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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↗

Functional magnetic resonance imaging in anesthetized patients: a relevant step toward real-time intraoperative functional neuroimaging.

OBJECTIVE: The introduction of intraoperative 1.5-T magnetic resonance imaging may provide up-to-date functional information in the surgical environment. However, feasible passive paradigms that allow the examination of anesthetized patients will be a precondition for intraoperative functional magnetic resonance imaging (fMRI). The aim of this study is to evaluate the feasibility of a recently developed passive fMRI paradigm for functional neuroimaging in anesthetized patients. METHODS: We investigated four anesthetized patients with intracranial pathological conditions not related to the sensorimotor cortex. All patients had been anesthetized with standard total intravenous anesthesia for more than 24 hours before the fMRI scan. Anesthesia and monitoring were sustained during the scanning procedure. A simultaneous electrical stimulation of the median and tibial nerves was applied to elicit a cortical activation using a custom-designed magnetoelectrically shielded conductor. Statistical evaluation using Statistical Parametric Mapping software (Wellcome Department of Imaging Neuroscience, University College, London, England) and the Talairach Daemon Client (Version 1.1; Research Imaging Center, University of Texas Health Science Center, San Antonio, TX) followed. RESULTS: Three of four patients showed a good activation of the sensorimotor cortex under anesthesia. In one patient, no significant activation was observed, presumably as a result of increased body impedance because of severe edema. Standard dosages of the narcotics did not influence the cortical response; however, stimulation intensity had to be increased compared with awake patients. We did not detect relevant interferences with magnetic resonance imaging arising from the technical setup. CONCLUSION: The method presented proved to be a feasible paradigm for fMRI evaluation of the sensorimotor cortex in anesthetized patients and thus forms a relevant step toward real intraoperative functional neuroimaging.

Aged↗

Repetitive sensorimotor training for arm and hand in a patient with locked-in syndrome.

The locked-in syndrome is characterized by quadriplegia, preserved consciousness and inability to respond to the outside world. In recent years, the repetitive execution of identical movements has been demonstrated to be crucial for the recovery of arm and hand function in stroke patients. The present study aimed at investigating the efficiency of repetitive training in a patient suffering from locked-in syndrome due to an occlusion of the basilar artery. Seven months after the brainstem lesion and after a 15-week period of standard inpatient therapy, the repetitive training was applied to the (most affected) right upper extremity in addition to usual therapy. After 42 weeks of the repetitive training for the right arm, it was applied to the left arm. The ranges of active motion as well as functional motor capacity and muscle tone were regularly assessed. During those phases when the repetitive sensorimotor training was applied to the right or left arm, the ranges of active motion, muscle strength and functional motor capacity of the trained arm increased significantly accompanied by a continuous normalization of muscle tone in the flexor muscle groups. Since the prominent functional improvements of the right and left arms were observed during those phases when the repetitive training was applied, these effects were likely to be due to the training rather than to the standard rehabilitation program or extraneous influences. The repetitive sensorimotor training, therefore, appears to be appropriate to improve motor function of the arm and hand and to accelerate the time course of recovery even in patients with almost complete central paralysis of both arms.

Arm↗

Effects of ankle joint effusion on lower leg function.

BACKGROUND: Inversion ankle sprains are among the most frequently encountered injuries in and outside of sport. Altered feedback from joint damage and/or edema may negatively affect dynamic stabilization, thereby increasing the patients' susceptibility to further injury. In order to understand better how the sensorimotor system responds to the presence of ankle edema during a functional task, further examination is warranted. OBJECTIVE: To quantify muscle activation in the peroneal, tibialis anterior, and soleus musculature as well as to determine ankle joint peak torque, peak power, and root mean square (RMS) power during a closed kinetic chain activity following artificial ankle effusion. DESIGN: Dependent variables were compared within subjects across time intervals and between groups. SETTING: All data were collected in the biomechanics laboratory. PARTICIPANTS: Subjects were 20 healthy, neurologically sound volunteers (age 21.9 +/- 2.1 y, height 174.5 +/- 9.3 cm, mass 79.3 +/- 15.9 kg) with no lower extremity injuries. INTERVENTIONS: Subjects were prepared for surface electrodes on the peroneus longus (PL), tibialis anterior (TA), soleus (Sol), and medial malleolus (ground). Anthropometric measures for the lower extremity were recorded for use by the Omnikinetic closed chain dynamometer. Measurements were taken prior to ankle effusion (baseline), immediately following effusion (post), and again at 30 minutes. MAIN OUTCOME MEASUREMENTS: Testing consisted of 6 repetitions at 35% of 1-repetition max and a constant speed of 1.5 Hz. Separate two-way MANOVAs with repeated measures on time intervals were used to detect differences between groups (effusion and control) over time for torque, power, and RMS power and for peak and average EMG. RESULTS: An overall time x group interaction was detected for EMG (F4,72=3.878; P=0.007) and kinetic variables (F6,70=5.55; P=0.0001). Average and peak PL EMG decreased immediately following effusion (Sidak's; P=0.048), and average EMG remained depressed 30 minutes following effusion (Sidak's; P=0.02). Immediately posteffusion, a decrease in ankle torque was detected (Sidak's; P=0.007). No differences in TA or Sol EMG, power, or RMS power were detected (P>0.05). CONCLUSIONS: Decreases in ankle plantarflexion torque and PL EMG indicate that a neuromuscular deficit exists in the presence of edema that could increase the susceptibility for further ankle injury.

Adult↗

The influence of normal aging on the cortical processing of a simple motor task.

OBJECTIVE: To assess the influence of normal aging on the cortical physiology of motor behavior. METHODS: The authors studied cortical activation in eight elderly (55 to 76 years of age) and eight younger (18 to 27 years of age) healthy subjects while they performed a simple motor task. A 28-channel EEG was recorded; task-related power changes associated with repetitive, metronome-paced (1 Hz) finger movements were computed as a measure of cortical activation. RESULTS: Distinct, age-dependent activation patterns were expressed in four distinct frequency ranges: low-alpha (10 to 11 Hz), high-alpha (12 to 13 Hz), low-beta (16 to 17 Hz), and high-beta (22 to 23 Hz) bands. The main findings were a greater overall activation and, more specifically, a pronounced bilateral activation of sensorimotor regions in elderly subjects for both alpha bands. Additionally, in the elderly subjects there was increased activation of the mesial frontocentral cortex (supplementary motor area region) in the high-beta band, whereas younger volunteers had a prominent activation of the left lateral premotor and sensorimotor region in this frequency range. CONCLUSIONS: These findings demonstrate that the functional anatomy of the human motor system changes during normal aging. It appears that, for a given motor task, the aging brain recruits additional primary sensorimotor and premotor regions of both hemispheres.

Adolescent↗

Long-term functional consequences of transient occlusion of the middle cerebral artery in rats: a 1-year follow-up of the development of epileptogenesis and memory impairment in relation to sensorimotor deficits.

Post-stroke seizures occur in 5-20% of patients. Modeling of stroke-induced seizures in animals provides a useful tool for investigating the molecular basis of epileptogenesis and for developing therapies for stroke patients at increased risk for epileptogenesis. The questions addressed in the study were: (1) Do rats develop spontaneous seizures after transient occlusion of the middle cerebral artery (MCAO)? (2) Is epileptogenesis associated with impaired hippocampus-dependent spatial learning and memory? (3) Are the functional abnormalities linked to axonal plasticity in the dentate gyrus? (4) Does the sensorimotor impairment induced by MCAO predict the risk of epileptogenesis? Adult male Sprague-Dawley rats were subjected to MCAO for 120 min. Development of spontaneous seizures was monitored by 1 week of continuous video-electroencephalographic (EEG) recordings at 3, 7, and 12 months after MCAO. Spontaneous seizures were not detected during 1-year follow-up in ischemic rats. Animals were, however, impaired in the spatial memory task (P<0.001), which was not associated with altered hippocampal LTP or abnormal mossy fiber sprouting (Timm staining). Animals also had a long-lasting sensorimotor deficit (P<0.05). The present study indicates that MCAO causes long-lasting sensorimotor and spatial memory impairment, but does not induce epileptogenesis or spontaneous seizures.

Animals↗

Parallel cortical networks for volitional control of swallowing in humans.

A number of studies have demonstrated the involvement of parallel networks in the control of voluntary sequential motor procedures. We sought to determine whether a parallel network organization may be found for complex, sequentially based motor systems that are the product of both voluntary and automatic control processes. Specifically, we sought to determine whether the cortical organizational scheme for voluntary repetitive swallowing in adult humans is characterized by a hierarchical dual-projection model or by modules organized into parallel systems. We utilized functional magnetic resonance imaging (fMRI) to investigate cortical function during normal swallowing tasks in eight healthy human adults. Subjects performed both dry (saliva) and bolus (3 ml/bolus of water) swallows. Activation during swallowing tasks localized to sensorimotor areas (M1, S1, and SMA), S2, premotor cortex, posterior parietal cortex, cingulate gyrus, inferior frontal gyrus, the cerebellum, the insular cortex, auditory cortex, corpus callosum, and the basal ganglia and thalamus. Principal components analysis (PCA) of these regions revealed five functional clusters or modules: (1) sensorimotor areas and cingulate gyrus; (2) inferior frontal gyrus, S2, corpus callosum, basal ganglia and thalamus; (3) premotor cortex and posterior parietal cortex; (4) cerebellum; and (5) insula. Analysis of the functional relationship between these areas demonstrated two parallel loops defined by connections to either the cerebellum or insula and connected through the sensorimotor-cingulate module. Path analysis was performed to test the hypothesis of modules organized into parallel loops versus a hierarchical dual-projection model consisting of two separate, singular hierarchical serial pathways from the sensorimotor cortex or insula to the thalamus. These results support the model of modules organized into parallel loops (P=0.8), but not the hierarchical dual-projection model (P<0.0001). Organization of the control of voluntary repetitive swallowing into two parallel systems may confer the ability to effectively coordinate and integrate this highly complex sequentially based motor behavior.

Adult↗

Synchronised oscillations of the human sensorimotor cortex.

Oscillations are a prominent feature of macroscopic human sensorimotor cortical activity as recorded non-invasively with electroencephalography (EEG) and magnetoencephalography (MEG). The advent of whole-scalp MEG systems allowing rapid non-invasive recording from the entire cortex and accurate localisation of neural sources, and the development of refined signal analysis methods are important factors that led to an increasing interest in studies of sensorimotor oscillations during the last 10 years. Investigations on healthy subjects revealed frequency-specific localisation and modality-specific reactivity of 10 Hz and 20 Hz sensorimotor oscillations. Task-specific coherence between motor cortical and electromyographic oscillations, reflecting cortico-motoneuronal coupling, point towards a functional role of precentral oscillations in the cortical control of voluntary movements. Furthermore, abnormal cortico-motoneuronal coupling may underlie clinical symptoms of motor disorders, such as tremor. Thus, investigation of oscillatory sensorimotor activity proceeds from phenomenology to function and provides an interesting approach to address questions in human motor physiology and pathophysiology.

Cortical Synchronization↗

Age-related decline of presumptive inhibitory synapses in the sensorimotor cortex as revealed by the physical disector.

The synapse, as the site of functional neural interaction, has been suggested as a possible substrate for age-related impairment of cognitive ability. Using the physical disector probe with tissue prepared for ultrastructural analysis, we find an age-related decline in the numerical density of presumptive inhibitory synapses in layer 2 of the sensorimotor cortex of the Brown Norway x Fisher 344 rat. This age-related decline in presumptive inhibitory synapses is maintained when the density of synapses is combined with the numerical density of neurons quantified from the same anatomical space to arrive at a ratio of synapses per neuron. The numerical density of these synapses declines between middle-aged (18 months) and old (29 months) animals by 36% whereas numerical density of neurons does not change between these ages, resulting in a decline in the ratio of presumptive inhibitory synapses per neuron in this cortical area. This study demonstrates a deficit in the intrinsic inhibitory circuitry of the aging neocortex, which suggests an anatomical substrate for age-related cognitive impairment.

Aging↗

A new view of hemineglect based on the response properties of parietal neurones.

Lesion studies of the parietal cortex have led to a wide range of conclusions regarding the coordinate reference frame in which hemineglect is expressed. A model of spatial representation in the parietal cortex has recently been developed in which the position of an object is not encoded in a particular frame of reference, but instead involves neurones computing basis functions of sensory inputs. In this type of representation, a nonlinear sensorimotor transformation of an object is represented in a population of units having the response properties of neurones that are observed in the parietal cortex. A simulated lesion in a basis-function representation was found to replicate three of the most important aspects of hemineglect: (i) the model behaved like parietal patients in line-cancellation and line-bisection experiments; (ii) the deficit affected multiple frames of reference; and (iii) the deficit could be object-centred. These results support the basis-function hypothesis for spatial representations and provide a testable computational theory of hemineglect at the level of single cells.

Apraxias↗

Functional skill regression in late-stage dementias.

One hundred fifty-two institutionalized persons with late-stage dementia were rated with a geriatric developmental screening scale that notes cognitive, language, sensorimotor, and self-care abilities. The results showed that the loss of functional abilities in late-stage dementias seems to occur in reverse order of their development in childhood. Developmental congruence was noted within these persons regardless of diagnosis. In addition, the average functional age rating correlated well with scores from the Folstein Mini Mental State examination (MMS) (Folstein, Folstein, & McHugh, 1975): The close correlation between scores indicates that the MMS is a fast and simple tool for predicting not only cognitive impairment but also the approximate stage of functional development.

Activities of Daily Living↗

Functional topography of the secondary somatosensory cortex for nonpainful and painful stimuli: an fMRI study.

The regional activity of the contralateral primary (SI) and the bilateral secondary (SII) somatosensory areas during median nerve stimulations at five intensity levels (ranging from nonpainful motor threshold to moderate pain) was studied by means of functional magnetic resonance imaging (fMRI). The aim was to characterize the functional topography of SII compared to SI as a function of the stimulus intensity. Results showed that the galvanic stimulation of the median nerve activated the contralateral SI at all stimulus intensities. When considered as a single region, SII was more strongly activated in the contralateral than in the ipsilateral hemisphere. When a finer spatial analysis of the SII responses was performed, the activity for the painful stimulation was localized more posteriorly compared to that for the nonpainful stimulation. This is the first report on such a SII segregation for transient galvanic stimulations. The activity (relative signal intensity) of this posterior area increased with the increase of the stimulus intensity. These results suggest a spatial segregation of the neural populations that process signals conveyed by dorsal column-medial lemniscus (nonpainful signals) and neospinothalamic (painful signals) pathways. Further fMRI experiments should evaluate the functional properties of these two SII subregions during tasks involving sensorimotor integration, learning, and memory demands.

Adult↗

Accumbens D2 modulation of sensorimotor gating in rats: assessing anatomical localization.

The normal reduction in acoustic startle amplitude caused by a weak prepulse (prepulse inhibition; PPI) is deficient in schizophrenic patients and in rats after systemic or intraaccumbens treatment with the D2 dopamine agonist quinpirole. We examined the anatomical substrates of the PPI-disruptive effects of intraaccumbens quinpirole. PPI was significantly reduced in a dose-dependent manner by quinpirole infusion into the medial accumbens shell region, the lateral accumbens core region, and an intermediate central region. There was a weak tendency for this quinpirole effect to be more pronounced in core and central accumbens regions than in the medial and anteromedial accumbens. Using the retrograde tracer Nuclear yellow, shell and core regions were verified to receive different patterns of limbic cortical innervation. Although the accumbens appears to have a complex and functionally diversified intrinsic anatomy, the accumbens D2 modulation of sensorimotor gating appears to be distributed across several different accumbens subregions.

Acoustic Stimulation↗

Transplantation of fetal neocortex ameliorates sensorimotor and locomotor deficits following neonatal ischemic-hypoxic brain injury in rats.

Ischemic brain injury in neonates can result in the degeneration of cortical and subcortical areas of brain and is associated with neurologic deficits. One approach to restoring function in conditions of ischemic brain injury is the use of neural transplants to repair damaged connections. This approach has been shown to reestablish neural circuitry and to ameliorate associated motor deficits in models of neonatal sensorimotor cortex damage. In this study, we utilized the Rice et al. rodent model of neonatal ischemic-hypoxic (IH) brain injury to assess whether transplantation of fetal neocortical tissue can promote functional recovery in tests of sensorimotor and locomotor ability throughout development and as adults. We show that animals that received neocortical grafts 3 days following the IH injury performed significantly better as adults on two measures of motor ability, the Rota-Rod treadmill and apomorphine-induced rotations, than did control animals that received sham transplants after the IH injury. Transplants were identifiable in 72% of the animals 10-12 weeks after implantation. Histochemical studies revealed that while the transplanted tissue did not establish normal cortical cytoarchitecture, cells and fibers within the grafts stained for nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d), choline acetyl transferase (ChAT), cholecystokinin (CCK), and glial fibrillary acidic protein (GFAP). These results suggest that transplantation of fetal neocortical tissue following IH injury in the neonatal period is associated with amelioration of motor deficits and that the grafted tissue demonstrated a neurochemical phenotype that resembled normal neocortex. This approach warrants continued investigation in light of potential therapeutic uses.

Animals↗

The central sulcal vein: a landmark for identification of the central sulcus using functional magnetic resonance imaging.

The authors evaluated the anatomical location of the central sulcus (CS) in 24 cerebral hemispheres (eight in which tumors were located centrally, 16 in controls) using: 1) classic anatomical landmarks seen on magnetic resonance (MR) imaging (24 hemispheres); 2) functional MR imaging (24 hemispheres); and 3) intraoperative electrical stimulation mapping (eight hemispheres). On MR imaging the CS was identified with certainty in 79% of hemispheres (four of eight in patients, 15 of 16 in controls). Functional MR imaging identified a parenchymal "motor hand area" in only 83% (20 of 24 hemispheres; five of eight in patients, 15 of 16 in controls); this area was located in the precentral gyrus in 16 (80%) of 20, additionally in the postcentral gyrus in 10 (50%) of 20, and exclusively in the postcentral gyrus in four (20%) of 20. In contrast, functional MR imaging detected one to three sulcal veins presumably draining blood from the adjacent motor hand area in 100% (24 of 24) of the hemispheres studied, and anatomical MR imaging and intraoperative mapping localized these veins in the CS. It is concluded that sulcal veins lying deep within the CS: 1) drain activated blood from the adjacent pre- or postcentral cortex during performance of a motor hand task; 2) can be identified easily with functional MR imaging; and 3) are an anatomical landmark for noninvasive identification of the CS and thus the sensorimotor strip. The detection of these veins provides a more consistent landmark than the detection of parenchymal motor areas by functional MR imaging; this technique may be used when classic anatomical landmarks fail to identify the sensorimotor strip.

Adult↗

Metabolic mapping of rat striatum: somatotopic organization of sensorimotor activity.

Diseases that affect the striatum produce movement disorders, for which rats have been a useful model. To determine the organization of functional, neural activity in the rat striatum related to motor activity, we used electrical stimulation of the motor cortex and [14C]deoxyglucose autoradiography. The stimulation produced movements of each of three body regions. Both the motor and somatosensory cortex were activated. Image analysis was used to objectively localize peak activation and to provide a map for further stereotaxic and localization studies. In the anterior striatum, in the dorsolateral sector, regions of peak activation were well separated for each body region: the hindlimb peak activation was dorsomedial, the forelimb ventrolateral and vibrissae medial. Also, the activation fields were larger in anterior than in posterior striatum. Furthermore, activation ipsilateral to movement was present and the peak localization was offset from peaks contralateral to movement. In addition, there were activation regions in lateral striatum where body region representations may overlap. This is the first demonstration of a global striatal somatotopy that separates the limbs and vibrissae in rats. The functional average revealed by the deoxyglucose autoradiography showed a predominant isotropic or rod-like representation of sensorimotor activity for the limbs in striatum during movement and confirms aspects of the anatomy known for the corticostriate system in primates: metabolism was 'patchy,' and extended throughout long anteroposterior domains in striatum. These extensive and patchy arrangements suggest integrative, combinational and/or associative networks.

Animals↗

Where is 'where' in the human auditory cortex?

We examine the functional characteristics of auditory cortical areas that are sensitive to spatial cues in the human brain, and determine whether they can be dissociated from parietal lobe mechanisms. Three positron emission tomography (PET) experiments were conducted using a speaker array permitting quasi free-field sound presentation within the scanner. Posterior auditory cortex responded to sounds that varied in their spatial distribution, but only when multiple complex stimuli were presented simultaneously, implicating this cortical system in disambiguation of overlapping auditory sources. We also found that the right inferior parietal cortex is specifically recruited in localization tasks, and that its activity predicts behavioral performance, consistent with its involvement in sensorimotor integration and spatial transformation. These findings clarify the functional roles of posterior auditory and parietal cortices, and help to reconcile competing models of auditory cortical organization.

Acoustic Stimulation↗

Phase correction in sensorimotor synchronization: nonlinearities in voluntary and involuntary responses to perturbations.

When finger taps are synchronized with an auditory sequence, both a global phase shift (PS) and a local event onset shift (EOS) in the sequence elicit a phase correction response (PCR) on the next tap. The PCR to an expected PS is intended and large, whereas that to an expected EOS is unintended and smaller. PCR magnitude increases linearly with perturbation magnitude up to about +/-15% of the sequence period (500 milliseconds). With larger perturbations, voluntary PCRs increase more slowly whereas involuntary PCRs reach an asymptote. These results, obtained previously in a blocked design [J. Exp. Psychol. Human Percept. Perform. (in press)], were replicated in a randomized design and in two additional task contexts that varied participants' intentions while neutralizing their expectations. Neither design nor expectations seemed to play a role. However, considerable individual differences were noted. The results confirm that phase correction is partially automatic and partially subject to voluntary control, and they provide empirical estimates of error correction functions that may be useful in formal modeling of sensorimotor synchronization behavior.

Adult↗