Nelson Espinosa

Validity of the finger tapping test in Parkinson’s disease, elderly and young healthy subjects: Is there a role for central fatigue?

OBJECTIVE The main goal of this work is to evaluate the validity of the finger tapping test (FT) to detect alterations in rhythm formation. METHODS We use FT to study the alterations in motor rhythm in three different groups: Parkinsons patients, elderly healthy controls, and young healthy control subjects (HY). The test was performed in COMFORT and FAST tapping modes and repeated on two different days. RESULTS For the variables analyzed (frequency and variability) both modes were repeatable in all groups. Also, intra-class correlation coefficients showed excellent levels of consistency between days. The test clearly differentiated the groups in both FAST and COMFORT modes. However, when fatigue was analyzed, a decrease in the tapping frequency was observed in HY during the FAST mode only. The amplitude of motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) was early-potentiated but not delayed-depressed, both for COMFORT and FAST modes. This suggests that fatigue was not of cortico-spinal origin. Other forms of central fatigue are discussed. CONCLUSIONS FT at FAST mode is not a valid test to detect differences in rhythm formation across the groups studied; fatigue is a confounding variable in some groups if the test is performed as fast as possible. SIGNIFICANCE COMFORT mode is recommended in protocols including the FT for evaluating rhythm formation.

Spatiotemporal Gait Patterns During Overt and Covert Evaluation in Patients With Parkinson’s Disease and Healthy Subjects: Is There a Hawthorne Effect?

Parkinsons disease (PD) and aging lead to gait impairments. Some of the disturbances of gait are focused on step length, cadence, and temporal variability of gait cycle. Under experimental conditions gait can be overtly evaluated, but patients with PD are prone to expectancy effects; thus it seems relevant to determine if such evaluation truly reflects the spontaneous gait pattern in such patients, and also in healthy subjects. Thirty subjects (15 subjects with PD and 15 healthy control subjects) were asked to walk using their natural, preferred gait pattern. In half of the trials subjects were made aware that they were being evaluated (overt evaluation), while in the rest of the trials the evaluation was performed covertly (covert evaluation). During covert evaluation the gait pattern was modified in all groups. Gait speed was significantly increased (P = .022); step cadence and average step length were also significantly modified, the average step length increased (P = .002) and the cadence was reduced (P ≤ .001). Stride cycle time variability was unchanged significantly (P = .084). These changes were not significantly different compared between elderly and young healthy controls either. Due to the small sample size, a note of caution is in order; however, the significant results suggest that covert evaluation of gait might be considered to complement experimental evaluations of gait.

Antagonist muscle co-activation during straight walking and its relation to kinematics: Insight from young, elderly and Parkinson's disease

Increased antagonist muscle co-activation of the lower limb during walking seems to be an adaptive process to the physiological changes of aging, in order to gain joint stability. In the healthy subjects this view seems to be reinforced by the fact that the co-activation index (CAI) increases when the gait is faster. The few reports on antagonist co-activation in Parkinsons disease (PD) patients indicate that they have larger co-activation than the healthy elderly, supporting the idea of the stabilization role of CAI during gait, as postural instability is a cardinal feature of PD. However it has also been reported that there is a reduction of the CAI when increasing velocity in PD or normal elderly. This questions the role of co-activation in stabilization during increased velocity. In this study we have analyzed the gait of healthy subjects (young and elderly), and PD patients (with and without freezing of gait, FOG) in order to better understand the relation between co-activation and gait kinematics, and to gain insight into the pathological changes associated with FOG in PD. We used Multiple Linear Regression models to study the relationship in shank muscles between CAI, velocity and cadence. Our results indicate that, for all groups of interest, the relationship between co-activation and the kinematics of gait is poor, due to the high degree of variability, questioning the explanatory value of the index.

Different sources of nitric oxide mediate neurovascular coupling in the lateral geniculate nucleus of the cat

Understanding the link between neuronal responses (NRs) and metabolic signals is fundamental to our knowledge of brain function and it is a milestone in our efforts to interpret data from modern non invasive optical techniques such as fMRI, which are based on the close coupling between metabolic demand of active neurons and local changes in blood flow. The challenge is to unravel the link. Here we show, using spectrophotometry to record oxyhaemoglobin and methemoglobin (surrogate markers of cerebral flow and nitric oxide levels respectively) together with extracellular neuronal recordings in vivo and applying a multiple polynomial regression model, that the markers are able to predict up about 80% of variability in NR. Furthermore, we show that the coupling between blood flow and neuronal activity is heavily influenced by nitric oxide (NO). While NRs show the typical saturating response, blood flow shows a linear behaviour during contrast-response curves, with nitric oxide from different sources acting differently for low and high intensity.

Central fatigue induced by short-lasting finger tapping and isometric tasks: A study of silent periods evoked at spinal and supraspinal levels

The neural substrates of fatigue induced by muscular activity have been addressed in depth in relation to isometric tasks. For these activities, when fatigue develops, it has been noted that the duration of the silent periods (SPs) increases in response to both transcranial magnetic stimulation (TMS) of primary motor cortex or electric cervicomedullary stimulation (CMS). However, fatigue is known to be task-dependent and the mechanisms giving rise to a decrease in motor performance during brief, fast repetitive tasks have been less studied. We hypothesized that fatigue induced by repetitive fast finger tapping may have physiological mechanisms different from those accounting for fatigue during an isometric contraction, even in cases of matched effort durations. In these tasks, we examined the contribution of spinal and supraspinal motor circuits to the production of fatigue. The tapping rate and maximal voluntary contractions (MVC), and TMS- and CMS-evoked SPs were obtained at the time of fatigue, and while subjects maintained maximal muscle activation after fast finger-tapping (or isometric activity) of different durations (10 or 30s). Results showed different mechanisms of fatigue triggered by isometric contraction and repetitive movements, even of short duration. Short-lasting repetitive movements induce fatigue within intracortical inhibitory circuits. They increased TMS-SPs, but not CMS-SPs. On the other hand, isometric contraction had a clear impact on spinal circuits. The consideration of these differences might help to optimize the study of fatigue in physiological conditions and neurological disorders.

Effects of movement imitation training in Parkinson's disease: A virtual reality pilot study

BACKGROUND Hypometria is a clinical motor sign in Parkinsons disease. Its origin likely emerges from basal ganglia dysfunction, leading to an impaired control of inhibitory intracortical motor circuits. Some neurorehabilitation approaches include movement imitation training; besides the effects of motor practice, there might be a benefit due to observation and imitation of un-altered movement patterns. In this sense, virtual reality facilitates the process by customizing motor-patterns to be observed and imitated. OBJECTIVE To evaluate the effect of a motor-imitation therapy focused on hypometria in Parkinsons disease using virtual reality. METHODS We carried out a randomized controlled pilot-study. Sixteen patients were randomly assigned in experimental and control groups. Groups underwent 4-weeks of training based on finger-tapping with the dominant hand, in which imitation was the differential factor (only the experimental group imitated). We evaluated self-paced movement features and cortico-spinal excitability (recruitment curves and silent periods in both hemispheres) before, immediately after, and two weeks after the training period. RESULTS Movement amplitude increased significantly after the therapy in the experimental group for the trained and un-trained hands. Motor thresholds and silent periods evaluated with transcranial magnetic stimulation were differently modified by training in the two groups; although the changes in the input-output recruitment were similar. CONCLUSIONS This pilot study suggests that movement imitation therapy enhances the effect of motor practice in patients with Parkinsons disease; imitation-training might be helpful for reducing hypometria in these patients. These results must be clarified in future larger trials.

Effects on EEG of Low (1Hz) and High (15Hz) Frequency Repetitive Transcranial Magnetic Stimulation of the Visual Cortex: A Study in the Anesthetized Cat

Here we confirm our earlier findings that showed 1Hz rTMS over the primary visual cortex of the anesthetized cat, known to cause inhibition of the cortex, induces an increase in power in the slow, delta band of the EEG. We also demonstrate that these inhibitory effects of 1Hz rTMS may be measured as changes of spatiotemporal receptive field pa- rameters at the single cell level. We extend these observations to show that higher frequency stimulation of the cortex at 15Hz has the opposite effect of decreasing delta activity, which was also accompanied by significant increases in theta, alpha and beta bands. This highly reproducible EEG change may be useful as a simple marker to predict inhibitory or ex- citatory rTMS effects known to be dependent upon stimulation frequency.

Functional two-way analysis of variance and bootstrap methods for neural synchrony analysis

BackgroundPairwise association between neurons is a key feature in understanding neural coding. Statistical neuroscience provides tools to estimate and assess these associations. In the mammalian brain, activating ascending pathways arise from neuronal nuclei located at the brainstem and at the basal forebrain that regulate the transition between sleep and awake neuronal firing modes in extensive regions of the cerebral cortex, including the primary visual cortex, where neurons are known to be selective for the orientation of a given stimulus. In this paper, the estimation of neural synchrony as a function of time is studied in data obtained from anesthetized cats. A functional data analysis of variance model is proposed. Bootstrap statistical tests are introduced in this context; they are useful tools for the study of differences in synchrony strength regarding 1) transition between different states (anesthesia and awake), and 2) affinity given by orientation selectivity.ResultsAn analysis of variance model for functional data is proposed for neural synchrony curves, estimated with a cross-correlation based method. Dependence arising from the experimental setting needs to be accounted for. Bootstrap tests allow the identification of differences between experimental conditions (modes of activity) and between pairs of neurons formed by cells with different affinities given by their preferred orientations. In our test case, interactions between experimental conditions and preferred orientations are not statistically significant.ConclusionsThe results reflect the effect of different experimental conditions, as well as the affinity regarding orientation selectivity in neural synchrony and, therefore, in neural coding. A cross-correlation based method is proposed that works well under low firing activity. Functional data statistical tools produce results that are useful in this context. Dependence is shown to be necessary to account for, and bootstrap tests are an appropriate method with which to do so.

Balancing the excitability of M1 circuitry during movement observation without overt replication

Although observation of a movement increases the excitability of the motor system of the observer, it does not induce a motor replica. What is the mechanism for replica suppression? We performed a series of experiments, involving a total of 66 healthy humans, to explore the excitability of different M1 circuits and the spinal cord during observation of simple movements. Several strategies were used. In the first and second experimental blocks, we used several delay times from movement onset to evaluate the time-course modulation of the cortico-spinal excitability (CSE), and its potential dependency on the duration of the movement observed; in order to do this single pulse transcranial magnetic stimulation (TMS) over M1 was used. In subsequent experiments, at selected delay times from movement-onset, we probed the excitability of the cortico-spinal circuits using three different approaches: (i) electric cervicomedullary stimulation (CMS), to test spinal excitability, (ii) paired-pulse TMS over M1, to evaluate the cortical inhibitory-excitatory balance (short intracortical inhibition (SICI) and intracortical facilitation (ICF)], and (iii) continuous theta-burst stimulation (cTBS), to modulate the excitability of M1 cortical circuits. We observed a stereotyped response in the modulation of CSE. At 500 ms after movement-onset the ICF was increased; although the most clear-cut effect was a decrease of CSE. The compensatory mechanism was not explained by changes in SICI, but by M1-intracortical circuits targeted by cTBS. Meanwhile, the spinal cord maintained the elevated level of excitability induced when expecting to observe movements, potentially useful to facilitate any required response to the movement observed.

Cross nearest-spike interval based method to measure synchrony dynamics

A new synchrony index for neural activity is defined in this paper. The method is able to measure synchrony dynamics in low firing rate scenarios. It is based on the computation of the time intervals between nearest spikes of two given spike trains. Generalized additive models are proposed for the synchrony profiles obtained by this method. Two hypothesis tests are proposed to assess for differences in the level of synchronization in a real data example. Bootstrap methods are used to calibrate the distribution of the tests. Also, the expected synchrony due to chance is computed analytically and by simulation to assess for actual synchronization.