Motor cortex rules for learning and memory

Primary motor cortex has a complex, interconnected anatomical and functional architecture with dynamic properties. Recent evidence suggests that, concomitantly with regulating muscle activity and movements, the motor cortex makes key contributions to learning and remembering motor skills.     

Anticipatory activity in primary motor cortex codes memorized movement sequences

Movement sequences, defined both by the component movements and by the serial order in which they are produced, are fundamental building blocks of motor behavior. The serial order of sequence production is strongly encoded in medial motor areas. It is not known to what extent sequences are further elaborated or encoded in primary motor cortex. Here, we describe cells in the primary motor cortex of the monkey that show anticipatory activity exclusively related to a specific memorized sequence of upcoming movements. In addition, the injection of muscimol, a GABA agonist, into motor cortex resulted in an increase in the error rate during sequence production, without concomitant effects on nonsequenced motor performance. Our results challenge the role of medial motor areas in the control of well-practiced movement sequences and suggest that motor cortex contains a complete apparatus for the planning and production of this complex behavior.     

The cortical control of movement revisited

Recently, we found that electrical stimulation of motor cortex caused monkeys to make coordinated, complex movements. These evoked movements were arranged across the cortex in a map of spatial locations to which the hand moved. We suggest that some of the subdivisions previously described within primary motor and premotor cortex may represent different types of actions that monkeys tend to make in different regions of space. According to this view, primary and premotor cortex may fit together into a larger map of manual space.     

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.     

Asymmetric division: a kinesin for spindle positioning

The meiotic spindles of animal eggs move to extremely asymmetric positions, close to the cell cortex. A recent paper has identified a motor complex that may move the meiotic spindle toward the cortex in Caenorhabditis elegans eggs.     

The role of primary motor cortex in goal-directed movements: insights from neurophysiological studies on non-human primates

Neurophysiological studies on non-human primates have provided a large body of information on the response patterns of neurons in primary motor cortex during volitional motor tasks. Rather than finding a single simple pattern of activity in primary motor cortex neurons, these studies illustrate that neural activity in this area reflects many different types of information, including spatial goals, hand motion, joint motion, force output and electromyographic activity. This richness in the response characteristics of neurons makes estimates of any single variable on motor performance from population signals imprecise and prone to errors. It initially seems puzzling that so many different types of information are represented in primary motor cortex. However, such richness in neural responses reflects its important role in converting high-level behavioral goals generated in other cortical regions into complex spatiotemporal patterns to control not only alpha-motoneuron activity but also other features of spinal processing.     

Cortical control of motor behavior at the cellular level

The studies reviewed in this paper describe the relations of single-cell activity in central motor structures to complex visuomotor tasks and document the fact that various cortical areas process visuomotor information in parallel. Moreover, the studies provide clear evidence that the map in the motor cortex is modifiable and dynamically maintained.     

Efficient Endocytic Uptake and Maturation in Drosophila Oocytes Requires Dynamitin/p50

Dynactin is a multi-subunit complex that functions as a regulator of the Dynein motor. A central component of this complex is Dynamitin/p50 (Dmn). Dmn is required for endosome motility in mammalian cell lines. However, the extent to which Dmn participates in the sorting of cargo via the endosomal system is unknown. In this study, we examined the endocytic role of Dmn using the Drosophila melanogaster oocyte as a model. Yolk proteins are internalized into the oocyte via clathrin-mediated endocytosis, trafficked through the endocytic pathway, and stored in condensed yolk granules. Oocytes that were depleted of Dmn contained fewer yolk granules than controls. In addition, these oocytes accumulated numerous endocytic intermediate structures. Particularly prominent were enlarged endosomes that were relatively devoid of Yolk proteins. Ultrastructural and genetic analyses indicate that the endocytic intermediates are produced downstream of Rab5. Similar phenotypes were observed upon depleting Dynein heavy chain (Dhc) or Lis1. Dhc is the motor subunit of the Dynein complex and Lis1 is a regulator of Dynein activity. We therefore propose that Dmn performs its function in endocytosis via the Dynein motor. Consistent with a role for Dynein in endocytosis, the motor colocalized with the endocytic machinery at the oocyte cortex in an endocytosis-dependent manner. Our results suggest a model whereby endocytic activity recruits Dynein to the oocyte cortex. The motor along with its regulators, Dynactin and Lis1, functions to ensure efficient endocytic uptake and maturation.     

Influence of long-term intracortical microstimulation on the motor cortex

Long-term (0.5–1 s) stimulation of the hand region of the motor cortex in both macaque and human through a microelectrode by a series of biphasic current pulses of small amplitude evokes different complex, coordinated movements of the hand. There are two different opinions on how these movements are produced. The first hypothesis associates the movements with the presence of specific subregions in the motor cortex, which reflect different ethologically relevant categories of movement. According to the second hypothesis, these evoked complex movements are the artifacts of electrical stimulation. This article discusses the results of a number of studies in favor of each of the hypotheses. The conclusion about the validity of the first hypothesis is based on the analysis of the results of microstimulation and their comparison with the data obtained by the latest methods without the use of electric current. Moreover, this finding suggests the possibility of testing the condition changes of the monkey motor cortex through analysis the characteristics of the movements caused by long-term microstimulation.     

Thalamic inputs to the motor cortex studied in cats by retrograde axonal horseradish peroxidase transport

Thalamic afferent inputs of the motor cortex (area 4) were studied in cats by retrograde axonal transport of horseradish peroxidase (HRP). The main concentration of HRP-labeled neurons was found in rostral zones of the relay nuclei (of the ventrolateral and ventrobasal complex). A few labeled neurons were found in the mediodorsal association nucleus, where their distribution is quite local. HRP-labeled neurons of nonspecific intralaminar nuclei, projecting into the motor cortex, are present only in single numbers and show no tendency toward grouping in any parts of these nuclei. The results are evidence that the motor cortex receives heterogeneous afferentation from various thalamic nuclei, and it is evidently this which guarantees the reliability of transmission of incoming information.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 17, No. 2, pp. 250–255, March–April, 1985.     

Illusory sensation of movement induced by repetitive transcranial magnetic stimulation

Human movement sense relies on both somatosensory feedback and on knowledge of the motor commands used to produce the movement. We have induced a movement illusion using repetitive transcranial magnetic stimulation over primary motor cortex and dorsal premotor cortex in the absence of limb movement and its associated somatosensory feedback. Afferent and efferent neural signalling was abolished in the arm with ischemic nerve block, and in the leg with spinal nerve block. Movement sensation was assessed following trains of high-frequency repetitive transcranial magnetic stimulation applied over primary motor cortex, dorsal premotor cortex, and a control area (posterior parietal cortex). Magnetic stimulation over primary motor cortex and dorsal premotor cortex produced a movement sensation that was significantly greater than stimulation over the control region. Movement sensation after dorsal premotor cortex stimulation was less affected by sensory and motor deprivation than was primary motor cortex stimulation. We propose that repetitive transcranial magnetic stimulation over dorsal premotor cortex produces a corollary discharge that is perceived as movement.     

Top-down control of motor cortex ensembles by dorsomedial prefrontal cortex

Dorsomedial prefrontal cortex is critical for the temporal control of behavior. Dorsomedial prefrontal cortex might alter neuronal activity in areas such as motor cortex to inhibit temporally inappropriate responses. We tested this hypothesis by recording from neuronal ensembles in rodent dorsomedial prefrontal cortex during a delayed-response task. One-third of dorsomedial prefrontal neurons were significantly modulated during the delay period. The activity of many of these neurons was predictive of premature responding. We then reversibly inactivated dorsomedial prefrontal cortex while recording ensemble activity in motor cortex. Inactivation of dorsomedial prefrontal cortex reduced delay-related firing, but not response-related firing, in motor cortex. Finally, we made simultaneous recordings in dorsomedial prefrontal cortex and motor cortex and found strong delay-related temporal correlations between neurons in the two cortical areas. These data suggest that functional interactions between dorsomedial prefrontal cortex and motor cortex might serve as a top-down control signal that inhibits inappropriate responding.     

Features of corticofugal effects of the motor area of the cortex on processing of heterogeneous afferentation in the parafascicular complex of the thalamus in the cat

Evoked potentials to somatic and visual stimuli were recorded in the parafascicular complex (parafascicular nuclei--centrum medianum--Pf--CM) of the thalamus of cats anaesthetized by nembutal. Cooling of the motor cortex was also used. The influence of the motor cortex on processing of the visual and somatic afferent signals at the thalamic level was found to be direct but different by its character. The motor cortex exerted unidirectional facilitatory modulatory action of a tonic type on the processing of visual afferentation and general facilitatory influence against the background of which particular excitatory and inhibitory effects were seen which it exerted on the processing of somatic signals. Episodically the motor cortex completely controlled the afferent inputs activated by somatic impulses. The motor cortical area non-equally influenced afferentation of the same modality forming the different components of the evoked potentials in Pf--CM. On the base of our present and earlier obtained data an idea has been formed of existence of a general principle of differentiated influences of polysensory areas on heterogeneous afferentation on nonspecific and association thalamic nuclei, and of realization of these influences through separation of functionally isolated subsystems in descending pathways. Each of the subsystems by closing separate thalamo-cortical circuits might transmit signals of a single modality.     

The organization of instrumental food-procuring movements in rats]

The roles of the lateral hypothalamus, basolateral nucleus of the amygdalar complex, the second field of the frontal cortex, and ventromedial thalamic nucleus in organization of the fast ballistic food-procuring movements were studied in albino rats. Sequences of uni- and bilateral destruction of the brain structures were assessed by photorecording. Movement-related neuronal activity in these structures was recorded in freely moving animals. A specific involvement of each of the above listed structures in organization of food-procuring movements was shown. The lateral hypothalamus seems to participate in initiation of the motor program and its efficient realization, the basolateral amygdala appears to produce activatory, training, and stabilizing effects. The second field of the motor cortex leads in movement acquisition (i.e., in memorizing) and decision making about triggering the program. The idea about the relay role of the thalamic motor nucleus is supplemented by understanding of its more complex integrative function.     

Complex movements evoked by microstimulation of precentral cortex

Electrical microstimulation was used to study primary motor and premotor cortex in monkeys. Each stimulation train was 500 ms in duration, approximating the time scale of normal reaching and grasping movements and the time scale of the neuronal activity that normally accompanies movement. This stimulation on a behaviorally relevant time scale evoked coordinated, complex postures that involved many joints. For example, stimulation of one site caused the mouth to open and also caused the hand to shape into a grip posture and move to the mouth. Stimulation of this site always drove the joints toward this final posture, regardless of the direction of movement required to reach the posture. Stimulation of other cortical sites evoked different postures. Postures that involved the arm were arranged across cortex to form a map of hand positions around the body. This stimulation-evoked map encompassed both primary motor and the adjacent premotor cortex. We suggest that these regions fit together into a single map of the workspace around the body.     

Altered Rolandic Gamma-Band Activation Associated with Motor Impairment and Ictal Network Desynchronization in Childhood Epilepsy

Epilepsy is associated with an abnormal expression of neural oscillations and their synchronization across brain regions. Oscillatory brain activation and synchronization also play an important role in cognition, perception and motor control. Childhood epilepsy is associated with a variety of cognitive and motor deficits, but the relationship between altered functional brain responses in various frequency ranges and functional impairment in these children remains poorly understood. We investigated functional magnetoencephalographic (MEG) responses from motor cortex in multiple functionally relevant frequency bands following median nerve stimulation in twelve children with epilepsy, including four children with motor impairments. We demonstrated that children with motor impairments exhibit an excessive gamma-band response from Rolandic cortex, and that the magnitude of this Rolandic gamma response is negatively associated with motor function. Abnormal responses from motor cortex were also associated with ictal desynchronization of oscillations within Rolandic cortex measured using intracranial EEG (iEEG). These results provide the evidence that ictal disruption of motor networks is associated with an altered functional response from motor cortex, which is in turn associated with motor impairment.     

Swallowing dynein: a missing link in RNA localization?

Localization of bicoid messenger RNA to the anterior cortex of the developing oocyte is essential for correct anterior-posterior patterning of the Drosophila embryo. It now seems that the Swallow protein functions as an adaptor, bridging bicoid mRNA to dynein, a molecular motor that would transport the complex anteriorly along microtubules.     

The importance of being agranular: a comparative account of visual and motor cortex

The agranular cortex is an important landmark-anatomically, as the architectural flag of mammalian motor cortex, and historically, as a spur to the development of theories of localization of function. But why, exactly, do agranularity and motor function go together? To address this question, it should be noted that not only does motor cortex lack granular layer four, it also has a relatively thinner layer three. Therefore, it is the two layers which principally constitute the ascending pathways through the sensory (granular) cortex that have regressed in motor cortex: simply stated, motor cortex does not engage in serial reprocessing of incoming sensory data. But why should a granular architecture not be demanded by the downstream relay of motor instructions through the motor cortex? The scant anatomical evidence available regarding laminar patterns suggests that the pathways from frontal and premotor areas to the primary motor cortex actually bear a greater resemblance to the descending, or feedback connections of sensory cortex that avoid the granular layer. The action of feedback connections is generally described as "modulatory" at a cellular level, or "selective" in terms of systems analysis. By contrast, ascending connections may be labelled "driving" or "instructive". Where the motor cortex uses driving inputs, they are most readily identified as sensory signals instructing the visual location of targets and the kinaesthetic state of the body. Visual signals may activate motor concepts, e.g. "mirror neurons", and the motor plan must select the appropriate muscles and forces to put the plan into action, if the decision to move is taken. This, perhaps, is why "driving" motor signals might be inappropriate-the optimal selection and its execution are conditional upon both kinaesthetic and motivational factors. The argument, summarized above, is constructed in honour of Korbinian Brodmann's centenary, and follows two of the fundamental principles of his school of thought: that uniformities in cortical structure, and development imply global conservation of some aspects of function, whereas regional variations in architecture can be used to chart the "organs" of the cortex, and perhaps to understand their functional differences.     

Mapping behavioral repertoire onto the cortex

A traditional view of the motor cortex in the primate brain is that it contains a map of the body arranged across the cortical surface. This traditional topographic scheme, however, does not capture the actual pattern of overlaps, fractures, re-representations, and multiple areas separated by fuzzy borders. Here, we suggest that the organization of the motor cortex, premotor cortex, supplementary motor cortex, frontal eye field, and supplementary eye field can in principle be understood as a best-fit rendering of the motor repertoire onto the two-dimensional cortical sheet in a manner that optimizes local continuity.