scholarly journals Effects of Muscimol Inactivation of the Cerebellar Nuclei on Precision Grip

2004 ◽  
Vol 91 (3) ◽  
pp. 1240-1249 ◽  
Author(s):  
Joël Monzée ◽  
Trevor Drew ◽  
Allan M. Smith

A single monkey was trained to perform a grasp, lift, and hold task in which a stationary hand- held object was sometimes subjected to brief, predictable force-pulse perturbations. The displacement, grip, and lifting forces were measured as well the three-dimensional forces and torques to quantify specific motor deficits after reversible inactivation of the cerebellar nuclei. A prior single-cell recording study in the same monkey provided the stereotaxic coordinates used to guide intranuclear injections of muscimol. In total, 34 penetrations were performed at 28 different loci throughout the cerebellar nuclei. On each penetration, two 1.0-μl injections of 5 μg/μl muscimol, were made 1.0 mm apart either within the nuclei or in the white matter just lateral or posterior to the dentate nucleus. Injections in the region corresponding to the anterior interpositus nucleus produced pronounced dynamic tremor and dysmetric movements of the ipsilateral arm when the animal performed unrestrained reaching and grasping movements. In contrast, no relatively short-latency (15-20 min.) deficits were observed after injection in the dentate nucleus, although some effects were observed after several hours. When tested in a primate chair with the forearm supported and restrained at the wrist and elbow, the monkey performed the lift and hold task without tremor or dysmetria. However, with the restraint removed, the forces and torques applied to the manipulandum were poorly controlled and erratic. The monkey's arm was ataxic and a 5-Hz intention tremor was clearly visible. In addition, the animal was generally unable to compensate for the predictable perturbations and the anticipatory grip force increases were absent. However, overall the results suggest that reversible cerebellar nuclear inactivation with muscimol has little effect on isolated distal movements of the wrist and fingers.

2016 ◽  
Vol 23 (4) ◽  
pp. 546-555 ◽  
Author(s):  
Emilia Sbardella ◽  
Neeraj Upadhyay ◽  
Francesca Tona ◽  
Luca Prosperini ◽  
Laura De Giglio ◽  
...  

Background and objective: The dentate nucleus, which is the largest of the cerebellar nuclei, plays a critical role in movement and cognition. The aim of our study was to assess any changes in dentate functional connectivity (FC) in adult relapsing remitting multiple sclerosis (RR-MS) patients and to investigate possible clinical correlates. Materials and methods: In all, 54 patients and 24 healthy subjects (HS) underwent multimodal magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI), three-dimensional-T1-weighted and resting state (RS) functional images; they also underwent a cognitive evaluation, that is, attention and information processing speed, by means of the Paced Auditory Serial Addition Test (PASAT). Patients were also scored according to Expanded Disability Status Scale (EDSS). RS-MRI data were analysed using FMRIB Software Library (FSL) tools, with the seed-based method to identify dentate FC. Results: When compared with HS, patients exhibited brain atrophy and widespread DTI abnormalities, as well as greater FC between the dentate nucleus and cortical areas, particularly in the frontal and parietal lobes. Within these areas, FC in patients correlated inversely with clinical impairment. Finally, FC correlated inversely with lesion load and microstructural brain damage. Conclusion: Our findings indicate that dentate FC at rest is altered in MS patients. Whether these functional changes are induced by the disease and play a compensatory role remains to be established.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Kim Rijkers ◽  
Véronique M. P. Moers-Hornikx ◽  
Roelof J. Hemmes ◽  
Marlien W. Aalbers ◽  
Yasin Temel ◽  
...  

Clinical and experimental evidence suggests a role for the cerebellum in seizure control, while no data are available on cerebellar activity between seizures. We hypothesized that interictal regional activity of the deep cerebellar nuclei is reduced in epilepsy and tested this in an animal model by using ΔFosB and cytochrome oxidase (COX) (immuno)histochemistry. The expression of these two markers of neuronal activity was analysed in the dentate nucleus (DN), interpositus nucleus (IN), and fastigial nucleus (FN) of the cerebellum of fully amygdala kindled rats that were sacrificed 48 hours after their last seizure. The DN and FN of kindled rats exhibited 25 to 29% less ΔFosB immunopositive cells than their respective counterpart in sham controls (P<0.05). COX expression in the DN and FN of kindled animals was reduced by 32 to 33% compared to respective control values (P<0.05). These results indicate that an epileptogenic state is characterized by decreased activity of deep cerebellar nuclei, especially the DN and FN. Possible consequences may include a decreased activation of the thalamus, contributing to further seizure spread. Restoration of FN activity by low frequency electrical stimulation is suggested as a possible treatment option in chronic epilepsy.


2004 ◽  
Vol 91 (3) ◽  
pp. 1230-1239 ◽  
Author(s):  
Joël Monzée ◽  
Allan M. Smith

Two monkeys were trained to lift and hold an instrumented object at a fixed height for 2.5 s using a precision grip. The device was equipped with load cells to measure both the grip and lifting or load forces. On selected blocks of 20-30 trials, a downward force-pulse perturbation was applied to the object after 1.5 s of stationary holding. The animals were required to resist the perturbation to obtain a fruit juice reward. The perturbations invariably elicited a reflex-like, time-locked increase in grip force at latencies between 50 and 100 ms. In this study, we searched for single cells in the interpositus and dentate nuclei with activity related to grasping and lifting, and we tested 127/150 task-related cells for their responses to the perturbation. Of the 127 cells, reflex-like increases or decreases in discharge frequency occurred in 75 cells (59%) at a mean latency of 36 ms. Preparatory increases in grip force preceding the perturbation appeared gradually and increased in strength with repetition in 39/127 (31%) cells. These preparatory increases did not immediately disappear when the perturbations were withdrawn but decreased progressively over repeated trials. Although a few cells showed anticipatory activity without a reflex-like response (15/127 or 12%), the majority of these cells (24/39) displayed both anticipatory and reflex-like responses. From an examination of the histological sections, cells with both anticipatory and reflex-like responses appeared to be confined to the dorsal anterior interpositus, adjacent to, but not within, the dentate nucleus. These results confirm and extend the suggestion by Dugas and Smith that the cerebellum plays a major role in organizing anticipatory responses to predictable perturbations in a manner that medial and lateral premotor areas of the cerebral cortex do not.


2000 ◽  
Vol 84 (6) ◽  
pp. 2984-2997 ◽  
Author(s):  
Per Jenmalm ◽  
Seth Dahlstedt ◽  
Roland S. Johansson

Most objects that we manipulate have curved surfaces. We have analyzed how subjects during a prototypical manipulatory task use visual and tactile sensory information for adapting fingertip actions to changes in object curvature. Subjects grasped an elongated object at one end using a precision grip and lifted it while instructed to keep it level. The principal load of the grasp was tangential torque due to the location of the center of mass of the object in relation to the horizontal grip axis joining the centers of the opposing grasp surfaces. The curvature strongly influenced the grip forces required to prevent rotational slips. Likewise the curvature influenced the rotational yield of the grasp that developed under the tangential torque load due to the viscoelastic properties of the fingertip pulps. Subjects scaled the grip forces parametrically with object curvature for grasp stability. Moreover in a curvature-dependent manner, subjects twisted the grasp around the grip axis by a radial flexion of the wrist to keep the desired object orientation despite the rotational yield. To adapt these fingertip actions to object curvature, subjects could use both vision and tactile sensibility integrated with predictive control. During combined blindfolding and digital anesthesia, however, the motor output failed to predict the consequences of the prevailing curvature. Subjects used vision to identify the curvature for efficient feedforward retrieval of grip force requirements before executing the motor commands. Digital anesthesia caused little impairment of grip force control when subjects had vision available, but the adaptation of the twist became delayed. Visual cues about the form of the grasp surface obtained before contact was used to scale the grip force, whereas the scaling of the twist depended on visual cues related to object movement. Thus subjects apparently relied on different visuomotor mechanisms for adaptation of grip force and grasp kinematics. In contrast, blindfolded subjects used tactile cues about the prevailing curvature obtained after contact with the object for feedforward adaptation of both grip force and twist. We conclude that humans use both vision and tactile sensibility for feedforward parametric adaptation of grip forces and grasp kinematics to object curvature. Normal control of the twist action, however, requires digital afferent input, and different visuomotor mechanisms support the control of the grasp twist and the grip force. This differential use of vision may have a bearing to the two-stream model of human visual processing.


Author(s):  
Frederik Grosse ◽  
Stefan Mark Rueckriegel ◽  
Ulrich-Wilhelm Thomale ◽  
Pablo Hernáiz Driever

Abstract Purpose Diaschisis of cerebrocerebellar loops contributes to cognitive and motor deficits in pediatric cerebellar brain tumor survivors. We used a cerebellar white matter atlas and hypothesized that lesion symptom mapping may reveal the critical lesions of cerebellar tracts. Methods We examined 31 long-term survivors of pediatric posterior fossa tumors (13 pilocytic astrocytoma, 18 medulloblastoma). Patients underwent neuronal imaging, examination for ataxia, fine motor and cognitive function, planning abilities, and executive function. Individual consolidated cerebellar lesions were drawn manually onto patients’ individual MRI and normalized into Montreal Neurologic Institute (MNI) space for further analysis with voxel-based lesion symptom mapping. Results Lesion symptom mapping linked deficits of motor function to the superior cerebellar peduncle (SCP), deep cerebellar nuclei (interposed nucleus (IN), fastigial nucleus (FN), ventromedial dentate nucleus (DN)), and inferior vermis (VIIIa, VIIIb, IX, X). Statistical maps of deficits of intelligence and executive function mapped with minor variations to the same cerebellar structures. Conclusion We identified lesions to the SCP next to deep cerebellar nuclei as critical for limiting both motor and cognitive function in pediatric cerebellar tumor survivors. Future strategies safeguarding motor and cognitive function will have to identify patients preoperatively at risk for damage to these critical structures and adapt multimodal therapeutic options accordingly.


1997 ◽  
Vol 78 (1) ◽  
pp. 271-280 ◽  
Author(s):  
Mary M. Werremeyer ◽  
Kelly J. Cole

Werremeyer, Mary M. and Kelly J. Cole. Wrist action affects precision grip force. J. Neurophysiol. 78: 271–280, 1997. When moving objects with a precision grip, fingertip forces normal to the object surface (grip force) change in parallel with forces tangential to the object (load force). We investigated whether voluntary wrist actions can affect grip force independent of load force, because the extrinsic finger muscles cross the wrist. Grip force increased with wrist angular speed during wrist motion in the horizontal plane, and was much larger than the increased tangential load at the fingertips or the reaction forces from linear acceleration of the test object. During wrist flexion the index finger muscles in the hand and forearm increased myoelectric activity; during wrist extension this myoelectric activity increased little, or decreased for some subjects. The grip force maxima coincided with wrist acceleration maxima, and grip force remained elevated when subjects held the wrist in extreme flexion or extension. Likewise, during isometric wrist actions the grip force increased even though the fingertip loads remained constant. A grip force “pulse” developed that increased with wrist force rate, followed by a static grip force while the wrist force was sustained. Subjects could not suppress the grip force pulse when provided visual feedback of their grip force. We conclude that the extrinsic hand muscles can be recruited to assist the intended wrist action, yielding higher grip-load ratios than those employed with the wrist at rest. This added drive to hand muscles overcame any loss in muscle force while the extrinsic finger flexors shortened during wrist flexion motion. During wrist extension motion grip force increases apparently occurred from eccentric contraction of the extrinsic finger flexors. The coactivation of hand closing muscles with other wrist muscles also may result in part from a general motor facilitation, because grip force increased during isometric knee extension. However, these increases were related weakly to the knee force. The observed muscle coactivation, from all sources, may contribute to grasp stability. For example, when transporting grasped objects, upper limb accelerations simultaneously produce inertial torques at the wrist that must be resisted, and inertial loads at the fingertips from the object that must be offset by increased grip force. The muscle coactivation described here would cause similarly timed pulses in the wrist force and grip force. However, grip-load coupling from this mechanism would not contribute much to grasp stability when small wrist forces are required, such as for slow movements or when the object's total resistive load is small.


1998 ◽  
Vol 79 (5) ◽  
pp. 2245-2254 ◽  
Author(s):  
Xiaofeng Lu ◽  
Okihide Hikosaka ◽  
Shigehiro Miyachi

Lu, Xiaofeng, Okihide Hikosaka, and Shigehiro Miyachi. Role of monkey cerebellar nuclei in skill for sequential movement. J. Neurophysiol. 79: 2245–2254, 1998. To examine whether the cerebellum is involved in learning and memory of visuomotor sequences, we trained two monkeys on a sequential button press task and inactivated different portions of the cerebellar nuclei by injecting a small amount of muscimol (γ-aminobutyric acid agonist). Before the injection experiments started, the monkeys had learned a set of sequences ( n = 21 and 12) extensively. After each injection, we had the monkeys perform the learned sequences and, in addition, learn new sequences. We found deficits in learning/memory by the injections into the dorsal and central part of the dentate nucleus. The number of errors increased significantly for the learned sequences but not for the new sequences. This effect was present only when the hand ipsilateral to the muscimol injection was used. Consistent with this result, anticipatory saccades, the occurrence of which is correlated closely with motor skill, also became less frequent particularly when the ipsilateral hand was used. No effect on learning/memory was observed after injections into the ventral or lateral parts of the dentate nucleus, interpositus nucleus, or fastigial nucleus. In contrast, hand movements became slower after ipsilateral injections at all of the injection sites. These results suggest that, among the cerebellar nuclei, the dentate nucleus, especially its dorsal and central regions, is related to the storage and/or retrieval of long-term memory for motor skill.


2000 ◽  
Vol 47 (10) ◽  
pp. 1366-1375 ◽  
Author(s):  
A. Fagergren ◽  
O. Ekeberg ◽  
H. Forssberg

2020 ◽  
Vol 19 (6) ◽  
pp. 778-787
Author(s):  
Kenichi Yamada ◽  
Masaki Watanabe ◽  
Kiyotaka Suzuki ◽  
Yuji Suzuki

Abstract The objective of this study was to investigate lobule-specific cerebellar structural alterations relevant to clinical behavioral characteristics of Prader-Willi syndrome (PWS). We performed a case-control study of 21 Japanese individuals with PWS (age; median 21.0, range 13–50 years, 14 males, 7 females) and 40 age- and sex-matched healthy controls with typical development. Participants underwent 3-Tesla magnetic resonance imaging. Three-dimensional T1-weighted images were assessed for cerebellar lobular volume and adjusted for total intracerebellar volume (TIV) using a spatially unbiased atlas template to give a relative volume ratio. A region of interest analysis included the deep cerebellar nuclei. A correlation analysis was performed between the volumetric data and the clinical behavioral scores derived from the standard questionnaires (hyperphagia, autism, obsession, and maladaptive index) for global intelligence assessment in paired subgroups. In individuals with PWS, TIV was significantly reduced compared with that of controls (p < 0.05, family-wise error corrected; mean [standard deviation], 1014.1 [93.0] mm3). Decreased relative lobular volume ratios were observed in posterior inferior lobules with age, sex, and TIV as covariates (Crus I, Crus II, lobules VIIb, VIIIa, VIIIb, and IX). However, increased ratios were found in the dentate nuclei bilaterally in individuals with PWS (p < 0.01); the mean (standard deviation) × 10−3 was as follows: left, 1.58 (0.26); right, 1.67 (0.30). The altered lobular volume ratios showed negative correlations with hyperphagic and autistic characteristics and positive correlations with obsessive and intellectual characteristics. This study provides the first objective evidence of topographic patterns of volume differences in cerebellar structures consistent with clinical behavioral characteristics in individuals with PWS and strongly suggests a cerebellar contribution to altered functional brain connectivity in PWS.


2020 ◽  
Vol 16 (8) ◽  
pp. e1008081 ◽  
Author(s):  
Lina K. Klein ◽  
Guido Maiello ◽  
Vivian C. Paulun ◽  
Roland W. Fleming

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