Sensorimotor integration in focal task-specific hand dystonia: a magnetoencephalographic assessment.

To obtain a direct sensorimotor integration assessment in primary hand cortical areas (M1) of patients suffering from focal task-specific hand dystonia, magnetoencephalographic (MEG) and opponens pollicis electromyographic (EMG) activities were acquired during a motor task expressly chosen not to induce dystonic movements in our patients, to disentangle abnormalities indicating a possible substrate on which dystonia develops. A simple isometric contraction was performed either alone or in combination with median nerve stimulation, i.e. when a non-physiological sensory inflow was overlapping with the physiological feedback. As control condition, median nerve stimulation was also performed at rest. The task was performed bilaterally both in eight patients and in 16 healthy volunteers. In comparison with results in controls we found that in dystonic patients: i) MEG-EMG coherence was higher; ii) it reduced much less during galvanic stimulation in the hemisphere contralateral to the dystonic arm, simultaneously with iii) stronger inhibition of the sensory areas responsiveness due to movement; iv) the cortical component including contributions from sensory inhibitory and motor structures was reduced and v) much more inhibited during movement. It is documented that a simultaneous cortico-muscular coherence increase occurs in presence of a reduced M1 responsiveness to the inflow from the sensory regions. This could indicate an unbalance of the fronto-parietal functional impact on M1, with a weakening of the parietal components. Concurrently, signs of a less differentiated sensory hand representation--possibly due to impaired inhibitory mechanisms efficiency--and signs of a reduced repertoire of voluntary motor control strategies were found.

Homocysteine and electroencephalographic rhythms in Alzheimer disease: a multicentric study.

High plasma concentration of homocysteine is an independent risk factor for Alzheimer's disease (AD), due to microvascular impairment and consequent neural loss [Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D'Agostino RB, Wilson PW, Wolf PA (2002) Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med 346(7):476-483]. Is high plasma homocysteine level related to slow electroencephalographic (EEG) rhythms in awake resting AD subjects, as a reflection of known relationships between cortical neural loss and these rhythms? To test this hypothesis, we enrolled 34 mild AD patients and 34 subjects with mild cognitive impairment (MCI). Enrolled people were then subdivided into four sub-groups of 17 persons: MCI and AD subjects with low homocysteine level (MCI- and AD-, homocysteine level <11 micromol/l); MCI and AD subjects with high homocysteine level (MCI+ and AD+, homocysteine level >or=11 micromol/l). Resting eyes-closed EEG data were recorded. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic tomography (LORETA). Results showed that delta (frontal and temporal), theta (central, frontal, parietal, occipital, and temporal), alpha 1 (parietal, occipital, and temporal), and alpha 2 (parietal and occipital) sources were stronger in magnitude in AD+ than AD- group. Instead, no difference was found between MCI- and MCI+ groups. In conclusion, high plasma homocysteine level is related to unselective increment of cortical delta, theta, and alpha rhythms in mild AD, thus unveiling possible relationships among that level, microvascular concomitants of advanced neurodegenerative processes, and synchronization mechanisms generating EEG rhythms.

What is the relationship among atherosclerosis markers, apolipoprotein E polymorphism and dementia?

Evidence suggests the important role of vascular factors both in vascular dementia (VaD) and Alzheimer disease (AD) pathogenesis. However, the relationship between apolipoprotein E (APOE) polymorphism and markers of atherosclerosis is still controversial. The aim of the study was to investigate the interplay between APOE polymorphisms and atherosclerosis in patients with AD and VaD. In this cross-sectional study, 101 demented (68 AD and 33 VaD) patients underwent APOE genotyping and neck vessel ultrasound to evaluate carotid artery disease [intima-media thickness (IMT) and plaques]. Patients with AD carrying epsilon4 allele presented increased IMT values with respect to non-epsilon4 carriers and VaD patients, whereas no relation was found between APOE polymorphisms and the presence or grade of carotid plaques both in AD and VaD patients. The epsilon4 APOE allele may promote intima-media thickening, interacting with other factors contributing to AD development.

Sensory-motor interaction in primary hand cortical areas: a magnetoencephalography assessment.

Movement control requires continuous and reciprocal exchange of information between activities of motor areas involved in the task program execution and those elaborating proprioceptive sensory information. Our aim was to investigate the sensorimotor interactions in the region dedicated to hand control in healthy humans, focusing onto primary sensory and motor cortices, by selecting the time window at very early latencies. Through magnetoencephalographic recordings, we obtained a simultaneous assessment of sensory cortex activity modulation due to movement and of motor cortex activity modulation due to sensory stimulation, by eliciting a galvanic stimulation to the nerve (the median nerve) innervating a muscle (the opponens pollicis), at rest or during voluntary contraction. The primary sensory and motor cortices activities were investigated respectively through excitability in response to sensory stimulation and the cortico-muscular coherence. The task was performed bilaterally. A clear reduction of the cortico-muscular coherence was found in the short time window following stimuli (between around 150-450 ms). In the same time period, the motor control of isometric contraction was preserved. This could suggest that cortical component of voluntary movement control was transiently mediated by neuronal firing rate tuning more than by cortico-muscular synchronization. In addition to the known primary sensory cortex inhibition due to movement, a more evident reduction was found for the component known to include a contribution from primary motor areas. Gating effects were lower in the dominant left hemisphere, suggesting that sensorimotor areas dominant for hand control benefit of narrowing down gating effects.

Conversion from mild cognitive impairment to Alzheimer's disease is predicted by sources and coherence of brain electroencephalography rhythms.

Objective. Can quantitative electroencephalography (EEG) predict the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD)? Methods. Sixty-nine subjects fulfilling criteria for MCI were enrolled; cortical connectivity (spectral coherence) and (low resolution brain electromagnetic tomography) sources of EEG rhythms (delta=2-4 Hz; theta=4-8 Hz; alpha 1=8-10.5 Hz; alpha 2=10.5-13 Hz: beta 1=13-20 Hz; beta 2=20-30 Hz; and gamma=30-40) were evaluated at baseline (time of MCI diagnosis) and follow up (about 14 months later). At follow-up, 45 subjects were still MCI (MCI Stable) and 24 subjects were converted to AD (MCI Converted). Results. At baseline, fronto-parietal midline coherence as well as delta (temporal), theta (parietal, occipital and temporal), and alpha 1 (central, parietal, occipital, temporal, limbic) sources were stronger in MCI Converted than stable subjects (P<0.05). Cox regression modeling showed low midline coherence and weak temporal source associated with 10% annual rate AD conversion, while this rate increased up to 40% and 60% when strong temporal delta source and high midline gamma coherence were observed respectively. Interpretation. Low-cost and diffuse computerized EEG techniques are able to statistically predict MCI to AD conversion.

Optical measurement of breathing: algorithm volume calibration and preliminary validation on healthy trained subjects.

The use of optical technologies may be beneficial when measuring breathing biomechanics. The purpose of this study was twofold: i) to enhance the optoelectronic plethysmography (OEP) algorithm performance for the volume estimation by the use of a novel volume calibration procedure and ii) to compare the OEP volumes gained by a commercial optoelectronic system against actual respiratory volumes measured by a breath-by-breath gas analyzer (BbB). The OEP volume algorithm calibration was performed by the use of a novel volume calibration procedure based on both a calibrator device that delivered known volumes changes and one ad-hoc designed software for the static and dynamic calibration analysis. OEP algorithm threshold, accuracy, repeatability and the volume algorithm calibration were investigated. Tidal volume (VT) measurements performed simultaneously by the calibrated OEP algorithm and BbB analyzer were compared. VT measured simultaneously by OEP and BbB was collected during submaximal exercise tests in five trained healthy participants in two conditions (with hunched shoulders and in normal shoulder position). The two methods were compared by linear regression and Bland-Altman analysis in both positions. The average difference between methods and the discrepancy were calculated. The OEP-BbB correlation was high in both positions, R2=0.92 and R2=0.97 for hunch and normal one, respectively. Bland-Altman analysis demonstrated that OEP algorithm systematic difference was lower than 100mL. The limits of agreement assessed in both positions are comparable. The difference between measurements suggesting that OEP may be a useful tool to analyze chest wall volume changes and breathing mechanics during intense exercise.

Wearing-off detection in clinical practice: the wearing off real practice key (WORK-PD) study in Parkinson's disease.

OBJECTIVE: Verifying the validity and feasibility of the WOQ-19 as a useful tool in routine clinical practice and in management of patients. METHODS: 532 consecutive Parkinson's disease (PD) patients were recruited from 6 different neurological outpatient units, specialized in movement disorders, of central Italy. Inclusion criteria were diagnosis of PD and any current pharmacological treatment of PD while exclusion criteria were evident cognitive or depressive impairment, infusion with dopamine agonists or Duodopa, or Deep Brain Stimulation therapy. Patients were asked to complete the Italian version of WOQ-19 before the neurological visit. A medical form for the collection of demographic and clinical data of patients and for the evaluation of comprehensibility and usability the WOQ-19 was filled by the neurologist during the visit. RESULTS: Our data confirmed that WOQ-19 was able to identify WO in 69% of patients, a percentage similar to the recently reported in the Italian WOQ-19 validation study. Motor symptoms were more frequent than non-motor symptoms (80% vs. 20%). Patients who experienced WO had a higher age of PD onset, more severe disease, longer disease duration and were more likely to be female. CONCLUSIONS: The WOQ-19 was understandable for the patient, easily administered and suitable for routine outpatient use. It could be also particularly useful in clinical practice in the early identification of non-motor symptoms, often under reported by patients and revealed only with clinical support.

Elevation of serum copper levels in Alzheimer's disease.

OBJECTIVE: To determine whether serum trace metals and oxidative species are related to abnormal cognition in AD. METHODS: The authors studied serum peroxides, copper, iron, transferrin, and antioxidant capacity in 79 patients with AD (mean age 74.3 years; 25 men, 54 women) and in 76 cognitively normal individuals (mean age 70.1 years; 33 men, 43 women). The relation of these oxidative and trace metals to APOE epsilon4 allele frequency, neuropsychological performance, and cerebrovascular or atrophic burden, as estimated by brain MRI and ultrasonography of cerebral vessels, was evaluated. RESULTS: Copper level was higher (p < 0.001) in subjects with AD than control subjects (specificity = 95%, sensitivity = 60%) with a cutoff serum level of 16 micro mol/L (1.02 mg/L). An increase of 1 micro mol/L in serum copper accounted for 80% of the risk of having AD and correlated with poor neuropsychological performance and medial temporal lobe atrophy (p < 0.03). Antioxidant capacity decreased and correlated with medial temporal lobe atrophy (p < 0.009) and with APOE epsilon4 allele (p = 0.004). CONCLUSIONS: Copper may play a role in neurodegenerative processes in AD, and serum copper measurement may prove to be a peripheral diagnostic marker for AD.

Botulinum toxin injected in the gastric wall reduces body weight and food intake in rats.

BACKGROUND: Botulinum toxin is a powerful, long-acting inhibitor of muscular contractions in both voluntary and smooth muscle. It acts by blocking the release of the neurotransmitter acetylcholine. In the stomach, propulsive contractions of the antrum are necessary for the gastric contents to pass into the duodenum. AIMS: To investigate whether intramuscular injections of botulinum toxin type A into the gastric antrum of rats would cause a reduction in food intake and hence body weight, by inhibition of gastric emptying. MATERIALS AND METHODS: This was a prospective, randomized, 3-way parallel group study in rats. The first group was anaesthetized, laparotomized and given 20 U of botulinum toxin type A by intramuscular injection into the gastric antrum (botulinum toxin type A group, n=14). The second group was anaesthetized, laparotomized and injected with saline (sham group, n=14) and the third group did not have any intervention (control group, n=5). Food intake was measured daily for 7 weeks and body weight was measured daily for 10 weeks. RESULTS: There was a significant difference in loss of body weight between the two treated groups (14.0 +/- 8.2% botulinum toxin type A group, 4.4 +/- 2.7% sham group; P < 0.001). Further, the time to reach the weight nadir was significantly longer in the botulinum toxin type A group (8.7 +/- 3.9 days) compared with the sham group (5.3 +/- 3.8 days; P < 0.04). There were no significant differences between the sham and control groups for any of the body weight parameters. The minimum dietary intake was significantly lower in the botulinum toxin type A group than in the sham group (37.8 +/- 21.8% of the basal value in the botulinum toxin type A group, vs. 65.5 +/- 32.0 in the sham group, P < 0.05). In addition, the time to reach the nadir was significantly prolonged (8.2 +/- 3.5 days, botulinum toxin type A group vs. 4.9 +/- 1.7 days, sham group, P < 0.001). CONCLUSIONS: The parallel reduction of body weight and food intake in botulinum toxin type A treated animals is consistent with a long lasting inhibition of the antral pump. This is probably due to slowed gastric emptying leading to early satiety. Patients with morbid obesity might benefit from endoscopic injections of botulinum toxin type A into the stomach wall.

Review article: the use of botulinum toxin in the alimentary tract.

New and future indications for the treatment of disorders of the alimentary tract using local injections of botulinum toxin are reviewed. Clinical experience shows that overactive smooth muscle sphincters may be weakened to treat disorders such as achalasia or chronic anal fissure. By contrast, injections placed into the sphincter of Oddi have proven less effective for postcholecystectomy pain syndrome. Experimental evidence suggests that food intake may be reduced by weakening the distal stomach with botulinum toxin. This approach may possibly lead to the treatment of obesity. There are some new possible indications for the use of botulinum toxin on the alimentary tract, and infantile hypertrophic pyloric stenosis seems to be the most promising new development.

Detection of fetal auditory evoked responses by means of magnetoencephalography.

MagnetoEncephaloGraphy (MEG) is proposed as a non-invasive technique to detect the physiological activity of fetal brain, due to its ability to record brain activity without direct contact with the head and the transparency of magnetic signals in passing through extracerebral fetal layers and the mother's abdomen. Healthy women with uncomplicated pregnancies and fetuses in breech presentation were examined; gestational ages at time of study ranged between 36 and 40 weeks. In order to evaluate fetal well-being, ultrasound and cardiotocographic data were assessed a few days before and after MEG recording sessions. The participating women were placed in a semi-reclining position in a magnetically shielded room; here the presentation of the fetus and precise region of the mother's abdomen corresponding to the fetal head were determined by ultrasound investigation in order to place the MEG detecting system as near as possible to the fetal brain. MEG recordings were performed by means of a 28-channel neuromagnetic system. Every MEG recording session was performed during the acoustic stimulation of fetuses, in order to detect the cerebral events evoked by peripheral stimuli. The auditory stimuli were delivered from a plastic tube placed on mother's abdomen, near the fetal head, and consisted of a 300 ms 103 dB pure tone at 500 and 1000 Hz, presented at a 0.4 c/s repetition rate. In six cases following accurate digital subtraction of maternal and fetal electrocardiographic (EKG) signals we remained with a stimulus-related response peaking at about 250 ms; this was considered to originate from the fetal brain. In favour of this in three cases a clear dipolar distribution was evident at the peak of brain response centered on the fetal head and consistent with a brain generator. Despite several technical problems requiring solution before a possible routine clinical application, MEG has been found to be suitable for the non-invasive exploration of the fetal brain.

Spatial properties and interhemispheric differences of the sensory hand cortical representation: a neuromagnetic study.

We performed a neuromagnetic investigation of the sensory hand cortical representation in the two hemispheres of 20 healthy volunteers. The localizations within the brain hemispheres of the cortical Equivalent Current Dipoles (ECDs) activated with the shortest latencies (N20 m and P30 m components) by separate stimulation of contralateral median nerve, thumb and little finger were analysed. The ECD spatial coordinates were in agreement with the known somatotopy of the sensory homunculus: little finger more medial and posterior, thumb more lateral and anterior, median nerve in-between. By considering the ECDs to thumb and little finger stimulation the boundaries of the hand cortical representation in primary sensory cortex, the 'hand extension' was evaluated as the distance between the two. This parameter was similar on the two hemispheres, the 'hand extension' being 17 mm and 12 mm for N20 m and P30 m components, respectively, with a standard deviation of 5 mm. We provide for the first time the ECDs localization of left and right median nerve, thumb and little finger, as well as the 'hand extension' values, and their interhemispheric differences as a normative data set describing the organization of primary sensory cortical areas reserved to the hand in the healthy population. This approach permits objective measurements of absolute values, as well as of interhemispheric differences, of the sensory hand area following a monohemispheric lesion as well as to non-invasively follow-up its reorganization during clinical recovery.

On the reorganization of sensory hand areas after mono-hemispheric lesion: a functional (MEG)/anatomical (MRI) integrative study.

The topography of primary sensory cortical hand area following a monohemispheric lesion (sudden = stroke; progressive = neoplasm) was investigated in relationship with clinical recovery of sensorimotor deficits. Twenty seven patients with monohemispheric lesions were studied in a clinically stabilized condition. Functional informations from magnetoencephalography (MEG) were integrated with anatomical data from magnetic resonance imaging (MRI). MEG localizations of the neurons firing at early latencies in primary sensory cortex after separate stimulation of median nerve, thumb and little fingers of each hand were carried out. Characteristics of cerebral equivalent current dipoles (ECDs) activated by each contralateral stimulation, the 'hand extension' (i.e., the distance in millimetres between ECDs of first and fifth digits), as well as interhemispheric differences of the tested parameters were investigated. Finally, ECDs' locations were integrated with MRI. Lesions involving cortical (C) or subcortical (s.c.) areas receiving sensory input from the hand were often combined to increase interhemispheric asymmetry of the tested parameters (22% for C and 49% for s.c. lesions). This might be due to an activation of neuronal districts which in the affected hemisphere (AH) differ from those normally activated in the unaffected hemisphere (UH) and in the control population. Moreover, the 'hand extension' was enlarged on the AH--more frequently after a SC lesion--mainly due to a medial shift of the little finger ECD, combined to a tendency of both finger ECDs to shift frontally. After a C lesion, responses from the AH were often stronger than normal. Spatial reorganizations were also seen in the UH (7% of C and 14% of SC lesions). 'Hand extension' in the UH was selectively enlarged for the P30m only when combined with a similar enlargement in the AH. Significant interhemispheric asymmetries due to neuronal reorganization in the AH were associated with worse clinical outcomes compared to patients without asymmetries.

Botulinum toxin type-A treatment in spastic paraparesis: a neurophysiological study.

OBJECTIVE: The aim of this study was to verify the action of Botulinum toxin type-A (BoNT-A) by means of neurophysiological techniques, in patients presenting lower limb spasticity and requiring BoNT-A injections in the calf muscles, due to the poor response to medical antispastic treatment. SUBJECTS AND METHOD: Patients presenting paraparesis were enrolled. They underwent clinical evaluation for spasticity according to the Ashworth scale and neurophysiological recordings including: motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) of the leg area; compound motor action potential (cMAP) to tibial nerve stimulation, F-wave, and H-reflex before the treatment and 24 h, 2 weeks and 1 month after the injection of BoNT-A. In all patients, gastrocnemius was treated and in some cases soleus or tibialis posterior muscles were also injected. RESULTS: In all patients, BoNT-A injections induced a clear clinical improvement as showed by the reduced spasticity values of the Ashworth scale. A significant increment of MEP latency and central conduction time (CCT) duration were observed 2 weeks after the treatment only in the injected muscles. CONCLUSIONS: Prolonged MEP latencies and CCT after BoNT-A injections is probably due to a central alteration in responsiveness of spinal motor neurons to descending impulses from the corticospinal tracts. Such changes represent objective parameters heralding clinical efficacy of treatment.

A neuromagnetic normative data set for hemispheric sensory hand cortical representations and their interhemispheric differences.

Somatotopy of human hand primary sensory cortex has been studied neuromagnetically [C. Baumgartner, A. Doppelbauer, L. Deecke, D.S. Barth, J. Zeitlhofer, G. Lindinger, W.W. Sutherling, Neuromagnetic investigation of somatotopy of human hand somatosensory cortex, Exp. Brain Res. 87 (1991) 641-648.] [1]. Investigation of sensory cortex devoted to the hand will be of major importance in relation to clinical recovery after sensorimotor deficits as well as an index of plasticity phenomena following alterations of peripheral nerves inputs. Here a normative data set has been constructed, on the basis of the neuromagnetic investigation of the primary sensory hand cortical representation in the two hemispheres of 20 healthy volunteers. This can be used to evaluate interhemispheric differences of the 'sensory' hand areas during experimental paradigms in the healthy as well as following patients with monohemispheric lesions. The localizations in each hemisphere of the cortical Equivalent Current Dipoles (ECDs) activated with the shortest latencies (N20m and P30m components) by separate stimulation of left and right median nerve, thumb and little finger were analysed. By considering the ECDs to thumb and little finger stimulation the boundaries of the hand cortical representation in primary sensory cortex, the 'hand extension' was measured as the distance between the two. For all the considered parameters (related to N20m and P30m ECDs: latency, strength, spatial position in the individual head, 'hand extension', interhemispheric differences) the appropriate variable distribution was considered and by including the 98% of the healthy population normative limits were calculated.

Influence of botulinum toxin site of injections on healing rate in patients with chronic anal fissure.

BACKGROUND: Botulinum toxin induces healing in patients with idiopathic anal fissure. METHODS: Fifty patients affected by posterior anal fissure were treated with 20 units of botulinum toxin, injection in the internal anal sphincter on each side of the posterior midline (group I) or on each side of the anterior midline (group II). RESULTS: At 2 months evaluation, a healing scar was observed in 15 patients of group I and in 22 patients of group II(P = 0.025). Resting anal pressure was significantly different from the baseline values at 1-month as well as at 2-month check-ups in both groups, but the values were significantly lower in patients of group II. CONCLUSIONS: The intersite comparison revealed that anterior injection of the internal anal sphincter resulted in improved lowering of resting anal pressure and produced an earlier healing scar.

Acute challenge with apomorphine in Huntington's disease: a double-blind study.

Apomorphine (1.5 or 3 mg) or placebo was acutely administered to choreic patients affected by Huntington's disease in a double-blind fashion. The patients were evaluated before the administration, and at 15-min intervals for 2 h afterward, by means of a rating scale for Huntington's disease. As compared to baseline, the total score improved by 38.54% after 1.5 mg and by 30.41% after 3 mg; no variations were observed after placebo. Several items of the scale improved after the administration of 1.5 mg. An average 35.25% improvement was observed in items measuring the intensity of chorea (at rest, with arms outstretched, during conversation, and voluntary movements of the limbs); in addition, motor impersistence (as measured by tongue protrusion) and the capability to suppress associated movements (as measured by head movements during saccades) improved by an average of 31.46 and 61%, respectively. Some items of the scale improved after the administration of 3 mg. Items measuring the intensity of chorea improved by an average of 30.41%; in addition, the extent of vertical gaze improved by 63.77%. These data indicate that apomorphine brings about a transient symptomatic improvement of chorea and of other associated clinical features in Huntington's disease. The time course observed for the antichoreic activity is only partially consistent with the antiparkinsonian action of apomorphine.

Movement-induced uncoupling of primary sensory and motor areas in focal task-specific hand dystonia.

INTRODUCTION: Due to growing evidence of sensorimotor integration impairment in focal task-specific hand dystonia, we aimed at describing primary sensory (S1) and primary motor (M1) cortex source activities and their functional cross-talk during a non-dystonia-inducing sensorimotor task free of biases generated by the interfering with the occurrence of dystonic movements. METHOD: Magnetoencephalographic brain signals and opponens pollicis (OP) electromyographic activities were acquired at rest and during a simple isometric contraction performed either alone or in combination with median nerve stimulation. The task was performed separately with the right and left hand by eight patients suffering from focal task-specific hand dystonia and by eight healthy volunteers. Through an ad hoc procedure Functional Source Separation (FSS), distinct sources were identified in S1 (FSS1) and M1 (FSM1) devoted to hand control. Spectral properties and functional coupling (coherence) between the two sources were assessed in alpha [8,13]Hz, beta [14,32]Hz and gamma [33,45]Hz frequency bands. RESULTS: No differences were found between spectral properties of patients and controls for either FSM1 or FSS1 cerebral sources. Functional coupling between FSM1 and FSS1 (gamma band coherence), while comparable between dystonic patients and healthy controls at rest, was selectively reduced in patients during movement. All findings were present in both hemispheres. DISCUSSION: Because previous literature has shown that gamma-band sensory-motor synchronization reflects an efficiency index of sensory-motor integration, our data demonstrate that, in dystonic patients, uncoupling replaces the functional coupling required for efficient sensory-motor control during motor exertion. The presence of bi-hemispheric abnormalities in unilateral hand dystonia supports the presence of an endophenotypic trait.

Sensorimotor Cortex Reorganization in Alzheimer's Disease and Metal Dysfunction: A MEG Study.

Objective. To verify whether systemic biometals dysfunctions affect neurotransmission in living Alzheimer's disease (AD) patients. Methods. We performed a case-control study using magnetoencephalography to detect sensorimotor fields of AD patients, at rest and during median nerve stimulation. We analyzed position and amount of neurons synchronously activated by the stimulation in both hemispheres to investigate the capability of the primary somatosensory cortex to reorganize its circuitry disrupted by the disease. We also assessed systemic levels of copper, ceruloplasmin, non-Cp copper (i.e., copper not bound to ceruloplasmin), peroxides, transferrin, and total antioxidant capacity. Results. Patients' sensorimotor generators appeared spatially shifted, despite no change of latency and strength, while spontaneous activity sources appeared unchanged. Neuronal reorganization was greater in moderately ill patients, while delta activity increased in severe patients. Non-Cp copper was the only biological variable appearing to be associated with patient sensorimotor transmission. Conclusions. Our data strengthen the notion that non-Cp copper, not copper in general, affects neuronal activity in AD. Significance. High plasticity in the disease early stages in regions controlling more commonly used body parts strengthens the notion that physical and cognitive activities are protective factors against progression of dementia.