus ambiguus neurons is unknown. This study examined at the electron microscopic level whether premotor cardiac parasympathetic nucleus ambiguus neurons possess postsynaptic opioid receptors and whether mu-opioid receptor agonists alter voltage-gated calcium currents in these neurons. Premotor cardiac parasympathetic nucleus ambiguus neurons were identified in the rat using retrograde fluorescent tracers. One series of experiments utilized dual-labeling immunocytochemical methods combined with electron microscopic analysis to determine if premotor cardiac parasympathetic nucleus ambiguus neurons contain mu-opioid receptors. In a second series of experiments whole cell patch clamp methodologies were used to determine whether activation of postsynaptic opioid receptors altered voltage-gated calcium currents in premotor cardiac parasympathetic nucleus ambiguus neurons in brainstem slices. The perikarya and 78% of the dendrites of premotor cardiac parasympathetic nucleus ambiguus neurons contain mu-opioid receptors. Voltage-gated calcium currents in premotor cardiac parasympathetic nucleus ambiguus neurons were comprised nearly entirely of omega-agatoxin-sensitive P/Q-type voltage-gated calcium currents. Activation of mu-opioid receptors inhibited these voltage-gated calcium currents and this inhibition was blocked by pretreatment with pertusis toxin. The mu-opioid receptor agonist endomorphin-1, but not the mu-opioid receptor agonist endomorphin-2, inhibited the calcium currents. In summary, mu-opioid receptors are located postsynaptically on premotor cardiac parasympathetic nucleus ambiguus neurons. The mu-opioid receptor agonist endomorphin1 inhibited the omega-agatoxin-sensitive P/Q-type voltage-gated calcium currents in premotor cardiac vagal nucleus ambiguus neurons. This inhibition is mediated via a G-protein mediated pathway which was blocked by pretreatment with pertusis toxin. It is possible that the inhibition of calcium currents may act to indirectly facilitate the activity of premotor cardiac parasympathetic nucleus ambiguus neurons by disinhibition, such as by a reduction in inhibitory calcium activated potassium currents.     

大鼠动眼神经核的传入结构联系

目的：观察大鼠动眼神经核传入纤维的来源和特征。方法：采用ＨＲＰ标记法对２０只大鼠动眼神经核进行了逆行追踪研究。结果：脑干到动眼神经核的投射主要来源有同侧的舌下前置核;对侧的展神经核,脑桥尾侧网状核,Ｃａｊａｌ Ｄａｒｋｓｃｈｅｗｉｔｓｃｈ核,中脑网状核。结论：展神经核、前庭神经核、舌下前置核和网状结构是眼水平运动相关的直接运动前结构,它们的损伤都会影响两眼水平协同运动,但展神经核核间神经元起着最重     

Direct hypothalamic innervation of the trigeminal motor nucleus: a retrograde tracer study

It is currently thought that the hypothalamus influences motor output through connections with premotor structures which in turn project to motor nuclei. However, hypocretinergic/orexinergic projections to different motor pools have recently been demonstrated. The present study was undertaken to examine whether hypocretinergic/orexinergic neurons are the only source of projections from the hypothalamus to the trigeminal motor nucleus in the guinea-pig. Cholera toxin subunit b was injected into the trigeminal motor nucleus in order to retrogradely label premotor neurons. Two anatomically separated populations of labeled neurons were observed in the hypothalamus: one group was distributed along the dorsal zone of the lateral hypothalamic area, the lateral portion of the dorsomedial hypothalamic nucleus and the perifornical nucleus; the other was located within the periventricular portion of the dorsomedial hypothalamic nucleus. Numerous cholera toxin subunit b+ neurons in both populations displayed glutamate-like immunoreactivity. In addition, premotor neurons containing hypocretin/orexin were distributed throughout the lateral dorsomedial hypothalamic nucleus, perifornical nucleus and lateral hypothalamic area. Other premotor neurons were immunostained for melanin concentrating hormone; these cells, which were located within the lateral hypothalamic area and the perifornical nucleus, were intermingled with glutamatergic and hypocretinergic/orexinergic neurons. Nitrergic premotor neurons were located only in the periventricular zone of the dorsomedial hypothalamic nucleus. None of the hypothalamic premotor neurons were GABAergic, cholinergic or monoaminergic. The existence of diverse neurotransmitter systems projecting from the hypothalamus to the trigeminal motor pool indicates that this diencephalic structure may influence the numerous functions that are subserved by the trigeminal motor system.     

Intermittent visuomotor processing in the human cerebellum, parietal cortex, and premotor cortex

The cerebellum, parietal cortex, and premotor cortex are integral to visuomotor processing. The parameters of visual information that modulate their role in visuomotor control are less clear. From motor psychophysics, the relation between the frequency of visual feedback and force variability has been identified as nonlinear. Thus we hypothesized that visual feedback frequency will differentially modulate the neural activation in the cerebellum, parietal cortex, and premotor cortex related to visuomotor processing. We used functional magnetic resonance imaging at 3 Tesla to examine visually guided grip force control under frequent and infrequent visual feedback conditions. Control conditions with intermittent visual feedback alone and a control force condition without visual feedback were examined. As expected, force variability was reduced in the frequent compared with the infrequent condition. Three novel findings were identified. First, infrequent (0.4 Hz) visual feedback did not result in visuomotor activation in lateral cerebellum (lobule VI/Crus I), whereas frequent (25 Hz) intermittent visual feedback did. This is in contrast to the anterior intermediate cerebellum (lobule V/VI), which was consistently active across all force conditions compared with rest. Second, confirming previous observations, the parietal and premotor cortices were active during grip force with frequent visual feedback. The novel finding was that the parietal and premotor cortex were also active during grip force with infrequent visual feedback. Third, right inferior parietal lobule, dorsal premotor cortex, and ventral premotor cortex had greater activation in the frequent compared with the infrequent grip force condition. These findings demonstrate that the frequency of visual information reduces motor error and differentially modulates the neural activation related to visuomotor processing in the cerebellum, parietal cortex, and premotor cortex.     

Characterization of premotor interneurones by their input patterns--application of principal component analysis to cat cervical interneurones

Principal component analysis of input patterns of cat C6-C8 interneurones (300 cells) revealed that identified premotor interneurones (11 cells) activated from skin afferents and projecting to T1 motoneurones possessed a special input pattern, characterized by restricted distribution on the plane of the first (Prin 1) versus second (Prin 2) principal component (high positive values of both components). These premotor neurones were located mostly in laminae V-VI. Among other laminae V-VI cells descending in the lateral funiculus to T1 similar to such premotor neurones, there were cells distributed similarly on the Prin 1-2 plane. Further, a majority of interneurones antidromically activated from the T1 motor nucleus at low thresholds also showed a distribution on the plane similar to the premotor neurones. We suggest that premotor neurones of this input pattern constitute a major group among laminae V-VI premotor neurones projecting to T1.     

Spatiotemporal dynamics of brain activity during the transition from visually guided to memory-guided force control

It is well established that the prefrontal cortex is involved during memory-guided tasks whereas visually guided tasks are controlled in part by a frontal-parietal network. However, the nature of the transition from visually guided to memory-guided force control is not as well established. As such, this study examines the spatiotemporal pattern of brain activity that occurs during the transition from visually guided to memory-guided force control. We measured 128-channel scalp electroencephalography (EEG) in healthy individuals while they performed a grip force task. After visual feedback was removed, the first significant change in event-related activity occurred in the left central region by 300 ms, followed by changes in prefrontal cortex by 400 ms. Low-resolution electromagnetic tomography (LORETA) was used to localize the strongest activity to the left ventral premotor cortex and ventral prefrontal cortex. A second experiment altered visual feedback gain but did not require memory. In contrast to memory-guided force control, altering visual feedback gain did not lead to early changes in the left central and midline prefrontal regions. Decreasing the spatial amplitude of visual feedback did lead to changes in the midline central region by 300 ms, followed by changes in occipital activity by 400 ms. The findings show that subjects rely on sensorimotor memory processes involving left ventral premotor cortex and ventral prefrontal cortex after the immediate transition from visually guided to memory-guided force control.