Altered Sensorimotor Research Articles

Effects of ankle instability on running gait ankle angles and its variability in young adults

BackgroundConsidering that proprioceptive deficits seem to be responsible for chronic ankle instability, the precise control of ankle angles during running may be impaired. Thus, the aim of the study was to evaluate the influence of chronic ankle instability on intra-individual variability of ankle kinematics during running. MethodsLower extremity running gait kinematics of 12 recreational athletes with chronic ankle instability (mean age: 24years, SD: 3years; strides analyzed: 40.0, SD=1.7) and 12 matched healthy controls (mean age: 27years, SD: 6years; strides analyzed: 40.2, SD=2.5) were registered on a treadmill. Mean ankle angles (inversion/eversion, plantarflexion/dorsiflexion) and intra-individual standard deviations (variability) were calculated at each percent of the running gait cycle. Group differences were examined using statistical parameter mapping. To estimate effect sizes, Hedges' g was calculated. FindingsNo group differences in the inversion/eversion or plantar-/dorsiflexion ankle angle were found. The inversion/eversion variability was significantly higher (P<.050) in individuals with chronic ankle instability during the stance and swing phase. The highest Hedges' g values were registered at 15% (g=0.575, P<.000) and 95% (g=0.551, P=.002) of the running gait cycle. The plantar-/dorsiflexion ankle angle variability showed no significant differences. InterpretationPatients with chronic ankle instability exhibit a higher variability of ankle kinematics during running. This indicates altered sensorimotor control which is probably an underlying mechanism of chronic ankle instability. Thus, variability measures may help to better quantify treatment effects in future.

High-fat diet feeding alters olfactory-, social-, and reward-related behaviors of mice independent of obesity.

High-fat diet (HFD) consumption causes obesity, which is associated with well-known increased health risks. Moreover, obesity has been associated with altered sensorimotor and emotional behaviors of humans and mice. This study attempted to dissociate the influence of HFD-induced obesity on behaviors from the influence of HFD consumption itself. C57BL male mice were randomly allocated to a low-fat diet (LFD) group, an HFD-induced obesity (DIO) group, or a pair-fed HFD-feeding nonobese (HFD) group. A comprehensive behavioral test battery was performed on all three groups to assess sensorimotor functions, anxiety- and depression-like behaviors, reward-related behaviors, social behaviors, and learning/memory functions. Both the DIO and HFD groups exhibited disturbed olfaction, blunted ethanol preference, and enhanced social interactions. The DIO group exhibited blunted sucrose preference, shorter latency before falling off during the rotarod test, and a lower response to mechanical stimuli. The HFD-fed nonobese mice showed altered behaviors related to olfaction, social interactions, and rewards that were similar to those of the DIO mice. This finding suggests that HFD consumption alters a variety of behaviors independent of obesity.

The novel adaptive rotating beam test unmasks sensorimotor impairments in a transgenic mouse model of Parkinson’s disease

Development of disease modifying therapeutics for Parkinson’s disease (PD), the second most common neurodegenerative disorder, relies on availability of animal models which recapitulate the disease hallmarks. Only few transgenic mouse models, which mimic overexpression of alpha-synuclein, show dopamine loss, behavioral impairments and protein aggregation. Mice overexpressing human wildtype alpha-synuclein under the Thy-1 promotor (Thy1-aSyn) replicate these features. However, female mice do not exhibit a phenotype. This was attributed to a potentially lower transgene expression located on the X chromosome. Here we support that female mice overexpress human wildtype alpha-synuclein only about 1.5 fold in the substantia nigra, compared to about 3 fold in male mice. Since female Thy1-aSyn mice were shown previously to exhibit differences in corticostriatal communication and synaptic plasticity similar to their male counterparts we hypothesized that female mice use compensatory mechanisms and strategies to not show overt motor deficits despite an underlying endophenotype. In order to unmask these deficits we translated recent findings in PD patients that sensory abnormalities can enhance motor dysfunction into a novel behavioral test, the adaptive rotating beam test. We found that under changing sensory input female Thy1-aSyn mice showed an overt phenotype. Our data supports that the integration of sensorimotor information is likely a major contributor to symptoms of movement disorders and that even low levels of overexpression of human wildtype alpha-synuclein has the potential to disrupt processing of these information. The here described adaptive rotating beam test represents a sensitive behavioral test to detect moderate sensorimotor alterations in mouse models.

Post-Movement Beta Activity in Sensorimotor Cortex Indexes Confidence in the Estimations from Internal Models.

For optimal sensorimotor control, sensory feedback and feedforward estimation of a movement's sensory consequences should be weighted by the inverse of their corresponding uncertainties, which require recursive updating in a dynamic environment. We show that post-movement beta activity (13-30 Hz) over sensorimotor cortex in young healthy subjects indexes the evaluation of uncertainty in feedforward estimation. Our work contributes to the understanding of the function of beta oscillations in sensorimotor control, and provides further insight into how aberrant beta activity can contribute to the pathophysiology of movement disorders.

Body Position Influences Which Neural Structures Are Recruited by Lumbar Transcutaneous Spinal Cord Stimulation.

Transcutaneous stimulation of the human lumbosacral spinal cord is used to evoke spinal reflexes and to neuromodulate altered sensorimotor function following spinal cord injury. Both applications require the reliable stimulation of afferent posterior root fibers. Yet under certain circumstances, efferent anterior root fibers can be co-activated. We hypothesized that body position influences the preferential stimulation of sensory or motor fibers. Stimulus-triggered responses to transcutaneous spinal cord stimulation were recorded using surface-electromyography from quadriceps, hamstrings, tibialis anterior, and triceps surae muscles in 10 individuals with intact nervous systems in the supine, standing and prone positions. Single and paired (30-ms inter-stimulus intervals) biphasic stimulation pulses were applied through surface electrodes placed on the skin between the T11 and T12 inter-spinous processes referenced to electrodes on the abdomen. The paired stimulation was applied to evaluate the origin of the evoked electromyographic response; trans-synaptic responses would be suppressed whereas direct efferent responses would almost retain their amplitude. We found that responses to the second stimulus were decreased to 14%±5% of the amplitude of the response to the initial pulse in the supine position across muscles, to 30%±5% in the standing, and to only 80%±5% in the prone position. Response thresholds were lowest during standing and highest in the prone position and response amplitudes were largest in the supine and smallest in the prone position. The responses obtained in the supine and standing positions likely resulted from selective stimulation of sensory fibers while concomitant motor-fiber stimulation occurred in the prone position. We assume that changes of root-fiber paths within the generated electric field when in the prone position increase the stimulation thresholds of posterior above those of anterior root fibers. Thus, we recommend conducting spinal reflex or neuromodulation studies with subjects lying supine or in an upright position, as in standing or stepping.

Neural correlates of altered sensorimotor gating in boys with Tourette Syndrome: A combined EMG/fMRI study

Objectives: It has been hypothesised that altered sensorimotor gating might be a core problem in Tourette Syndrome (TS). However, the underlying neurophysiological mechanisms are elusive. Methods: We applied functional magnetic resonance imaging (fMRI) to investigate the neural correlates of altered sensorimotor gating by means of prepulse inhibition (PPI) in 22 boys with TS and 22 healthy boys using tactile PPI. The electromyography of the startle response was recorded simultaneously to the acquisition of the fMRI images. Results: As expected, PPI of the startle response was reduced in boys with TS compared to the healthy boys. We found decreased PPI-related blood oxygen level-dependent (BOLD) activity in boys with TS in the middle frontal gyrus, postcentral gyrus, superior parietal cortex, cingulate gyrus and caudate body. In boys with TS PPI of the startle response was positively correlated to PPI-related BOLD activity in the superior parietal cortex. Conclusions: Our findings indicate that deficient sensorimotor gating in boys with TS is associated with reduced recruitment of brain regions responsible for the higher-order integration of somatosensory stimuli. Due to our strict sample selection we were able to reduce confounding by neural adaptation processes, long-term medication, gender or comorbidities.

The Vestibular-Evoked Postural Response of Adolescents with Idiopathic Scoliosis Is Altered

Adolescent idiopathic scoliosis is a multifactorial disorder including neurological factors. A dysfunction of the sensorimotor networks processing vestibular information could be related to spine deformation. This study investigates whether feed-forward vestibulomotor control or sensory reweighting mechanisms are impaired in adolescent scoliosis patients. Vestibular evoked postural responses were obtained using galvanic vestibular stimulation while participants stood with their eyes closed and head facing forward. Lateral forces under each foot and lateral displacement of the upper body of adolescents with mild (n = 20) or severe (n = 16) spine deformation were compared to those of healthy control adolescents (n = 16). Adolescent idiopathic scoliosis patients demonstrated greater lateral displacement and net lateral forces than controls both during and immediately after vestibular stimulation. Altered sensory reweighting of vestibular and proprioceptive information changed balance control of AIS patients during and after vestibular stimulation. Therefore, scoliosis onset could be related to abnormal sensory reweighting, leading to altered sensorimotor processes.

Altered sensorimotor activation patterns in idiopathic dystonia-an activation likelihood estimation meta-analysis of functional brain imaging studies.

Dystonia is characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements or postures. Functional neuroimaging studies have yielded abnormal task‐related sensorimotor activation in dystonia, but the results appear to be rather variable across studies. Further, study size was usually small including different types of dystonia. Here we performed an activation likelihood estimation (ALE) meta‐analysis of functional neuroimaging studies in patients with primary dystonia to test for convergence of dystonia‐related alterations in task‐related activity across studies. Activation likelihood estimates were based on previously reported regional maxima of task‐related increases or decreases in dystonia patients compared to healthy controls. The meta‐analyses encompassed data from 179 patients with dystonia reported in 18 functional neuroimaging studies using a range of sensorimotor tasks. Patients with dystonia showed bilateral increases in task‐related activation in the parietal operculum and ventral postcentral gyrus as well as right middle temporal gyrus. Decreases in task‐related activation converged in left supplementary motor area and left postcentral gyrus, right superior temporal gyrus and dorsal midbrain. Apart from the midbrain cluster, all between‐group differences in task‐related activity were retrieved in a sub‐analysis including only the 14 studies on patients with focal dystonia. For focal dystonia, an additional cluster of increased sensorimotor activation emerged in the caudal cingulate motor zone. The results show that dystonia is consistently associated with abnormal somatosensory processing in the primary and secondary somatosensory cortex along with abnormal sensorimotor activation of mesial premotor and right lateral temporal cortex. Hum Brain Mapp 37:547–557, 2016. © 2015 Wiley Periodicals, Inc.

Functional ankle instability assessment

Capsulo-ligamentous damages caused by traumatic inversion during lateral ankle sprains frequently cause Chronic ankle Instability (CAI). CAI is the consequence of passive (mechanical origin) and/or active (functional origin) articular stabilization mechanisms. The detection of patients affected by functional CAI, with objective parameters, is crucial for rehabilitation specialists and physical trainers. Orthostatic performance analysis if often used to this end. However, classical surface and velocity CoP values are not adapted and a specific parameter, the Time-To-Boundary has been proposed [1] , [2] . Moreover, even if isokinetic tests are considered as the “gold standard” methodology to assess ankle evertors deficit, there is no clear consensus about a relation between torque performances and CAI. It is also important to keep in mind that such measure and analysis methodologies are unsuitable in a field environment and thus underused by rehabilitation specialists and physical trainers. The aim of this presentation is to propose alternative and original tests, easy to use in daily practice and able to assess sensorimotor alterations and muscular impairments typically associated with functional CAI.

Dental Occlusal Changes Induce Motor Cortex Neuroplasticity

Modification to the dental occlusion may alter oral sensorimotor functions. Restorative treatments aim to restore sensorimotor functions; however, it is unclear why some patients fail to adapt to the restoration and remain with sensorimotor complaints. The face primary motor cortex (face-M1) is involved in the generation and control of orofacial movements. Altered sensory inputs or motor function can induce face-M1 neuroplasticity. We took advantage of the continuous eruption of the incisors in Sprague-Dawley rats and used intracortical microstimulation (ICMS) to map the jaw and tongue motor representations in face-M1. Specifically, we tested the hypothesis that multiple trimming of the right mandibular incisor, to keep it out of occlusal contacts for 7 d, and subsequent incisor eruption and restoration of occlusal contacts, can alter the ICMS-defined features of jaw and tongue motor representations (i.e., neuroplasticity). On days 1, 3, 5, and 7, the trim and trim-recovered groups had 1 to 2 mm of incisal trimming of the incisor; a sham trim group had buccal surface trimming with no occlusal changes; and a naive group had no treatment. Systematic mapping was performed on day 8 in the naive, trim, and sham trim groups and on day 14 in the trim-recovered group. In the trim group, the tongue onset latency was shorter in the left face-M1 than in the right face-M1 (P < .001). In the trim-recovered group, the number of tongue sites and jaw/tongue overlapping sites was greater in the left face-M1 than in the right face-M1 (P = 0.0032, 0.0016, respectively), and the center of gravity was deeper in the left than in the right face-M1 (P = 0.026). Therefore, incisor trimming and subsequent restoration of occlusal contacts induced face-M1 neuroplasticity, reflected in significant disparities between the left and right face-M1 in some ICMS-defined features of the tongue motor representations. Such neuroplasticity may reflect or contribute to subjects’ ability to adapt their oral sensorimotor functions to an altered dental occlusion.

Limb Heaviness

Poststroke fatigue and limb heaviness are 2 perceptual problems that commonly occur after stroke. Previous work suggests that poststroke fatigue may be related to altered sensorimotor processing whereas limb heaviness is often considered an association of muscle weakness. To address the hypothesis that the perception of limb heaviness may also be a problem of altered sensorimotor control, we investigated whether it was more closely related to poststroke fatigue or muscle weakness. In 69 chronic stroke survivors, we found that those with high perceived limb heaviness (31 individuals) also reported significantly higher levels of fatigue (4.8/7) than those with no perceived limb heaviness (38 individuals, fatigue score = 2.68/7), but there was no difference in weakness between the 2 groups. This intriguing finding is discussed in relation to effort perception and sensory processing. The association between limb heaviness and poststroke fatigue and a dissociation from muscle weakness gives rise to the hypothesis that limb heaviness maybe a centrally arising sensorimotor disorder.

Altered sensory motor integration of obese adults

Altered sensory motor integration of obese adults

Altered movement patterns and muscular activity during single and double leg squats in individuals with anterior cruciate ligament injury.

BackgroundIndividuals with Anterior Cruciate Ligament (ACL) injury often show altered movement patterns, suggested to be partly due to impaired sensorimotor control. Here, we therefore aimed to assess muscular activity during movements often used in ACL-rehabilitation and to characterize associations between deviations in muscular activity and specific altered movement patterns, using and further exploring the previously developed Test for substitution Patterns (TSP).MethodsSixteen participants (10 women) with unilateral ACL rupture performed Single and Double Leg Squats (SLS; DLS). Altered movement patterns were scored according to TSP, and Surface Electromyography (SEMG) was recorded bilaterally in six hip, thigh and shank muscles. To quantify deviations in muscular activity, SEMG ratios were calculated between homonymous muscles on injured and non-injured sides, and between antagonistic muscles on the same side. Correlations between deviations of injured/non-injured side SEMG ratios and specific altered movement patterns were calculated.ResultsInjured/non-injured ratios were low at transition from knee flexion to extension in quadriceps in SLS, and in quadriceps and hamstrings in DLS. On injured side, the quadriceps/hamstrings ratio prior to the beginning of DLS and end of DLS and SLS, and tibialis/gastrocnemius ratio at end of DLS were lower than on non-injured side. Correlations were found between specific altered movement patterns and deviating muscular activity at transition from knee flexion to extension in SLS, indicating that the more deviating the muscular activity on injured side, the more pronounced the altered movement pattern. “Knee medial to supporting foot” correlated to lower injured/non-injured ratios in gluteus medius (rs = −0.73, p = 0.001), “lateral displacement of hip-pelvis-region” to lower injured/non-injured ratios in quadriceps (rs = −0.54, p = 0.03) and “displacement of trunk” to higher injured/non-injured ratios in gluteus medius (rs = 0.62, p = 0.01).ConclusionsDeviations in muscular activity between injured and non-injured sides and between antagonistic muscular activity within injured as compared to non-injured sides indicated specific alterations in sensorimotor control of the lower limb in individuals with ACL rupture. Also, correlations between deviating muscular activity and specific altered movement patterns were suggested as indications of altered sensorimotor control. We therefore advocate that quantitative assessments of altered movement patterns should be considered in ACL-rehabilitation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-015-0472-y) contains supplementary material, which is available to authorized users.

Increased CCN2, substance P and tissue fibrosis are associated with sensorimotor declines in a rat model of repetitive overuse injury.

Key clinical features of cumulative trauma disorders include pain, muscle weakness, and tissue fibrosis, although the etiology is still under investigation. Here, we characterized the temporal pattern of altered sensorimotor behaviors and inflammatory and fibrogenic processes occurring in forearm muscles and serum of young adult, female rats performing an operant, high repetition high force (HRHF) reaching and grasping task for 6, 12, or 18weeks. Palmar mechanical sensitivity, cold temperature avoidance and spontaneous behavioral changes increased, while grip strength declined, in 18-week HRHF rats, compared to controls. Flexor digitorum muscles had increased MCP-1 levels after training and increased TNFalpha in 6-week HRHF rats. Serum had increased IL-1beta, IL-10 and IP-10 after training. Yet both muscle and serum inflammation resolved by week 18. In contrast, IFNγ increased at week 18 in both muscle and serum. Given the anti-fibrotic role of IFNγ, and to identify a mechanism for the continued grip strength losses and behavioral sensitivities, we evaluated the fibrogenic proteins CCN2, collagen type I and TGFB1, as well as the nociceptive/fibrogenic peptide substance P. Each increased in and around flexor digitorum muscles and extracellular matrix in the mid-forearm, and in nerves of the forepaw at 18weeks. CCN2 was also increased in serum at week 18. At a time when inflammation had subsided, increases in fibrogenic proteins correlated with sensorimotor declines. Thus, muscle and nerve fibrosis may be critical components of chronic work-related musculoskeletal disorders. CCN2 and substance P may serve as potential targets for therapeutic intervention, and CCN2 as a serum biomarker of fibrosis progression.

Alterations in stride-to-stride variability during walking in individuals with chronic ankle instability

The aim of this study was to evaluate stride-to-stride variability of the lower extremity during walking in individuals with and without chronic ankle instability (CAI) using a nonlinear analysis. Twenty-five participants with self-reported CAI and 27 healthy control participants volunteered for this study. Participants walked on a motor-driven treadmill for 3min at their selected speed. Lower extremity kinematics in the sagittal and frontal planes were recorded using a passive retroreflective marker motion capture system. The temporal structure of walking variability was analyzed with sample entropy (SampEn). The CAI group produced lower SampEn values in frontal-plane ankle kinematics compared to the control group (P=.04). No significant group differences were observed for SampEn values of other kinematics (P>.05). Participants with CAI demonstrated less stride-to-stride variability of the frontal plane ankle kinematics compared to healthy controls. Decreased variability of walking patterns demonstrated by participants with CAI indicates that the presence of CAI may be associated with a less adaptable sensorimotor system to environmental changes. The altered sensorimotor function associated with CAI may be targets for clinical interventions, and it is critical to explore how interventions protocols affect sensorimotor system function.

Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects

BackgroundAfter no research in humans for >40 years, there is renewed interest in using lysergic acid diethylamide (LSD) in clinical psychiatric research and practice. There are no modern studies on the subjective and autonomic effects of LSD, and its endocrine effects are unknown. In animals, LSD disrupts prepulse inhibition (PPI) of the acoustic startle response, and patients with schizophrenia exhibit similar impairments in PPI. However, no data are available on the effects of LSD on PPI in humans. MethodsIn a double-blind, randomized, placebo-controlled, crossover study, LSD (200 μg) and placebo were administered to 16 healthy subjects (8 women, 8 men). Outcome measures included psychometric scales; investigator ratings; PPI of the acoustic startle response; and autonomic, endocrine, and adverse effects. ResultsAdministration of LSD to healthy subjects produced pronounced alterations in waking consciousness that lasted 12 hours. The predominant effects induced by LSD included visual hallucinations, audiovisual synesthesia, and positively experienced derealization and depersonalization phenomena. Subjective well-being, happiness, closeness to others, openness, and trust were increased by LSD. Compared with placebo, LSD decreased PPI. LSD significantly increased blood pressure, heart rate, body temperature, pupil size, plasma cortisol, prolactin, oxytocin, and epinephrine. Adverse effects produced by LSD completely subsided within 72 hours. No severe acute adverse effects were observed. ConclusionsIn addition to marked hallucinogenic effects, LSD exerts methylenedioxymethamphetamine-like empathogenic mood effects that may be useful in psychotherapy. LSD altered sensorimotor gating in a human model of psychosis, supporting the use of LSD in translational psychiatric research. In a controlled clinical setting, LSD can be used safely, but it produces significant sympathomimetic stimulation.

Differences in joint-position sense and vibratory threshold in runners with and without a history of overuse injury.

A relationship between altered postural control and injury has been reported in sports. Sensorimotor function serves a fundamental role in postural control and is not often studied in runners. Persons who sustain running injury may have altered sensorimotor function contributing to risk of injury or reinjury. To determine if differences in knee and ankle proprioception or plantar sensation exist between injured and noninjured runners. Retrospective case-control study. University campus. Twenty runners with a history of lower-extremity overuse injury and 20 noninjured runners were examined. Injured runners were subcategorized into 2 groups based on site of injury: foot/ankle and knee/hip. Active absolute joint-repositioning error of the ankle at 20° inversion and 10° eversion and the knee at 15° and 40° flexion was assessed using an isokinetic dynamometer. Vibratory threshold at the calcaneus, arch, and great toe was determined for each subject using a handheld electric sensory threshold instrument. Runners in the injured-foot/ankle group had increased absolute error during ankle-eversion repositioning (6.55° ± 3.58°) compared with those in the noninjured (4.04° ± 1.78°, P = .01) and the hip/knee (3.63° ± 2.2°, P = .01) groups. Runners in the injured group, as a whole, had greater sensitivity in the arch of the plantar surface (2.94 ± 0.52 V) than noninjured runners (2.38 ± 0.53 V, P = .02). Differences in ankle-eversion proprioception between runners with a history of ankle and foot injuries and noninjured runners were observed. Runners with a history of injury also displayed an increased vibratory threshold in the arch region compared with noninjured runners. Poor ankle-joint-position sense and increased plantar sensitivity suggest altered sensorimotor function after injury. These factors may influence underlying postural control and contribute to altered loading responses commonly observed in injured runners.

S87: Utility of multichannel surface EMG in understanding altered sensorimotor organization in writer’s cramp

S87: Utility of multichannel surface EMG in understanding altered sensorimotor organization in writer’s cramp

Measurement of cervical sensorimotor control: The reliability of a continuous linear movement test

BackgroundCervical sensorimotorcontrol (cSMC) is traditionally assessed by head repositioning accuracy (HRA) measurements. A disadvantage of the HRA measurements is their static character and lack of visual feedback. In 2008, Sjölander et al. developed a continuous linear movement test (CLMT). This CLMT uses several kinematic parameters, such as reduced range of motion (ROM), velocity and movement smoothness, to quantify altered sensorimotor functions. ObjectiveInvestigate the inter and intra rater reliability of a CLMT. DesignReliability study. MethodsFifty asymptomatic adults were recruited. Five outcome measures were obtained: the time (t) needed to perform one movement, variation in time (var-t), ROM, peak velocity (peak-v) and Jerk index (Cj).A 3D analysis of cervical movements during the CLMT was made using ZEBRIS™. MATLAB™ was used to process data provided by the ZEBRIS™ device. These data were used to calculate ICC or κw-values, depending on the normality of the distribution, using SPSS. ResultsThe intra rater reliability shows slight to moderate agreement for t (ICC: 0.19-0.42 and κw: 0.42) and peak-v (κw: 0.27–0.47), moderate to substantial agreement for var-t (ICC: 0.54–0.73) and ROM (ICC: 0.43–0.65) and fair to substantial agreement for Cj (κw: 0.27–0.69).The inter rater reliability shows moderate to almost perfect agreement for t (ICC: 0.54–0.93), almost perfect agreement for var-t (κw: 0.81–0.96) and ROM (ICC: 0.86–0.95), slight to moderate agreement for peak-v (κw: −0.03–0.44) and slight to fair agreement for Cj (κw: 0.00–0.31). ConclusionTime and ROM are presently the most reliable outcome measures. However, it must be noted that the discriminant validity of the time parameters needs further investigation.

Parkinson׳s disease-related modulation of functional connectivity associated with the striatum in the resting state in a nonhuman primate model

The goal of this study was to describe Parkinson׳s disease (PD)-related modulation of functional connectivity (FC) associated with the striatum in the resting state in a nonhuman primate model of early-stage PD. Weekly intravenous injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (0.5mg/kg body weight) were performed until parkinsonian motor symptoms developed in four macaques. After 13 weeks of MPTP treatment, all monkeys displayed parkinsonian symptoms. During the course of the experiment, each animal underwent four magnetic resonance imaging scans and four positron emission tomography (PET) scans with the vesicular monoamine transporter 2 (VMAT2)-selective ligand 9-[18F] fluoropropyl-(+)-dihydrotetrabenazine, performed prior to the beginning of MPTP administration as well as after 4, 9, and 13 MPTP injections. The FC profile of the striatum was evaluated using a seed voxel correlation approach and post hoc region of interest analysis on resting-state functional magnetic resonance imaging data. The PET images were subjected to region of interest analysis to examine brain regional reductions in VMAT2 density in the PD model. Significant reductions in the connectivity pattern of the striatal regions were observed: limbic striatum and left hippocampus; caudate nucleus/associative and brain regions, including the right pre-supplementary motor area and bilateral dorsolateral prefrontal cortex; putamen/associative region and left inferior temporal gyrus or right orbital and medial prefrontal cortex; and putamen/motor and cortical structures, including the right superior temporal gyrus and bilateral postcentral gyrus. Subsequent PET studies showed the progressive loss of striatal VMAT2 in the striatum with the presentation of parkinsonism. Significant differences between the specific uptake ratio reductions in each striatal subdivision were not found. By using a long-term, low-dose MPTP-lesioned nonhuman primate model, this study demonstrated PD-related decreased corticostriatal FC in a resting state; moreover, altered sensorimotor integration was also found in early-stage PD.