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[The pharmacological testing of intracortical interneuronal connections].

An attempt is made to study the influence of acetylcholine on functional connections of cortical neurons and their frequency characteristics. Multiunit activity was recorded in the sensorimotor cortex of immobilized and freely moving rats. Crosscorrelation analysis was used. Influence of acetylcholine (Ach) and Ca chelator ethyleneglicoltetraacetat (EGTA) on the functional characteristics of the neighbouring neurons was studied in the first series of experiments. The substances were iontophoretically applied to the sensorimotor cortex neurons of the immobilized unanesthetized rats. Application of Ach led to variation in the frequency characteristics of single neurons and in the majority cases did not affect the neuronal interrelations. EGTA application, independently on the background frequency of the neuronal activity, resulted in disappearance of interneuronal connections which recovered after the end of EGTA effect. The second series of experiments was carried out in freely moving rats. System injection of galantamine essentially increased the frequency of activity of the cortical neurons not affecting their network activity. We suppose that intracortical relations can be realized independently on the extracortical influences which are manifested in variations in the background impulsation of the single neurons. Qualitative estimation of Ach influence on the functional characteristics of the cortical neurons do not reveal Ach effects on formation of intracortical connections. The technique used by us may be applied in further studies of intracortical neurons connections.

Acetylcholine↗

Signal-, set-, and movement-related activity in the human premotor cortex.

Single unit recording studies in non-human premotor cortex have revealed neurons with motor-related activity. Other neurons, however, seem to be involved in prior movement selection and preparation processes, and have activity related to visual instruction signals or movement preparation ('set'). We have used single pulse transcranial magnetic stimulation (TMS) to identify similar processes in human subjects. In Experiment 1 subjects performed a cued movement task while being stimulated with TMS over three sites: sensorimotor cortex, posterior premotor cortex and anterior premotor cortex. TMS slowed movements when applied at 140 ms after the visual cue over the anterior premotor site, at 180 ms after the visual cue over the posterior premotor site, and at 220 ms and later after the visual cue over the sensorimotor cortex. The results are consistent with a change from signal to movement-related processing when moving from premotor to motor cortex. In Experiment 2 there was a preparatory set period between the instruction signal that informed subjects which movement to make and the 'go' signal that informed them when to actually make the movement. TMS was applied over the anterior premotor site and the sensorimotor site during the set period. At both sites TMS had similar effects on slowing subsequent movements. The results suggest set activity in both premotor and motor cortices in human subjects.

Brain↗

Microstructural white matter changes in carriers of the DYT1 gene mutation.

We tested the hypothesis that the DYT1 genotype is associated with a disorder of anatomical connectivity involving primarily the sensorimotor cortex. We used diffusion tensor magnetic resonance imaging (DTI) to assess the microstructure of white matter pathways in mutation carriers and control subjects. Fractional anisotropy (FA), a measure of axonal integrity and coherence, was reduced (p < 0.005) in the subgyral white matter of the sensorimotor cortex of DYT1 carriers. Abnormal anatomical connectivity of the supplementary motor area may contribute to the susceptibility of DYT1 carriers to develop clinical manifestations of dystonia.

Adult↗

Brain cortical activation during guitar-induced hand dystonia studied by functional MRI.

Focal hand dystonia in musicians is a strongly task-related movement disorder. Typically, symptoms become apparent only when players execute specific overpracticed skilled exercises on their instrument. We therefore examined five guitarists with functional MRI during dystonic symptom provocation by means of an adapted guitar inside the magnet. The activation patterns obtained in comparable nondystonic guitarists and in the study patients when performing normal-hand exercise served as references. A 1.5-T system equipped with echo-speed gradients and single-shot echoplanar imaging software was used. Data acquisition was centered on the cortical motor system encompassed in eight contiguous slices. Dystonic musicians compared with both control situations showed a significantly larger activation of the contralateral primary sensorimotor cortex that contrasted with a conspicuous bilateral underactivation of premotor areas. Our results coincide with studies of other dystonia types in that they show an abnormal recruitment of cortical areas involved in the control of voluntary movement. However, they do suggest that the primary sensorimotor cortex, rather than being underactive in idiopathic dystonic patients, may be overactive when tested during full expression of the task-induced movement disorder.

Adult↗

Frequency-dependent changes of regional cerebral blood flow during finger movements.

To study the effect of the repetition rate of a simple movement on the distribution and magnitude of neuronal recruitment, we measured regional CBF (rCBF) in eight normal volunteers, using positron emission tomography and 15O-labeled water. An auditory-cued, repetitive flexion movement of the right index finger against the thumb was performed at very slow (0.25 and 0.5 Hz), slow (0.75 and 1 Hz), fast (2 and 2.5 Hz), and very fast (3 and 4 Hz) rates. The increase of rCBF during movement relative to the resting condition was calculated for each pair of movement conditions. Left primary sensorimotor cortex showed no significant activation at the very slow rates. There was a rapid rise of rCBF between the slow and the fast rates, but no further increase at the very fast rates. The right cerebellum showed similar changes. Changes in the left primary sensorimotor cortex and the cerebellum likely reflect the effect of the movement rate. The posterior supplementary motor area (SMA) showed its highest activation at the very slow rates but no significant activation at the very fast rates. Changes correlating with those in the SMA were found in the anterior cingulate gyrus, right prefrontal area, and right thalamus. The decreases in CBF may reflect a progressive change in performance from reactive to predictive.

Adult↗

[The formation of conditioned reflexes to a complex signal in ontogeny under the conditions of an alternation choice].

Formation of conditioned reflex to simultaneous complex stimulus (light + sound) and its components was studied in alternation task (Go/Go) in kittens aged 1.5-10 months. Low percentage of correct reactions (48-57%) and preference of one of the two reinforced directions were shown in kittens aged 1.5-5 months. Successful learning in alternation task was attained in kittens which began to be trained at the age of 6 months. Extirpation of sensorimotor cortex in the trained animals aged 7 months and older induced a decrease of the level of correct reactions from 75-80% to 20-40% and preference of one direction. The problems of parallel development of interaction between the sensory and motor systems and sensorimotor cortex are discussed.

Acoustic Stimulation↗

Corticospinal neurons exhibit a novel pattern of cytoskeletal gene expression after injury.

We examined changes in the expression of major cytoskeletal protein mRNAs in adult hamster corticospinal neurons after axotomy. While a number of studies had determined that peripheral neurons exhibit major alterations in cytoskeletal gene expression after axotomy, no previous studies had addressed the question of whether or not intrinsic mammalian CNS neurons, which do not have the ability to successfully regenerate axons after injury, alter their expression of tubulin and neurofilament genes after injury. In the present study we used in situ hybridization methods to examine this issue. 35S-labeled cDNA probes for the low molecular weight neurofilament protein (NF-L) mRNA and an alpha-tubulin mRNA species (M alpha 1) were used for in situ hybridizations of sections of the sensorimotor cortex obtained 2, 7, and 14 days after unilateral axotomy of the corticospinal tract in the caudal medulla. Film as well as emulsion autoradiography showed dramatic decreases in both alpha-tubulin and NF-L mRNA levels within axotomized neurons in layer Vb of the sensorimotor cortex. Tubulin mRNA levels were decreased as early as 2 days after injury whereas NF-L mRNA levels were not decreased until later times. Ribosomal RNA (rRNA) levels in axotomized corticospinal neurons were also examined using in situ hybridization with a 35S-labeled rDNA probe. These studies showed only a slight decrease in rRNA levels in corticospinal neurons at 14 days after axotomy. Immunoblotting experiments of total protein from corticospinal axons in the medulla were performed to assess whether the axonal composition immediately proximal to the injury site reflected changes in cell body gene expression. Both alpha-tubulin and NF-L levels were found to decrease in corticospinal axons by 28 days after injury. These findings, to our knowledge, are the first to demonstrate that a class of mammalian CNS neurons have an intrinsically different cytoskeletal response to axonal injury than do PNS neurons. The failure to upregulate tubulin gene expression following injury may contribute to the ineffective regenerative response of these long-tract CNS neurons.

Amidines↗

A positron emission tomography study of self-paced finger movements at different frequencies.

Regional cerebral blood flow was measured in six right-handed volunteers using positron emission tomography during tasks involving repetitive self-paced finger tapping at five different frequencies. The contralateral primary sensorimotor cortex, the pre-supplementary motor area and the cingulate motor area showed significant activation during self-paced finger tapping tasks, compared with the resting state. A positive correlation between the regional cerebral blood flow and the movement frequency was found only in the primary sensorimotor cortex. In the pre-supplementary motor area and the cingulate motor area, however, activity increased when the subject employed movement frequencies faster or slower than his own pace. The same tendency was noted with respect to the relative variability of the inter-tapping interval. The results therefore indicate that the activity of the pre-supplementary motor area and the cingulate motor area may well be related to the increased difficulty in motor control rather than to the execution of the movement itself.

Adolescent↗

[Event-related desynchronization and Parkinson disease. Importance in the analysis of the phase of preparation for movement].

This study was aimed at determining the spatiotemporal distribution of event-related desynchronization (ERD) during self-paced voluntary movement in order to establish the interest of this method for the analysis of movement programming in Parkinson's disease. Desynchronization of mu rhythm was recorded 2 s before to 0.5 s after right then left self-paced voluntary wrist flexions from 11 leads covering the primary sensorimotor cortex (central), supplementary motor area (frontocentral) and parietal cortex (parietocentral). Recordings were obtained from ten control subjects, ten patients treated for Parkinson's disease (bilateral symptoms) and 20 patients presenting with right or left hemiparkinsonism before and after chronic administration of L-dopa. In the control group, ERD started over the contralateral primary sensorimotor cortex 1,750 ms before movement and was bilateral just before performance of the movement. In both treated and de novo Parkinson's disease groups, decrease in ERD latency (1,000 to 1,250 ms before movement) was only observed when movements were performed with the akinetic hand and corresponded to a decrease in motor cortical activity. This confirmed that programming of movement is affected in Parkinson's disease. Earlier ERD with central ipsilateral distribution were also observed, suggesting that other cortical areas might be activated to compensate for dysfunction of movement programming and to increase the level of cortical activity required for performance of the movement. The administration of L-dopa to de novo hemiparkinsonians patients resulted in increased ERD latency over contralateral and ipsilateral central areas. As in the treated Parkinson's disease group, frontocentral ERD could also be recorded. L-dopa would thus partially restore the affected motor programmation and modulate cortical activation in both supplementary motor area and primary motor cortex, the later receiving more afferences from basal ganglia.

Antiparkinson Agents↗

Origins and conducting pathways of motor evoked potentials elicited by transcranial magnetic stimulation in cats.

Spinal cord motor evoked potentials (MEPs-S) were elicited in cats by transcranial magnetic stimulation. The MEPs-S recorded from the epidural electrode at the first lumbar (L1) level consisted of four negative peaks (N1, 2.56; N2, 3.19; N3, 4.06; N4, 4.99 ms) followed by small, multiphasic waves. The mean conduction velocities of N1-N3 of the MEPs-S were calculated to be 90 to 115 m/s, which is consistent with extrapyramidal tract activation. A direct brain stem electrical stimulation and sequential transection of the spinal cord studies showed that N1-N3 of the MEPs-S originated primarily from the brain stem and conducted in the ventral funiculus of the spinal cord, which corresponded to the extrapyramidal tracts (e.g., the reticulospinal and vestibulospinal tracts). We also showed that N1 and N2 of the MEPs-S originated mainly from the lower medulla or upper cervical and that N3 originated from the lower pons or upper medulla (vestibular nucleus). On the other hand, N4 of the MEPs-S had a conduction velocity of 70 m/s, which disappeared by ablation of the sensorimotor cortex and pyramidotomy. A dorsal hemisection of the spinal cord, resulting in the disappearance of N4 of the MEPs-S, indicated that it conducted in the dorsolateral funiculus of the spinal cord. These results suggest that N4 of the MEPs-S originates from the sensorimotor cortex and conducts in the lateral corticospinal tract. MEPs-S by transcranial magnetic stimulation in cats constituted complex responses in both the pyramidal and extrapyramidal tracts.

Animals↗

Cortical metabolism in posterolateral thalamic stroke: PET study.

In 8 patients with small unilateral posterolateral thalamic (or, in one case, thalamocapsular) stroke (infarction or hemorrhage) selected on strict clinical (pure hemisomatosensory deficit without hemiparesis, visual field defect or neuropsychological impairment) and MRI criteria, we studied cortical energy metabolism using positron emission tomography with the 18F-fluorodeoxyglucose or the 15O-oxygen method. We found no significant ipsi- or contra-lateral metabolic depression either in the whole cortical mantle or in the sensorimotor cortex. These results support the hypothesis that location of thalamic stroke is a major determinant of the ipsilateral cortical hypometabolism characteristic of cognitively impaired patients with thalamic lesions and further emphasize the influence of the "non-specific" thalamocortical system on resting cortical metabolism. The lack of sensorimotor cortex hypometabolism in our patients suffering from hemidysesthesia and/or -hyperpathia also suggests that cortical metabolism is unaltered in thalamic pain.

Aged↗

Morphine suppression of neurotransmitter release evoked by sensory stimulation in vivo.

The effects of morphine and naloxone on the release of acetylcholine and amino acid neurotransmitters from sensorimotor cortex were studied employing an in vivo superfusion cannula. Morphine (20 mg/kg) reduced the spontaneous release of acetylcholine but had no detectable effect on the spontaneous release of amino acids. It also suppressed the release of acetylcholine and amino acid neurotransmitters evoked by sensory stimulation of the contralateral sensorimotor cortex via the brachial plexus. Naloxone (5 mg/kg) prevented all of these inhibitory actions of morphine. Naloxone also caused a significant increase in spontaneous acetylcholine release.

Acetylcholine↗

Focal traumatic brain injury causes widespread reductions in rat brain norepinephrine turnover from 6 to 24 h.

The effect of right sensorimotor traumatic brain injury (TBI) in male Sprague-Dawley rats on brain norepinephrine (NE) turnover was assessed by measuring the decline of endogenous NE levels following tyrosine hydroxylase inhibition produced with alpha-methyl-p-tyrosine. Right sensorimotor cortex contusions were produced by a pneumatically driven piston which depressed the dural surface by 2 mm at 3.2 m/s. TBI rats were compared to uninjured, anesthetized controls at 6 h and 24 h after surgery. While NE turnover was not affected at the lesion site at 6 h after TBI, it was either abolished or decreased by 33-75% bilaterally in the hypothalamus and in the cerebral cortex surrounding and rostral to the lesion site. In the cortex caudal to the lesion site, NE turnover was completely abolished. NE turnover in cerebral cortex opposite the lesion site and in the contralateral cerebellum was decreased by 51 and 43%, respectively, at 6 h. At 24 h, NE turnover was either abolished or decreased bilaterally by 45-92% in all cortical areas, in the hypothalamus, cerebellum, locus coeruleus and medulla. Thus, right sensorimotor cortex contusion causes a marked, early and widespread depression of brain NE turnover. Since amphetamine increases NE turnover, this may explain the dramatic improvement in behavioral deficits which occurs following amphetamine administration at 24 h after such lesions.

Animals↗

Neuroimaging evidence for cortical involvement in the preparation and in the act of swallowing.

This study employed whole head magnetoencephalography and synthetic aperture magnetometry to investigate the cortical topography of the preparation and the execution of volitional and reflexive water swallowing and of a simple tongue movement. Concerning movement execution, activation of the mid-lateral primary sensorimotor cortex was strongly lateralized to the left during volitional water swallowing, less strongly lateralized to the left during reflexive water swallowing, and not lateralized at all during tongue movement. In contrast, the preparation for both volitional water swallowing and tongue movement showed a bilateral activation of the primary sensorimotor cortex. No activation was seen prior to reflexive water swallowing. Activation of the left insula and frontal operculum was observed only during both the preparation and the execution of volitional water swallowing. These new findings suggest a left hemispheric dominance for the cortical control of swallowing in humans.

Adult↗

Localization of partial epilepsy using magnetic and electric measurements.

Dipole methods applied to brain electric and magnetic fields have made several significant advances in investigation of epilepsy and sensorimotor cortex. The magnetoencephalogram (MEG) and the MEG-electroencephalogram (EEG) combination have contributed substantially. The MEG-EEG combination has shown a mean accuracy of somatosensory evoked response (SER) localization of the central fissure similar to electrocorticography (ECoG), resolution of ambiguity in ECoG of alternative configurations of hand sensorimotor cortex, and resolution of ambiguity of the causes of the difference between EEG and ECoG map patterns. MEG has shown simple dipolar maps of the temporal lobe interictal spike, localization estimates with about 6 mm error, and spatial separation of propagating multiple sources. MEG and EEG have shown a new neocortical propagation pathway in the temporal lobe, noninvasive estimates of the area of the spike focus, and complementary detection sensitivity. Application of spatiotemporal multiple dipole modeling in the simplest field using MEG has given a realistic quantification of spike zones. MEG and EEG have shown simple dipolar patterns for seizure origin, suggesting focality of some frontal seizures, and appears to increase EEG utility. Improved accuracy may result from a combined methodology including MEG and EEG. Dipole methods have potential utility as a noninvasive diagnostic procedure in epilepsy.

Brain Mapping↗

Functional MRI and intraoperative brain mapping to evaluate brain plasticity in patients with brain tumours and hemiparesis.

OBJECTIVE: To support the hypothesis about the potential compensatory role of ipsilateral corticofugal pathways when the contralateral pathways are impaired by brain tumours. METHODS: Retrospective analysis was carried out on the results of functional MRI (fMRI) of a selected group of five paretic patients with Rolandic brain tumours who exhibited an abnormally high ipsilateral/contralateral ratio of activation-that is, movements of the paretic hand activated predominately the ipsilateral cortex. Brain activation was achieved with a flexion extension of the fingers. Statistical parametric activation was obtained using a t test and a threshold of p<0.001. These patients, candidates for tumour resection, also underwent cortical intraoperative stimulation that was correlated to the fMRI spatial data using three dimensional reconstructions of the brain. Three patients also had postoperative control fMRI. RESULTS: The absence of fMRI activation of the primary sensorimotor cortex normally innervating the paretic hand for the threshold chosen, was correlated with completely negative cortical responses of the cortical hand area during the operation. The preoperative fMRI activation of these patients predominantly found in the ipsilateral frontal and primary sensorimotor cortices could be related to the residual ipsilateral hand function. Postoperatively, the fMRI activation returned to more classic patterns of activation, reflecting the consequences of therapy. CONCLUSION: In paretic patients with brain tumours, ipsilateral control could be implicated in the residual hand function, when the normal primary pathways are impaired. The possibility that functional tissue still remains in the peritumorous sensorimotor cortex even when the preoperative fMRI and the cortical intraoperative stimulations are negative, should be taken into account when planning the tumour resection and during the operation.

Aged↗

Differential modulation of subcortical target and cortex during deep brain stimulation.

The combination of electrical deep brain stimulation (DBS) with functional imaging offers a unique model for tracing brain circuitry and for testing the modulatory potential of electrical stimulation on a neuronal network in vivo. We therefore applied parametric positron emission tomography (PET) analyses that allow characterization of rCBF responses as linear and nonlinear functions of the experimentally modulated stimulus (variable stimulator setting). In patients with electrodes in the thalamic ventrointermediate nucleus (VIM) for the treatment of essential tremor (ET) here we show that variations in voltage and frequency of thalamic stimulation have differential effects in a thalamo-cortical circuitry. Increasing stimulation amplitude was associated with a linear raise in rCBF at the thalamic stimulation site, but with a nonlinear rCBF response in the primary sensorimotor cortex (M1/S1). The reverse pattern in rCBF changes was observed with increasing stimulation frequency. These results indicate close connectivity between the stimulated nucleus (VIM) and primary sensorimotor cortex. Likewise, stimulation parameter-specific modulation occurs at this simple interface between an electrical and a cerebral system and suggests that the scope of DBS extends beyond an ablation-like on-off effect: DBS could rather allow a gradual tuning of activity within a neuronal circuit.

Aged↗

Functional consequences of acute cocaine treatment depend on route of administration.

The 2-[14C]deoxyglucose method was used to compare the effects of the acute administration of cocaine by two different routes, intravenous and intraperitoneal, on rates of local cerebral glucose utilization in freely moving rats. Doses were initially chosen on the basis of their ability to elicit equivalent increases in locomotor activity during the experimental procedure, and the time of cocaine administration relative to 2-[14C]deoxyglucose infusion was chosen so that the maximal behavioral effect occurred during maximal tracer incorporation. Changes in glucose utilization following the intraperitoneal administration of cocaine (10 mg/kg, 10 min before 2-deoxyglucose infusion) were restricted to the nigrostriatal system and related structures involved in the production of movement. Increased activity was observed in the substantia nigra pars reticulata, globus pallidus, and sensorimotor cortex. In contrast, intravenous cocaine administration (1 mg/kg, 2 min before tracer infusion) produced more widespread changes in rates of glucose utilization including portions of both the mesocorticolimbic and nigrostriatal systems. Areas in which metabolic activity was altered included the caudate-putamen, globus pallidus, substantia nigra pars reticulata, sensorimotor cortex, olfactory tubercle, nucleus accumbens, and medial prefrontal cortex. Both intravenous and intraperitoneal cocaine produced similar increases in locomotor activity. Additional studies indicated that the absence of metabolic activation in the mesocorticolimbic system following acute intraperitoneal cocaine was not the result of the specific dose chosen or the length of time between cocaine administration and radiotracer infusion, as no changes in metabolic activity in mesocorticolimbic structures were evident when these parameters were varied.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗