Magdalena Sabate

Brain lateralization of motor imagery: motor planning asymmetry as a cause of movement lateralization

Movement asymmetry in humans and animals is often considered as being induced by the brain lateralization of the motor system. In the present work, the hemispheric asymmetry for motor planning as a cause of behavioral lateralization was examined. This study was carried out on normal volunteers and patients suffering unilateral brain damage caused by a stroke. Motor planning was evaluated by using the motor imagery of hand movement, a mental representation of a motor pattern that includes its internal simulation but not its real execution. The present study shows marked similarities between virtual movement executed during motor imagery and real movements. Thus, performance time showed a high correlation between real and virtual movements in the following conditions: (1) during dominant and non-dominant hand movements; (2) in simple and complex motor tasks; (3) in young control subjects; (4) in stroke patients; and (5) control subjects aged-matched to stroke patients. Brain strokes increased the performance time in both real and virtual movements. Left-brain strokes decreased the velocity of the real movements in both hands, whereas right-brain strokes mainly disturbed movements in the left hand. A similar effect was observed for virtual movements, suggesting a left-brain dominance for motor planning in humans. However, two-handed movement tasks suggest a complex interaction during motor planning, an interaction that facilitates motor performance during mirror movements and delays motor execution during non-mirror movements.

Obstructive and restrictive pulmonary dysfunctions in Parkinson's disease

Pulmonary dysfunction was investigated in fifty-eight Parkinsons patients. Clinical disability was assessed by the Unified Parkinsons Disease Rating Scale. Pulmonary dysfunction was studied by spirometry with flow-volume loops, body plethysmography with lung volumes computation and maximal inspiratory and expiratory static mouth pressures. Forced vital capacity (FVC), forced expiratory volume in 1 min (FEV1), FEV1/FVC% and arterial PO2 and PCO2 were significantly below normal values. Residual volume (RV) and total rows were above normal values. Thirty-six had upper airway obstruction as judged by inspiratory flow peaks (PIF) < 3 l/s and FEV1/PEF (expiratory flow peak) > 8.5 l/min and MEF50/MIF50 > 1. Eighteen patients had a central (FEV1 < 80% and FEV1/FVC% < 80% of normal values) or peripheral (maximal expiratory flow between 75% and 25% of FVC and maximal expiratory flow after expiration of 50% below 70% of normal values) obstructive pattern. Sixteen patients had a restrictive dysfunction as judged by a total lung capacity < 85% or FVC < 80% with FEV1/FVC% > 80%. Sixteen patients had air trapping (RV > 120% and RV/TLC > 40%) and seven patients had lung insufflation (TLC > 120%). Rigidity, Rx signs of cervical arthrosis and limitations for passive movement of neck were higher in patients with central or peripheral airway obstruction. Bradykinesia and Rx signs of dorsal arthrosis was higher in patients with upper airway obstruction. Restrictive dysfunction was not related to tremor, rigidity or bradykinesia. The present data support the hypothesis that Parkinson patients present a high risk for pneumologic disturbances. These pulmonary dysfunctions are induced by the simultaneous action of a group of factors including the degree of bradykinesia or rigidity and the musculoskeletal limitations of vertebral column probably induced by chronic anomalous posture.

Parkinson's disease as a result of aging

It is generally considered that Parkinsons disease is induced by specific agents that degenerate a clearly defined population of dopaminergic neurons. Data commented in this review suggest that this assumption is not as clear as is often thought and that aging may be critical for Parkinsons disease. Neurons degenerating in Parkinsons disease also degenerate in normal aging, and the different agents involved in the etiology of this illness are also involved in aging. Senescence is a wider phenomenon affecting cells all over the body, whereas Parkinsons disease seems to be restricted to certain brain centers and cell populations. However, reviewed data suggest that Parkinsons disease may be a local expression of aging on cell populations which, by their characteristics (high number of synaptic terminals and mitochondria, unmyelinated axons, etc.), are highly vulnerable to the agents promoting aging. The development of new knowledge about Parkinsons disease could be accelerated if the research on aging and Parkinsons disease were planned together, and the perspective provided by gerontology gains relevance in this field.

Obstructive and restrictive pulmonary dysfunction increases disability in Parkinson disease

OBJECTIVE The purpose of this study was to determine in Parkinson disease the impact of pulmonary dysfunction on daily living activities (DLA). PATIENTS Extrapyramidal motor impairment, pulmonary dysfunction, and DLA disabilities were studied in 58 Parkinson patients consecutively enrolled in a rehabilitation service at a university hospital. MAIN OUTCOME MEASURES Extrapyramidal motor impairments were assessed by the Unified Parkinsons Disease Rating Scale (UPDRS) and the DLA disabilities by the UPDRS, Hoehn-Yahr, and Schwab-England scales. The pulmonary dysfunctions were assessed by spirometry with flow-volume loops, body plethysmography with lung volumes computation, and maximal inspiratory and expiratory static mouth pressures. RESULTS Parkinson patients showed important modifications of pulmonary function with a decrease in forced vital capacity, forced expiratory volume in the first minute, and arterial PO2, and an increase in residual volume and total airway resistance (RAW). In addition, they showed a high incidence of airway ventilatory obstructions and restrictive dysfunction. The impact of lung disease on daily living activities in Parkinson disease patients was higher in subjects with restrictive pulmonary dysfunctions (Schwab-England test and turning in bed and adjusting bedclothes, walking, falling, and freezing when walking items of UPDRS) and airway obstructions (handling utensils, dressing and hygiene items of UPDRS). CONCLUSIONS Airway obstructions or restrictive pulmonary dysfunctions present a high prevalence in Parkinson disease, contributing as a main factor for DLA dysfunctions. The evaluation and rehabilitation of respiratory disturbances should be systematically included in the management of these patients.

Disturbance of motor imagery after cerebellar stroke.

The authors studied the possible involvement of the cerebellum in nonexecutive motor functions needed for a normal performance of complex motor patterns by analyzing (using chronometric evaluation) finger movement sequences and their respective motor imagery (a mental simulation of motor patterns). Patients suffering from a cerebellar stroke (n=11) were compared with aged-matched control volunteers (n=11). Patients that had apparently recovered from a unilateral cerebellar stroke showed a marked slowing of motor performance in both hands (ipsi- and contralateral to lesion). This effect was accompanied by a similar slowing of motor imagery, suggesting that the cerebellum, traditionally implicated in the control of motor execution, is also involved in nonexecutive motor functions such as the planning and internal simulation of movements.

Hand movement distribution in the motor cortex: the influence of a concurrent task and motor imagery

The aim of this work was to study the relevance of the primary motor cortex (M1) for motor functions different to the simple execution of motor orders. The M1 activity during the performance with individual fingers of a simple motor task (tonic flexion), a motor task that includes a complex motor computation but not motor execution (motor imagery), and a motor task that involves both the computation and execution of movements (phasic movement) was evaluated by functional magnetic resonance imaging (fMRI). The possible influence of other cortical tasks on the M1 activation induced by finger movements was assessed by evaluating the effect of a distracting concurrent task (numeric calculation). Data show that both the dimension of the area activated and the intensity of response were higher during motor planning than during motor execution. There is a mosaic-like distribution for motor-planning M1 functions, with the movement of individual fingers being controlled from several M1 loci. The concurrent mental-task induces a rapid functional reconfiguration of M1, adding M1 subsets to motor programming but excluding others. Present data support the involvement of the M1 in more than just simple motor execution, showing broader and more intense modifications during motor tasks not accompanied by movements (motor imagery) than during the execution of simple motor acts (tonic flexion).

Glial regulation of nonsynaptic extracellular glutamate in the substantia nigra

GLU is the main neurotransmitter in the brain, where it induces a synaptic excitatory action. There is recent evidence for an extracellular nonsynaptic GLU (EnS‐GLU) pool in different brain nuclei that, released from glial cells, may act on extrasynaptic GLU receptors of cells located far from the position in which it was released. In the present work, the EnS‐GLU pool was studied with microdialysis in the rat substantia nigra (SN). We observed an EnS‐GLU pool that increased in a Ca2+‐dependent manner during cell depolarization. The selective alteration of with methionine sulfoximide (MSO) and fluorocitrate induced marked modifications in EnS‐GLU suggesting that EnS‐GLU is dependent on glial cells. Glutamine administration increased GLU, suggesting that neurons are also involved in EnS‐GLU modulation. GLU administered in the rostral SN showed a long‐distance diffusion to the caudal SN. The ionotropic GLU receptors agonist N‐methyl‐D‐aspartate and kainate and the metabotropic GLU receptors agonist ACPD increased EnS‐GLU and decreased extracellular glutamine. Taken together, these data indicate that nigral glia releases GLU, which probably performs a volume transmitter role.

Adapting movement planning to motor impairments: the motor-scanning system.

Previous studies have reported a similar duration for movement execution (real movement) and its internal simulation with motor imagery (virtual movement). The present work has studied the real movement-virtual movement relationship for complex sequences of finger movements after different acute and chronic brain lesions and after a long-lasting restriction of right-hand movements. Age, hand-movement restriction and lesions of pyramidal system, basal ganglia and cerebellum did not prevent the high real movement-virtual movement correlation. The data suggest that movement execution and its internal simulation share the same neuronal basis. However, the calculation of virtual delay (a useful procedure for detecting small real movement-virtual movement differences) showed significant real movement-virtual movement mismatches, suggesting the existence of a separate and selective system that, continuously scanning the competence of the different elements participating in motor behavior, adjusts the planning of future movements to the real capability of the motor system.

Firing regulation in dopaminergic cells: effect of the partial degeneration of nigrostriatal system in surviving neurons

Two mechanisms for firing rate regulation were identified in dopaminergic nigrostriatal cells (DA cells), one of a renewal nature which prevents short and long interspike intervals (ISIs) and the other of a no‐renewal nature which compensates long ISIs with short ISIs and vice versa. Renewal regulation was found in 96% of DA cells and less frequently in nigrocollicular (63%), nigrothalamic (61%) and nigropeduncular (50%) nigral GABA cells. No‐renewal regulation was found in 77% of DA cells, and was only observed in 8% of GABA cells. Thus, most DA cells showed both regulatory mechanisms, which justifies the low variability in their firing rate and the low oscillation of extracellular striatal dopamine previously reported. DA cells surviving a partial degeneration of the nigrostriatal system did not show alterations in their firing rate and burst firing but presented a marked disturbance for no‐renewal regulation. Under these conditions, small fluctuations in firing rate are not compensated for in time, which could be one of the factors responsible for the motor fluctuations often observed in advanced Parkinsons disease.

Striatal glutamate induces retrograde excitotoxicity and neuronal degeneration of intralaminar thalamic nuclei: their potential relevance for Parkinson's disease

An over‐stimulation of nigral glutamate (GLU) receptors has been proposed as a cause of the progression of the dopamine (DA) cell degeneration (excitotoxicity) which characterizes Parkinsons disease. The possible toxic action of striatal GLU (retrograde excitotoxicity) on these cells, and on other neurons which innervate the striatum and which also degenerate in Parkinsons disease (thalamostriatal cells of the intralaminar thalamic nuclei), is still practically unexplored. The retrograde excitotoxicity of striatal GLU on DAergic mesostriatal and GLUergic thalamostriatal cells was tested here by studying these cells 6 weeks after striatal perfusion of GLU by reverse microdialysis. GLU perfusion induced the striatal denervation of thalamic inputs (as revealed by vesicular glutamate transporter 2) and the remote degeneration of intralaminar neurons. In both centres, these effects were accompanied by microglial activation. Similar responses were not observed for nigrostriatal neurons, which showed no dopaminergic striatal denervation, no microglial activation in the substantia nigra and no changes in the number of dopaminergic cells in the substantia nigra. The inhibition of DAergic transmission increased the extrasynaptic GLU levels in the striatum (evaluated by microdialysis), an effect observed after the local administration of agonists and antagonists of DAergic transmission, and after the peripheral administration of levodopa (which increased the DA and decreased the GLU levels in the striatum of rats with an experimental DAergic denervation of this centre). The data presented show that striatal GLU induced a retrograde excitotoxicity which did not affect all striatal inputs in the same way and which could be involved in the cell degeneration of the intralaminar nuclei of the thalamus generally observed in Parkinsons disease.