Background The dorsolateral prefrontal cortex (DLPFC) plays a crucial role in cognitive-motor integration through its top-down regulation of the primary motor cortex (M1). However, the functional lateralization of the left and right DLPFC and the differences between intra-hemispheric and inter-hemispheric regulation of M1, particularly in populations with brain injury, remain controversial and insufficiently studied. Objective This study aimed to systematically achieve the following four objectives using a dual-site paired-pulse transcranial magnetic stimulation (TMS) technique: (1) to evaluate the integrated regulatory effects of bilateral DLPFC on M1; (2) to compare the differences in regulatory effects between ipsilateral and contralateral DLPFC; (3) to analyze the impact of functional lateralization of the left and right DLPFC on their regulation of M1; (4) to investigate the effects of brain injury on the DLPFC-M1 regulatory pathway by comparing healthy participants and stroke patients. Methods A total of 30 right-handed participants were enrolled, including 20 stroke patients in the recovery phase (divided into left and right lesion groups) and 10 healthy volunteers. These three participant groups were tested under conditions that varied the targeted motor cortex (M1) side, yielding four key experimental conditions for analysis. Accordingly, a paired-pulse TMS paradigm was employed. Following a conditioning stimulus (CS) applied to the left or right DLPFC, a test stimulus (TS) was delivered to the ipsilateral or contralateral M1 after an inter-stimulus interval of 20 ms. The amplitude of the motor evoked potential (MEP) was recorded. Results In experiments targeting the left M1, both the healthy group (Experiment 1) and the patient group (Experiment 3) exhibited significant regulatory effects ( χ 2 = 12.2, p = 0.002; χ 2 = 9.6, p = 0.008). Post-hoc analysis revealed that, compared to baseline, both ipsilateral DLPFC ( p = 0.011; p = 0.022) and contralateral DLPFC ( p = 0.005; p = 0.022) significantly enhanced M1 excitability, with no significant difference between the two ( p = 1.000). However, in experiments targeting the right M1 across all groups (Experiments 2 and 4), no significant regulatory effect of DLPFC was observed ( χ 2 = 0.2, p = 0.905). Conclusion This study confirms that, at rest, the bilateral DLPFC exerts a stable and non-specific facilitatory regulation on the left M1. This effect persists in the affected M1 of stroke patients, suggesting plasticity in the relevant pathways after injury. The negative findings for the right M1 reveal a lateralization characteristic in DLPFC-M1 regulation. These results provide an important basis for elucidating the physiological mechanisms of cognitive-motor circuits and for developing targeted neurorehabilitation strategies.

Sensory experiences in the real world cut across timescales from milliseconds to seconds. Emerging evidence suggests that somatosensory processing is sensitive to the temporal structure of the stimuli in the sub-second scale, yet only a few select ranges within this scale have been studied. To process real-world information, the integration of tactile inputs must occur over a much broader temporal range. To address temporal integration across timescales, we studied scalp EEG signals from somatosensory cortex in response to a train of tactile stimuli presented to the fingertips with varying inter-stimulus intervals (ISIs) spanning hundreds of milliseconds to several seconds. We captured the variations in cortical signals as a function of the subsequent ISIs (next interval structure). We tracked cortical tactile processing through its early (<75 ms), intermediate (75 to 150 ms), and late stages (150 to 300 ms). We find that the early and late stages of cortical activity were sensitive to the previous ISI; EEG signals were suppressed with ISIs <500 ms and enhanced with longer ISIs, with this effect persisting even when ISIs were approximately 8 s. The intermediate stage of cortical activity was sensitive to both the previous and the penultimate ISIs. Our findings suggest that the specific somatosensory cortical processing stages integrate temporal structure across timescales to enable complex sensory experiences.

In the present study, 43 Italian school-age children (age range = 7-14 years, 16 females) with (N = 19) and without DD (N = 24) were presented with pairs of visual displays separated by varying interstimulus intervals and performed either a temporal integration or segregation task despite an identical visual input. Children with DD had lower accuracy and slower RTs for longer temporal intervals. Additionally, efficiency (combined accuracy and speed trade-off) increased as a function of age only in the DD group, most markedly for the integration condition. Results suggest that visual temporal processing deficits in DD may depend on short-term/working memory liability as well as the existence of possibly differentiated developmental trajectories for integration and segregation abilities.

Spatial activation of motor evoked potentials depends on paired-pulse transcranial magnetic stimulation orientation and intensity.

The known fluctuations in ovarian hormone concentrations across the eumenorrheic menstrual cycle contribute to modulations in cortical excitability and inhibition. However, how such changes affect spike-timing-dependent plasticity (STDP) has not been systematically studied. This research aimed to determine the effect of the menstrual cycle on corticospinal excitability and STDP. Twelve eumenorrheic female participants (age: 25 ± 5 years), visited the lab in three menstrual cycle phases: early follicular (EF), late follicular (LF), and mid-luteal (ML). Visits comprised of corticospinal excitability (motor evoked potential [MEP]/Mmax), short-intracortical inhibition (SICI), and intracortical facilitation (ICF) measures, recorded in the resting first dorsal interosseous. Followed by a paired associative stimulation (PAS) protocol, utilising ulnar nerve and transcranial magnetic stimulation (25 ms interstimulus interval) to elicit neuroplasticity. To assess the time course of STDP, measurements were repeated at 15 and 30-minutes post PAS. Corticospinal excitability (MEP/Mmax) was greater in the LF phase (p≤0.001) compared to EF and ML, with no phase effects observed for SICI or ICF (p≥0.170). PAS elicited an increase in MEP/Mmax across all phases at 15-minutes (112 ± 5, 116 ± 5, and 114 ± 7% baseline, p≤0.037), whereas at 30-minutes only ML was facilitated (126 ± 5% baseline, p=0.044). The present data demonstrates facilitatory STDP can be induced with PAS across the tested menstrual cycle phases, but responses are prolonged and potentiated in the ML phase. Additionally, increased corticospinal excitability in the LF phase is likely due to intrinsic changes within the descending tract, as no changes in intracortical neurotransmission were observed.

In the nucleus accumbens (NAc), a brain region known for its role in reward, medium spiny neurons (MSNs) receive glutamatergic inputs from the medial prefrontal cortex (mPFC) and the basolateral amygdala (BLA), two brain regions implicated in mediating alcohol's effects. Previously, we reported that in 8-week-old male C57Bl/6j mice, mPFC and BLA inputs synapse onto the same MSNs where they reciprocally inhibit each other presynaptically in a strict time-dependent manner, a phenomenon called synaptic gating. However, the influence of sex and age on synaptic gating and its sensitivity to binge alcohol drinking remained unknown. This study investigates the effects of alcohol, age, and sex on BLA-mPFC and mPFC-BLA synaptic gating. To investigate this biological question, we performed whole-cell recordings from NAc core MSNs while independently optogenetically stimulating BLA and mPFC inputs in succession, using interstimulus intervals of 40, 65, 115, and 165 ms, in 6-, 8-, and 12-week-old male and female C57Bl/6j mice. We found that, in alcohol-naïve mice, the ability of cortical inputs to inhibit the transmission of information from the BLA region changes with age. Regarding the influence of sex, mPFC gating of BLA synaptic transmission was significantly stronger in 8-week-old males compared with age-matched females, a difference that disappeared in 12-week-old mice. Interestingly, the observed synaptic gating sex difference disappeared in binge alcohol drinking mice. Furthermore, binge alcohol drinking had a greater effect on BLA → mPFC gating in older (12-week-old) than in younger (8-week-old) mice. Overall, our results show that age and sex influence how NAc MSNs process cortical and amygdala information through synaptic gating, a phenomenon disrupted by binge alcohol drinking.

The neurophysiological correlates of click rate discrimination in children.

Previous studies have shown that supraspinal excitability is higher during arm cycling than a position- and intensity-matched tonic contraction, but the underlying mechanisms remain unclear. This study aimed to determine whether long-interval intracortical inhibition (LICI) occurs during arm cycling and if LICI differs between arm cycling and tonic contraction. A paired-pulse transcranial magnetic stimulation (TMS) protocol assessed LICI using a supramaximal conditioning pulse that produced a silent period of approximately 150 ms, followed by a test pulse with a 100 ms interstimulus interval. Stimulation occurred at the 4 o'clock position to align the test pulse with the ascending limb of the biceps brachii EMG profile during the elbow flexion phase. Additionally, a single-pulse TMS stimulation was delivered 100 ms after the 4 o'clock position. Motor-evoked potentials (MEPs) were measured as ratios: a position-matched ratio of test pulse-evoked MEP over single pulse-evoked MEP. MEP ratios were analyzed for peak-to-peak amplitude during arm cycling and tonic contraction. Results showed that LICI was present during arm cycling (t(13) = 3.5, p < 0.001, 95% CI [-3.2, -0.75], but no significant difference in LICI was found between arm cycling and tonic contraction (t(13) = 1.3, p = 0.242, 95% CI [-0.23, -0.06]). These findings suggest that while LICI is present during arm cycling, it is not task-dependent.

Homosynaptic depression (HD) refers to the reduction in the magnitude of the monosynaptic spinal reflex resulting from prior activation of the circuit, often evoked with the H-reflex. Previous literature has reported HD of the soleus H-reflex is reduced post-stroke. However, it remains unclear if HD plays a role in functional impairments. The goal of this study was to characterize HD of the soleus H-reflex in individuals with post-stroke gait impairments and examine the relationship with functional measures of gait. Our results revealed that individuals after stroke experienced reduced depression at longer (8s) interstimulus intervals compared to age-matched neurologically intact individuals. However, we did not observe a difference in the change in HD across interstimulus intervals between groups, contrary to previous reports. This finding could not be explained by age of participants. In addition, we found a strong correlation between faster gait speed and reduced change in depression in individuals after stroke. While the underlying mechanisms linking HD with gait are unclear, this finding represents the first piece of evidence of the potential role of HD in function. Further research is needed to understand the parameters that guide HD and clarify how useful the mechanism is for improving the assessment and treatment of post-stroke impairments.

Generative mechanisms of perception such as predictive coding are used to explain how the brain perceives the world; such mechanisms are often experimentally probed using "deviant" stimuli that violate established patterns (including mismatch negativity), which also elicit responses related to lower-level processes such as stimulus-specific adaptation. However, little is still known about brain responses that indicate the strength of sensory predictions or reinforcement of sensory representations. Repetition positivity (RP) is a positive polarity evoked potential that gradually increases with each repetition of a stimulus, and is thought to reflect progressive strengthening of auditory sensory memory and/or habituation to repetitive stimuli. The aim of this study was to compare RP that follows a change in stimulus frequency with that following a change in stimulus intensity, the latter having not previously been studied. We used roving sequences of isochronous 5 kHz pure tones (300 ms duration, 300ms inter-stimulus interval), which changed in frequency by 1 kHz (Experiment 1) or in intensity by 12 dB (Experiment 2) after every 30 stimuli. All changes were roving, such that an increase would be followed by a decrease, and vice versa. Event-related potentials recorded with EEG indicated that frequency changes in either direction were followed by RP, whilst only intensity increases were followed by RP, and only a weak visual trend toward RP was apparent for intensity decreases. Observed RP was best explained by a logarithmic function over successive stimuli. RP robustly follows increases, but not necessarily decreases, in stimulus intensity, which appears smaller in amplitude than that elicited by similarly salient frequency changes, and reaches a plateau sooner. These observations offer insight into how intensity is processed similarly yet differently to other sensory attributes in an adaptive or predictive coding framework, and might have future utility in the study of clinical conditions related to aberrant predictive mechanisms.

Astrocytes exhibit intracellular calcium fluctuations in response to neuronal activity. Repeated receptor stimulation can induce a transient suppression of calcium signaling-a refractory period-yet the underlying mechanisms and timescales of this phenomenon during behavior remain poorly understood. Here, we present a biophysically grounded computational model of astrocytic calcium signaling that incorporates a novel feedback mechanism mediated by conventional protein kinase C (cPKC) and predicts the refractory phenomenon. Unlike previous models developed in vitro, our model is directly validated using in vivo two-photon calcium imaging data from behaving mice. It closely recapitulates astrocytic calcium dynamics across both time and frequency domains, including the emergence of refractory periods and their negative correlation with inter-stimulus intervals. Simulations further predict the timing of recovery from refractory states, consistent with experimental observations. This work provides a mechanistic explanation for astrocytic refractory behavior and establishes a framework for integrating computational modeling with in vivo functional imaging.

ABSTRACTThe evaluation of cortical inhibition (CI) in dorsolateral prefrontal cortex (DLPFC) using transcranial magnetic stimulation combined with electroencephalography (TMS‐EEG) has focused great attention in recent years. One of the most common procedures to assess such inhibition is the short‐interval cortical inhibition (SICI), a paired‐pulse paradigm defined by the interstimulus interval (ISI). While SICI was initially defined and extensively used in studies targeting the motor cortex, its application to the DLPFC is relatively recent. However, little is known about how ISI values affect the DLFPC, especially in terms of the TMS‐evoked potentials (TEP). This study aims to quantitatively compare the effects of different ISI values in the SICI protocol on CI in the DLPFC by assessing TEPs. Eighteen healthy subjects underwent the SICI protocol using two different ISIs: 2 ms and 4 ms. TMS‐EEG responses for both ISIs were characterized in terms of amplitude, latency, peak‐to‐peak amplitudes, and the area under the rectified curve of the TEPs. The results indicate that TEPs differed depending on the ISI used, finding a significantly greater inhibition with 2 ms ISI, as reflected by a more pronounced reduction in TEP amplitude. These findings are consistent with previous literature on motor cortex stimulation, suggesting that a greater reduction in TEP, and hence greater inhibition, is likely achieved with a 2 ms ISI. Therefore, the study helps in the standardization of SICI protocol in DLFPC.

.SignificanceThe combination of two-photon calcium imaging and targeted two-photon optogenetic stimulation, termed all-optical interrogation, provides spatial and temporal precision when recording and manipulating neural circuit activity in vivo. All-optical experiments often use red-shifted opsins in combination with green fluorescent reporters of neuronal activity. However, their excitation spectra still partially overlap, meaning that the imaging laser can excite the opsin. Although some care has been taken in the past to understand the effects of this spectral overlap; further work is required to understand its impact on the findings of all-optical studies.AimWe aimed to investigate whether two-photon imaging of the green fluorescent calcium reporter GCaMP6s at 920 nm increase the rate of response desensitization in neurons targeted for two-photon stimulation at 1035 nm expressing the red-shifted opsin C1V1.ApproachWe systematically varied either the inter-stimulus interval or the duration of two-photon calcium imaging during targeted two-photon optogenetic stimulation of mouse layer 2/3 barrel cortex or visual cortex neurons.ResultsWe found that two-photon imaging at 920 nm decreases trial-by-trial photostimulation responses in targeted C1V1-expressing neurons—an effect that is exacerbated at shorter inter-stimulus intervals. This is consistent with the imaging laser increasing the rate of opsin desensitization. Reduced photostimulation responses are not limited to targeted cells and are found across the field of view. Such network effects are less pronounced at shorter imaging doses.ConclusionsOur results provide methodological optimizations that enable trial-by-trial decreases in photostimulation response to be mitigated in all-optical experiments. This will reduce an external source of trial-by-trial variability in future all-optical experiments.

Studies revealed that contact-heat stimulations mediate pain perception due to temporal summation of second pain (TSSP). How heat intensity affects the reliability of the pain rating of individuals with different heat tolerance is not well examined. This study investigated (1) the influence of the preceding contact-heat stimuli with different levels of intensity on the reliability of subjective pain rating and (2) the differences in reliability of subjective pain rating of participants with high and low sensory sensitivity or heat tolerance. Participants with intact sensory function were divided into (1) high (n = 17) and low (n = 13) sensitivity groups based on the cutoff temperature of 42°C or (2) high (n = 18) and low (n = 12) pain-tolerance groups based on the cutoff temperature of 47°C equivalent to numerical rating scale (NRS) of 7. In each trial, participants were given a pair of 2-s contact-heat stimuli (an interstimulus interval of 2.5 s) at the left thenar eminence and were asked to report an NRS rating. Four blocks of intensity combinations were given: Low-Low, High-High, Low-High, and High-Low conditions, with 72 trials in each block. Findings revealed that high heat-tolerance group results had lower intraclass correlation coefficients (ICCs) when contact-heat stimuli were preceded by another with higher intensity (ICC = 0.551-0.747) compared to those preceded by lower intensity (ICC = 0.724-0.818). In contrast, the ICCs of the low heat-tolerance group were found to be relatively higher regardless of heat intensity (ICC = 0.595-0.806). The TSSP effect reflected by lower pain rating reliability appears to be induced in the high heat-tolerance group when a contact-heat stimulation is preceded by another stimulation with higher intensity but with the same duration. This is possibly due to the longer offset time of contact-heat stimulations with higher intensity, and also the top-down modulatory effects in this high heat-tolerance group. Further electrophysiological studies would be needed to investigate the underlying neural processes of TSSP in individuals with different heat tolerance.

Impaired sensorimotor synchronization is observed in children with autism spectrum disorder (ASD), yet the underlying mechanism of this impairment remains unclear. The current study investigated the impact of the inter-stimulus interval and the modality of stimulus on synchronization performance in children with ASD. Twenty-one high-functioning children with ASD and 21 typically developing (TD) children participated in a finger-tapping task. There were no significant group differences in age, gender, or IQ. Results showed that children with ASD exhibited greater asynchrony at longer time intervals and lower efficiency in multisensory integration compared to TD children. Notably, children with ASD were able to benefit from multisensory cues to improve their sensorimotor synchronization at longer intervals. Children's synchronization performance was correlated with total IQ, fluid reasoning, and visual spatial ability. These findings shed light on the underlying mechanism of atypical synchronization in children with ASD and provide a new avenue for developing targeted training on sensorimotor synchronization for children with ASD.

Restless limbs syndrome (RLS) is a neurological disorder characterized by an uncontrollable urge to move the limbs. Although it affects up to 10% of the general population, its underlying mechanisms remain poorly understood. Neurophysiological excitability testing may help elucidate mechanisms related to sensorimotor integration, axonal ion channel dysfunction and impaired neural inhibition. This study aimed to assess both CNS and PNS function by examining cortical, spinal and peripheral nerve excitability within the same individuals for the first time. To investigate potential widespread excitability changes in RLS, we specifically analysed hand muscles, offering new insights into the extent of neural involvement beyond the lower limbs. The study included 56 RLS patients, divided into treated and untreated groups, along with 32 healthy controls. Notably, none of the patients experienced symptoms in their hands. Cortical excitability was assessed via threshold-tracking transcranial magnetic stimulation (TMS) to evaluate intracortical inhibition and facilitation. Sensory-motor integration was measured via long-latency reflexes (LLRs), while spinal cord excitability was assessed using F-waves, H-reflexes and RIII-reflexes. Axonal excitability was examined using the extended TRONDNF protocol. TMS revealed a significant reduction in short-interval intracortical inhibition (SICI) in patients, particularly at inter-stimulus intervals (ISIs) of 2.5 and 3 ms. When averaging across ISIs from 1 to 7 ms, patients on medication exhibited significantly less inhibition compared to healthy controls. Long-interval intracortical inhibition (LICI) was also reduced at ISIs of 150 and 200 ms, while facilitation parameters remained within normal ranges. Patients exhibited increased amplitude of the second component of the LLR recorded from the abductor pollicis brevis, whereas RIII reflex measurements showed no significant differences. Axonal excitability testing revealed a graded increase in hyperpolarization-activated currents in patients with more severe symptoms. The observed reductions in SICI and LICI suggest impaired intracortical inhibition in the M1 hand area, offering indirect evidence of cortical dysfunction in regions clinically unaffected by the disease. The increased LLR amplitudes further indicate altered sensorimotor integration at the cortical level, whereas the absence of significant changes in RIII reflexes suggests that segmental spinal dysfunction within the pain pathway of the upper limbs is unlikely. Finally, axonal excitability findings point to a potential role of hyperpolarization-activated currents in either contributing to or predisposing individuals to RLS symptoms.

Aim Hemispheric asymmetry is well established in tactile processing, with higher cortical responses observed on the contralateral side of the stimulation area. However, the effect of the interstimulus interval on lateralization is poorly understood. In this context, we aimed to reveal the effects of repeated non-painful tactile stimuli on brain responses and hemispheric lateralization via static ISIs. Methods Twenty-six healthy participants (13 females; mean age 22.2 ± 3.30 years) participated in the study. Tactile stimuli were delivered to the index fingertip of the right hand via a pneumatic stimulator with static ISIs (2s, 4s, and 8s applied as separate sessions). Electroencephalography was performed throughout the procedure. We determined the ROI and primarily analysed nine electrodes (Fz, Cz, Pz, F3, C3, P3, F4, C4, and P4). We measured the peak-to-peak maximum amplitudes (PPmaxN2P3) between N200 and P300, labelling N200 as N2 and P300 as P3. Results The results revealed no significant differences in the amplitudes of PPmaxN2P3 between the ipsilateral and contralateral hemispheres. Constant ISI manipulation altered the laterality of non-painful tactile stimuli. Furthermore, the amplitude of the brain responses would be higher in both the ipsilateral and contralateral hemispheres when the ISI increased. The evaluation of the duration of PPmaxN2P3 was prolonged in the frontal, central, and parietal areas. Conclusion The results indicate that manipulation of the interstimulus interval (ISI) can potentially negate the traditional contralateral advantage observed in tactile processing.

Contour erasure describes the phenomenon that after brief flicker adaptation at the edge of an object, the object disappears and is replaced by the background – highlighting the importance of edges in perceiving a surface. The underlying mechanism remains unknown. The current study investigates the characteristics and functional properties of contour erasure, and its relationship with related phenomena such as perceptual filling-in, forward masking, and contrast adaptation. We used a homogeneous disk as a target, and circles that corresponded to the outline of the target disk as the adapter. Using a two-alternative forced choice (2AFC) paradigm, each trial began with a counterphase flickering adapter, followed by the target randomly presented in one of the two locations. Participants indicated the target location with a button press. The target detection threshold elevation relative to the no adaptation condition was used as an index of the adaptation effect. We manipulated two spatial properties (eccentricity and the adapter size) plus three temporal properties (adapter flickering rate, adaptation duration, and interstimulus interval [ISI]). Results indicated that the adaptation effect increased with eccentricity, flickering rate (plateauing at 6 hertz [Hz]) and adaptation duration, but decreased with longer ISI and for adapter sizes that were larger than the target. The target threshold first increased then decreased as the adapter size decreased from that of the target, indicating a size tuning that is slightly smaller than the target. Our results indicate that contour erasure shares some of the key features of other well-known perceptual phenomena like filling in and contrast adaptation.

A crucial ability of our cognition is the perception of objects and their motions. We can perceive objects as moving by connecting them across space and time. This is possible even when the objects are not present continuously, as in the case of apparent motion displays like the Ternus display, consisting of two sets of stimuli, shifted to the left or right, separated by a variable inter-stimulus interval (ISI). This is an ambiguous display, which can be perceived as both stimuli moving uniformly to the right (group motion) or one stimulus moving across the stationary center stimulus (element motion), depending on which stimuli are connected over time. Which percept is seen can be influenced by the ISI and the stimulus features. Previous experiments have shown that the Ternus effect also exists in the auditory modality and that the auditory Ternus is also dependent on the ISI. This is a first indication that correspondence might work similarly in the visual and auditory modality. To test this idea further, we investigated whether the auditory Ternus effect is dependent on the stimulus features by creating a frequency-based bias using a high and a low sinewave tone as Ternus stimuli. This bias was compatible either with the element-motion or with the group-motion percept. Our results showed an influence of this feature bias in addition to an ISI effect, suggesting that the visual and the auditory modalities might both use the same mechanism to connect objects across space and time.

Post-activation depression of spinal reflexes is reduced following central motor lesions, including spinal cord injury (SCI), and has long been proposed to contribute to signs and symptoms associated with spasticity. To evaluate this hypothesis, we assessed post-activation depression in individuals with chronic SCI, both males and females with and without stretch reflex hyperexcitability (SRH) as well as in age-matched controls. Post-activation depression was assessed by recording the soleus H-reflex every 10 s using paired pulses at interstimulus intervals (ISIs) of 1, 2, and 4 s, and test reflexes amplitudes set at 20 and 40% of maximal motor response (M-max). Stretch reflexes were elicited by rapid (>300°/s) passive dorsiflexion of the ankle, and spasticity was clinically assessed in all SCI participants using the Modified Ashworth Scale (MAS) in plantarflexor muscles. We found that post-activation depression was more pronounced at shorter ISIs and at lower test reflex amplitudes (20% M-max) across all groups. However, post-activation depression was significantly reduced in individuals with SCI compared with controls, with no differences observed between SCI participants with and without SRH. Moreover, the magnitude of post-activation depression did not correlate with stretch reflex amplitude or MAS scores. These findings indicate that while post-activation depression is reduced after SCI, this decrease does not correlate with either SRH or the severity of clinical spasticity as assessed by the MAS.