Sensory Gating in the Auditory System: Classical and Novel Stimulus Paradigms.

PURPOSE: Sensory gating is a phenomenon where the cortical response to the second stimulus in a pair of identical stimuli is inhibited. It is most often assessed in a conditioning-testing paradigm. Both active and passive neuronal mechanisms have been implicated in sensory gating. The present study aimed to assess if sensory gating is caused by an active neural mechanism associated with stimulus redundancy. METHOD: The study was carried out on 20 young neurotypical adults. We assessed the gating phenomenon using identical and nonidentical stimuli pairs presented in an electrophysiological conditioning-testing paradigm. We hypothesized that the novel stimulus in the nonidentical stimulus pair would not exhibit the sensory gating effects (reduction in the amplitude of cortical potentials to the second stimuli in the pair), owing to stimulus novelty. RESULTS: Contrary to our expectations, the response analyses of the cortical auditory evoked potentials revealed that adults gated repetitive and novel stimuli similarly. CONCLUSIONS: The findings are discussed in relation to the significance of methodological factors in evaluating sensory gating. We believe that additional research using oddball presentation of novel stimuli along with appropriate analysis methods is necessary before drawing any conclusions on the mechanisms underlying sensory gating.

Neural oscillations underlying the neural gating of respiratory sensations in generalized anxiety disorder.

Individuals with generalized anxiety disorder (GAD) have been shown to have altered neural gating of respiratory sensations (NGRS) using respiratory-related evoked potentials (RREP); however, corresponding neural oscillatory activities remain unexplored. The present study aimed to investigate altered NGRS in individuals with GAD using both time and time-frequency analysis. Nineteen individuals with GAD and 28 healthy controls were recruited. Paired inspiratory occlusions were delivered to elicit cortical neural activations measured from electroencephalography. The GAD group showed smaller N1 amplitudes to the first stimulus (S1), lower evoked gamma and larger evoked beta oscillations compared to controls. Both groups showed larger N1, P3, beta power and theta power in response to S1 compared to S2, suggesting a neural gating phenomenon. These findings suggest that N1, gamma and beta frequency oscillations may be indicators for altered respiratory sensation in GAD populations and that the N1, P3, beta and theta oscillations can reflect the neural gating of respiratory sensations.

Magnetoencephalography reveals impaired sensory gating and change detection in older adults in the somatosensory system.

Brain electrophysiological responses can provide information about age-related decline in sensory-cognitive functions with high temporal accuracy. Studies have revealed impairments in early sensory gating and pre-attentive change detection mechanisms in older adults, but no magnetoencephalographic (MEG) studies have been undertaken into both non-attentive and attentive somatosensory functions and their relationship to ageing. Magnetoencephalography was utilized to record cortical somatosensory brain responses in young (20-28 yrs), middle-aged (46-56 yrs), and older adults (64-78 yrs) under active and passive somatosensory oddball conditions. A repeated standard stimulus was occasionally replaced by a deviant stimulus (p = .1), which was an electrical pulse on a different finger. We examined the amplitudes of M50 and M100 responses reflecting sensory gating, and later components reflecting change detection and attention shifting (M190 and M250 for the passive condition, and M200 and M350 for the active condition, respectively). Spatiotemporal cluster-based permutation tests revealed that older adults had significantly larger M100 component amplitudes than young adults for task-irrelevant stimuli in both passive and active condition. Older adults also showed a reduced M250 component and an altered M350 in response to deviant stimuli. The responses of middle-aged adults did not differ from those of younger adults, but this study should be repeated with a larger sample size. By demonstrating changes in both somatosensory gating and attentional shifting mechanisms, our findings extend previous research on the effects of ageing on pre-attentive and attentive brain functions.

Sex difference in association between cognitive and P50 deficits in patients with chronic schizophrenia.

A large number of studies have reported that sensory gating disorders represented by P50 inhibition may be involved in the pathophysiological process of schizophrenia. However, few studies have explored the relationship between sensory gating disorders and cognitive dysfunction in patients with schizophrenia. This study aimed to explore sex differences in the relationship between cognitive and P50 deficits in patients with chronic schizophrenia, which has not been reported. A total of 183 chronic schizophrenia patients (128 males and 55 females) and 166 healthy controls (76 males and 90 females) participated in this study. The MATRICS Consensus Cognitive Battery (MCCB) was measured for cognitive function and P50 components for the sensory gating in all participants. The Positive and Negative Syndrome Scales (PANSS) was used to assess the psychopathological symptoms in patients. Female patients performed significantly better than male patients in several cognitive domains of MCCB (all p < 0.01). There were no significant differences in P50 components between male and female patients (all p > 0.05). Further analysis showed that in female patients, latency of S2 was negatively correlated with reasoning and problem-solving domain of MCCB (p < 0.05), and P50 ratio was negatively correlated with social cognition domain of MCCB (p < 0.05). In male patients, there was no any correlation between P50 and cognitive domains of MCCB. Our results suggest that there is a sex difference in the association between P50 deficiency and cognitive impairment in Chinese Han patients with schizophrenia.

Effects of total sleep deprivation on sensorimotor gating in humans.

Sensorimotor gating is a measure of pre-attentional information processing and can be measured by prepulse inhibition (PPI) of the startle reflex. Sleep deprivation has been shown to disrupt PPI in animals and humans, and has been proposed as an early phase 2 model to probe antipsychotic efficacy in heathy humans. To further investigate the reliability and efficacy of sleep deprivation to produce PPI deficits we tested the effects of total sleep deprivation (TSD) on PPI in healthy controls in a highly controlled sleep laboratory environment. Participants spent 4 days and nights in a controlled laboratory environment with their sleep monitored with polysomnography. Participants were randomly assigned to either normal sleep on all 4 nights (N = 17) or 36 h of TSD on the 3rd or 4th night (N = 40). Participants were assessed for sleepiness using the Karolinska Sleepiness Scale (KSS) and underwent a daily PPI task (interstimlulus intervals 30-2000 ms) in the evening. Both within-subject effects (TSD vs. normal sleep in TSD group alone) and between-subject effects (TSD vs. no TSD group) of TSD on PPI were assessed. TSD increased subjective sleepiness measured with the KSS, but did not significantly alter overall startle, habituation or PPI. Sleep measures including duration, rapid eye movement and slow wave sleep duration were also not associated with PPI performance. The current results show that human sensorimotor gating may not be reliably sensitive to sleep deprivation. Further research is required for TSD to be considered a dependable model of PPI disruption for drug discovery in humans.

High visual perceptual load reduces prepulse inhibition induced by task-unrelated and task-related sound.

Prepulse inhibition (PPI) is an automatic and pre-attentive sensorimotor gating process. Several studies have shown that advanced cognitive functions can modulate PPI. This study aimed to further elucidate the modulatory effect of attentional resource allocation on PPI. We examined the differences in PPI between high and low attentional loads. First, we verified that the adapted feature versus combination visual search paradigm could produce high and low perceptual load differences according to the task demands. Second, we measured the participants' task-unrelated PPI during the visual search task and found that the PPI in the high-load condition was significantly lower than that in the low-load condition. To further elucidate the role of attentional resources, we tested task-related PPI using a dual-task paradigm in which participants were instructed to complete a visual task with an auditory discrimination task. We found a result similar to that of the task-unrelated experiment. The participants in the high-load condition had less PPI than those in the low-load condition. Finally, we ruled out the possibility that the working memory load explains the modulation of PPI. In line with the theory of PPI modulation, these results suggest that allocating limited attentional resources to the prepulse modulates PPI. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

P50 sensory gating, cognitive deficits and depressive symptoms in first-episode antipsychotics-naïve schizophrenia.

OBJECTIVE: Sensory gating P50 (SG-P50) may be involved in the pathophysiological mechanisms of impaired cognition in schizophrenia (SCZ). Comorbid depressive symptoms are common in SCZ patients and are also found to be associated with their cognitive impairment. However, it is unclear whether SG-P50 is abnormal in first episode antipsychotics naïve (FEAN) SCZ patients with depressive symptoms. Our aimed to investigate the relationships between SG-P50, depressive symptoms and neurocognition in FEAN-SCZ patients. METHODS: We recruited 103 FEAN-SCZ patients (depression: n = 63; non-depression: n = 40) and 55 healthy controls. SG-P50 was measured using the standard auditory dual-click (S1&S2) paradigm. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale-17 (HDRS-17). Cognitive performance was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). RESULTS: Compared with non-depressive patients, depressive patients had a significantly larger S2 amplitude (p = 0.005) and a higher S2/S1 ratio at trend level (p = 0.075) after corrected. There were significant differences in the scores of CPT-IP and Mazes (NAB) between depressive and non-depressive FEAN-SCZ patients (both p values < 0.05). For all patients, the SG-P50 S2/S1 ratio was significantly correlated with HDRS-17 score (r = 0.23, p = 0.020) and MCCB-Symbol coding (r = -0.16, p = 0.043). For depressive FEAN-SCZ patients, S2 amplitude was an independent predictor of the MCCB-Mazes (NAB) (ß = -0.31, t = -2.52, p = 0.015). CONCLUSIONS: SG-P50 deficit may be an informational biomarker for depressive symptoms and neurocognitive impairments in FEAN-SCZ patients.

Decreased activation of parvalbumin interneurons in the medial prefrontal cortex in intact inbred Roman rats with schizophrenia-like reduced sensorimotor gating.

Prepulse inhibition (PPI) allows assessing schizophrenia-like sensorimotor gating deficits in rodents. Previous studies indicate that PPI is modulated by the medial prefrontal cortex (mPFC), which is in agreement with our findings showing that PPI differences in the Roman rats are associated with divergences in mPFC activity. Here, we explore whether differences in PPI and mPFC activity in male Roman rats can be explained by (i) differences in the activation (c-Fos) of inhibitory neurons (parvalbumin (PV) interneurons); and/or (ii) reduced excitatory drive (PSD-95) to PV interneurons. Our data show that low PPI in the Roman high-avoidance (RHA) rats is associated with reduced activation of PV interneurons. Moreover, the RHA rats exhibit decreased density of both PV interneurons and PSD-95 puncta on active PV interneurons. These findings point to reduced cortical inhibition as a candidate to explain the schizophrenia-like features observed in RHA rats and support the role of impaired cortical inhibition in schizophrenia.

Smoking affects the association between cognitive impairment and P50 inhibition defects in patients with chronic schizophrenia: A case-control study.

OBJECTIVE: Smoking affects sensory gating, as assessed by the event related potential P50, which is evoked by auditory stimuli and is considered to be involved in the pathophysiology of schizophrenia (SCZ). However, few studies have compared sensory gating and cognitive performance between smoking and non-smoking SCZ patients in the Chinese Han population. METHODS: We recruited two groups of Chinese subjects: 128 male chronic SCZ patients and 76 male healthy controls, measuring cognition with the MATRICS Consensus Cognitive Battery (MCCB) and sensory gating with the P50 EEG components. Based on their smoking status, they were further divided into 4 subgroups: smoking SCZ patients, non-smoking SCZ patients, smoking healthy controls, and non-smoking healthy controls. We assessed psychopathological symptoms of the patients using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Compared with healthy controls, SCZ patients had lower MCCB total score and scores of all 10 tests (all p < 0.05), while SCZ patients had higher S2 amplitudes and P50 ratios (both p < 0.05). When comparing smoking versus non-smoking SCZ patients, non-smokers had significantly better spatial span (p < 0.05). Furthermore, the S1 amplitude was negatively correlated with the Brief Visuospatial Memory Test (BVMT-R) in smoking patients (p < 0.05), while the S1 latency was negatively correlated with spatial span in non-smoking patients (p < 0.01). CONCLUSIONS: Our finding shows a difference in the relationship between sensory gated P50 and cognition in smoking and non-smoking SCZ patients, suggesting that nicotine may improve cognitive and P50 deficits in SCZ patients.

The relationships between motor behavior and sensory gating in the ball rotation task.

During voluntary muscle contraction, sensory information induced by electrostimulation of the nerves supplying the contracting muscle is inhibited and the amplitude of the corresponding somatosensory evoked potential (SEP) decreases. This phenomenon is called "gating." The reduction of the SEP amplitude is reportedly significantly larger when task performance is high. However, the relationship between dexterous movement skills and gating remains unclear. In this study, we investigated through a ball rotation (BR) task how dexterous movement skills affect the SEP amplitudes. Thirty healthy subjects performed the BR task comprising the rotation of two wooden balls as quickly as possible. We estimated the median number of ball rotations for each participant and classified the participants into two (fast and slow) groups based on the results. Moreover, we recorded SEPs, while the subjects performed BR tasks or rested. SEP amplitude reduction (P45) was significantly larger in the fast than in the slow group. We also observed that the P45 amplitude during the BR task was attenuated even more so in the case of the participants with better dexterous movement skills. Our results suggest that the participants with better dexterous movement skills might display stronger somatosensory information suppression because of increasing the motor cortex activity and the afferent input during the BR task.

Tics: neurological disorders determined by a deficit in sensorimotor gating processes.

Tic related disorders affect 4-20% of the population, mostly idiopathic, can be grouped in a wide spectrum of severity, where the most severe end is Tourette Syndrome (TS). Tics are arrhythmic hyperkinesias to whom execution the subject is forced by a "premonitory urge" that can be classified as sensory tic, just-right experience or urge without obsession. If an intact volitional inhibition allows patients to temporarily suppress tics, a lack or deficit in automatic inhibition is involved in the genesis of the disorder. Studies have assessed the presence of intrinsic microscopic and macroscopic anomalies in striatal circuits and relative cortical areas in association with a hyperdopaminergic state in the basal forebrain. Prepulse inhibition (PPI) of the startle reflex is a measure of inhibitory functions by which a weak sensory stimulus inhibits the elicitation of a startle response determined by a sudden intense stimulus. It is considered an operation measure of sensorimotor gating, a neural process by which unnecessary stimuli are eliminated from awareness. Evidence points out that the limbic domain of the CSTC loops, dopamine and GABA receptors within the striatum play an important role in PPI modulation. It is conceivable that a sensorimotor gating deficit may be involved in the genesis of premonitory urge and symptoms. Therefore, correcting the sensorimotor gating deficit may be considered a target for tic-related disorders therapies; in such case PPI (as well as other indirect estimators of sensorimotor gating) could represent therapeutic impact predictors.

Dynamic brain functional network based on EEG microstate during sensory gating in schizophrenia.

Objective.Cognitive impairment is one of the core symptoms of schizophrenia, with an emphasis on dysfunctional information processing. Sensory gating deficits have consistently been reported in schizophrenia, but the underlying physiological mechanism is not well-understood. We report the discovery and characterization of P50 dynamic brain connections based on microstate analysis.Approach.We identify five main microstates associated with the P50 response and the difference between the first and second click presentation (S1-S2-P50) in first-episode schizophrenia (FESZ) patients, ultra-high-risk individuals (UHR) and healthy controls (HCs). We used the signal segments composed of consecutive time points with the same microstate label to construct brain functional networks.Main results.The microstate with a prefrontal extreme location during the response to the S1 of P50 are statistically different in duration, occurrence and coverage among the FESZ, UHR and HC groups. In addition, a microstate with anterior-posterior orientation was found to be associated with S1-S2-P50 and its coverage was found to differ among the FESZ, UHR and HC groups. Source location of microstates showed that activated brain regions were mainly concentrated in the right temporal lobe. Furthermore, the connectivities between brain regions involved in P50 processing of HC were widely different from those of FESZ and UHR.Significance.Our results indicate that P50 suppression deficits in schizophrenia may be due to both aberrant baseline sensory perception and adaptation to repeated stimulus. Our findings provide new insight into the mechanisms of P50 suppression in the early stage of schizophrenia.

Regulation of sensorimotor gating via Disc1/Huntingtin-mediated Bdnf transport in the cortico-striatal circuit.

Sensorimotor information processing underlies normal cognitive and behavioral traits and has classically been evaluated through prepulse inhibition (PPI) of a startle reflex. PPI is a behavioral dimension deregulated in several neurological and psychiatric disorders, yet the mechanisms underlying the cross-diagnostic nature of PPI deficits across these conditions remain to be understood. To identify circuitry mechanisms for PPI, we performed circuitry recording over the prefrontal cortex and striatum, two brain regions previously implicated in PPI, using wild-type (WT) mice compared to Disc1-locus-impairment (LI) mice, a model representing neuropsychiatric conditions. We demonstrated that the corticostriatal projection regulates neurophysiological responses during the PPI testing in WT, whereas these circuitry responses were disrupted in Disc1-LI mice. Because our biochemical analyses revealed attenuated brain-derived neurotrophic factor (Bdnf) transport along the corticostriatal circuit in Disc1-LI mice, we investigated the potential role of Bdnf in this circuitry for regulation of PPI. Virus-mediated delivery of Bdnf into the striatum rescued PPI deficits in Disc1-LI mice. Pharmacologically augmenting Bdnf transport by chronic lithium administration, partly via phosphorylation of Huntingtin (Htt) serine-421 and its integration into the motor machinery, restored striatal Bdnf levels and rescued PPI deficits in Disc1-LI mice. Furthermore, reducing the cortical Bdnf expression negated this rescuing effect of lithium, confirming the key role of Bdnf in lithium-mediated PPI rescuing. Collectively, the data suggest that striatal Bdnf supply, collaboratively regulated by Htt and Disc1 along the corticostriatal circuit, is involved in sensorimotor gating, highlighting the utility of dimensional approach in investigating pathophysiological mechanisms across neuropsychiatric disorders.

Orexin deficiency affects sensorimotor gating and its amphetamine-induced impairment.

The orexin neuropeptides have an important role in the regulation of the sleep/wake cycle and foraging, as well as in reward processing and emotions. Furthermore, recent research implicates the orexin system in different behavioral endophenotypes of neuropsychiatric diseases such as social avoidance and cognitive flexibility. Utilizing orexin-deficient mice, the present study tested the hypothesis that orexin is involved in two further mouse behavioral endophenotypes of neuropsychiatric disorders, i.e., sensorimotor gating and amphetamine sensitivity. The data revealed that orexin-deficient mice expressed a deficit in sensorimotor gating, measured by prepulse inhibition of the startle response. Amphetamine treatment impaired prepulse inhibition in wildtype and heterozygous orexin-deficient mice, but had no effects in homozygous orexin-deficient mice. Furthermore, locomotor activity and center time in the open field was not affected by orexin deficiency but was similarly increased or decreased, respectively, by amphetamine treatment in all genotypes. These data indicate that the orexin system modulates prepulse inhibition and is involved in mediating amphetamine's effect on prepulse inhibition. Future studies should investigate whether pharmacological manipulations of the orexin system can be used to treat neuropsychiatric diseases associated with deficits in sensorimotor gating, such as schizophrenia or attention deficit hyperactivity disorder.

Selective 5HT3 antagonists and sensory processing: a systematic review.

Ondansetron is a selective serotonin (5HT3) receptor antagonist that is under evaluation as an adjunctive treatment for schizophrenia, and a novel treatment for hallucinations in Parkinson's disease. Ondansetron reverses sensory gating deficits and improves visuoperceptual processing in animal models of psychosis, but it is unclear to what extent preclinical findings have been replicated in humans. We systematically reviewed human studies that evaluated the effects of ondansetron and other 5HT3 receptor antagonists on sensory gating deficits or sensory processing. Of 11 eligible studies, eight included patients with schizophrenia who were chronically stable on antipsychotic medication; five measured sensory gating using the P50 suppression response to a repeated auditory stimulus; others included tests of visuoperceptual function. Three studies in healthy participants included tests of visuoperceptual and sensorimotor function. A consistent and robust finding (five studies) was that ondansetron and tropisetron (5HT3 antagonist and α7-nicotinic receptor partial agonist) improved sensory gating in patients with schizophrenia. Tropisetron also improved sustained visual attention in non-smoking patients. There was inconsistent evidence of the effects of 5HT3 antagonists on other measures of sensory processing, but interpretation was limited by the small number of studies, methodological heterogeneity and the potential confounding effects of concomitant medication in patients. Despite these limitations, we found strong evidence that selective 5HT3 antagonists (with or without direct α7-nicotinic partial agonist effects) improved sensory gating. Future studies should investigate how this relates to potential improvement in neurocognitive symptoms in antipsychotic naive patients with prodromal or milder symptoms, in order to understand the clinical implications.

The Auditory P50 Gating in Mild Cognitive Impairment: A Case-Control Study.

Objective: Auditory P50 gating changed might be a neurophysiological biomarker of the diagnosis of Mild Cognitive Impairment (MCI). We aimed to determine the impact of MCI in auditory P50 gating. Methods: All recruited participants completed structured questionnaires and finished auditory P50 gating measure. Results: A total of 20 MCI patients and 17 controls had been recruited. MCI patients had a significant higher reduction of P50 gating at Fz site, when compared to controls (1.21 ± .68 vs .66 ± .37, P = .00). Zero point five was the best cut off point to distinguish MCI and control of auditory P50 gating S2/S1 at Fz site. The P50 average amplitude at Pz site in MCI patients was significantly higher than controls (2.62 ± 1.20 vs 1.70 ± .74, P = .01). Conclusion: MCI patients might have impaired the ability of inhibiting the repeated stimulus.

Selective attention involves a feature-specific sequential release from inhibitory gating.

Selective attention is a fundamental cognitive mechanism that allows our brain to preferentially process relevant sensory information, while filtering out distracting information. Attention is thought to flexibly gate the communication of irrelevant information through top-down alpha-rhythmic (8-12 Hz) functional connections, which influence early visual processing. However, the dynamic effects of top-down influence on downstream visual processing remain unknown. Here, we used electroencephalography to investigate local and network effects of selective attention while subjects attended to distinct features of identical stimuli. We found that attention-related changes in the functional brain network organization emerge shortly after stimulus onset, accompanied by an overall decrease of functional connectivity. Signatures of attentional selection were evident from a sequential release from alpha-band parietal gating in feature-selective areas. The directed connectivity paths and temporal evolution of this release from gating were consistent with the sensory effect of each feature, providing a neural basis for how visual processing quickly prioritizes relevant information in functionally specialized areas.

Revisiting the relationship between neural correlates of sensory gating and self-reported sensory gating inventory: An MEG investigation.

BACKGROUND: Accumulated evidence has revealed that bilateral superior temporal gyrus (STG), inferior frontal gyrus (IFG), and inferior parietal lobule (IPL) are involved in the processes of sensory gating (SG). However, it remains unknown which neural correlate(s) of SG specifically reflect individuals' perceptual experiences, as measured by the Sensory Gating Inventory (SGI). Thus, this study aims to investigate the relationship of SGI with cortical SG-related regions. Furthermore, we examine whether SG hemispheric asymmetry exists, which is still an inconclusive issue. METHODS: Twenty-two healthy young adults performed the auditory paired-stimulus paradigm during magnetoencephalographic recordings. SG of M50 and M100 was measured as ratios (S2/S1) and differences (S1-S2). They were also evaluated with SGI, which factored into three categories of Perceptual Modulation, Distractibility, and Over-Inclusion. SG in the STG, IFG, and IPL were compared between left and right hemispheres, and were used to determine the relationship with SGI. RESULTS: Only M100 SG differences (S1-S2) of the right IFG were significantly correlated with scores of Perceptual Modulation (partial r = -0.392, p = 0.040) and total SGI scores (partial r = -0.387, p = 0.041). However, we did not find significant lateralization of M50 SG and M100 SG in any studying region. CONCLUSIONS: The individual's perceptual experience is specifically related to electrophysiological SG function of the right IFG.

Altered sensorimotor integration in multiple sclerosis: A combined neurophysiological and functional MRI study.

OBJECTIVE: To explore whether abnormal thalamic resting-state functional connectivity (rsFC) contributes to altered sensorimotor integration and hand dexterity impairment in multiple sclerosis (MS). METHODS: To evaluate sensorimotor integration, we recorded kinematic features of index finger abductions during somatosensory temporal discrimination threshold (STDT) testing in 36 patients with relapsing-remitting MS and 39 healthy controls (HC). Participants underwent a multimodal 3T structural and functional MRI protocol. RESULTS: Patients had lower index finger abduction velocity during STDT testing compared to HC. Thalamic rsFC with the precentral and postcentral gyri, supplementary motor area (SMA), insula, and basal ganglia was higher in patients than HC. Intrathalamic rsFC and thalamic rsFC with caudate and insula bilaterally was lower in patients than HC. Finger movement velocity positively correlated with intrathalamic rsFC and negatively correlated with thalamic rsFC with the precentral and postcentral gyri, SMA, and putamen. CONCLUSIONS: Abnormal thalamic rsFC is a possible substrate for altered sensorimotor integration in MS, with high intrathalamic rsFC facilitating finger movements and increased thalamic rsFC with the basal ganglia and sensorimotor cortex contributing to motor performance deterioration. SIGNIFICANCE: The combined study of thalamic functional connectivity and upper limb sensorimotor integration may be useful in identifying patients who can benefit from early rehabilitation to prevent upper limb motor impairment.