Cortical control of motor sequences

The neural substrate of sequence learning is well known. However, we lack a clear understanding of the detailed functional properties of many of the areas involved. The reason for this discrepancy lies, in part, in the fact that two types of processes, implicit and explicit, subserve motor sequence learning, and these often interact with each other. The most significant recent advances have been the elucidation of the very complex relationships between medial motor areas and the temporal and ordinal control of sequences, and the demonstration that motor cortex is an important site for sequence storage and production. The challenge for the future will be to develop a coherent and internally consistent theory of sequence control.     

Interaction between Hippocampal and Striatal Systems Predicts Subsequent Consolidation of Motor Sequence Memory

The development of fast and reproducible motor behavior is a crucial human capacity. The aim of the present study was to address the relationship between the implementation of consistent behavior during initial training on a sequential motor task (the Finger Tapping Task) and subsequent sleep-dependent motor sequence memory consolidation, using functional magnetic resonance imaging (fMRI) and total sleep deprivation protocol. Our behavioral results indicated significant offline gains in performance speed after sleep whereas performance was only stabilized, but not enhanced, after sleep deprivation. At the cerebral level, we previously showed that responses in the caudate nucleus increase, in parallel to a decrease in its functional connectivity with frontal areas, as performance became more consistent. Here, the strength of the competitive interaction, assessed through functional connectivity analyses, between the caudate nucleus and hippocampo-frontal areas during initial training, predicted delayed gains in performance at retest in sleepers but not in sleep-deprived subjects. Moreover, during retest, responses increased in the hippocampus and medial prefrontal cortex in sleepers whereas in sleep-deprived subjects, responses increased in the putamen and cingulate cortex. Our results suggest that the strength of the competitive interplay between the striatum and the hippocampus, participating in the implementation of consistent motor behavior during initial training, conditions subsequent motor sequence memory consolidation. The latter process appears to be supported by a reorganisation of cerebral activity in hippocampo-neocortical networks after sleep.     

Medial wall motor areas and skeletomotor control

The results of recent studies in primates provide convincing evidence that the cortex on the medial wall of the hemisphere contains multiple areas concerned with the generation and control of body movement. Highlights of these findings include the demonstration that each of these motor areas has substantial direct projections to the spinal cord, somatotopically organized projections to the primary motor cortex, a 'motor' map, revealed by intracortical stimulation, and neuronal activity that precedes trained hand movements.     

Distinctions between dorsal and ventral premotor areas: anatomical connectivity and functional properties

The dorsal and ventral premotor areas, together with the primary motor cortex, are believed to have major roles in preparing and executing limb movements. Recent studies have expanded our knowledge of the dorsal and ventral premotor areas, which occupy the lateral part of area 6 in the frontal cortex. It is becoming clear that these two premotor areas, through involvement in distinct cortical networks, take part in unique aspects of motor planning and decision making. New lines of evidence also implicate the lateral premotor areas in planning motor behavior and selecting actions.     

Human medial frontal cortex mediates unconscious inhibition of voluntary action

Within the medial frontal cortex, the supplementary eye field (SEF), supplementary motor area (SMA), and pre-SMA have been implicated in the control of voluntary action, especially during motor sequences or tasks involving rapid choices between competing response plans. However, the precise roles of these areas remain controversial. Here, we study two extremely rare patients with microlesions of the SEF and SMA to demonstrate that these areas are critically involved in unconscious and involuntary motor control. We employed masked-prime stimuli that evoked automatic inhibition in healthy people and control patients with lateral premotor or pre-SMA damage. In contrast, our SEF/SMA patients showed a complete reversal of the normal inhibitory effect--ocular or manual--corresponding to the functional subregion lesioned. These findings imply that the SEF and SMA mediate automatic effector-specific suppression of motor plans. This automatic mechanism may contribute to the participation of these areas in the voluntary control of action.     

Theta Rhythms Coordinate Hippocampal–Prefrontal Interactions in a Spatial Memory Task

Decision-making requires the coordinated activity of diverse brain structures. For example, in maze-based tasks, the prefrontal cortex must integrate spatial information encoded in the hippocampus with mnemonic information concerning route and task rules in order to direct behavior appropriately. Using simultaneous tetrode recordings from CA1 of the rat hippocampus and medial prefrontal cortex, we show that correlated firing in the two structures is selectively enhanced during behavior that recruits spatial working memory, allowing the integration of hippocampal spatial information into a broader, decision-making network. The increased correlations are paralleled by enhanced coupling of the two structures in the 4- to 12-Hz theta-frequency range. Thus the coordination of theta rhythms may constitute a general mechanism through which the relative timing of disparate neural activities can be controlled, allowing specialized brain structures to both encode information independently and to interact selectively according to current behavioral demands.     

Theta rhythms coordinate hippocampal-prefrontal interactions in a spatial memory task

Decision-making requires the coordinated activity of diverse brain structures. For example, in maze-based tasks, the prefrontal cortex must integrate spatial information encoded in the hippocampus with mnemonic information concerning route and task rules in order to direct behavior appropriately. Using simultaneous tetrode recordings from CA1 of the rat hippocampus and medial prefrontal cortex, we show that correlated firing in the two structures is selectively enhanced during behavior that recruits spatial working memory, allowing the integration of hippocampal spatial information into a broader, decision-making network. The increased correlations are paralleled by enhanced coupling of the two structures in the 4- to 12-Hz theta-frequency range. Thus the coordination of theta rhythms may constitute a general mechanism through which the relative timing of disparate neural activities can be controlled, allowing specialized brain structures to both encode information independently and to interact selectively according to current behavioral demands.     

Differential Grey Matter Changes in Sensorimotor Cortex Related to Exceptional Fine Motor Skills

Functional changes in sensorimotor representation occur in response to use and lesion throughout life. Emerging evidence suggests that functional changes are paralleled by respective macroscopic structural changes. In the present study we used voxel-based morphometry to investigate sensorimotor cortex in subjects with congenitally malformed upper extremities. We expected increased or decreased grey matter to parallel the enlarged or reduced functional representations we reported previously. More specifically, we expected decreased grey matter values in lateral sensorimotor cortex related to compromised hand function and increased grey matter values in medial sensorimotor cortex due to compensatory foot use. We found a medial cluster of grey matter increase in subjects with frequent, hand-like compensatory foot use. This increase was predominantly seen for lateral premotor, supplementary motor, and motor areas and only marginally involved somatosensory cortex. Contrary to our expectation, subjects with a reduced number of fingers, who had shown shrinkage of the functional hand representation previously, did not show decreased grey matter values within lateral sensorimotor cortex. Our data suggest that functional plastic changes in sensorimotor cortex can be associated with increases in grey matter but may also occur in otherwise macroscopically normal appearing grey matter volumes. Furthermore, macroscopic structural changes in motor and premotor areas may be observed without respective changes in somatosensory cortex.     

Cholinergic induction of seizures in the rat prefrontal cortex

Intracerebral microinjection of the cholinergic agonist, carbachol, into the medial prefrontal cortex of the rat, induced a profound behavioral syndrome consisting of repetitive, stereotyped forepaw treading in an upright posture. Electroencephalographic analysis revealed multiple bursts of sharp waves, 200-300 microV, accompanying the carbachol-elicited motor behavior. Pretreatment with intraperitoneal doses of three anticonvulsant drugs, clonazepam, diazepam, and pentobarbital, blocked the manifestation of the motor behavior. These observations suggest that activation of cholinergically innervated regions of the rat medial prefrontal cortex induces an atypical form of seizures.     

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.     

Parietal and hippocampal contribution to topokinetic and topographic memory.

This paper reviews the involvement of the parietal cortex and the hippocampus in three kinds of spatial memory tasks which all require a memory of a previously experienced movement in space. The first task compared, by means of positron emission tomography (PET) scan techniques, the production, in darkness, of self-paced saccades (SAC) with the reproduction, in darkness, of a previously learned sequence of saccades to visual targets (SEQ). The results show that a bilateral increase of activity was seen in the depth of the intraparietal sulcus and the medial superior parietal cortex (superior parietal gyrus and precuneus) together with the frontal sulcus but only in the SEQ task, which involved memory of the previously seen targets and possibly also motor memory. The second task is the vestibular memory contingent task, which requires that the subject makes, in darkness, a saccade to the remembered position of a visual target after a passively imposed whole-body rotation. Deficits in this task, which involves vestibular memory, were found predominantly in patients with focal vascular lesions in the parieto-insular (vestibular) cortex, the supplementary motor area-supplementary eye field area, and the prefrontal cortex. The third task requires mental navigation from the memory of a previously learned route in a real environment (the city of Orsay in France). A PET scan study has revealed that when subjects were asked to remember visual landmarks there was a bilateral activation of the middle hippocampal regions, left inferior temporal gyrus, left hippocampal regions, precentral gyrus and posterior cingulate gyrus. If the subjects were asked to remember the route, and their movements along this route, bilateral activation of the dorsolateral cortex, posterior hippocampal areas, posterior cingulate gyrus, supplementary motor areas, right middle hippocampal areas, left precuneus, middle occipital gyrus, fusiform gyrus and lateral premotor area was found. Subtraction between the two conditions reduced the activated areas to the left hippocampus, precuneus and insula. These data suggest that the hippocampus and parietal cortex are both involved in the dynamic aspects of spatial memory, for which the name ''topokinetic memory'' is proposed. These dynamic aspects could both overlap and be different from those involved in the cartographic and static aspects of ''topographic'' memory.     

Observation-based learning for brain-machine interfaces

Canonically, 'mirror neurons' are cells in area F5 of the ventral premotor cortex that are active during both observation and execution of goal-directed movements. Recently, cells with similar properties have been observed in a number of other areas in the motor system, including the primary motor cortex. Mirror neurons are a part of a system whose function is thought to involve the prediction and interpretation of the sensory consequences of our own actions as well as the actions of others. Mirror-like responses are relevant to the development of brain-machine interfaces (BMIs) because they provide a robust way to map neural activity to behavior, and because they represent high-level information about goals and intentions that may have utility in future BMI applications.     

Differences of the medial lemniscus and spinothalamic tract according to the cortical termination areas: A diffusion tensor tractography study

Abstract

We investigated differences of the medial lemniscus and its thalamocortical pathway (ML), and the spinothalamic tract and its thalamocortical pathway (STT) according to the cortical termination areas. We found that the ML and STT terminated in the motor cortex and the somatosensory cortex. The ML may be closely related to the motor cortex for motor planning and execution, while the STT may be closely related to the cerebral cortex for somatosensory function and motor execution.     

Functional Analogs of the Motor and Premotor Areas of Neocortex in Developing White Rats

To study functional characteristics of the brain cortex motor areas in developing white rats and to determine their interlocation in rat pups at the different age and at critical terms of formation of motor representations in the process of postnatal development, mapping of neocortex frontal areas at the age up to 1.5 months was performed using intracortical microstimulation method. It has been shown that for first 10 days of postnatal development the microstimulation is not effective to evoke corticomotor reactions. An earlier appearance of functional activity of the non-primary motor cortex has been established, as compared with that of the primary motor cortex. It is suggested that there occurs a parallel, but heterochronous formation of primary and non-primary motor areas at the frontal neocortex territory.     

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.     

Levodopa Effects on Hand and Speech Movements in Patients with Parkinson’s Disease: A fMRI Study

Levodopa (L-dopa) effects on the cardinal and axial symptoms of Parkinson’s disease (PD) differ greatly, leading to therapeutic challenges for managing the disabilities in this patient’s population. In this context, we studied the cerebral networks associated with the production of a unilateral hand movement, speech production, and a task combining both tasks in 12 individuals with PD, both off and on levodopa (L-dopa). Unilateral hand movements in the off medication state elicited brain activations in motor regions (primary motor cortex, supplementary motor area, premotor cortex, cerebellum), as well as additional areas (anterior cingulate, putamen, associative parietal areas); following L-dopa administration, the brain activation profile was globally reduced, highlighting activations in the parietal and posterior cingulate cortices. For the speech production task, brain activation patterns were similar with and without medication, including the orofacial primary motor cortex (M1), the primary somatosensory cortex and the cerebellar hemispheres bilaterally, as well as the left- premotor, anterior cingulate and supramarginal cortices. For the combined task off L-dopa, the cerebral activation profile was restricted to the right cerebellum (hand movement), reflecting the difficulty in performing two movements simultaneously in PD. Under L-dopa, the brain activation profile of the combined task involved a larger pattern, including additional fronto-parietal activations, without reaching the sum of the areas activated during the simple hand and speech tasks separately. Our results question both the role of the basal ganglia system in speech production and the modulation of task-dependent cerebral networks by dopaminergic treatment.     

Lesions of the Precentral Gyrus in Nonhuman Primates: A Pre-Medline Bibliography

Many contemporary investigators are unaware of the important papers involving lesions of the primate primary motor cortex published prior to those revealed by a computer search of the literature (i.e., papers published prior to about 1966). In order to increase awareness of these reports, we present here an annotated bibliography of these papers beginning with that of Ferrier and Yeo (1884). We provide evidence that these papers can provide valuable information on the function of the primate motor cortex and on recovery of behavior after brain lesions, and are also useful for sharpening the questions posed by more refined modern studies.     

A neural mechanism for the immediate recall of sequences

Summary Lashley's suggestion that serial behavior has a dual organization, central facilitation of the entire sequence plus scanning of the individual movements, is taken as the starting point for the construction of a model to illustrate in more detail how the nervous system might work during such behavior.Two stages in the learning of a sequence are distinguished: 1. immediate reproduction of a presented sample, and 2. reproduction of habitual responses by association, without the necessity of recent access to the original sample. The model is primarily concerned with performances of the first type.Neurons of a scanning chain, which always fire one another in the same order, acquire temporary connections with the movements to be recalled. The connections fade rapidly with disuse so that the same scanning chain can be used again with different combinations of movements.The same mechanism will also permit the recall of sequences of words, or other habitual movement complexes, as if they were individual movements. It is assumed that such habitual motor patterns as words are under the control of higher-order cell assemblies which regulate the sequences of movements within the response, and thus substitute for the general scanning mechanism. This leaves the scanner free to form temporary associations with the higher-order cell assemblies for the words.It is suggested that the scanning mechanism is actuated only by unpredictable inputs so that the elements within a habitual series do not acquire unnecessary connections with the scanning neurons. The arousal system is known to have this characteristic of not being disturbed by the expected, and it seems likely that the two systems are intimately related.     

Areal distributions of cortical neurons projecting to different levels of the caudal brain stem and spinal cord in rats

Distributions of corticospinal and corticobulbar neurons were revealed by tetramethylbenzidine (TMB) processing after injections of wheatgerm agglutinin conjugated to horseradish peroxidase (WGA:HRP) into the cervical or lumbar enlargements of the spinal cord, or medullary or pontine levels of the brain stem. Sections reacted for cytochrome oxidase (CO) allowed patterns of labeled neurons to be related to the details of the body surface map in the first somatosensory cortical area (SI). The results indicate that a number of cortical areas project to these subcortical levels: (1) Projection neurons in granular SI formed a clear somatotopic pattern. The hindpaw region projected to the lumbar enlargement, the forepaw region to the cervical enlargement, the whisker pad field to the lower medulla, and the more rostral face region to more rostral brain stem levels. (2) Each zone of labeled neurons in SI extended into adjacent dysgranular somatosensory cortex, forming a second somatotopic pattern of projection neurons. (3) A somatotopic pattern of projection neurons in primary motor cortex (MI) paralleled SI in mediolateral sequence corresponding to the hindlimb, forelimb, and face. (4) A weak somatotopic pattern of projection neurons was suggested in medial agranular cortex (Agm), indicating a premotor field with a rostromedial-to-caudolateral representation of hindlimb, forelimb, and face. (5) A somatotopic pattern of projection neurons representing the foot to face in a mediolateral sequence was observed in medial parietal cortex (PM) located between SI and area 17. (6) In the second somatosensory cortical area (SII), neurons projecting to the brain stem were immediately adjacent caudolaterally to the barrel field of SI, whereas neurons projecting to the upper spinal cord were more lateral. No projection neurons in this region were labeled by the injections in the lower spinal cord. (7) Other foci of projection neurons for the face and forelimb were located rostral to SII, providing evidence for a parietal ventral area (PV) in perirhinal cortex (PR) lateral to SI, and in cortex between SII and PM. None of these regions, which may be higher-order somatosensory areas, contained labeled neurons after injections in the lower spinal cord. Thus, more cortical fields directly influence brain stem and spinal cord levels related to sensory and motor functions of the face and forepaw than the hindlimb. The termination patterns of corticospinal and corticobulbar projections were studied in other rats with injections of WGA:HRP in SI.(ABSTRACT TRUNCATED AT 400 WORDS)     

Auditory processing in primate cerebral cortex.

Auditory information is relayed from the ventral nucleus of the medial geniculate complex to a core of three primary or primary-like areas of auditory cortex that are cochleotopically organized and highly responsive to pure tones. Auditory information is then distributed from the core areas to a surrounding belt of about seven areas that are less precisely cochleotopic and generally more responsive to complex stimuli than tones. Recent studies indicate that the belt areas relay to the rostral and caudal divisions of a parabelt region at a third level of processing in the cortex lateral to the belt. The parabelt and belt regions have additional inputs from dorsal and magnocellular divisions of the medial geniculate complex and other parts of the thalamus. The belt and parabelt regions appear to be concerned with integrative and associative functions involved in pattern perception and object recognition. The parabelt fields connect with regions of temporal, parietal, and frontal cortex that mediate additional auditory functions, including space perception and auditory memory.