A reappraisal of rat motor cortex organization by intracortical microstimulation

The organization of the motor cortex was reinvestigated with intracortical microstimulation, in light-anaesthetized (ketamine) rats. A posterolateral (PL) vibrissae area was found in addition to the rostral one, and blinks of the contralateral eyelids were elicited from a part of this PL area. Several cortical representations such as neck or tail were largely overlapping with neighbouring areas. Vegetative effects (mainly myosis and swallowing) were obtained from a medial cortical strip. Within the PL vibrissae area, a topical arrangement related to the vibrissal rows was observed, whereas in the leg areas, no individual representation of muscles could be evidenced. These results are compared with the maps previously published, and discussed in terms of specificity, musculotopy and overlapping of motor areas.     

The somatotopic organization of the supplementary motor area: intracortical microstimulation mapping

The somatotopic organization of the supplementary motor area (SMA) is commonly held to consist of a rostrocaudal sequence of orofacial, forelimb, and hindlimb representations. Recently, however, this somatotopy has been questioned. Studies of regional cerebral blood flow in humans and the movements evoked by intracortical electrical stimulation in cynomolgus monkeys have been unable to reveal evidence of distinct orofacial, forelimb, and hindlimb representations rostrocaudally situated along the medial cortex of the hemisphere. Partly on the basis of those results, it has been suggested that the SMA functions as a nontopographically organized "higher-order" motor center. The present study reexamines SMA organization by observing stimulation-evoked movements. The medial frontal cortex of 2 rhesus monkeys was mapped using a modified intracortical microstimulation technique. We observed a forelimb representation mainly on the medial surface of the hemisphere in both animals. Rostral or rostrolateral to the forelimb representation, depending on the individual, we evoked orofacial movements (including eye movements). Hindlimb movements were evoked from tissue overlapping, but largely caudal to, the forelimb representation. Thus, we conclude that there is a clear rostrocaudal progression of orofacial, forelimb, and hindlimb movement representations in the SMA.     

Excitation of visual cortex neurons by local intracortical microstimulation

The threshold current required for the excitation of visual cortex neurons in the vicinity (approximately 1 mm) of an intracortical stimulating electrode was measured as a function of the stimulus pulse duration in the anesthetized cat. For cortical neurons with latencies of activation from 0.4 to 3.4 ms and for stimulus pulse durations from 0.02 to 0.7 ms, the threshold current for all neurons tested decreased in an exponential fashion as the pulse width was increased. Rheobase current values (ampere-threshold) were 1.2 to 516 muA (mean 160 +/- 24 muA, N = 24) and chronaxie values were 0.07 to 0.79 ms (mean 0.217 +/- 0.036 ms, N = 24). When the quantity of charge required for neuronal excitation was calculated, a quasilinear relationship was found between threshold charge and stimulus pulse width. The minimum threshold charge (coulomb-threshold) occurred for the briefest pulse widths tested and were 2 to 86 nC (mean 36.4 +/- 4.4 nC, N = 24). When the pulse energy index was calculated (threshold current squared multiplied by the pulse width), the minimum pulse energy capable of generating an evoked response (a single action potential) occurred when the pulse width was approximately 80% greater than the chronaxie. These studies demonstrate that the predictions derived from A. V. Hill's classical theory of nerve excitation are to a first approximation obeyed by visual cortex neurons. For the three parameters analyzed as a function of stimulus pulse width, the pulse current is minimized at long pulse durations, the pulse charge is minimized at short pulse durations, and the pulse energy is minimized at pulse widths of intermediate value.     

The motor cortex of the rat: Cytoarchitecture and microstimulation mapping

The first motor (MI) cortex of the rat was identified as the region from which movements could be evoked by the lowest intensity of electrical stimulation. The location of this region was correlated with Cytoarchitecture in the frontal and parietal cortex. Two frontal areas can be discerned in Nissl-stained sections: (1) the medial agranular field, marked by a pale-staining layer III and a compact layer II, and (2) the lateral agranular field, which has more homogeneous superficial layers and a broad layer V containing large, densely staining cells. Both of these regions project to the spinal cord and can therefore be included in the somatic sensorimotor cortex. MI in the rat coincides with the lateral agranular field but also overlaps with part of the adjacent granular cortex of the first somatic sensory (SI) representation. We conclude that the rat MI cortex can be identified by microstimulation techniques and by cytoarchitecture in the rat.     

The organization of the rat motor cortex: a microstimulation mapping study

In conclusion, the rat primary motor cortex appears to be organized into irregularly shaped patches of cortex devoted to particular movements. The location of major subdivisions such as the forelimb or hindlimb areas is somatotopic and is consistent from animal to animal, but the internal organization of the pattern of movements represented within major subdivisions varies significantly between animals. The motor cortex includes both agranular primary motor cortex (AgL) and, in addition, a significant amount of the bordering granular somatic sensory cortex (Gr(SI)), as well as the rostral portion of the taste sensory insular or claustrocortex (Cl). The rat frontal cortex also contains a second, rostral motor representation of the forelimb, trunk and hindlimb, which is somatotopically organized and may be the rat's supplementary motor area. Both of these motor representations give rise to direct corticospinal projections, some of which may make monosynaptic connections with cervical enlargement motoneurons. Medial to the primary motor cortex, in cytoarchitectonic field AgM, is what appears to be part of the rat's frontal eye fields, a region which also includes the vibrissae motor representation. The somatic motor cortical output organization pattern in the rat is remarkably similar to that seen in the primate, whose primary, supplementary and frontal eye field cortical motor regions have been extensively studied.     

The organization of the rat motor cortex: A microstimulation mapping study

In conclusion, the rat primary motor cortex appears to be organized into irregularly shaped patches of cortex devoted to particular movements. The location of major subdivisions such as the forelimb or hindlimb areas is somatotopic and is consistent from animal to animal, but the internal organization of the pattern of movements represented within major subdivisions varies significantly between animals. The motor cortex includes both agranular primary motor cortex (AgL) and, in addition, a significant amount of the bordering granular somatic sensory cortex (Gr(SI)), as well as the rostral portion of the taste sensory insular or claustrocortex (Cl). The rat frontal cortex also contains a second, rostral motor representation of the forelimb, trunk and hindlimb, which is somatotopically organized and may be the rat's supplementary motor area. Both of these motor representations give rise to direct corticospinal projections^21,42,51,57, some of which may make monosynaptic connections with cervical enlargement motorneurons¹⁶. Medial to the primary motor cortex, in cytoarchitectonic field AgM, is what appears to be part of the rat's frontal eye fields, a region which also includes the vibrissae motor representation. The somatic motor cortical output organization pattern in the rat is remarkably similar to that seen in the primate, whose primary, supplementary and frontal eye field cortical motor regions have been extensively studied.     

Perceived timing of cutaneous vibration and intracortical microstimulation of human somatosensory cortex

BackgroundIntracortical microstimulation (ICMS) of somatosensory cortex can partially restore the sense of touch. Though ICMS bypasses much of the neuraxis, prior studies have found that conscious detection of touch elicited by ICMS lags behind the detection of cutaneous vibration. These findings may have been influenced by mismatched stimulus intensities, which can impact temporal perception.ObjectiveEvaluate the relative latency at which intensity-matched vibration and ICMS are perceived by a human participant.MethodsOne person implanted with microelectrode arrays in somatosensory cortex performed reaction time and temporal order judgment (TOJ) tasks. To measure reaction time, the participant reported when he perceived vibration or ICMS. In the TOJ task, vibration and ICMS were sequentially presented and the participant reported which stimulus occurred first. To verify that the participant could distinguish between stimuli, he also performed a modality discrimination task, in which he indicated if he felt vibration, ICMS, or both.ResultsWhen vibration was matched in perceived intensity to high-amplitude ICMS, vibration was perceived, on average, 48 ms faster than ICMS. However, in the TOJ task, both sensations arose at comparable latencies, with points of subjective simultaneity not significantly different from zero. The participant could discriminate between tactile modalities above chance level but was more inclined to report feeling vibration than ICMS.ConclusionsThe latencies of ICMS-evoked percepts are slower than their mechanical counterparts. However, differences in latencies are small, particularly when stimuli are matched for intensity, implying that ICMS-based somatosensory feedback is rapid enough to be effective in neuroprosthetic applications.     

Intact intracortical microstimulation (ICMS) representations of rostral and caudal forelimb areas in rats with quinolinic acid lesions of the medial or lateral caudate-putamen in an animal model of Huntington's disease

Neurotoxic, cell-specific lesions of the rat caudate-putamen (CPu) have been proposed as a model of human Huntington's disease and as such impair performance on many motor tasks, including skilled forelimbs tasks such as reaching for food. Because the CPu and motor cortex share reciprocal connections, it has been proposed that the motor deficits are due in part to a secondary disruption of motor cortex. The purpose of the present study was to examine the functionality of the motor cortex using intracortical microstimulation (ICMS) following neurotoxic lesions of the CPu. ICMS maps have been shown to be sensitive indicators of motor skill, cortical injury, learning, and experience. Long-evans hooded rats received a sham, a medial, or a lateral CPu lesion using the neurotoxin, quinolinic acid (2,3-pyridinedicarboxylic acid). Two weeks later the motor cortex was stimulated under light ketamine anesthesia. Neither lateral nor medial lesions of the CPu altered the stimulation threshold for eliciting forelimb movements, the type of movements elicited, or the size of the rostral forelimb (RFA) and caudal forelimb areas (CFA) from which movements were elicited. The preservation of ICMS forelimb movement representations (the forelimb map) in rats with cell-specific CPu lesions suggests motor impairments following lesions of the lateral striatum are not due to the disruption of the motor map. Therefore, the impairments that follow striatal cell loss are due either to alterations in circuitry that is independent of motor cortex or to alterations in circuitry afferent to the motor cortex projections.     

The interfascicular trigeminal nucleus: A precerebellar nucleus in the mouse defined by retrograde neuronal tracing and genetic fate mapping

We have found a previously unreported precerebellar nucleus located among the emerging fibers of the motor root of the trigeminal nerve in the mouse, which we have called the interfascicular trigeminal nucleus (IF5). This nucleus had previously been named the tensor tympani part of the motor trigeminal nucleus (5TT) in rodent brain atlases, because it was thought to be a subset of small motor neurons of the motor trigeminal nucleus innervating the tensor tympani muscle. However, following injection of retrograde tracer in the cerebellum, the labeled neurons in IF5 were found to be choline acetyltransferase (ChAT) negative, indicating that they are not motor neurons. The cells of IF5 are strongly labeled in mice from Wnt1Cre and Atoh1 CreER lineage fate mapping, in common with the major precerebellar nuclei that arise from the rhombic lip and that issue mossy fibers. Analysis of sections from mouse Hoxa3, Hoxb1, and Egr2 Cre labeled lineages shows that the neurons of IF5 arise from rhombomeres caudal to rhombomere 4, most likely from rhombomeres 6–8. We conclude that IF5 is a significant precerebellar nucleus in the mouse that shares developmental gene expression characteristics with mossy fiber precerebellar nuclei that arise from the caudal rhombic lip. J. Comp. Neurol. 521:697–708, 2013. © 2012 Wiley Periodicals, Inc.     

Organization of rat vibrissa motor cortex and adjacent areas according to cytoarchitectonics, microstimulation, and intracellular stimulation of identified cells

The relationship between motor maps and cytoarchitectonic subdivisions in rat frontal cortex is not well understood. We use cytoarchitectonic analysis of microstimulation sites and intracellular stimulation of identified cells to develop a cell-based partitioning scheme of rat vibrissa motor cortex and adjacent areas. The results suggest that rat primary motor cortex (M1) is composed of three cytoarchitectonic areas, the agranular medial field (AGm), the agranular lateral field (AG1), and the cingulate area 1 (Cg1), each of which represents movements of different body parts. Vibrissa motor cortex corresponds entirely and for the most part exclusively to AGm. In area AG1 body/head movements can be evoked. In posterior area Cg1 periocular/eye movements and in anterior area Cg1 nose movements can be evoked. In all of these areas stimulation thresholds are very low, and together they form a complete representation of the rat's body surface. A strong myelinization and an expanded layer 5 characterize area AGm. We suggest that both the strong myelinization and the expanded layer 5 of area AGm may represent cytoarchitectonic specializations related to control of high-speed whisking behavior.     

Thalamic projections to motor, prefrontal, and somatosensory cortex in the sheep studied by means of the horseradish peroxidase retrograde transport method

In this study the motor, prefrontal, and somatosensory areas of the sheep cerebral cortex were defined on the basis of their thalamic afferents traced with the horseradish peroxidase method. The motor area (areas 4 and 6) occupies the cruciate gyrus. It receives a substantial projection from the thalamic nuclei ventralis anterior, ventralis lateralis, medialis dorsalis, and centralis lateralis and a smaller one from the nuclei ventralis medialis, centralis medialis, paracentralis, lateralis dorsalis, lateralis posterior, centromedianus, parafascicularis, suprageniculatus, ventralis posterolateralis, and the midline nuclei. Area 4 receives afferents mainly from the nuclei ventralis anterior, ventralis lateralis, medialis dorsalis, and lateralis posterior, whereas area 6 receives afferents mainly from the nuclei ventralis anterior, medialis dorsalis, and lateralis posterior and fewer afferents from the nucleus ventralis medialis. The prefrontal area occupies the gyrus proreus and receives numerous afferents from the nucleus medialis dorsalis and fewer from the nuclei lateralis posterior and ventralis medialis. The area extending between the lateral fissure, the coronal sulcus, the presylvian sulcus, and the rostral branch of the lateral fissure is connected mainly with sensory thalamic nuclei. Thalamic afferents were found to emanate from the nuclei ventralis posteromedialis (its parvicellular part included), ventralis posterolateralis, ventralis medialis, paracentralis, lateralis posterior, medialis dorsalis, centromedianus, suprageniculatus, paraventricularis, the substantia nigra, and the ventral part of the lateral geniculate nucleus. The first somatosensory area (Johnson et al., '74, J. Comp. Neurol. 158:81-108) was found to extend between the coronal, the diagonal, and the anterior suprasylvian sulci and to receive afferents almost exclusively from the nucleus ventralis posteromedialis.     

Organization of the projections from the pericruciate cortex to the pontomedullary reticular formation of the cat: A quantitative retrograde tracing study

Dextran-amines were used as retrograde tracers to investigate the organization of cortical projections to different cytoarchitectonic regions of the pontomedullary reticular formation of the cat. Injections into the nucleus reticularis pontis oralis resulted in labelling of neurones in the proreus cortex and area 6a|iB of the premotor cortex, with little labelling in the motor cortex (area 4). This labelling was predominantly ipsilateral to the injection site. In contrast, injections into the nucleus reticularis pontis caudalis (NRPc), nucleus reticularis gigantocellularis (NRGc), and nucleus reticularis magnocellularis (NRMc) resulted in bilateral labelling—primarily in areas 6aβ, 6aγ, and in the rostromedial region of area 4—with little labelling in the proreus cortex. In general, the cortical projections to the caudal NRGc and the NRMc were larger than those to the NRPc. More than 25% of the total projections to each of the latter three reticular regions arose from the medial part of area 4. Labelling in the hindlimb regions of area 4 was largest following the NRMc injections and smallest after injections in the NRPc. The projections to the NRPc originated from more medial parts of areas 4 and 6 than did the projections to the caudal region of the NRGc. These results suggest that areas 4 and 6 may be able to differentially activate different regions of the pontomedullary reticular formation depending on the movement that is made and perhaps also on the context of that movement. J. Comp. Neurol. 388:228–249, 1997. © 1997 Wiley-Liss, Inc.     

Task-free electrocorticography frequency mapping of the motor cortex

ObjectiveElectrocortical stimulation mapping (ESM) is the current gold standard for functional mapping of the eloquent cortex prior to epilepsy surgery. The procedure is, however, time-consuming and quite demanding for patients. Electrocorticography frequency mapping (ECoG mapping) has been suggested as an adjunct method. Here, we investigated whether it is possible to perform mapping of motor regions using ECoG data of spontaneous movements.MethodsUsing the video registration of seven epilepsy patients who underwent electrocorticography and ESM, we selected periods of spontaneous hand and arm movements and periods of rest. Frequency analysis was performed, and electrodes showing a significant change in power (4–7, 8–14, 15–25, 26–45 or 65–95 Hz) were compared with those being identified as relevant for hand and/or arm movement by ESM.ResultsAll frequency bands showed a high specificity (>0.80), and the 65–95 Hz frequency band additionally had a high sensitivity (0.82) for identifying ESM positive electrodes.ConclusionsOur data show a good match between ECoG mapping of spontaneous movements and ESM data.SignificanceThe accurate match suggests that ECoG mapping of the motor cortex using spontaneous movements may be a valuable complement to ESM, especially when other options requiring patient cooperation fail.     

Stereotactic functional mapping of the cat motor cortex

Epidural motor cortex stimulation is an increasingly used method to control refractory neuropathic pain although its mechanisms of action remain poorly understood. Animal models are currently developed that allow reproducing the conditions of this neurosurgical approach and clarifying its mechanisms. In this study we validate a new stereotactic functional map of the cat motor cortex carried out in epidural conditions, thus allowing future experimentations that closely mimic the technique used in humans.     

Absence of responses to microstimulation at the hand-face border in baboon primary motor cortex

Intracortical microstimulation (ICMS) was used to map the primary motor cortex of four adult female baboons, anesthetized with a mixture of halothane and nitrous oxide and supplemented with sodium pentobarbital. The sequence of observed muscle contractions in response to ICMS provided evidence of an orderly mototopic representation of the tongue, face, hand, forearm and upper body. A zone of cortex unresponsive to microstimulation was consistently observed at the border between the face and hand representation of the mototopic map. This zone was observed in all four animals and was consistent over time. Repeated confirmations of the unresponsive nature of these regions were obtained both early and late in the same experiment. No motor-unit responses or muscle contractions were detected by electromyographic (EMG) recording during stimulation of the unresponsive zones. The absence of both visually observed and EMG-recorded contractions and the fact that muscle contractions could be elicited from adjacent regions of cortex with ICMS as low as 1-5 microA provide compelling evidence that the finding reflects a true physiological condition rather than an experimental artifact.     

Organization of projections from the medial agranular cortex to the superior colliculus in the rat: a study using anterograde and retrograde tracing methods

The organization of corticotectal projections from the medial agranular cortex (AGm), which has been considered to contain rat's frontal eye field, was examined using anterograde and retrograde tracing techniques. When biotinylated dextranamine (BDA) injections were made into the rostral part of the AGm, small numbers of BDA-labeled axons were found in the rostral two-thirds of the superior colliculus (SC) while some labeled axons were seen in the caudal one-third of the SC. These labeled axons were distributed mainly in the lateral part of the stratum griseum intermediale. On the other hand, after BDA injections into the caudal part of the AGm, moderate to dense plexuses of labeled axons were found in the rostral two-thirds of the SC while some labeled axons were seen in the caudal one-third of the SC. These labeled axons were distributed in the ventromedial and dorsolateral marginal zones of the stratum griseum intermediale as well as in the stratum griseum profundum. The corticotectal projections were largely uncrossed. After combined injections of BDA into the caudal part of the AGm on one side and cholera toxin B subunit (CTb) into the paramedian pontine reticular formation on the opposite side or into the interstitial nucleus of Cajal on the same side, the overlapping distributions of BDA-labeled axons and CTb-labeled neurons were found in the ventromedial marginal zone of the stratum griseum intermediale ipsilateral to the site of BDA injection. These results suggest that the caudal part of the AGm plays a more significant role in the oculomotor function than does the rostral part of the AGm.     

Functional organization of human supplementary motor cortex studied by electrical stimulation

The presence of somatotopic organization in the human supplementary motor area (SMA) remains a controversial issue. In this study, subdural electrode grids were placed on the medial surface of the cerebral hemispheres in 13 patients with intractable epilepsy undergoing evaluation for surgical treatment. Electrical stimulation mapping with currents below the threshold of afterdischarges showed somatotopic organization of supplementary motor cortex with the lower extremities represented posteriorly, head and face most anteriorly, and the upper extremities between these two regions. Electrical stimulation often elicited synergistic and complex movements involving more than one joint. In transitional areas between neighboring somatotopic representations, stimulation evoked combined movements involving the body parts represented in these adjacent regions. Anterior to the supplementary motor representation of the face, vocalization and speech arrest or slowing of speech were evoked. Various sensations were elicited by electrical stimulation of SMA. In some cases a preliminary sensation of "urge" to perform a movement or anticipation that a movement was about to occur were evoked. Most responses were contralateral to the stimulated hemisphere. Ipsilateral and bilateral responses were elicited almost exclusively from the right (nondominant) hemisphere. These data suggest the presence of combined somatotopic organization and left-right specialization in human supplementary motor cortex.