The reduction of plasticity with age has been shown by many previous papers in animal experiments. This issue can be studied in humans because several non-invasive brain stimulation techniques induce ...synaptic plasticity in the human brain. We investigated the influence of individuals’ age on the responder rate of the long-term potentiation (LTP)-like effect induced by quadripulse magnetic stimulation (QPS). The participants were 107 healthy volunteers: 53 older participants (Mean ± SD 65.0 ± 1.5 years) and 54 younger participants (37.2 ± 8.7). The quadripulse stimulation with 5-ms inter-pulse interval (QPS5) was applied over the primary motor cortex (M1). We measured motor evoked potentials (MEPs) before QPS, and at five time points after QPS for up to 25 min. In each participant, average MEP amplitude (size) ratios were quantified. We first classified participants as responders and non-responders simply by comparing the size ratio with 1.0 for consistency with previous studies, then as “significant responders”, “non-responders”, and “opposite responders” for more detailed analysis by comparing the size ratio with the mean and standard deviation of the MEP size ratios of the sham condition. The degree of LTP-like effects induced by QPS5 was significantly smaller in the older group compared to the younger group. Also, the rates of responders and significant responders were lower in the older group (58 and 47%, respectively) compared to the younger group (80 and 76%, respectively). The age of the participants significantly affected the LTP-like effect induced by QPS5, which suggests that brain plasticity decreases with age.
The '3-second rule' has been proposed based on miscellaneous observations that a time period of around 3 seconds constitutes the fundamental unit of time related to the neuro-cognitive machinery in ...normal humans. The aim of paper was to investigate the temporal processing in patients with spinocerebellar ataxia type 6 (SCA6) and SCA31, pure cerebellar types of spinocerebellar degeneration, using a synchronized tapping task. Seventeen SCA patients (11 SCA6, 6 SCA31) and 17 normal age-matched volunteers participated. The task required subjects to tap a keyboard in synchrony with sequences of auditory stimuli presented at fixed interstimulus intervals (ISIs) between 200 and 4800 ms. In this task, the subjects required non-motor components to estimate the time of forthcoming tone in addition to motor components to tap. Normal subjects synchronized their taps to the presented tones at shorter ISIs, whereas as the ISI became longer, the normal subjects displayed greater latency between the tone and the tapping (transition zone). After the transition zone, normal subjects pressed the button delayed relative to the tone. On the other hand, SCA patients could not synchronize their tapping with the tone even at shorter ISIs, although they pressed the button delayed relative to the tone earlier than normal subjects did. The earliest time of delayed tapping appearance after the transition zone was 4800 ms in normal subjects but 1800 ms in SCA patients. The span of temporal integration in SCA patients is shortened compared to that in normal subjects. This could represent non-motor cerebellar dysfunction in SCA patients.
Time Distortion in Parkinsonism Terao, Yasuo; Honma, Motoyasu; Asahara, Yuki ...
Frontiers in neuroscience,
03/2021, Volume:
15
Journal Article
Peer reviewed
Open access
Although animal studies and studies on Parkinson's disease (PD) suggest that dopamine deficiency slows the pace of the internal clock, which is corrected by dopaminergic medication, timing deficits ...in parkinsonism remain to be characterized with diverse findings. Here we studied patients with PD and progressive supranuclear palsy (PSP), 3-4 h after drug intake, and normal age-matched subjects. We contrasted perceptual (temporal bisection, duration comparison) and motor timing tasks (time production/reproduction) in supra- and sub-second time domains, and automatic versus cognitive/short-term memory-related tasks. Subjects were allowed to count during supra-second production and reproduction tasks. In the time production task, linearly correlating the produced time with the instructed time showed that the "subjective sense" of 1 s is slightly longer in PD and shorter in PSP than in normals. This was superposed on a prominent trend of underestimation of longer (supra-second) durations, common to all groups, suggesting that the pace of the internal clock changed from fast to slow as time went by. In the time reproduction task, PD and, more prominently, PSP patients over-reproduced shorter durations and under-reproduced longer durations at extremes of the time range studied, with intermediate durations reproduced veridically, with a shallower slope of linear correlation between the presented and produced time. In the duration comparison task, PD patients overestimated the second presented duration relative to the first with shorter but not longer standard durations. In the bisection task, PD and PSP patients estimated the bisection point (BP50) between the two supra-second but not sub-second standards to be longer than normal subjects. Thus, perceptual timing tasks showed changes in opposite directions to motor timing tasks: underestimating shorter durations and overestimating longer durations. In PD, correlation of the mini-mental state examination score with supra-second BP50 and the slope of linear correlation in the reproduction task suggested involvement of short-term memory in these tasks. Dopamine deficiency didn't correlate significantly with timing performances, suggesting that the slowed clock hypothesis cannot explain the entire results. Timing performance in PD may be determined by complex interactions among time scales on the motor and sensory sides, and by their distortion in memory.
Transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS) have been used for human physiological analyses and treatment of movement disorders. In this review, we present three new TMS ...utilities for scientific research or clinical application for movement disorders. 1) Confirmation of animal findings. Functional modulation of particular brain areas induced by rTMS can produce changes in task performance. This indicates that the area stimulated by rTMS should play some role in the target task. One example of this use is the study of functional differences between the presupplementary motor area (preSMA) and SMA in a sequential learning task. 2) Utility of cerebellar stimulation. Cerebellar functional changes in basal ganglia disorders are a hot topic in this field. These changes have been studied by cerebellar inhibition using a paired TMS coil experiment. Several researchers have recently used rTMS over the cerebellum as a treatment option for movement disorders. 3) rTMS enhancement of the effects of rehabilitation. The combination of rTMS and conventional rehabilitation may enhance rehabilitation efficacy. For example, rTMS over the lumbar gait (locomotion) center may enhance functional recovery of the gait more robustly than conventional rehabilitation alone in patients with a spinal cord injury.
Highlights • Paradigm parameters, such as inter-burst interval (IBI), duration of the procedure and pulse wave-form have significant effects on cortical excitability changes induced by QPS. • QPS at ...an IBI of 5 s, delivering 1440 monophasic pulses over 30 minutes, was found to be optimal for increasing cortical excitability changes in M1. • The excitatory QPS of 5 ms, given at an IBI of 5 s over M1, induced an expected motor cortical facilitation in 80% of subjects in this cohort.
•We studied how deep brain stimulation (DBS) affects eye movements made during visual scanning.•DBS increased the amplitude of voluntary saccades, but not reflexive saccades.•DBS mainly affects ...voluntary saccades mediated by the basal ganglia.
Deep brain stimulation (DBS) can provide insights into the workings of the basal ganglia (BG) by interfering with their function. In patients with Parkinson's disease (PD) treated with DBS of the subthalamic nucleus, we studied the effect of DBS on scanning eye movements.
In the visual memory task, subjects viewed images of various complexities for later recall. In visual search tasks, subjects looked for and fixated one odd target ring, embedded among 48 Landolt rings, which either stood out or not from the distractors. We compared the parameters of scanning saccades when DBS was on and off.
In the visual memory task, DBS increased the amplitude of saccades scanning simple but not complex drawings. In the visual search tasks, DBS showed no effect on saccade amplitude or frequency.
Saccades when viewing simple images were affected by DBS since they are internally guided saccades, for which the involvement of BG is large. In contrast, saccades when viewing complex images or during visual search, made with the help of visual cues in the images (externally guided saccades) and less dependent on BG, were resistant to the effect of DBS.
DBS affects saccades differentially depending on the task.
Parkinson's disease (PD) is associated with various cognitive impairments. However, the nature of cognitive modification in patients with PD remains to be elucidated. In the present study, we ...examined whether patients with PD could correct and maintain subjective time duration and line length estimation. After training sessions, in which participants repeatedly memorized either a duration or a length, we compared a learning performance in 20 PD patients with 20 healthy controls. In the case of duration in the PD patients, the learned durations immediately returned to baseline of pre-training within a few minutes. However, the patients' ability to learn length estimation remained unimpaired. In contrast, healthy controls were able to retain the learned duration and length estimations. Time compression in PD's internal clock may become entrained to their altered duration estimation even after learning of accurate time duration. These deficits may be associated with disrupting cognitive modification in PD.
Parkinson's disease (PD) is a neurological disorder caused by degeneration of dopaminergic neurons in the midbrain. PD patients mainly suffer from motor symptoms, which significantly impact their ...daily lives. The diagnostic criteria for PD include the presence of muscle rigidity, tremor, and postural reflex disturbances. The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is the standard tool for evaluating PD symptoms, part III of which is dedicated to motor symptoms. That part involves a comprehensive set of specific physical examinations, and physicians assign semi quantitative scores from 0 to 4. However, this approach faces notable challenges, including the requirement for movement-disorder experts proficient in using MDS-UPDRS and the presence of substantial inter rater variability even among experts. Overcoming these challenges requires a quantitative and objective assessment method. Given that the rating of motor symptoms predominantly involves assessing kinematic characteristics, the integration of sensor-based devices and machine learning techniques holds the potential to outperform human experts in symptom evaluations. This study used the Leap Motion optical motion-capture device to quantitatively measure and analyze hand movements while 45 PD patients performed the following 3 tasks from the MDS-UPDRS part III: finger tapping (FT), hand opening and closing (OC), and forearm pronation and supination (PS). Data from these tasks were collected and processed, resulting in the extraction of 31 movement patterns for each task. Additionally, 69 statistical features were extracted from each movement pattern, yielding 2139 features for each task. We subsequently employed a random forest algorithm to select the top 15% of features based on the reduction of Gini impurity. These selected features were subsequently fed into a sequential-forward-floating-selection algorithm, combined with a support vector machine, to identify relevant feature combinations and predict the severity of the motor symptoms. The classification accuracy was 87.0% for FT, 93.2% for OC, and 92.2% for PS. One-way analysis of variance identified 13 features of the OC task that were significantly more discriminative for classifying the movement disability of PD patients (<inline-formula> <tex-math notation="LaTeX">{p} </tex-math></inline-formula><0.05). This study highlights the effectiveness of combining sensor-based measurements with machine learning for symptom assessment, which demonstrated performance
Sense of time (temporal sense) is believed to be processed by various brain regions in a complex manner, among which the basal ganglia, including the striatum and subthalamic nucleus (STN), play ...central roles. However, the precise mechanism for processing sense of time has not been clarified. To examine the role of the STN in temporal processing of the sense of time by directly manipulating STN function by switching a deep brain stimulation (DBS) device On/Off in 28 patients with Parkinson's disease undergoing STN-DBS therapy. The test session was performed approximately 20 min after switching the DBS device from On to Off or from Off to On. Temporal sense processing was assessed in three different tasks (time reproduction, time production, and bisection). In the three temporal cognitive tasks, switching STN-DBS to Off caused shorter durations to be produced compared with the switching to the On condition in the time production task. In contrast, no effect of STN-DBS was observed in the time bisection or time reproduction tasks. These findings suggest that the STN is involved in the representation process of time duration and that the role of the STN in the sense of time may be limited to the exteriorization of memories formed by experience.
We investigated the relationship between the involvement of the cauda equina in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and the increment of cerebrospinal fluid (CSF) ...protein. We measured cauda equina conduction time (CECT) in 14 CIDP patients using magnetic stimulation with a MATS coil. Statistical analysis revealed that CECT and CSF protein had a significant positive linear correlation. Conduction time of the peripheral nerve trunk, in contrast, had no significant linear correlation with CSF protein. We revealed that the involvement of the cauda equina and increment of CSF protein are closely related. In CIDP cases with elevated CSF protein, spinal nerves including the cauda equina are very likely involved.
•Cauda equina conduction time (CECT) was measured in CIDP.•CECT and CSF protein had a significant positive, linear correlation.•If the CSF protein increases, spinal nerves may be involved in CIDP.
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