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Modulation of behavior and cortical motor activity in healthy subjects by a chronic administration of a serotonin enhancer.

UNLABELLED: SSRIs are postulated to modulate motor behavior. A single dose of selective serotoninergic reuptake inhibitors (SSRIs) like fluoxetine, paroxetine, or fluvoxamine, has been shown to improve motor performance and efficiency of information processing for simple sensorimotor tasks in healthy subjects. At a cortical level, a single dose of SSRI was shown to induce a hyperactivation of the primary sensorimotor cortex (S1M1) involved in the movement (Loubinoux, I., Boulanouar, K., Ranjeva, J. P., Carel, C., Berry, I., Rascol, O., Celsis, P., and Chollet, F., 1999. Cerebral functional magnetic resonance imaging activation modulated by a single dose of the monoamine neurotransmission enhancers fluoxetine and fenozolone during hand sensorimotor tasks. J. Cereb. Blood Flow Metab. 19 1365--1375, Loubinoux, I., Pariente, J., Boulanouar, K., Carel, C., Manelfe, C., Rascol, O., Celsis, P., and Chollet, F., 2002. A Single Dose of Serotonin Neurotransmission Agonist Paroxetine Enhances Motor Output. A double-blind, placebo-controlled, fMRI study in healthy subjects. NeuroImage 15 26--36). Since SSRIs are usually given for several weeks, we assessed the behavioral and cerebral effects of a one-month chronic administration of paroxetine on a larger group. In a double-blind, placebo controlled and crossover study, 19 subjects received daily 20 mg paroxetine or placebo, respectively, over a period of 30 days separated by a wash-out period of 3 months. After each period, the subjects underwent an fMRI (active or passive movement, dexterity task, sensory discrimination task) and a behavioral evaluation. Concurrently, a TMS (transcranial magnetic stimulation) study was conducted (Gerdelat-Mas, A., Loubinoux, I., Tombari, D., Rascol, O., Chollet, F., Simonetta-Moreau, M., 2005. Chronic administration of selective serotonin re-uptake inhibitor (SSRI) paroxetine modulates human motor cortex excitability in healthy subjects. NeuroImage 27,314--322). RESULTS: On the one hand, paroxetine improved motor performances at the finger tapping test (P=0.02) without affecting choice reaction time, strength and dexterity significantly. Subjects were also faster in processing the spatial incongruency between a stimulus and the motor response (P=0.04). In order to differentiate behavioral components, a principal component analysis was performed on all motor tests, and several characteristics were differentiated: strength, speed, skill, attention, and motor response coding. Paroxetine would improve the efficiency of motor response coding (MANOVA on the factors; factor 3, P=0.01). On the other hand, the chronic administration induced a significant hypoactivation of S1M1 whatever the task: motor or sensory, simple or complex (random effect analysis, P<0.05). The hypoactivation correlated with the improvement of performances at the finger tapping test (P<0.05) suggesting more efficiency in cerebral motor processing. CONCLUSIONS: Our results showed a clear modulation of sensory and motor cerebral activation after a chronic paroxetine administration. An improvement in both behavior and cerebral efficiency was suggested. It could be hypothesized that monoamines, by an unspecific effect, may tune the response of pyramidal neurons to optimize performances.

Adult↗

Introduction of magnetoencephalography to stereotactic techniques.

Magnetoencephalography (MEG), a noninvasive functional brain mapping technique, was used for preoperative localization of the sensorimotor cortex in patients harboring lesions involving these eloquent regions. Prior to surgery, MEG source locations were transferred onto high-resolution MRI pictures which were then used for preoperative evaluation, risk analysis, and planning. We have developed a process to transform the MEG-derived sensorimotor localization coordinates into the COMPASS stereotactic coordinate system. Thus the MEG-derived functional information is incorporated into the stereotactic database, enabling the simultaneous visualization of functional and anatomical data. This information can be used for the selection of cases and in planning safe approaches for computer-assisted volumetric resections. The integration of MEG and stereotactic neurosurgery also allows a more precise comparison between MEG and intraoperative direct electrocorticographic mapping (ECoG). Seven patients were studied with good correlation between MEG and intraoperative mapping. In 4, the correlation was only based on gross visual comparison between intraoperative identification of the gyrus pattern and MEG photographs. The availability of the MEG coordinates in the stereotactic system, however, allows a more precise correlation between MEG and ECoG. In all 3 patients studied in this manner, the MEG coordinates (pinpointed to a precise cortical representation of a few millimeters) overlapped with ECoG results. In summary, we compared functional MEG data to intraoperative ECoG and conclude that the introduction of MEG into stereotactic neurosurgery can provide precise functional and anatomic information for image-guided surgical planning and resection.

Brain Mapping↗

The window of opportunity for administration of magnesium therapy following focal brain injury is 24 h but is task dependent in the rat.

The present study was conducted to establish the window of opportunity for the administration of a regimen of MgCl2 pharmacotherapy following focal injury to the brain. Rats were subjected to unilateral electrolytic lesions of the sensorimotor cortex (SMC) and administered a regimen of MgCl2 (1.0 mmol/kg) or 0.9% saline (1.0 ml/kg) beginning either 15 min, 8 h or 24 h after injury. Subsequent injections were administered 24 and 72 h after the initial treatment. Behavioral testing assessed recovery of function on several sensorimotor behaviors for 24 days following injury. The results of the present study suggest that treatment with a regimen of MgCl2 significantly facilitated recovery of function on the forelimb-->forelimb and vibrissae-->forelimb placing tests when administered 15 min, 8 h or 24 h after injury compared with saline-treated rats. Recovery of locomotor placing was significantly facilitated at 15 min and 8 h but not at 24 h compared with saline-treated rats. In addition, the ability of MgCl2 to limit neuronal loss in the ipsilateral ventral posterior lateral (VPL) nucleus of the thalamus was seen at only the 15-min treatment interval. These results suggest that the window of opportunity for MgCl2 pharmacotherapy is 24 h, task dependent and is much shorter for protecting neurons in the VPL.

Animals↗

Sparing of function after neonatal frontal lesions correlates with increased cortical dendritic branching: a possible mechanism for the Kennard effect.

This study examined the possibility that the presence or absence of behavioral sparing following neonatal frontal lesions might be correlated with changes in the complexity of dendritic branching. Rats were given bilateral frontal lesions in either adulthood, the day of birth, or on day 10. Ninety days later the animals were trained in a spatial navigation task. The animals' brains were then processed for Golgi-Cox staining and the dendritic branching of the pyramidal cells in the parietal cortex was analyzed. Frontal cortical lesions in newborn rats produced a severe behavioral deficit in the water task whereas frontal removal at 10 days of age allowed sparing of function relative to adult operates (that is, the Kennard effect). Analysis of dendritic arbor in sensorimotor cortex revealed that the day-10 animals exhibited a dramatic proliferation of dendritic arbor relative to control rats. In contrast, the day-1 animals had slightly less dendritic branching than control animals. Rats with frontal lesions in adulthood showed a small, but significant, increase in dendritic branching. The correlation between behavioral sparing and the increase in dendritic arborization following neonatal lesions may be illustrative of a general mechanism underlying the Kennard effect.

Animals↗

Dynamic cortical involvement in implicit and explicit motor sequence learning. A PET study.

We examined the dynamic involvement of different brain regions in implicit and explicit motor sequence learning using PET. In a serial reaction time task, subjects pressed each of four buttons with a different finger of the right hand in response to a visually presented number. Test sessions consisted of 10 cycles of the same 10-item sequence. The effects of explicit and implicit learning were assessed separately using a different behavioural parameter for each type of learning: correct recall of the test sequence for explicit learning and improvement of reaction time before the successful recall of any component of the test sequence for implicit learning. Regional cerebral blood flow was measured repeatedly during the task, and a parametric analysis was performed to identify brain regions in which activity was significantly correlated with subjects' performances: i.e. with correct recall of the test sequence or with reaction time. Explicit learning, shown as a positive correlation with the correct recall of the sequence, was associated with increased activity in the posterior parietal cortex, precuneus and premotor cortex bilaterally, also in the supplementary motor area (SMA) predominantly in the left anterior part, left thalamus, and right dorsolateral prefrontal cortex. In contrast, the reaction time showed a different pattern of correlation during different learning phases. During the implicit learning phase, when the subjects were not aware of the sequence, improvement of the reaction time was associated with increased activity in the contralateral primary sensorimotor cortex (SM1). During the explicit learning phase, the reaction time was significantly correlated with activity in a part of the frontoparietal network. During the post-learning phase, when the subjects achieved all components of the sequence explicitly, the reaction time was correlated with the activity in the ipsilateral SM1 and posterior part of the SMA. These results show that different sets of cortical regions are dynamically involved in implicit and explicit motor sequence learning.

Adult↗

Potentials associated with the Go/No-Go paradigm in traumatic brain injury.

Surface event-related potentials associated with visually triggered movements (Go) and the inhibition of planned movements (No-Go) were examined in seven healthy subjects and five postacute traumatic brain injured (TBI) subjects. Analysis showed that the cortical potential P1-N1 was similarly affected by condition in both the control and TB1 groups. Although TB1 subjects showed smaller P1-N1 amplitudes (Go = 2.91 uV; No-Go = 3.95 uV; p < .03) relative to control subjects (Go = 4.82 uV; No-Go = 6.03 uV; p < .03), both groups showed larger amplitudes in the No-Go condition. A bipolar lead (C3'-C3") over the sensorimotor cortex showed a reversal of polarity between Go and No-Go conditions which was synchronized with the EMG activity in all control subjects. This signal reversal and timing of potentials was absent in four of the five TB1 subjects' waveforms, suggesting difficulty in sensorimotor processes associated with movement control. In addition, TB1 subjects displayed a number of atypical stimulus-locked waveforms, which are discussed relative to the specific functional impairments of individual subjects. The results highlight the potential usefulness of such paradigms as the Go/No-Go procedure in the analyses of electroencephalographic waveforms and of the effects of TBI.

Adolescent↗

Stimulation of internal capsule, thalamic sensory nucleus (VPM) and cerebral cortex inhibited deafferentation hyperactivity provoked after gasserian ganglionectomy in cat.

Facilitation of the opiate-mediated system provides relief of excess pain but not of deafferentation pain. Influence on neuronal hyper-activity, which was provoked after the deafferentation of the peripheral trigeminal nerve (deafferentation hyperactivity; DH), by stimulation of the internal capsule (IC), VPM nucleus of the thalamus and by the cerebral sensorimotor cortex, was examined. This experiment demonstrates that a suppressive effect is exerted on the sustained neuronal hyperactivity, which was proved to have a close relationship with deafferentation pain. In the preliminary experiment, it was confirmed that DH was provoked by coagulation of unilateral (left side) Gasserian ganglion in 29 adult cats, who were allowed to survive up to 72 days. DH, sustained high amplitude discharge without any stimuli on the face or neck, was detected in the subnucleus caudalis of the spinal trigeminal nucleus (STNcd) of the denervated side. DH was never suppressed by facilitation of the opiate-mediated system. 87 of 113 neurones identified in the STNcd of the denervated side showed DH in another 18 cats. In 30 of 55 neurones examined, DH was conspicuously suppressed by the stimulation of contralateral (right) side, 11 of 29 neurones by ipsilateral IC. Five of 13 neurones were suppressed by contralateral VPM stimulation, 2 of 3 neurones by ipsilateral stimulation. Stimulation of cortical area, SM1 of MS1, in other 15 cats, considerably suppressed DH in STNcd. Microinjection of wheat-germ-agglutinin in the cerebral cortex revealed in direct projection of the descending fibre from MS1 to STNcd and brain stem reticular formation via IC.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Prestimulus oscillations enhance psychophysical performance in humans.

The presence of various ongoing oscillations in the brain is correlated with behavioral states such as restful wakefulness or drowsiness. However, even when subjects aim to maintain a high level of vigilance, ongoing oscillations exhibit large amplitude variability on time scales of hundreds of milliseconds to seconds, suggesting that the functional state of local cortical networks is continuously changing. How this volatility of ongoing oscillations influences the perception of sensory stimuli has remained essentially unknown. We investigated the relationship between prestimulus neuronal oscillations and the subjects' ability to consciously perceive and react to somatosensory stimuli near the threshold of detection. We show that, for prestimulus oscillations at approximately 10, 20, and 40 Hz detected over the sensorimotor cortex, intermediate amplitudes were associated with the highest probability of conscious detection and the shortest reaction times. In contrast, for 10 and 20 Hz prestimulus oscillations detected over the parietal region, the largest amplitudes were associated with the best performance. Our data indicate that the prestimulus oscillatory activity detected over sensorimotor and parietal cortices has a profound effect on the processing of weak stimuli. Furthermore, the results suggest that ongoing oscillations in sensory cortices may optimize the processing of sensory stimuli with the same mechanism as noise sources in intrinsic stochastic resonance.

Adult↗

Sensorimotor electroencephalogram rhythmic activity: a functional gate mechanism.

Neurophysiological evidence for a negative feedback loop in somatosensory thalamic nuclei has provided a basis for understanding the origins of rhythmic activity in the electroencephalogram (EEG) of sensorimotor cortex. Studies reviewed here suggest that state-specific activation of this mechanism is responsible both for a variable pattern of rhythmic frequencies during wakefulness and the spindle burst pattern during sleep. It is proposed further that these rhythms index immobility and a common set of physiological changes in sensorimotor function, including reduced excitability in both afferent and efferent pathways. It is hypothesized, therefore, that the closing of a thalamic "inhibitory gate" is indicated by the occurrence of these rhythms. While a greater resolution of specific relationships is necessary, the study of these EEG patterns clearly provides a measure of complex physiological events in the nervous system, and can be also useful in identifying functional abnormalities.

Animals↗

A simple and a complex tic (Gilles de la Tourette's syndrome): their response to EEG sensorimotor rhythm biofeedback training.

This study presents a clinical treatment regime for the treatment of tic manifestation, both simple and complex. The response of a case of simple tic and a case of complex tic (Gilles de la Tourette's syndrome) to EEG sensorimotor rhythm biofeedback training are presented. Specifically, the simple and the complex tic, both of long duration, were eliminated via this EEG biofeedback training procedure. It is hypothesized that this exercising of the sensorimotor cortex resulted in increased activation of this cerebrocortical subsystem and was reflected in increased voluntary muscle control and a heightened threshold for random motor discharge, resulting in the elimination of both tics as in the response of cases of epilepsy with motor involvement to EEG sensorimotor rhythm biofeedback training. The additional psychophysiologic sequelae of the complex tic--attention deficit disorder--remediated in the manner of the response of learning-disabled to EEG sensorimotor rhythm biofeedback training.

Adolescent↗

Functional cortical changes in patients with multiple sclerosis and nonspecific findings on conventional magnetic resonance imaging scans of the brain.

Recent functional magnetic resonance imaging (fMRI) work has suggested that cortical reorganisation might have an adaptive role in limiting the clinical impact of multiple sclerosis (MS) structural damage. In this study, we investigated whether, in patients with MS, the presence and extent of structural damage of the normal-appearing brain tissue are associated with the extent of the movement-associated pattern of cortical activations. Using fMRI and a general search method, we assessed the patterns of brain activations associated with simple motor tasks in 12 right-handed patients with clinically definite MS and nonspecific T2-weighted abnormalities on conventional MRI scans of the brain and compared them with those from 12 sex- and age-matched right- handed healthy controls. Also investigated were the extent to which the fMRI changes correlated with normal-appearing white matter and grey matter (GM) pathology, measured using diffusion tensor MRI. When performing the simple motor task with the dominant hand, MS patients had more significant activations of the ipsilateral supplementary motor area (SMA), the ipsilateral superior frontal sulcus, the contralateral superior temporal gyrus, and the thalamus than controls. On the contrary, healthy subjects showed more significant activations of the medial part of the contralateral parieto-occipital fissure and the ipsilateral primary sensorimotor cortex (SMC) than patients with MS. In patients with MS, the relative activation of the ipsilateral SMA was correlated with the peak height (r = -0.88, P < 0.001) and position (r = 0.87, P < 0.001) of the GM mean diffusivity histogram. This study shows that cortical reorganisation occurs over a rather distributed sensorimotor network even in patients with MS and nonspecific abnormalities on conventional brain MRI scans. This suggests that, in patients with MS, an increased recruitment of movement-associated cortical network can be elicited by the presence of normal-appearing tissue pathology, which is independent of macroscopic T2-weighted abnormalities.

Adult↗

[Neuronal responses of the rate somatosensory cortex transplanted into the vibrissae representation field of the neocortex to the electrical stimulation of the recipient brain].

Neuronal responses of the rat somatosensory cortex grafted into damaged host barrel field to electrical stimulation of the host brain were investigated extracellularly in rats under light pentobarbital anaesthesia. The following structures of the host brain were stimulated: ventrobasal complex and posterior thalamic nuclei, ipsilateral area of vibrissae representation in the sensorimotor cortex and contralateral barrel field. Reactivity of the grafted neurones was lower, than in the intact barrel field, but the mean latencies of responses were not significantly different. Stimulation of the thalamic nuclei was more effective than that of the cortical areas both in grafted and intact barrel fields. Posttetanic depression after repetitive stimulation was often observed in the grafts, while posttetanic potentiation was more usual for the intact barrel field. The data show the sources of some functional afferent inputs to the grafts which may be responsible for neuronal reactions to somatosensory stimulation of the host animal.

Animals↗

Dynamic behaviors of growth cones extending in the corpus callosum of living cortical brain slices observed with video microscopy.

During development, axons of the mammalian corpus callosum must navigate across the midline to establish connections with corresponding targets in the contralateral cerebral cortex. To gain insight into how growth cones of callosal axons respond to putative guidance cues along this CNS pathway, we have used time-lapse video microscopy to observe dynamic behaviors of individual callosal growth cones extending in living brain slices from neonatal hamster sensorimotor cortex. Crystals of the lipophilic dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil) were inserted into the cortex in vivo to label small populations of callosal axons and their growth cones. Subsequently, 400 microns brain slices that included the injection site, the corpus callosum, and the target cortex were placed in culture and viewed under low-light-level conditions with a silicon-intensified target (SIT) camera. Time-lapse video observations revealed striking differences in growth cone behaviors in different regions of the callosal pathway. In the tract, which is defined as the region of the callosal pathway from the injection site to the corresponding target cortex, growth cones advanced rapidly, displaying continual lamellipodial shape changes and filopodial exploration. Forward advance was sometimes interrupted by brief pauses or retraction. Growth cones in the target cortex had almost uniform compact shapes that were consistently smaller than those in the tract. In cortex, axons adhered to straight radial trajectories and their growth cones extended at only half the speed of those in the tract. Growth cones in subtarget regions of the callosum beneath cortical targets displayed complex behaviors characterized by long pauses, extension of transitory branches, and repeated cycles of collapse, withdrawal, and resurgence. Video observations suggested that extension of axons into cortical targets could occur by interstitial branching from callosal axons rather than by turning behaviors of the primary growth cones. These results suggest the existence of guidance cues distinct for each of these callosal regions that elicit characteristic growth cone behaviors.

Animals↗

Single-shot interleaved z-shim EPI with optimized compensation for signal losses due to susceptibility-induced field inhomogeneity at 3 T.

A new single-shot echo-planar imaging (EPI) sequence with interleaved z-shim and optimized compensation for susceptibility-induced signal loss is proposed in this paper. Experiments on human brain demonstrated that the new method is able to regain signal dropout in brain areas with severe susceptibility-induced local gradients, while its image acquisition speed is comparable to that of conventional single-shot EPI techniques. Significant signal-to-noise ratio improvements were demonstrated in the ventral prefrontal and lateral temporal lobes with the new technique compared to a conventional EPI. Brain activation experiments with a bilateral finger-tapping task were performed with intentionally introduced local gradients near the left sensorimotor cortex, by a small gadolinium (Gd)-doped bottle placed on the left side of the head. The results of the functional experiments showed that the interleaved z-shim EPI sequence effectively recovered the signal loss caused by the Gd-doped bottle and reliably detected activation signals in bilateral sensorimotor regions, while the activation signals on the left side diminished considerably in a conventional EPI technique. The new technique, with the capability of reducing susceptibility artifacts and rapid scanning speed, may be particularly useful for event-related functional MRI experiments in the base of the brain, which are of great importance in neuropsychiatric studies.

Adult↗

Altered cortical activation with finger movement after peripheral denervation: comparison of active and passive tasks.

We wished to contrast cortical activation during hand movements in profoundly weak patients with motor neuropathy and in normal controls using a paradigm that is behaviourally matched between the two groups. Previous work has suggested that a passive movement task could be appropriate. Using functional magnetic resonance imaging (fMRI), we first characterised patterns of brain activation during active and passive index finger movements in healthy controls (n=10). Although the relative activation differences were highly variable, there was a trend for the mean number of significantly activated voxels in the primary motor cortex contralateral to the hand moved (CMC) to be lower for the passive than for the active task (40% relative decrease, P=0.09). There was a small posterior shift in the centre of mass of the CMC (mean, 8 mm, P<0.02) and of the ipsilateral sensorimotor cortex (IMC) (mean, 11 mm, P<0.05). No activation with passive movement was found in the patients with severe distal sensory neuropathy (n=2), suggesting that activation with passive movements is dependent on sensory feedback and unlikely to be due to mental imagery alone. In contrast, patients with severe pure motor neuropathies (MN, n=2) showed substantial increases in the volumes of activation compared to controls. The relative increases in numbers of voxels activated above threshold in different regions of interest for both the active (MN/controls: CMC, 2. 1; IMC, 8.1; supplementary motor area [SMA], 5.2) and passive (CMC, 2.6; IMC, 8.0; SMA, 5.1) tasks were similar. These results confirm expansion of cortical representation for finger movement in patients with motor neuropathy and demonstrate central reorganisation as a consequence of the motor nerve loss. An expanded representation for finger movement in the primary motor cortex with peripheral weakness suggests the possibility that the primary motor cortex may encode motor unit activation rather directly.

Adult↗

Features of cortically evoked swallowing in the awake primate (Macaca fascicularis).

Although the cerebral cortex has been implicated in the control of swallowing, the output organization of the cortical swallowing representation, and features of cortically evoked swallowing, remain unclear. The present study defined the output features of the primate "cortical swallowing representation" with intracortical microstimulation (ICMS) applied within the lateral sensorimotor cortex. In four hemispheres of two awake monkeys, microelectrode penetrations were made at </=1-mm intervals, initially within the face primary motor cortex (face-MI), and subsequently within the cortical regions immediately rostral, lateral, and caudal to MI. Two ICMS pulse trains [35-ms train, 0.2-ms pulses at 333 Hz, </=30 microA (short train stimulus, T/S); 3- to 4-s train, 0.2-ms pulses at 50 Hz, </=60 microA (continuous stimulus, C/S)] were applied at </=500-micron intervals along each microelectrode penetration to a depth of 8-10 mm, and electromyographic (EMG) activity was recorded simultaneously from various orofacial and laryngeal muscles. Evoked orofacial movements, including swallowing, were verified by EMG analysis, and T/S and C/S movement thresholds were determined. Effects of varying ICMS intensity on swallow-related EMG properties were examined by applying suprathreshold C/S at selected intracortical sites. EMG patterns of swallows evoked from various cortical regions were compared with those of natural swallows recorded as the monkeys swallowed liquid and solid material. Results indicated that swallowing was evoked by C/S at approximately 20% of 1,569 intracortical sites where ICMS elicited an orofacial motor response in both hemispheres of the two monkeys, typically at C/S intensities </=30 microA. In contrast, swallowing was not evoked by T/S in either monkey. Swallowing was evoked from four cortical regions: the ICMS-defined face-MI, the face primary somatosensory cortex (face-SI), the region lateral and anterior to face-MI corresponding to the cortical masticatory area (CMA), and an area >5 mm deep to the cortical surface corresponding to both the white matter underlying the CMA and the frontal operculum; EMG patterns of swallows elicited from these four cortical regions showed some statistically significant differences. Whereas swallowing ONLY was evoked at some sites, particularly within the deep cortical area, swallowing was more frequently evoked together with other orofacial responses including rhythmic jaw movements. Increasing ICMS intensity increased the magnitude, and decreased the latency, of the swallow-related EMG burst in the genioglossus muscle at some sites. These findings suggest that a number of distinct cortical foci may participate in the initiation and modulation of the swallowing synergy as well as in integrating the swallow within the masticatory sequence.

Animals↗

Physiological basis of voluntary activity inhibition induced by transcranial cortical stimulation.

Apart from exciting corticospinal cells and evoking a motor response, electrical or magnetic transcranial cortical stimulation (TCCS) delivered during voluntary activity produces a prolonged inhibition of activity, a silent period (SP), that can last up to 280 msec. The SP duration after TCCS is directly proportional to stimulus intensity. To determine the anatomic substrate and underlying physiological properties of the SP from TCCS, we (1) compared the SP from TCCS with the SP from cutaneous and mixed nerve stimulation, (2) studied the excitability cycle of spinal motor neurons in 3 double stimulus conditions: (a) after paired peripheral nerve stimulation, (b) after TCCS and peripheral nerve stimulation, and (c) after paired electrical TCCS, (3) investigated the timing of the excitability of the sensorimotor cortex measuring long latency responses from median nerve stimulation delivered inside the SP from TCCS. We found that after TCCS, spinal motor neuron segmental excitability is reduced for a period up to 100 msec. Inhibition at a suprasegmental, possibly cortical, level was even more prolonged for a period up to 160 msec, suggesting that at least the late part of the SP after TCCS is due to supraspinal inhibition. Determining the nature of the supraspinal inhibition such as the possible role of cortical inhibitory mechanisms may be useful in further understanding central mechanisms of voluntary motor control and sensorimotor processing.

Adult↗

The pattern of dendritic development in the cerebral cortex of the rat.

The pattern of dendritic development of layer V pyramidal cells in the neocortex of the rat was studied using a variety of quantitative techniques in an attempt to determine what rules govern dendritic differentiation. Animals were sacrificed on postnatal days (P) 1, 3, 5, 7, 10, 15, 20, 25, 30 and 60, their brains impregnated with the rapid Golgi technique, and cells from the sensorimotor cortex examined for maximal apical and basilar dendritic field, number of dendritic branches at 20 micron intervals from the cell body, number of apical and basilar branch types (branching order), length of dendritic branch segments, and dendritic spine density. Primary dendrites are formed early in development, with no new ones formed after P7-10. Once a dendritic segment has bifurcated, all further development appears to occur at the tip, i.e. the trunk does not seem to undergo additional elongation, and new branches do not appear to form from the trunk. There is a plateau in dendritic differentiation close to the cell body after approximately P20; however, there is a continued increase in the length of terminal dendritic branches in the distal portions of the dendritic field into adulthood. During early development, dendrites bifurcate on reaching approximately 20-30 microns; however, during adulthood additional length is added to terminal dendrites without branching. Dendritic spines increase dramatically early in development, and then decline on proximal dendrites but continue to increase on terminal branches into adulthood. These results suggest that the terminal portion of the dendritic field remains plastic into adulthood, and that during development several general rules govern the pattern of dendritic differentiation.

Aging↗