Effects of repetitive motor training on movement representations in adult squirrel monkeys: role of use versus learning

Current evidence indicates that repetitive motor behavior during motor learning paradigms can produce changes in representational organization in motor cortex. In a previous study, we trained adult squirrel monkeys on a repetitive motor task that required the retrieval of food pellets from a small-diameter well. It was found that training produced consistent task-related changes in movement representations in primary motor cortex (M1) in conjunction with the acquisition of a new motor skill. In the present study, we trained adult squirrel monkeys on a similar motor task that required pellet retrievals from a much larger diameter well. This large-well retrieval task was designed to produce repetitive use of a limited set of distal forelimb movements in the absence of motor skill acquisition. Motor activity levels, estimated by the total number of finger flexions performed during training, were matched between the two training groups. This experiment was intended to evaluate whether simple, repetitive motor activity alone is sufficient to produce representational plasticity in cortical motor maps. Detailed analysis of the motor behavior of the monkeys indicates that their retrieval behavior was highly successful and stereotypical throughout the training period, suggesting that no new motor skills were learned during the performance of the large-well retrieval task. Comparisons between pretraining and posttraining maps of M1 movement representations revealed no task-related changes in the cortical area devoted to individual distal forelimb movement representations. We conclude that repetitive motor activity alone does not produce functional reorganization of cortical maps. Instead, we propose that motor skill acquisition, or motor learning, is a prerequisite factor in driving representational plasticity in M1.     

Selective Synaptic Plasticity within the Cerebellar Cortex Following Complex Motor Skill Learning

Complex motor skill learning, but not mere motor activity, leads to an increase in synapse number within the cerebellar cortex. The present experiment used quantitative electron microscopy to determine which synapse types were altered in number. Adult female rats were allocated to either an acrobatic condition (AC), a voluntary exercise condition (VX), or an inactive condition (IC). AC animals were trained to traverse an elevated obstacle course requiring substantial motor coordination to complete. VX animals were housed with unlimited access to running wheels and IC animals received no motor training but were handled briefly each day. Results showed the AC animals to have significantly more parallel fiber to Purkinje cell synapses than both the VX and IC animals. No other synapse type was significantly altered. Thus, the learning-dependent increase in synapse number observed within the cerebellar cortex is accomplished primarily through the addition of parallel fiber synapses.     

Alterations in the thickness of motor cortical subregions after motor-skill learning and exercise

Behavioral manipulations such as housing in an enriched environment have been shown to increase brain weight and visual cortical thickness. The present study was designed to test whether skill learning or repetitive movements can alter the thickness of the motor cortex. One group of 6-mo-old Long-Evans female rats learned motor skills on an obstacle course that increased in difficulty over training and required balance and coordination. A second group ran voluntarily in exercise wheels attached to their home cage but had little opportunity for skill learning. The third group was handled daily but received no opportunity for learning or exercise. Each condition lasted 26–29 d. The skill-learning and exercise conditions had greater heart weight, and the exercise condition had greater adrenal gland weights than controls. The thickness of the motor cortex was measured in four coronal planes between −2.33 mm to −0.3 mm from bregma. Regions of interest that corresponded to published maps of forelimb and hind-limb representations were analyzed together. Rats in the skill-learning condition had significantly thicker medial cortical areas in the two anterior planes (−0.8 and −0.3 mm from bregma). These regions correspond to previously mapped hind-limb representations. The exercise group had greater thickness of the medial region at −0.8 mm from bregma. Cortical thickness in all conditions varied significantly along the medial to lateral axis. For both treatments, the effects were restricted to medial and anterior regions of interest rather than posterior or lateral regions of interest. The results indicate that robust exercise, in addition to skill learning, is capable of altering the thickness of the motor cortex, but that the effects are restricted rather than distributed within the regions studied.     

Cortical neuroanatomical correlates of behavioral deficits produced by lesion of the basal forebrain in rats

Morphological changes in the frontoparietal cortex were assessed in rats that exhibited deficits in a go/no go alternation task due to electrolytic lesion of the basal forebrain. Cortical area, laminar thickness, neuronal density, and soma area were examined in frontal, hindlimb, forelimb, and parietal areas of the cortex. Quantitative morphological analysis of the frontoparietal cortex in lesioned rats revealed a decrease in laminar thickness due to reduced soma size in particular cortical laminae. Neuronal density was not affected. These effects were present in all cortical areas examined and most pronounced in laminae II-III. Similar morphological changes were observed in the same cortical areas following lesions of the basal forebrain made with ibotenic acid, allowing a discrimination of lesion effects from those induced by damage to fibers of passage or differential behavioral testing. Lesions of the basal forebrain have previously been shown to produce both behavioral deficits and changes in cortical cholinergic activity. The cortical morphological changes observed in the present study following basal forebrain lesion provide further evidence for the importance of ascending cholinergic inputs to the cortex and their role in learning and memory.     

Finding parallels in fronto-striatal organization

Evidence suggests that lateral frontal cortex is hierarchically organized such that rostral frontal regions support more abstract representations than caudal regions. A recent fMRI study of language processing proposes that striatum may exhibit an analogous organization. We consider this hypothetical correspondence at both the cognitive and anatomical levels.     

Contrasting effects of motor and visual spatial learning tasks on dendritic arborization and spine density in rats

Rats were trained in four different learning tasks including the Morris-water task, a T-maze delayed nonmatch-to-sample task, a skilled unilateral reaching task, and a skilled bilateral string-pulling task. At the end of training the brains were harvested and stained using a Golgi-Cox procedure. Learning the spatial navigation task produced increased dendritic length and branching as well as decreased spine density in layer III pyramidal cells in occipital cortex. Learning the T-maze task increased dendritic branching in layer III medial but not orbital frontal cortex pyramidal cells and increased spine density in both regions. The motor learning tasks produced increased dendritic length and branching in layer V pyramidal cells in the forelimb cortex in the hemisphere contralateral to the trained limb in the unilateral skilled reaching task and in both limbs in the bilateral skilled pulling task. There were no changes in spine density in layer V in the motor tasks, but there was a decrease in spine density in layer III in the unilateral reaching task. Spatial and motor learning thus produce different patterns of change in layer III cortical pyramidal neurons. Furthermore, changes in spine density and dendritic length and branching are not tightly correlated and can increase and/or decrease independently of one another in learning tasks.     

Differential effects of post-training muscimol and AP5 infusions into different regions of the cingulate cortex on retention for inhibitory avoidance in rats.

Adult male Wistar rats were bilaterally implanted with indwelling cannulae in four different coordinates of the cingulate cortex: (1) the anterior cingulate (AC), (2) the rostral region of the posterior cingulate (RC), (3) the upper portion of the caudal region of the posterior cingulate (UC), and (4) the lower portion of the caudal region of the posterior cingulate (LC). After recovery, animals were trained in a step-down inhibitory avoidance task (3.0-s, 0.4-mA foot shock). Either immediately, or 90 or 180 min after training, animals received a 0.5-microl infusion of vehicle (phosphate buffer, pH 7.4), of muscimol (0.5 microg), or of AP5 (5.0 microg). Retention testing was carried out 24 h after training. Muscimol was amnestic when given into any of the three coordinates of the posterior cingulate cortex 90 min after training, and when given into LC immediately post-training. In addition, AP5 was amnestic when given into UC 90 min post-training, but not when given into any other region and/or at any other time. None of the treatments had any effect when given into AC. The results suggest that memory processing of the inhibitory avoidance task is regulated by the posterior but not by the anterior cingulate cortex, through muscimol-sensitive synapses, relatively late after training. AP5-sensitive synapses appear to play a very limited role in these processes, restricted to UC.     

Premovement activity of the pre-supplementary motor area and the readiness for action: studies of time-resolved event-related functional MRI

The supplementary motor area (SMA) is thought to play in important role in the preparation and organisation of voluntary movement. It has long been known that cortical activity begins to increase up to 2s prior to voluntary self-initiated movement. This increasing premovement activity measured in EEG is known as the Bereitschaftspotential or readiness potential. Modern functional brain imaging methods, using event-related and time-resolved functional MRI techniques, are beginning to reveal the role of the SMA, and in particular the more anterior pre-SMA, in premovement activity associated with the readiness for action. In this paper we review recent studies using event-related time-resolved fMRI methods to examine the time-course of activation changes within the SMA throughout the preparation, readiness and execution of action. These studies suggest that the pre-SMA plays a common role in encoding or representing actions prior to our own voluntary self-initiated movements, during motor imagery, and from the observation of others' actions. We suggest that the pre-SMA generates and encodes motor representations which are then maintained in readiness for action.     

Laminar-dependent dendritic spine alterations in the motor cortex of adult rats following callosal transection and forced forelimb use

Previously, the authors found that partial denervation of the motor cortex in adult animals can enhance this region's neuronal growth response to relevant behavioral change. Rats with partial corpus callosum transections that were forced to rely on one forelimb for 18 days had increased dendritic arborization of layer V pyramidal neurons in the opposite motor cortex compared to controls. This was not found as a result of denervation alone or of forced forelimb use alone. However, it seemed possible that each independent manipulation (i.e., forced forelimb use alone and callosal transections alone) resulted in neural structural alterations that were simply not revealed in measurements of dendritic branch number and/or not inclusive of layer V dendrites. This possibility was assessed in the current study with a reexamination of the Golgi-Cox impregnated tissue generated in the previous study. Tissue was quantified from rats that received either partial transections of the rostral two-thirds of the corpus callosum (CCX) or sham operations (Sham) followed either by 18 days of forced use of one forelimb (Use) or unrestricted use of both forelimbs (Cont). Measurements of apical and basilar dendrites from pyramidal neurons of layer II/III and layer V were performed to detect spine addition resulting from either increased spine density or the addition of dendritic material. As hypothesized, significant spine addition was found following forced forelimb use alone (Sham+Use) and callosal transections alone (CCX+Cont). However, forced use primarily increased spines on layer II/III pyramidal neurons, whereas callosal transections primarily increased dendritic spines on layer V pyramidal neurons in comparison to Sham+Cont. A much more robust increase in layer V dendritic spines was found in animals with the combination of forced forelimb use and denervation (CCX+Use). In contrast to the effects of forced use alone, however, CCX+Use rats failed to show major net increases in spines on layer II/III neurons. These results indicate that while callosal denervation may greatly enhance the neuronal growth and synaptogenic response to behavioral change in layer V, it may also limit spine addition associated with forced forelimb use in layer II/III of the motor cortex.     

Using transcranial magnetic stimulation methods to probe connectivity between motor areas of the brain

Transcranial magnetic stimulation is increasingly used as a tool to explore cortical motor function in healthy subjects and in patients with neurological disease or injury. This review describes a “twin coil” TMS approach that allows investigation of time related changes in functional connectivity between primary motor cortex and other areas in preparation for a forthcoming movement. Investigations into premotor–motor interactions show that these are specific to the type of task that is performed as well as the muscles used to control the movement, allowing us to monitor information flow within motor networks with millisecond time resolution.     

Interference produced by emotional conflict associated with anterior cingulate activation

The anterior cingulate cortex (ACC) is involved in cognition and emotion. In the classic Stroop task, presentation of stimuli that are in response conflict with one another produces activation in the caudal ACC. In the emotional Stroop task, presentation of emotionally salient stimuli produces activation in the rostral ACC. Presentation of stimuli that are emotionally conflicting should activate the caudal ACC; stimuli that are emotionally salient should activate the rostral ACC. We tested this prediction using functional magnetic resonance imaging while subjects made emotional valence judgments of words overlaid on emotional faces (word-face Stroop task). Emotionally incongruent pairs were responded to more slowly than emotionally congruent pairs. Emotionally incongruent trials were associated with increased activation within the caudal ACC, whereas no ACC activation was found in response to emotional saliency. These results support the conflict-monitoring model of caudal ACC and extend this function to conflict within the domain of emotional stimuli.     

Bimanual coordination and interhemispheric interaction

Bimanual coordination of skilled finger movements requires intense functional coupling of the motor areas of both cerebral hemispheres. This coupling can be measured non-invasively in humans with task-related coherence analysis of multi-channel surface electroencephalography. Since bimanual coordination is a high-level capability that virtually always requires training, this review is focused on changes of interhemispheric coupling associated with different stages of bimanual learning. Evidence is provided that the interaction between hemispheres is of particular importance in the early phase of command integration during acquisition of a novel bimanual task. It is proposed that the dynamic changes in interhemispheric interaction reflect the establishment of efficient bimanual ‘motor routines'. The effects of callosal damage on bimanual coordination and learning are reviewed as well as functional imaging studies related to bimanual movement. There is evidence for an extended cortical network involved in bimanual motor activities which comprises the bilateral primary sensorimotor cortex (SM1), supplementary motor area, cingulate motor area, dorsal premotor cortex and posterior parietal cortex. Current concepts about the functions of these structures in bimanual motor behavior are reviewed.     

皮层运动区和皮层下运动区在运动的认知控制中的作用

运动的认知控制是机体选择适合当前情境的运动的关键。皮层和皮层下运动区的不同脑区分别参与运动认知控制的不同方面, 同时又相互协作以确保各种运动的正确执行。运动前区(PMC)和初级运动区(M1)共同负责感觉与运动之间的转换, M1区、小脑和纹状体共同参与运动的学习和记忆, 辅助运动复合体(SMC)和M1区在运动的计划过程中发挥主导作用。基底神经节和前辅助运动区(pre-SMA)是对运动进行抑制的关键脑区。     

Neurophysiologic markers of primary motor cortex for laryngeal muscles and premotor cortex in caudal opercular part of inferior frontal gyrus investigated in motor speech disorder: a navigated transcranial magnetic stimulation (TMS) study

Transcranial magnetic stimulation studies have so far reported the results of mapping the primary motor cortex (M1) for hand and tongue muscles in stuttering disorder. This study was designed to evaluate the feasibility of repetitive navigated transcranial magnetic stimulation (rTMS) for locating the M1 for laryngeal muscle and premotor cortical area in the caudal opercular part of inferior frontal gyrus, corresponding to Broca’s area in stuttering subjects by applying new methodology for mapping these motor speech areas. Sixteen stuttering and eleven control subjects underwent rTMS motor speech mapping using modified patterned rTMS. The subjects performed visual object naming task during rTMS applied to the (a) left M1 for laryngeal muscles for recording corticobulbar motor-evoked potentials (CoMEP) from cricothyroid muscle and (b) left premotor cortical area in the caudal opercular part of inferior frontal gyrus while recording long latency responses (LLR) from cricothyroid muscle. The latency of CoMEP in control subjects was 11.75 ± 2.07 ms and CoMEP amplitude was 294.47 ± 208.87 µV, and in stuttering subjects CoMEP latency was 12.13 ± 0.75 ms and 504.64 ± 487.93 µV CoMEP amplitude. The latency of LLR in control subjects was 52.8 ± 8.6 ms and 54.95 ± 4.86 in stuttering subjects. No significant differences were found in CoMEP latency, CoMEP amplitude, and LLR latency between stuttering and control-fluent speakers. These results indicate there are probably no differences in stuttering compared to controls in functional anatomy of the pathway used for transmission of information from premotor cortex to the M1 cortices for laryngeal muscle representation and from there via corticobulbar tract to laryngeal muscles.     

Training-induced and electrically induced potentiation in the neocortex

Long-term potentiation (LTP) shares many properties with memory and is currently the most popular laboratory model of memory. Although it has not been proven that memory is based on an LTP-like mechanism, there is evidence that learning a motor skill can induce LTP-like effects. This evidence was obtained in a slice-preparation experiment, which precluded within-animal comparisons before and after training. In the present experiments, Long-Evans rats were unilaterally trained to acquire a forelimb reaching and grasping skill. Evoked potentials were found to be larger in motor cortex layer II/III in the trained, compared to the untrained, hemisphere in slice, acute, and chronic preparations. Consistent with previous research, the trained hemisphere was less amenable to subsequent LTP induction. Furthermore, the application of either LTP- or LTD-inducing stimulation during the training phase of the reaching task disrupted the acquisition of the skill, providing further evidence that memory may be based on an LTP mechanism.     

Cerebellar output: motor and cognitive channels

The input to the cerebellum has long been known to originate from widespread regions of the cerebral cortex including the frontal, parietal and temporal lobes. The output of the cerebellum, however, was thought to project mainly to the primary motor cortex. Recent anatomical observations have challenged this view. It is now apparent that cerebellar output goes to multiple cortical areas, including not only the primary motor cortex, but also areas of premotor and prefrontal cortex. In fact, there is growing evidence that each of the areas of cerebral cortex that project to the cerebellum is also the target of cerebellar output. The cerebellar output to individual cortical areas originates from distinct clusters of neurons in the deep nuclei which we have termed `output channels'. The individual output channels to the cortical areas we have examined display little or no overlap. Physiological recordings in awake trained primates indicate that neurons in different output channels appear to be involved in distinct aspects of behavior, and in both motor and cognitive functions. These observations indicate that the cerebellar influence on the cerebral cortex is more extensive than previously recognized.     

Relationships between movement initiation times and movement-related cortical potentials in Parkinson's disease

Movement-related cortical potentials recorded from the scalp reveal increasing cortical activity occurring prior to voluntary movement. Studies of set-related cortical activity recorded from single neurones within premotor and supplementary motor areas in monkeys suggest that such premovement activity may act to prime activity of appropriate motor units in readiness to move, thereby facilitating the movement response. Such a role of early stage premovement activity in movement-related cortical potentials was investigated by examining the relationship between premovement cortical activity and movement initiation or reaction times. Parkinson's disease and control subjects performed a simple button-pressing reaction time task and individual movement-related potentials were averaged for responses with short compared with long reaction times. For Parkinson's disease subjects but not for the control subjects, early stage premovement cortical activity was significantly increased in amplitude for faster reaction times, indicating that there is indeed a relationship between premovement cortical activity amplitude and movement initiation or reaction times. In support of studies of set-related cortical activity in monkeys, it is therefore suggested that early stage premovement activity reflects the priming of appropriate motor units of primary motor cortex, thereby reducing movement initiation or reaction times.PsycINFO classification: 2330; 2520; 2530     

Dorsal and ventral streams: a framework for understanding aspects of the functional anatomy of language

Despite intensive work on language-brain relations, and a fairly impressive accumulation of knowledge over the last several decades, there has been little progress in developing large-scale models of the functional anatomy of language that integrate neuropsychological, neuroimaging, and psycholinguistic data. Drawing on relatively recent developments in the cortical organization of vision, and on data from a variety of sources, we propose a new framework for understanding aspects of the functional anatomy of language which moves towards remedying this situation. The framework posits that early cortical stages of speech perception involve auditory fields in the superior temporal gyrus bilaterally (although asymmetrically). This cortical processing system then diverges into two broad processing streams, a ventral stream, which is involved in mapping sound onto meaning, and a dorsal stream, which is involved in mapping sound onto articulatory-based representations. The ventral stream projects ventro-laterally toward inferior posterior temporal cortex (posterior middle temporal gyrus) which serves as an interface between sound-based representations of speech in the superior temporal gyrus (again bilaterally) and widely distributed conceptual representations. The dorsal stream projects dorso-posteriorly involving a region in the posterior Sylvian fissure at the parietal-temporal boundary (area Spt), and ultimately projecting to frontal regions. This network provides a mechanism for the development and maintenance of "parity" between auditory and motor representations of speech. Although the proposed dorsal stream represents a very tight connection between processes involved in speech perception and speech production, it does not appear to be a critical component of the speech perception process under normal (ecologically natural) listening conditions, that is, when speech input is mapped onto a conceptual representation. We also propose some degree of bi-directionality in both the dorsal and ventral pathways. We discuss some recent empirical tests of this framework that utilize a range of methods. We also show how damage to different components of this framework can account for the major symptom clusters of the fluent aphasias, and discuss some recent evidence concerning how sentence-level processing might be integrated into the framework.     

Rapid modulation of distributed brain activity by Transcranial Magnetic Stimulation of human motor cortex

This paper reviews the effects of single and repetitive transcranial magnetic stimuli (rTMS) delivered to one cortical area and measured across distributed brain regions using electrophysiological measures (e.g. motor thresholds, motor evoked potentials, paired-pulse stimulation), functional neuroimaging (including EEG, PET and fMRI) and behavioural measures. Discussion is restricted to changes in excitability in the primary motor cortex and behaviour during motor tasks following transcranial magnetic stimulation delivered to primary motor and premotor areas. Trains of rTMS have lasting effects on the excitability of intrinsic and corticofugal neurones, altering the responsiveness of local and remote sites. These effects lead to distributed changes in synaptic activity at rest, and during a range of motor tasks. It is possible to impair or improve performance following rTMS, but for most simple motor tasks performance is unaltered. Changes in distributed activity observed with functional imaging during motor behaviour may represent compensatory activity, enabling maintenance of performance; stimulation of additional cortical areas appears to impair performance. A detailed understanding of the distributed changes in excitability following rTMS may facilitate future attempts to modulate motor behaviour in the healthy brain and for therapeutic purposes.     

Motor maps and synergies

Consider the process of raising and lowering the arm in the sagittal plane. Different parts of different muscles operate over different sectors of the angular range. How and why does the nervous system implement this differential muscle activation according to joint angle? We contend that such control depends on the adaptive formation of motor maps. These solve the problem of redundancy in the musculoskeletal system by connecting a relatively small number of cortical columns in the motor cortex to a large number of alpha motor neuron pools. We argue that motor maps are formed such that each functional muscle is activated in proportion to its moment arm about the movement. Because of this the required agonist and antagonist turning forces are generated with a minimum demand for metabolic energy. We know from biomechanical principles that, at any given posture, those muscle fibres that change length most in response to a small joint-angle change are those with the greatest moment arm. Likewise those that change least have the smallest. By establishing a model of the polynomial relationships between the lengths of functional muscles l and the corresponding changes in joint angles theta, the nervous system can generate signals partial differentiallj/ partial differentialthetai (where lj is the length of the jth functional muscle and thetai is the magnitude of the ith elemental movement). These signals create motor maps by modulating the gains of descending motor pathways. As a result, functional muscles are activated in proportion to their moment arms. This reduces the demand for metabolic energy to a minimum. Since moment arms change with joint angle, it also accounts for the experimental observations above. Such motor mapping effectively provides a minimum energy "wired-in" synergy. Established in utero, motor maps are the first stage of synergy formation and provide the basis for the development of subsequent task-dependent synergies.