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Quantitative EEG analysis during motor function and music perception in Tourette's syndrome.

Gilles de la Tourette's syndrome (TS) is a neurobehavioral disorder of childhood onset that is characterized by motor and vocal tics and associated behavioral disturbances including obsessive-compulsive symptoms. We performed 30 channel quantitative electroencephalograms (EEGs) on 13 Tourette patients and 26 controls and studied both resting and manumotor/music perception activation conditions. Resting EEGs did not show any differences between patients and controls, as known from the literature. However, during simple and complex hand movements, as well as music perception tasks, there were subtle differences predominantly in alpha frequency. They suggested reduced brain activation during motor tasks in frontal and central regions, and on music perception in temporal and parietal regions, respectively. These findings may add evidence to the functional neuroanatomy of Tourette syndrome, affecting more areas than disturbed motor circuits.

Adolescent↗

Peri-infarct reorganization of motor function in patients with pontine infarct.

OBJECTIVES: Combined functional MRI (fMRI) and diffusion tensor tractography (DTT) imaging provides a powerful vehicle for the investigation of motor recovery mechanisms. Using this combined method, we investigated the motor recovery mechanism in patients with pontine infarct. DESIGN: We evaluated six healthy control subjects and two patients with pontine infarct at 6 months from onset. fMRI was performed at 1.5 T with timed hand grasp-release movements. For DTT, we used each of the 32 noncollinear diffusion-sensitizing gradients. Three-dimensional reconstructions of the fiber tracts were obtained with FA <0.3, angle >45 degrees as termination criteria. RESULTS: fMRI data revealed activation only in the contralateral primary sensorimotor cortex during movement of either hand. DTI findings from controls and the unaffected hemisphere of the patients showed that the corticospinal tract descended through the known corticospinal tract pathway. However, the tracts of the affected hemisphere in the patients were observed to pass along peri-infarct areas (patient 1: lateral, patient 2: posterior) in the pons. CONCLUSIONS: It seems that the peri-infarct areas compensate for corticospinal tract damage at the pons; this may be one mechanism of motor recovery for patients with pontine infarct.

Adult↗

Polymer-encapsulated PC12 cells promote recovery of motor function in aged rats.

The feasibility of using polymer-encapsulated PC12 cells to ameliorate the motor deficits in aged rats was evaluated. Spontaneous locomotion and motor coordination was evaluated in young (5-6 month) and aged (24-25 month) rats. Aged animals tested for spontaneous locomotor activity in Digiscan animal activity monitors were found to be hypoactive relative to young animals. Compared to the young animals the aged animals: (1) remained suspended from a horizontal wire for less time, (2) were unable to descend a wooden pole covered with wire mesh in a coordinated manner, (3) fell more rapidly from a rotating rod, and (4) were unable to maintain their balance on a series of wooden beams with either a square or rounded top of varying widths. Prior to implantation PC12 cell-loaded capsules were chromatographically characterized for catecholamine release. Following baseline testing, aged animals received either no implant, empty capsules, or PC12 cell-loaded capsules implanted bilaterally into the striatum. Three weeks following surgery, animals were retested and a significant improvement in balance on the rotorod and wooden beams was observed in those aged animals receiving PC12 cell-loaded capsules. No recovery was observed in the animals receiving PC12 cell-loaded capsules on any of the other motor tasks. Likewise, no improvement was observed on any behavioral measure in those animals receiving empty capsules. Histological analysis revealed the presence of numerous surviving tyrosine hydroxylase-positive PC12 cells within the capsules. Encapsulated PC12 cells survive following implantation into aged rats and such a technique may be useful for treating some of the behavioral consequences of aging.

Aging↗

[The thalamus: motor functions].

Thalamic nuclei constitute the diencephalic relay system between different afferent systems and the telencephalon. The "motor" thalamus links cerebellar and pallidal afferents with the motor and pre-motor cortical regions. Separation of pallido-thalamo-cortical and cerebello-thalamo-cortical pathways is relatively complete: afferents of pallidal origin are relayed by thalamic nuclei VA, VLo and VLm and are projected onto prefrontal and supplementary motor areas whereas afferents of cerebellar origin are relayed in the VL and VPLo and then projected onto motor areas 4.6 and parietal areas 5 and 7. This report is concerned mainly with the analysis of the motor thalamus as a relay system for afferents of cerebellar origin. The anatomofunctional organization of the cerebello-thalamo-cortical tract possesses a topographic arrangement and also wide convergences and appears able to participate in the realization, through the motor cortex, of motor synergies and of co-ordinating postures and movements. The cerebello-cortical tract apparently plays a different role during learning of a movement and executing an automatized movement. For the latter, it is involved in their onset and in their completion. Its contribution to fine control of temporal parameters of motor commands or control of peripheral afferent messages is not decisive. During learning of a movement the cerebello-cortical tract plays a predominant role. According to Ito, the cerebellum is involved in the process of automatization of a movement, organized initially entirely by the cortex and then becoming progressively subcortical. Plasticity of cerebellar microcircuits could be the basis for these automatization processes expressed through the cerebello-thalamo-cortical tract.

Animals↗

Adenosinergic mechanisms underlying recovery of diaphragm motor function following upper cervical spinal cord injury: potential therapeutic implications.

OBJECTIVES: In adult rats, a latent respiratory motor pathway can be pharmacologically activated with 1,3-dimethylxanthine (theophylline) to restore respiratory-related activity to a hemidiaphragm paralysed by an ipsilateral upper cervical (C2) spinal cord hemisection. The purpose of this review is to describe mechanisms that underlie theophylline-induced recovery of respiratory-related function following C2 hemisection and to underscore the therapeutic potential of theophylline therapy in spinal cord injured patients with respiratory deficits. METHODS: Theophylline mediates recovery of respiratory-related activity via antagonism of central adenosine A(1) receptors. When administered chronically, the drug restores and maintains recovered function. Since theophylline is an adenosine receptor antagonist with affinity for both the adenosine A(1) and A(2) receptors, we assessed the relative contributions of each receptor to functional recovery. While A(1) receptor antagonism plays a predominant role, activation of the A(2) receptors by specific agonists subserves the A(1) receptor-mediated actions. That is, when an adenosine A(2) receptor agonist is administered first, it primes the system such that subsequent administration of the A(1) antagonist induces a greater degree of recovered respiratory activity than when the antagonist alone is administered. RESULTS: Chronic oral administration of theophylline in C2 hemisected animals demonstrates that even when animals have been weaned from the drug, theophylline-induced recovered respiratory actions persist. This suggests that in clinical application, it may not be necessary to maintain patients on long-term theophylline. We have shown that recovery of respiratory-related activity in the ipsilateral phrenic nerve can occur spontaneously 3-4 months after C2 hemisection. Theophylline administration after this post-injury period obliterates/negates the recovery function. This indicates strongly that there is therapeutic window (more acutely after injury) for the initiation of theophylline therapy. We have also demonstrated that peripheral (carotid bodies) adenosine A(1) receptors can be selectively activated to modulate theophylline-induced CNS actions. Blocking central adenosine receptors while simultaneously activating peripheral adenosine receptors minimizes the potential of respiratory muscle fatigue with theophylline. DISCUSSION: The significance of the current findings lies in the potential clinical application of theophylline therapy in spinal cord injured patients with respiratory deficits. The ultimate goal of theophylline therapy is to wean ventilator-dependent patients off ventilatory support. Thus far, our animal studies suggest that the onset of theophylline therapy must be soon after injury.

Animals↗

Correlation of corpus callosal morphometry with cognitive and motor function in periventricular leukomalacia.

PURPOSE: We aim to correlate size and shape of corpus callosum with severity of motor and cognitive impairments in children with periventricular leukomalacia (PVL). METHODS: Children with PVL were stratified based on the severity of their motor and cognitive impairments. An age-matched control group was established. The corpus callosum was identified on mid-sagittal T (1)-weighted spin-echo (TR/TE: 550/15) MR images. The shape characteristics of the corpus callosum were measured with respect to a template via a shape transformation. The degree of callosal-shape transformation was quantified by a deformation function, which in turn was compared, using point-wise T-tests, for controls versus patients, diplegic versus quadriplegic patients, and patients with mild versus severe cognitive impairment. RESULTS: 29 children with spastic cerebral palsy and PVL and 32 age-matched controls were identified. In the PVL group, the entire corpus callosum was significantly smaller than in the control group (p value = 0.001). Significant differences existed in the shape of the corpus callosum between patients with diplegic versus quadriplegic and between patients with severe versus mild cognitive impairment. CONCLUSION: Global and regional corpus callosal morphology can be quantified using deformation functions.

Adolescent↗

[2 objective procedures for the assessment of motor functions after surgery of the tongue and velum].

Commonly, only radiographic procedures have been used up to now for the assessment of intraoral movements during swallowing, speech and voluntary motor activities. In this article two methods for assessing intraoral function without involving radiation exposure are described: palatography and electromagnetic articulography. Palatography is particularly useful as a screening procedure for the evaluation of certain lingual motor activities in patients who had undergone tumor surgery. Electromagnetic articulography (EMA) allows vector analyses of lingual and soft palate movements. Data of normal subjects, surgically treated cleft palate and tumor patients are demonstrated. Both methods are biologically safe and non-invasive and do not interfere to any significant degree with the functions to be analysed.

Deglutition↗

Normal sphincter of oddi motor function.

With the introduction of endoscopic retrograde cholangiopancreatography (ERCP) manometry, the characteristics of sphincter of Oddi (SO) motor activity have been described. SO manometry is the only available method to measure SO motor activity directly and is usually performed at the time of ERCP. SO manometry is considered to be the gold standard for evaluating patients for sphincter dysfunction. This review reports the technique of SO manometry and normal values for SO manometry. SO motility is characterized by prominent phasic contractions superimposed on a tonic pressure. Elevated basal SO pressure is the most consistent and reliable criteria to diagnose SO dysfunction. Basal pressures obtained from the biliary sphincter are similar to the basal pressure obtained from the pancreatic sphincter. Abnormal SO manometric values are shown. Factors that influence SO pressures, and interpretation of SO manometric tracing are discussed. The most common and serious complication of SO manometry is post-manometry pancreatitis. In healthy volunteers with normal sphincter function, pancreatitis is almost never seen. However, in patients with SO dysfunction, the incidence of pancreatitis is high. The use of new nonperfused microtransducers may reduce this complication.

Catheterization↗

The third P-loop domain in cytoplasmic dynein heavy chain is essential for dynein motor function and ATP-sensitive microtubule binding.

Sequence comparisons and structural analyses show that the dynein heavy chain motor subunit is related to the AAA family of chaperone-like ATPases. The core structure of the dynein motor unit derives from the assembly of six AAA domains into a hexameric ring. In dynein, the first four AAA domains contain consensus nucleotide triphosphate-binding motifs, or P-loops. The recent structural models of dynein heavy chain have fostered the hypothesis that the energy derived from hydrolysis at P-loop 1 acts through adjacent P-loop domains to effect changes in the attachment state of the microtubule-binding domain. However, to date, the functional significance of the P-loop domains adjacent to the ATP hydrolytic site has not been demonstrated. Our results provide a mutational analysis of P-loop function within the first and third AAA domains of the Drosophila cytoplasmic dynein heavy chain. Here we report the first evidence that P-loop-3 function is essential for dynein function. Significantly, our results further show that P-loop-3 function is required for the ATP-induced release of the dynein complex from microtubules. Mutation of P-loop-3 blocks ATP-mediated release of dynein from microtubules, but does not appear to block ATP binding and hydrolysis at P-loop 1. Combined with the recent recognition that dynein belongs to the family of AAA ATPases, the observations support current models in which the multiple AAA domains of the dynein heavy chain interact to support the translocation of the dynein motor down the microtubule lattice.

Adenosine Triphosphate↗

Post-lesion transcommissural olivocerebellar reinnervation improves motor function following unilateral pedunculotomy in the neonatal rat.

In the adult mammalian central nervous system, reinnervation and recovery from trauma are limited. During development, however, post-lesion plasticity may generate alternate paths providing models to investigate reinnervation and repair. Sometimes, these paths are maladaptive, although the relationship between dysfunction and anatomical abnormality remains unknown. After unilateral transection of the neonatal rat olivocerebellar path (pedunculotomy), axons from the remaining inferior olive reinnervate Purkinje cells in the denervated hemicerebellum with appropriate topography and synaptic function. However, whether this new pathway confers beneficial behavioural effects remains unknown. We studied the behavioural sequelae in rats with and without transcommissural reinnervation using righting and vestibular-drop reflexes, simple locomotion (bridge), complex locomotion (wire) and motor coordination (rotarod) tests. In animals pedunculotomised on day 3 (Px3), which develop olivocerebellar reinnervation, dynamic postural adjustments and complex motor skills develop normally, whereas simple gait is broad-based and slightly delayed. In contrast, Px11 animals, which do not develop reinnervation, have delayed maturation of postural reflexes, gait and complex locomotor skills. In addition, when compared to control animals, their performance in locomotory tasks was slower and the complex task impaired. On the rotarod, control and Px3 animals learned to coordinate their gait and walked for longer at 10 and 20 rpm than Px11 animals. These results show that transcommissural olivocerebellar reinnervation is associated with almost normal motor development and the ability to synchronise gait at slow and moderate speeds, i.e. this reinnervation confers significant behavioural function and is therefore truly compensatory.

Age Factors↗

White matter hyperintensities are related to physical disability and poor motor function.

OBJECTIVE: To determine the impact of white matter hyperintensities (WMHs) on physical health and cognitive function in 60-64 year old individuals residing in the community. METHODS: A subsample of 478 persons aged 60-64 from a larger community sample underwent brain magnetic resonance imaging (MRI) scans. WMHs on T2 weighted FLAIR (fluid attenuated inversion recovery) MRI scans were assessed using an automated procedure. Subjects were assessed for global cognitive function, episodic memory, working memory (digit span), information processing speed (Symbol Digit Modalities Test; SDMT), fine motor dexterity (Purdue Pegboard), and grip strength, and completed the Physical Component Summary of the Short Form Health Survey (SF-12). Regression analyses were used to examine the effect of WMHs on physical and cognitive function. RESULTS: Deep and periventricular WMHs were present in all subjects, with women having slightly more lesions than men. WMHs were significantly associated with poorer reported physical health on the SF-12 scale, after adjusting for depression, cognitive function, and brain atrophy. WMHs were also related to lower scores on the Purdue Pegboard test, grip strength, choice reaction time, and SDMT, but not on tests of episodic memory, working memory, general intellectual function, and global cognitive function. On regression analyses, the Purdue Pegboard test and grip strength were related to physical disability. CONCLUSION: WMHs are common, albeit mild, in middle adult life. They are associated with physical disability, possibly through reduced speed, fine motor coordination, and muscular strength. They are also related to slowed information processing speed but not other cognitive functions.

Automation↗

Effects of clozapine, thioridazine, risperidone and haloperidol on behavioral tests related to extrapyramidal motor function.

Evidence indicates that the antipsychotic drug clozapine has a low propensity for the induction of extrapyramidal motor symptoms, and also that clozapine has therapeutic effects in patients with idiopathic Parkinson's disease. Because tacrine-induced tremulous jaw movements in rats have been suggested as a possible model of extrapyramidal motor dysfunctions, including parkinsonian tremor, the present work was undertaken to investigate the effects of clozapine on tremulous jaw movements. Clozapine decreased tacrine-induced tremulous jaw movements in a dose-related manner, with an ED50 of approximately 3.3 mg/kg. In order to determine the relative potency of this effect compared to other behavioral effects of clozapine, suppression of lever pressing was also studied. Clozapine reduced lever pressing in a dose-related manner, with an ED50 of approximately 5.4 mg/kg. This indicates that clozapine suppressed jaw movements at or below the doses required for suppression of lever pressing. In contrast, the typical antipsychotic drug haloperidol failed to suppress tacrine-induced tremulous jaw movements in doses up to 1.0 mg/kg, which is about 11-fold higher than the ED50 for suppression of lever pressing with that drug. Thioridazine and risperidone also suppressed tremulous jaw movements in roughly the same dose range at which lever pressing was reduced. It is possible that the suppression of tacrine-induced tremulous jaw movements by clozapine in rats is related to the unique behavioral and motor effects of clozapine. The ratio of potencies of these effects (i.e., suppression of tremulous jaw movements versus suppression of lever pressing) could be used as a behavioral procedure for assessing clozapine-like activity in novel compounds.

Animals↗

Neuropsychologic and motor function in small-for-gestation preschoolers.

The aim of this study was to evaluate neuropsychologic and motor performance in term small-for-gestation preschool children. A patient-based sample of 311 5-year-old children with birth weights less than the fifteenth percentile for gestation was compared with a random sample of 321 appropriate-for-gestation control subjects. The main assessment tools were subscales from the Wechsler Preschool and Primary Scale of Intelligence Revised, subscales from the Illinois Test of Psycholinguistic Abilities, tests of manual dexterity and figure copying, and the Peabody Developmental Motor Scales. The small-for-gestation children had mean scores on tests of visuospatial and visuomotor abilities that were one fourth standard deviation lower than appropriate-for-gestation control subjects and slightly lower scores on manual dexterity. The small-for-gestation children were comparable to appropriate-for-gestation children regarding motor performance. We therefore conclude that the neuropsychologic and neuromotor performance in preschool years of term small-for-gestation children is reassuring.

Child Development↗

Motor function under lower and higher controlled processing demands in early and continuously treated phenylketonuria.

This study examined motor control in 61 early and continuously treated patients with phenylketonuria (PKU) and 69 control participants, aged 7 to 14 years. The pursuit task demanded concurrent planning and execution of unpredictable movements, whereas the tracking task required a highly automated circular movement that could be planned in advance. PKU patients showed significantly poorer motor control in both tasks compared with control participants. Deficits were particularly observed for younger patients (age < 11 years). Differences between control participants and PKU patients were significantly greater in the pursuit task compared with the tracking task, indicating more serious deficits when a higher level of controlled processing is required. Correlations with historical phenylalanine levels indicated a later maturation of the level of control required by the pursuit task compared with the tracking task.

Adolescent↗

Anhedonia, depression, and motor functioning in Parkinson's disease during treatment with pramipexole.

Anhedonia, a core symptom of depression, correlates with motor alterations in major depressive disorder and has been assumed to be frequent in depressed patients with Parkinson's disease (PD). In the present study, the authors assessed for the first time frequency of anhedonia in patients with idiopathic Parkinson's disease (N = 657) and the relationship of anhedonia and parkinsonian motor deficits during treatment with pramipexole. Mild depression was present in 47% of the patients and moderate to severe depression in 22%. Anhedonic individuals included 45.7% of all patients and 79.7% of depressed Parkinson's disease patients. Anhedonic Parkinson's disease patients had greater motor deficits, restrictions in activities of daily living, and depression compared to nonanhedonic patients. Frequency of anhedonia and depression was significantly reduced during treatment with pramipexole. Future studies should further investigate antianhedonic efficacy of dopamine agonists including pramipexole in depressed patients with Parkinson's disease.

Activities of Daily Living↗

Functional motor asymmetries correlated with clinical findings in unmedicated schizophrenic patients.

Motor asymmetries were investigated in 28 unmedicated schizophrenic in-patients and 32 healthy controls. Of the patients, who were assessed as right-handers by a handedness questionnaire, 46.4% changed their motor laterality in at least one part of the tapping test series, probably because of a decrease of functional hemispheric asymmetry. These patients were characterized by more pronounced psychotic symptoms than those who did not change motor laterality. According to the tapping frequency, two groups of patients could be distinguished: the high- and the low-frequency group. In both groups certain tapping data could be correlated with characteristic clinical features. While the findings in the high-frequency group point to an enhanced activation level of the right hemisphere and appear to be correlated with the onset of positive symptoms and better prognosis, the findings in the low-frequency group may be a reflection of a disturbed function of the left frontal region and seem to be correlated with a gradual chronic development of predominant negative symptoms with worse prognostic implications.

Adult↗