Dissociation between behavior and motor cortical excitability before and during ballistic wrist flexion and extension in young and old adults.

PURPOSE: Aging is associated with slow reactive movement generation and poor termination. OBJECTIVE: We examined the hypothesis that the build-up of excitability in the primary motor cortex in the agonist muscle to generate ballistic wrist flexion and extension and in the antagonist to stop the movement, is lower and slower in old compared with young adults. METHODS: We measured the size of the motor potentials evoked (MEP) produced by transcranial magnetic stimulation (TMS), background integrated EMG (iEMG), and the MEP:iEMG ratio in healthy young (23 y, n = 14) and old adults' (73 y, n = 14) wrist flexors and extensors as they rapidly flexed or extended the wrist in response to an auditory cue. TMS was delivered at 80% of resting motor threshold randomly in 20 ms increments between 130 and 430 ms after the tone. RESULTS: Even though old compared to young adults executed the two wrist movements with ~23% longer movement duration and ~15% longer reaction time (both p < 0.05), the rise in MEP:iEMG ratio before the main similar in the two age groups. CONCLUSION: These data suggest that an adjustment of current models might be needed to better understand how and if age affects the build-up excitability accompanying movement generation and termination.

Paradoxical facilitation after depotentiation protocol can precede dyskinesia onset in early Parkinson's disease.

Loss of dopamine, a key modulator of synaptic signalling, and subsequent pulsatile non-physiological levodopa replacement is believed to underlie altered neuroplasticity in Parkinson's disease (PD). Animal models suggest that maladaptive plasticity (e.g. deficient depotentiation at corticostriatal synapses) is key in the development of levodopa-induced dyskinesia (LID), a common complication following levodopa replacement in PD. Human studies using transcranial magnetic stimulation protocols have shown similar depotentiation deficit in patients with LID. We hypothesized that subtle depotentiation deficits should precede LID if these deficits are mechanistically linked to LID onset. Moreover, patients on pulsatile levodopa-based therapy may show these changes earlier than those treated with levodopa-sparing strategies. We recruited 22 early non-dyskinetic PD patients (<5 years since diagnosis) and 12 age-matched healthy controls. We grouped patients into those on Levodopa-Based (n = 11) and Levodopa-Sparing therapies (n = 11). Patients were selected to obtain groups matched for age and disease severity. We used a theta-burst stimulation protocol to investigate potentiation and depotentiation in a single session. We report significant depotentiation deficits in the Levodopa-Based group, compared to both Levodopa-Sparing and Healthy Control groups. Potentiation and Depotentiation responses were similar between Levodopa-Sparing and Healthy Control groups. Although differences persist after accounting for potential confounds (e.g. levodopa-equivalent dose), these results may yet be caused by differences in disease severity and cumulative levodopa-equivalent dose as discussed in the text. In conclusion, we show for the first time that paradoxical facilitation in response to depotentiation protocols can occur in PD even prior to LID onset.

Reversal of LTP-Like Cortical Plasticity in Alzheimer's Disease Patients with Tau-Related Faster Clinical Progression.

Cerebrospinal fluid (CSF) concentrations of amyloid-ß (Aß), total tau (t-tau), and phosphorylated tau proteins are associated with different clinical progression in Alzheimer's disease (AD). We enrolled forty newly diagnosed AD patients, who underwent lumbar puncture, and carried out a K-means cluster analysis based on CSF biomarkers levels, resulting in two AD patient groups: Cluster 1 showed relatively high levels of Aß and low levels of tau; Cluster 2 showed relatively low levels of Aß and high levels of tau. Cortical plasticity was tested using the intermittent and continuous theta burst stimulation (iTBS and cTBS) protocols evoking respectively long-term potentiation (LTP) and depression (LTD). Cholinergic transmission was tested by the short-latency afferent inhibition protocol. Neurophysiological evaluation showed that the two AD groups differed in terms of cortical plasticity: after iTBS, Cluster 2 patients showed a remarkable reversal of LTP toward LTD that was not observed in Cluster 1. LTD and central cholinergic transmission did not differ between groups. Patients were assessed longitudinally with Mini-Mental State Examination at 6, 12, and 18 month follow-ups. Cluster 2 AD had a faster cognitive decline already evident at the 12 month follow-up. High tau CSF levels were associated with LTD-like cortical plasticity and faster clinical progression. These results suggest that more aggressive tau pathology is associated with prominent LTD-like mechanisms of cortical plasticity and faster cognitive decline.

Could the deep squat jump predict weightlifting performance?

This research was carried out with the aim of describing the deep squat jump (DSJ) and comparing it with the squat (SJ) and countermovement (CMJ) jumps, to introduce it as a strength testing tool in the monitoring and control of training in strength and power sports. Forty-eight male subjects (21 weightlifters, 12 triathletes, and 15 physical education students) performed 3 trials of DSJ, SJ, and CMJ with a 1-minute rest among them. For the weightlifters, snatch and clean and jerk results during the Spanish Championship 2004 and the 35th EU Championships 2007 were collected to study the relationship among vertical jumps and weightlifters' performance. A 1-way analysis of variance (ANOVA) showed significant differences between groups in the vertical jumps, with the highest jumps for the weightlifters and the lowest for the triathletes. An ANOVA for repeated measures (type of jump) showed better results for DSJ and CMJ than SJ in all groups. A linear regression analysis was performed to determine the association between weightlifting and vertical jump performances. Correlations among the weightlifting performance and the vertical jumps were also calculated and determined using Pearson r. Results have shown that both CMJ and DSJ are strongly correlated with weightlifting ability. Therefore, both measures can be useful for coaches as a strength testing tool in the monitoring and control of training in weightlifting.

Role of the cerebellum in externally paced rhythmic finger movements.

Several studies have suggested that the cerebellum has an important role in timing of subsecond intervals. Previous studies using transcranial magnetic stimulation (TMS) to test this hypothesis directly have produced inconsistent results. Here we used 1-Hz repetitive TMS (rTMS) for 10 min over the right or left cerebellar hemisphere to interfere transiently with cerebellar processing to assess its effect on the performance of a finger-tapping task. Subjects tapped with their right index finger for 1 min (synchronization phase) with an auditory or visual cue at 0.5, 1, or 2 Hz; they continued for a further 1 min at the same rate with no cues (continuation phase). The blocks of trials were performed in a random order. rTMS of the cerebellum ipsilateral to the movement increased the variability of the intertap interval but only for movements at 2 Hz that were made while subjects were synchronizing with an auditory cue. There was no effect on the continuation phase of the task when the cues were no longer present or on synchronization with a visual cue. Similar results were seen after stimulation over the contralateral dorsal premotor cortex but not after rTMS over supplementary motor area. There was no effect after rTMS over the ipsilateral right cervical nerve roots or over the ipsilateral primary motor cortex. The results support the hypothesis of neural network for event-related timing in the subsecond range that involves a cerebellar-premotor network.

Transcranial magnetic stimulation over dorsolateral prefrontal cortex in Parkinson's disease.

OBJECTIVE: Several studies have shown that repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) is effective in the treatment of depression in patients with Parkinson disease (PD). However, since research into the effect of this type of rTMS regime on motor function is limited, we studied the effect of rTMS over the DLPFC on the motor functions in PD patients. METHODS: Thirteen patients were randomly assigned into 2 groups, one receiving real-rTMS (90% of resting motor threshold, 10 Hz, 450 pulses-day for 10 consecutive days) over the DLPFC contralateral to the more affected side, and the other group receiving sham-rTMS. Assessment included a clinical motor evaluation using part III of the Unified Parkinson's Disease Rating Scale (UPDRS), and several motor tasks. The UPDRS was applied before and after 10 days of rTMS. Finger tapping, reach movement, grip movement and gait were measured in each session before and after the rTMS over the 10 day period. RESULTS: Statistical analysis (ANOVA for repeated measures; group *day *side *rTMS) only showed a significant effect for finger tapping, reach movement and gait for the factor day. No significant change was reported for the UPDRS in any group. CONCLUSIONS: Application of rTMS over the DLPFC as a 10 day course had no significant effect on motor functions and clinical motor status, and the improvement in performance of motor tasks can be attributed to the effects of practice. SIGNIFICANCE: rTMS over the DLPFC did not lead to any motor improvement in PD patients.

Time course of functional connectivity between dorsal premotor and contralateral motor cortex during movement selection.

The left dorsal premotor cortex (PMd) is thought to play a dominant role in the selection of movements made by either hand. We used transcranial magnetic stimulation to study the functional connectivity of the left PMd and right primary motor cortex (M1) during an acoustic choice reaction time (RT) task involving contraction of the thumb and forefinger. The facilitatory and inhibitory pathways that can be demonstrated between left PMd and right M1 at rest were suppressed during most of the reaction period. However, they were activated briefly at the start of the reaction period, depending on whether the cue indicated that the forthcoming movement had to be made with the left or the right hand. The facilitatory pathway was active at 75 ms in those trials in which the subjects were required to move the left hand, whereas the inhibitory pathway was active at 100 ms in trials in which the subjects had to move the right hand. These changes in excitability did not occur in hand muscles not used in the task. There were no significant changes in the excitability of intracortical circuits [short intracortical inhibition (SICI) and intracortical facilitation (ICF)] in the right M1. Interhemispheric interactions between the right PMd and left M1 were mainly inhibitory at rest and showed the same temporal profile of interhemispheric inhibition as for left PMd-right M1, although no evidence was found for facilitatory interactions. The results illustrate the importance of PMd not only in facilitating cued movements but also in suppressing movements that have been prepared but are not used.

Chronic neural adaptation induced by long-term resistance training in humans.

While it is known that resistance training causes changes in the central nervous system (CNS) in the initial stages of training, there have been few studies of cumulative or sustained neural adaptation to resistance training beyond the initial periods. To further investigate this we compared the electromyographic (EMG) response to transcranial magnetic stimulation (TMS) during voluntary contractions of ten subjects who have been training for more than 2 years, resistance-training (RT) group, and ten subjects that have never participated in resistance training (NT). The active motor threshold for biceps brachii was obtained during voluntary elbow flexion at 10% of maximal voluntary contraction (MVC). TMS was also delivered at 100% of the maximal stimulator output while the participants exerted forces ranging from 10 to 90% of MVC. Evoked force, motor-evoked potential (MEP) amplitude and latency from biceps brachii was recorded for each condition to explore changes in corticospinal excitability. The evoked force was significantly lower in the RT group in comparison with the NT group between 30 and 70% of MVC intensity (P<0.05). At 90% of MVC, nine subjects from the RT group showed an absence in the evoked force while this occurred in only five subjects from the NT group. The MEP amplitude and latency changed significantly (P<0.001) with increasing levels of contraction, without significant difference between groups. These results indicate that changes in the CNS are sustained in the log-term practices of resistance training and permit a higher voluntary activation at several intensities of the MVC.

Temporal variability of gait in Parkinson disease: effects of a rehabilitation programme based on rhythmic sound cues.

It has been suggested that sequential movements in patients with Parkinson's disease (PD) might be improved by the effects of external rhythmic cues. We studied spatiotemporal gait parameters and temporal gait variability in patients with PD and control subjects under different walking conditions in order to investigate whether rhythmic auditory cues could improve temporal variability. A total of 30 subjects were recruited, comprising 15 patients with idiopathic PD and 15 control subjects with no history of neurological disorder. As an indicator for temporal stability, we used the coefficient of variability (CV=standard deviation/mean X 100) of recorded intervals between two consecutive steps (gait variability). After control values were obtained, subjects underwent a Physical Rehabilitation Programme (PRP) consisting of a variety of motor tasks performed in combination with rhythmic sounds with different cadences. Sessions lasted 1h/day, five times a week for a period of four consecutive weeks. At the end of the PRP subjects were evaluated again. Following completion of the programme the patients' coefficients of variability improved significantly for the preferred gait (gait: t=2.950, p=0.011) but were not significantly different from those obtained in control subjects (gait: t=3.873, p=0.391). These results are consistent with and extend prior studies of rhythmic auditory facilitation in PD and suggest a valuable method of improving gait timing in these patients.