Repetitive Microstimulation Alters the Cortical Representation of Movements in Adult Rats

In order to examine the effects of repetitive stimulation on functional cortical organization, standard intracortical microstimulation (ICMS) techniques were used to generate maps of movement representations in motor cortex of rat. After identification of caudal and rostral forelimb fields and adjacent vibrissae and neck fields, one or more representational borders were defined in greater detail. Then a microelectrode was introduced into one of these representational fields, and ICMS current pulses were delivered at a rate of 1/sec for 1 to 3 hr. Following repetitive ICMS, significant changes in movement representations were observed using current levels that were either suprathreshold or subthreshold for evoking the site-specific movement. Electromyographic activity could be evoked at suprathreshold and near-threshold current levels, but not at the subthreshold current levels used here. Significant border shifts ranged from 210 to 670 μm. In each case in which shifts occurred, there appeared to be expansion of the movement represented at the repetitively stimulated site. The effects were progressive and reversible. These results suggest that at least under these unusual experimental circumstances, large representational changes can be generated very rapidly within motor cortex in the absence of any evident peripheral feedback.     

Repetitive microstimulation alters the cortical representation of movements in adult rats

In order to examine the effects of repetitive stimulation on functional cortical organization, standard intracortical microstimulation (ICMS) techniques were used to generate maps of movement representations in motor cortex of rat. After identification of caudal and rostral forelimb fields and adjacent vibrissae and neck fields, one or more representational borders were defined in greater detail. Then a microelectrode was introduced into one of these representational fields, and ICMS current pulses were delivered at a rate of 1/sec for 1 to 3 hr. Following repetitive ICMS, significant changes in movement representations were observed using current levels that were either suprathreshold or subthreshold for evoking the site-specific movement. Electromyographic activity could be evoked at suprathreshold and near-threshold current levels, but not at the subthreshold current levels used here. Significant border shifts ranged from 210 to 670 microns. In each case in which shifts occurred, there appeared to be expansion of the movement represented at the repetitively stimulated site. The effects were progressive and reversible. These results suggest that at least under these unusual experimental circumstances, large representational changes can be generated very rapidly within motor cortex in the absence of any evident peripheral feedback.     

Motor training induces experience-specific patterns of plasticity across motor cortex and spinal cord.

The motor cortex and spinal cord possess the remarkable ability to alter structure and function in response to differential motor training. Here we review the evidence that the corticospinal system is not only plastic but that the nature and locus of this plasticity is dictated by the specifics of the motor experience. Skill training induces synaptogenesis, synaptic potentiation, and reorganization of movement representations within motor cortex. Endurance training induces angiogenesis in motor cortex, but it does not alter motor map organization or synapse number. Strength training alters spinal motoneuron excitability and induces synaptogenesis within spinal cord, but it does not alter motor map organization. All three training experiences induce changes in spinal reflexes that are dependent on the specific behavioral demands of the task. These results demonstrate that the acquisition of skilled movement induces a reorganization of neural circuitry within motor cortex that supports the production and refinement of skilled movement sequences. We present data that suggest increases in strength may be mediated by an increased capacity for activation and/or recruitment of spinal motoneurons while the increased metabolic demands associated with endurance training induce cortical angiogenesis. Together these results show the robust pattern of anatomic and physiological plasticity that occurs within the corticospinal system in response to differential motor experience. The consequences of such distributed, experience-specific plasticity for the encoding of motor experience by the motor system are discussed.     

Topographic organization of baboon primary motor cortex: face, hand, forelimb, and shoulder representation

(1) The fine details of the motor organization of the forelimb, face, and tongue representation of the baboon (Papio h. anubis) primary motor cortex were studied in four adult animals, using intracortical microstimulation (ICMS). (2) A total of 293 electrode penetrations were made. ICMS was delivered to 10,052 sites, and of these, 6,186 sites were verified to have been located within the grey matter. Motor effects were evoked from 30% of these sites. (3) The baboon motor cortex is confined, in large part, to the cortical tissue lying along the anterior bank of the central sulcus. When the electrode penetrations were confined to the precentral gyrus, few sites were capable of evoking movement when stimulated by currents of 40 microA or less. (4) The details of the motor maps varied among the four animals; nonetheless, a general topographic organization existed, with the tongue musculature being represented most laterally, followed by a medial progression of the face, digits, wrist, forearm, and shoulder. Within the representation of a given body part, the muscles were organized as a mosaic, wherein the same muscle was multiply represented. (5) A zone of unresponsive cortex was observed to lie consistently between the face and forelimb representation in all four animals. Repeated electrode penetrations within the unresponsive zone failed to elicit muscle contractions even with stimulating currents as high as 80 microA. (6) Our results suggest that the baboon motor cortex is topographically organized; however, embedded within this overall pattern lies a fine-grained mosaic incorporating multiple representations of the same muscle.     

Distinct cortical circuit mechanisms for complex forelimb movement and motor map topography

Cortical motor maps are the basis of voluntary movement, but they have proven difficult to understand in the context of their underlying neuronal circuits. We applied light-based motor mapping of Channelrhodopsin-2 mice to reveal a functional subdivision of the forelimb motor cortex based on the direction of movement evoked by brief (10?ms) pulses. Prolonged trains of electrical or optogenetic stimulation (100-500?ms) targeted to anterior or posterior subregions of motor cortex evoked reproducible complex movements of the forelimb to distinct positions in space. Blocking excitatory cortical synaptic transmission did not abolish basic motor map topography, but the site-specific expression of complex movements was lost. Our data suggest that the topography of?movement maps arises from their segregated output projections, whereas complex movements evoked by prolonged stimulation require intracortical synaptic transmission.     

Topographic Organization of Baboon Primary Motor Cortex: Face,Hand, Forelimb,and Shoulder Representation

(1) The fine details of the motor organization of the forelimb, face, and tongue representation of the baboon (Papio h. anubis)primary motor cortex were studied in four adult animals, using intracortical microstimulation (ICMS). (2) A total of 293 electrode penetrations were made. ICMS was delivered to 10,052 sites, and of these, 6,186 sites were verified to have been located within the grey matter. Motor effects were evoked from 30% of these sites. (3)The baboon motor cortex is confined, in large part, to the cortical tissue lying along the anterior bank of the central sulcus. When the electrode penetrations were confined to the precentral gyrus, few sites were capable of evoking movement when stimulated by currents of 40 μA or less. (4)The details of the motor maps varied among the four animals; nonetheless, a general topographic organization existed, with the tongue musculature being represented most laterally, followed by a medial progression of the face, digits, wrist, forearm, and shoulder. Within the representation of a given body part, the muscles were organized as a mosaic, wherein the same muscle was multiply represented. (5) A zone of unresponsive cortex was observed to lie consistently between the face and forelimb representation in all four animals. Repeated electrode penetrations within the unresponsive zone failed to elicit muscle contractions even with stimulating currents as high as 80 μA. (6) Our results suggest that the baboon motor cortex is topographically organized; however, embedded within this overall pattern lies a fine-grained mosaic incorporating multiple representations of the same muscle.     

Representational plasticity in the mammalian brain cortex. (Review article)

The epithelial receptors are represented in the mammalian brain cortex in a genetically defined, strictly regulated manner. Until the 1970s, the cortical maps and the wiring of the central nervous system were thought to be rather static and unchangeable. Subsequently, however, studies of sensory and motor cortical maps in particular genetic strains of animals and in animals with different perinatal or adult histories have revealed that the map organization can be modified at any time between conception and death. Especially studies of the effects of peripheral and central lesions and of perceptual learning on the sensory and motor cortical representations have had a dramatic effect in alerting neuroscientists and therapists to the reorganizational capacity of the adult brain. From a theoretical aspect, these changes in the cortical maps provide useful models for an understanding of the changes that can occur in the integrative functions of complex brain networks throughout life.     

Comparison of electrical thresholds for evoking movements from sensori-motor areas of the cat cerebral cortex and its relation to motor training

Motor maps and electrical thresholds for evoking movements from motor areas of the cerebral cortex were evaluated in normal cats by using intracortical microstimulation techniques. Stainless steel chambers were implanted over craniotomies in adult cats trained to perform reaching and retrieval movements with their forelimbs. Prehensile motor training was continued and movement performance monitored for about 6-10 weeks during which the cortex was progressively explored with sharp tungsten electrodes inserted into cortical gyri (anterior and posterior sigmoid, and coronal) and the banks of sulci (cruciate, presylvian and coronal). Twice weekly, under light general anaesthesia, 3-4 tracks were made in either hemisphere till about 50 tracks were made in each hemisphere. Mean thresholds for evoking forelimb movements from different cytoarchitectonic areas (4gamma, 4delta, 6agamma and 3a) were compared and no consistent or significant differences were observed between the different areas. In the animals (4/6) which used either forelimb to perform the tasks, there were no consistent differences in the mean thresholds for evoking forelimb movements from the two hemispheres. However, in 2 animals, which used their right forelimbs predominantly or exclusively to perform all the tasks, mean thresholds for evoking forelimb movements was significantly higher in areas 4gamma and 6agamma of the left hemisphere (compared to the right); no consistent differences in the mean thresholds for evoking hindlimb or facial movements were observed between the two hemispheres. These findings suggest that ICMS thresholds for evoking forelimb movements may be similar in different sensorimotor areas of the cat cerebral cortex, and these thresholds could be influenced by motor training.     

Comparison of electrical thresholds for evoking movements from sensori-motor areas of the cat cerebral cortex and its relation to motor training

Motor maps and electrical thresholds for evoking movements from motor areas of the cerebral cortex were evaluated in normal cats by using intracortical microstimulation techniques. Stainless steel chambers were implanted over craniotomies in adult cats trained to perform reaching and retrieval movements with their forelimbs. Prehensile motor training was continued and movement performance monitored for about 6–10 weeks during which the cortex was progressively explored with sharp tungsten electrodes inserted into cortical gyri (anterior and posterior sigmoid, and coronal) and the banks of sulci (cruciate, presylvian and coronal). Twice weekly, under light general anaesthesia, 3–4 tracks were made in either hemisphere till about 50 tracks were made in each hemisphere. Mean thresholds for evoking forelimb movements from different cytoarchitectonic areas (4γ, 4δ, 6aγ and 3a) were compared and no consistent or significant differences were observed between the different areas. In the animals (4/6) which used either forelimb to perform the tasks, there were no consistent differences in the mean thresholds for evoking forelimb movements from the two hemispheres. However, in 2 animals, which used their right forelimbs predominantly or exclusively to perform all the tasks, mean thresholds for evoking forelimb movements was significantly higher in areas 4γ and 6aγ of the left hemisphere (compared to the right); no consistent differences in the mean thresholds for evoking hindlimb or facial movements were observed between the two hemispheres. These findings suggest that ICMS thresholds for evoking forelimb movements may be similar in different sensorimotor areas of the cat cerebral cortex, and these thresholds could be influenced by motor training.     

The emergence of somatotopic maps of the body in S1 in rats: the correspondence between functional and anatomical organization

Most of what we know about cortical map development and plasticity comes from studies in mice and rats, and for the somatosensory cortex, almost exclusively from the whisker-dominated posteromedial barrel fields. Whiskers are the main effector organs of mice and rats, and their representation in cortex and subcortical pathways is a highly derived feature of murine rodents. This specialized anatomical organization may therefore not be representative of somatosensory cortex in general, especially for species that utilize other body parts as their main effector organs, like the hands of primates. For these reasons, we examined the emergence of whole body maps in developing rats using electrophysiological recording techniques. In P5, P10, P15, P20 and adult rats, multiple recordings were made in the medial portion of S1 in each animal. Subsequently, these functional maps were related to anatomical parcellations of S1 based on a variety of histological stains. We found that at early postnatal ages (P5) medial S1 was composed almost exclusively of the representation of the vibrissae. At P10, other body part representations including the hindlimb and forelimb were present, although these were not topographically organized. By P15, a clear topographic organization began to emerge coincident with a reduction in receptive field size. By P20, body maps were adult-like. This study is the first to describe how topography of the body develops in S1 in any mammal. It indicates that anatomical parcellations and functional maps are initially incongruent but become tightly coupled by P15. Finally, because anatomical and functional specificity of developing barrel cortex appears much earlier in postnatal life than the rest of the body, the entire primary somatosensory cortex should be considered when studying general topographic map formation in development.     

Cervical sprouting of corticospinal fibers after thoracic spinal cord injury accompanies shifts in evoked motor responses.

The adult central nervous system (CNS) of higher vertebrates displays a limited ability for self repair after traumatic injuries, leading to lasting functional deficits [1]. Small injuries can result in transient impairments, but the mechanisms of recovery are poorly understood [2]. At the cortical level, rearrangements of the sensory and motor representation maps often parallel recovery [3,4]. In the sensory system, studies have shown that cortical and subcortical mechanisms contribute to map rearrangements [5,6], but for the motor system the situation is less clear. Here we show that large-scale structural changes in the spared rostral part of the spinal cord occur simultaneously with shifts of a hind-limb motor cortex representation after traumatic spinal-cord injury. By intracortical microstimulation, we defined a cortical area that consistently and exclusively yielded hind-limb muscle responses in normal adult rats. Four weeks after a bilateral transsection of the corticospinal tract (CST) in the lower thoracic spinal cord, we again stimulated this cortical field and found forelimb, whisker, and trunk responses, thus demonstrating reorganization of the cortical motor representation. Anterograde tracing of corticospinal fibers originating from this former hind-limb area revealed that sprouting greatly increased the normally small number of collaterals that lead into the cervical spinal cord rostral to the lesion. We conclude that the corticospinal motor system has greater potential to adapt structurally to lesions than was previously believed and hypothesize that this spontaneous growth response is the basis for the observed motor representation rearrangements and contributes to functional recovery after incomplete lesions.     

Multiple Representations of the Body and Input-Output Relationships in the Agranular and Granular Cortex of the Chronic Awake Guinea Pig

The organization of somatosensory input and the input-output relationships in regions of the agranular frontal cortex (AGr) and granular parietal cortex (Gr) were examined in the chronic awake guinea pig, using the combined technique of single-unit recording and intracortical microstimulation (ICMS). AGr, which was cytoarchitectonically subdivided into medial (AGrm) and lateral (AGrl) parts, also can be characterized on a functional basis. AGrl contains the head, forelimb, and most hindlimb representations; only a small number of hindlimb neurons are confined in AGrm. Different distributions of submodalities exist in AGr and Gr: AGr receives predominantly deep input (with the exception of the vibrissa region, which receives cutaneous input), whereas neurons of Gr respond almost exclusively to cutaneous input. The cutaneous or deep receptive field (RF) of each neuron was determined by natural peripheral stimulation. All studied neurons were activated by small RFs, with the exception of lip, nose, pinna, and limb units of lateral Gr (Grl), for which the RFs were larger.

Microelectrode mapping experiments revealed the existence of three spatially separate, incomplete body maps in which somatosensory and motor representations overlap. One body map, with limbs medially and head rostrolaterally, is contained in AGr. A second map, comparable to the first somatosensory cortex (SI) of other mammals, is found in Gr, with hindlimb, trunk, forelimb, and head representations in an orderly mediolateral sequence. An unresponsive zone separates the head area from the forelimb region. A third map, with the forelimb rostrally and the hindlimb caudally, lies adjacent and lateral to the SI head area. This limb representation, which is characterized by an upright and small size compared to that found in SI, can be considered to be part of the second somatosensory cortex (SII). A distinct head representation was not recognized as properly belonging to SII, but the evidence that neurons of the SI head region respond to stimulation of large RFs located in lips, nose, and pinna leads us to hypothesize that the SII face area overlaps that of SI to some extent, or, alternatively, that the two areas are strictly contiguous and the limits are ambiguous, making them difficult to distinguish.

The input-output relationships were based on the results of RF mapping and ICMS in the same electrode penetration. The intrinsic specific interconnections of cortical neurons whose afferent input and motor output is related to identical body regions show a considerable degree of refinement. The input-output correspondence is especially pronounced for neurons with small RFs. This study confirms and extends similar data recently reported for other rodents.     

Motor cortex representation of the upper-limb in individuals born without a hand

The body schema is an action-related representation of the body that arises from activity in a network of multiple brain areas. While it was initially thought that the body schema developed with experience, the existence of phantom limbs in individuals born without a limb (amelics) led to the suggestion that it was innate. The problem with this idea, however, is that the vast majority of amelics do not report the presence of a phantom limb. Transcranial magnetic stimulation (TMS) applied over the primary motor cortex (M1) of traumatic amputees can evoke movement sensations in the phantom, suggesting that traumatic amputation does not delete movement representations of the missing hand. Given this, we asked whether the absence of a phantom limb in the majority of amelics means that the motor cortex does not contain a cortical representation of the missing limb, or whether it is present but has been deactivated by the lack of sensorimotor experience. In four upper-limb amelic subjects we directly stimulated the arm/hand region of M1 to see 1) whether we could evoke phantom sensations, and 2) whether muscle representations in the two cortices were organised asymmetrically. TMS applied over the motor cortex contralateral to the missing limb evoked contractions in stump muscles but did not evoke phantom movement sensations. The location and extent of muscle maps varied between hemispheres but did not reveal any systematic asymmetries. In contrast, forearm muscle thresholds were always higher for the missing limb side. We suggest that phantom movement sensations reported by some upper limb amelics are mostly driven by vision and not by the persistence of motor commands to the missing limb within the sensorimotor cortex. We propose that prewired movement representations of a limb need the experience of movement to be expressed within the primary motor cortex.     

Motor Enrichment and the Induction of Plasticity Before or After Brain Injury

Voluntary exercise, treadmill activity, skills training, and forced limb use have been utilized in animal studies to promote brain plasticity and functional change. Motor enrichment may prime the brain to respond more adaptively to injury, in part by upregulating trophic factors such as GDNF, FGF-2, or BDNF. Discontinuation of exercise in advance of brain injury may cause levels of trophic factor expression to plummet below baseline, which may leave the brain more vulnerable to degeneration. Underfeeding and motor enrichment induce remarkably similar molecular and cellular changes that could underlie their beneficial effects in the aged or injured brain. Exercise begun before focal ischemic injury increases BDNF and other defenses against cell death and can maintain or expand motor representations defined by cortical microstimulation. Interfering with BDNF synthesis causes the motor representations to recede or disappear. Injury to the brain, even in sedentary rats, causes a small, gradual increase in astrocytic expression of neurotrophic factors in both local and remote brain regions. The neurotrophic factors may inoculate those areas against further damage and enable brain repair and use-dependent synaptogenesis associated with recovery of function or compensatory motor learning. Plasticity mechanisms are particularly active during time-windows early after focal cortical damage or exposure to dopamine neurotoxins. Motor and cognitive impairments may contribute to self-imposed behavioral impoverishment, leading to a reduced plasticity. For slow degenerative models, early forced forelimb use or exercise has been shown to halt cell loss, whereas delayed rehabilitation training is ineffective and disuse is prodegenerative. However, it is possible that, in the chronic stages after brain injury, a regimen of exercise would reactivate mechanisms of plasticity and thus enhance rehabilitation targeting residual functional deficits.     

Retinotopic organization of striate and extrastriate visual cortex in the golden hamster (Mesocricetus auratus).

The visual topography within striate and lateral extrastriate visual cortices was studied in adult hamsters. The cortical areas 17 and 18a in the left hemisphere were electrophysiologically mapped upon stimulation of the right eye, correlating receptive field positions in the visual field with cortical recording sites. Reference lesions were placed at selected cortical sites. Like in rats and other mammals, the lateral extrastriate cortex contained multiple representations of the visual field. Rostral area 18a contained the rostrolateral maps, with medial and lateral divisions. More caudally and sharing a common border with V1, maps in lateromedial, posterolateral and posterior areas were found. More laterally and forming a "third tier" of visual maps, anterolateral, laterolateral-anterior, laterolateral and laterolateral-posterior areas were found. There was also an indication of a possible pararhinal map. The plan so defined is virtually identical to that of rats. The results may be useful to understand a basic mammalian plan in the organization of the visual cortex.     

How does the cerebral cortex work? Learning, attention, and grouping by the laminar circuits of visual cortex

The organization of neocortex into layers is one of its most salient anatomical features. These layers include circuits that form functional columns in cortical maps. A major unsolved problem concerns how bottom-up, top-down, and horizontal interactions are organized within cortical layers to generate adaptive behaviors. This article models how these interactions help visual cortex to realize: (i) the binding process whereby cortex groups distributed data into coherent object representations; (ii) the attentional process whereby cortex selectively processes important events; and (iii) the developmental and learning processes whereby cortex shapes its circuits to match environmental constraints. New computational ideas about feedback systems suggest how neocortex develops and learns in a stable way, and why top-down attention requires converging bottom-up inputs to fully activate cortical cells, whereas perceptual groupings do not.     

Preserved cortical somatotopic and motor representations in tetraplegic humans

A rich literature has documented changes in cortical representations of the body in somatosensory and motor cortex. Recent clinical studies of brain–machine interfaces designed to assist paralyzed patients have afforded the opportunity to record from and stimulate human somatosensory, motor, and action-related areas of the posterior parietal cortex. These studies show considerable preserved structure in the cortical somato-motor system. Motor cortex can immediately control assistive devices, stimulation of somatosensory cortex produces sensations in an orderly somatotopic map, and the posterior parietal cortex shows a high-dimensional representation of cognitive action variables. These results are strikingly similar to what would be expected in a healthy subject, demonstrating considerable stability of adult cortex even after severe injury and despite potential plasticity-induced new activations within the same region of cortex. Clinically, these results emphasize the importance of targeting cortical areas for BMI control signals that are consistent with their normal functional role.     

Investigations into the organization of information in sensory cortex

One might take the exploration of sensory cortex in the first decades of the last century as the opening chapter of modern neuroscience. The combined approaches of (i) measuring effects of restricted ablation on functional capacities, both in the clinic and the laboratory, together with (ii) anatomical investigations of cortical lamination, arealization, and connectivity, and (iii) the early physiological probing of sensory representations, led to a fundamental body of knowledge that remains relevant to this day. In our time, there can be little doubt that its organization as a mosaic of columnar modules is the pervasive functional property of mammalian sensory cortex [Brain 120 (1997) 701]. If one accepts the assertion that columns and maps must improve the functioning of the brain (why else would they be the very hallmark of neocortex?), then the inevitable question is: exactly what advantages do they permit? In this review of our recent presentation at the workshop on Homeostasis, plasticity and learning at the Institut Henri Poincaré, we will outline a systematic approach to investigating the role of modular, map-like cortical organization in the processing of sensory information. We survey current evidence concerning the functional significance of cortical maps and modules, arguing that sensory cortex is involved not solely in the online processing of afferent data, but also in the storage and retrieval of information. We also show that the topographic framework of primary sensory cortex renders the encoding of sensory information efficient, fast and reliable.