Lee T. Robertson

Stimulus classification by ensembles of climbing fiber receptive fields

Although the local structure of the cerebellum is fairly uniform and its inputs are often widely shared, outputs from different regions of the cerebellar cortex reach different parts of the cerebellar and vestibular nuclei, which can affect the rest of the nervous system in different ways. In this review, we explain how different ensembles of climbing fiber responses in the anterior lobe and paramedian lobule can be generated by a tactile stimulus to the distal hindpaw. Apart from differing in degree of activation, the cortical regions differ also in the detailed pattern of the activation transmitted. The anterior lobe can distinguish a greater diversity of stimuli to various skin surfaces than can the paramedian median lobule. This differential classification of particular stimulus arrays by the two cerebellar regions could produce distinct patterns of neuronal activity in various corticonuclear compartments.

Assessments of axial motor control during deep brain stimulation in parkinsonian patients.

OBJECTIVEWe tested the hypothesis that bilateral deep brain stimulation (DBS) in the globus pallidus internus or the subthalamic nucleus improves various components of postural and oromotor function and that some of the components correlate with changes in the Unified Parkinson’s Disease Rating Scale (UPDRS) in patients with Parkinson’s disease. METHODSSix patients with Parkinson’s disease were evaluated for four postural and two orofacial UPDRS items, and quantitative tests of posture adjustments and oromotor control were performed while the patients were on and off DBS. Measurements of postural adjustments included reactive force and latency before a voluntary step. The oromotor assessments involved velocity and amplitude changes during voluntary jaw movement. RESULTSDBS significantly improved the total UPDRS motor score by an average of 44%, which included improvement of 18 to 54% in the postural and orofacial items. DBS also decreased foot lift-off latency significantly, but it produced a variable response to the preparatory postural force in the swing limb. DBS significantly improved jaw-opening velocity by 14 to 50% and jaw opening amplitude by 5 to 41%. Significant correlations for the percentage change from off and on DBS occurred among a few UPDRS items and foot lift-off latency and jaw-opening velocities. CONCLUSIONDBS in either the globus pallidus internus or the subthalamic nucleus induces improvements in bradykinesia of specific components of postural and oromotor control, which also can be measured by the postural and orofacial UPDRS items. In some Parkinson’s disease patients, DBS results in improvements in force or amplitude control, although these changes are not reflected in changes in UPDRS postural and orofacial items. A battery of quantitative and clinical tests must be used to evaluate the effects of DBS on axial motor control adequately.

Jaw movement dysfunction related to Parkinson's disease and partially modified by levodopa

OBJECTIVES--To test the hypotheses that Parkinsons disease can differentially produce deficits in voluntary and rhythmic jaw movements, which involve different neuronal circuits, and that levodopa treatment improves specific components of the motor deficit. METHODS--Patients with idiopathic Parkinsons disease and control subjects were tested on a series of jaw motor tasks that included simple voluntary movement, isometric clenching, and natural and paced rhythmic movements. Jaw movements were measured by changes in electromagnetic fields and EMG activity. Patients with Parkinsons disease with fluctuations in motor responses to levodopa were tested while off and on. RESULTS--During the off state, patients with Parkinsons disease were significantly worse than the control subjects on most tasks. The deficits included a decrease in amplitude and velocity during jaw opening and closing, aberrant patterns and low amplitude of EMG activity during clenching, and low vertical amplitude and prolonged durations of occlusion during rhythmic movements. No decrements were found in the amplitude of voluntary lateral jaw movements or the frequency of rhythmic movements. During the on state, improvements occurred in the patterns and level of EMG activity during clenching and in the vertical amplitude and duration of occlusion during rhythmic movements, although a significant decrement occurred in the lateral excursion of the jaw. CONCLUSIONS--Parkinsons disease affects the central programming of functionally related muscles involved in voluntary and rhythmic jaw movements and levodopa replacement influences only certain aspects of jaw movement, most likely those requiring sensory feedback.

Vibration perception thresholds of human maxillary and mandibular central incisors.

Tactile information from dental mechanoreceptors contributes to the perception of food bolus textures and the control of mastication. While numerous studies have measured the light-touch sensory thresholds of teeth, little information is available about the vibrotactile perception thresholds of teeth. This study uses an adaptive psychophysical procedure to determine thresholds of vibratory stimulation of maxillary and mandibular central incisors in 16 healthy human subjects. An electromechanical vibrator delivered labiolingual forces perpendicular to the long axis of the maxillary and mandibular incisors at 10 stimulation frequencies between 40 and 315 Hz. The median thresholds ranged between 44 and 104 mN. A linear regression analysis revealed a significant increase in the vibrotactile thresholds with increasing frequencies for stimulation of the maxillary and mandibular incisors. No significant differences were found between regression slopes of the thresholds of the maxillary and mandibular incisors. These results indicated that maxillary and mandibular incisors should be able to discriminate effectively among a variety of textures based on their ability to encode a wide range of vibration frequencies.

Vagal and somatic representation by the climbing fiber system in lobule V of the cat cerebellum

The organization of the climbing fiber representation of the vagal afferents and the body surface in the vermal and intermediate zones of lobule V was examined in cats anesthetized with alpha-chloralose. Extracellular single-unit recordings were made from 428 Purkinje cells. Electrical stimulation of the vagus nerve elicited climbing fiber responses in 40% of the cells, most of which had convergent somatic input. Activation of A delta vagal afferent fibers accounted for 65% of the responses, whereas the A beta fibers involved 27% and the C fibers included 8% of the responses. The responses driven by vagal nerve stimulation were encountered throughout the lobule, although a significantly increased representation of the vagus was identified for 3 longitudinal 0.5 mm wide sectors (two in the vermis and one in the intermediate region). In the vermis, the fine-grain organization consisted of a mixture of representations of the various parts of the body surface with and without convergent vagal input, although there was little convergence in the medial vermis where many of the responses were elicited by only vagal nerve stimulation. In the intermediate cortex, most of the vagal climbing fiber representation was convergent with forelimb input. These results suggest that vagal input into the cerebellum could have important modulatory effects on the cerebellar somatosensory input.

Morphological changes associated with chronic cerebellar stimulation in the human

✓ The histopathology associated with chronic cerebellar stimulation is described for three human cerebellum and brain-stem specimens obtained at autopsy. The specimens were from three severely epileptic patients who received cerebellar stimulation at 10 Hz for 6½ to 15 months. The electrode arrays were completely encapsulated with loose connective tissue that included a proliferation of capillaries, an infiltration of lymphocytes, and an occasional macrophage. The capsule of one of the specimens was tightly adherent to the underlying cerebellar cortex, which may have been caused by some trauma during the surgical placement of the electrodes. Severe injury of the cerebellar cortex was generally confined to between 1 and 2 mm directly beneath the electrode array, and included thinning of the molecular layer, and loss of most Purkinje cells, interneurons, and associated fibers. Abnormal Purkinje cell dendritic patterns and loss of climbing fibers were evident 3 to 4 mm from the cortical surface. At a depth o...

Climbing fiber representation of the renal afferent nerve in the vermal cortex of the cat cerebellum

In order to understand how the cerebellum may participate in various autonomic functions, it is necessary to first determine the occurrence and distribution of the various visceral inputs in the cerebellar cortex and their relation to other cerebellar afferents. This study examines the organization of climbing fiber responses (complex spikes) of Purkinje cells elicited by electrical stimulation of the renal afferent nerve and their relationship to climbing fiber responses representing the body surface. Visceral and somatic afferent responses were mapped in the lateral vermal cortex of lobules V to VII in chloralose-anesthetized cats. Extracellular single-unit recordings were made from 628 Purkinje cells, of which 14% had climbing fiber responses induced by renal afferent nerve stimulation. Except for one Purkinje cell, the renal climbing fiber input converged with somatic induced climbing fiber input. Tactile stimulation also elicited 54% of cells, which were unresponsive to the renal afferent nerve stimulation. The occurrence and distribution of the climbing fiber responses elicited by renal afferent nerve stimulation varied between lobules V, VI, and VII for the proportion of responsive units, the onset latencies, and topological organization. More renal responsive units were encountered in lobules V (18%) and VII (17%) than in lobule VI (6%), the average latency of renal climbing fiber responses was significantly longer in lobule VII than in lobules V and VI, and the latencies were also different among various parasagittal planes in lobules V and VII. The proportional representation of various body areas for cells with renal and somatic convergent input was different than for cells with only somatic representation. Proportionally, the forelimb had the greatest representation in lobule V, split receptive fields were frequently represented in lobule VI, and the face was well represented in lobule VII. The results of this study, in conjunction with studies showing climbing fiber representation of the vagal and splanchnic nerves, further substantiate role of the cerebellum in autonomic functions.

Detail, Proportion, and Foci among Face Receptive Fields of Climbing Fiber Responses in the Cat Cerebellum

This paper reports a theoretical analysis of the transformation from a tactile stimulus of the face to climbing fiber responses in three regions of the cat cerebellum. The database consisted of climbing fiber receptive fields on the face from 75 responses from the anterior lobe, 33 responses from the paramedian lobule (PML), and 52 responses from the crus IIp of the anesthetized cat. The receptive fields were similar in being composed of discrete areas on the skin, or skin compartments. The regional differences in the configurations of the receptive fields were reflected in which compartments most often combined to form receptive fields. Each region had a distinct pattern of the preponderance of skin compartments that combined to form receptive fields, and yet the preponderant compartments were all chosen from one composite set of compartments that applied to all three regions. The climbing fiber representation of the face differed over the three regions (1) in the parts of the face that were represented; (2) in the frequency with which certain areas were included in the receptive fields; and (3) in the details of the face that could be distinguished by differing ensembles of climbing fiber responses. The majority of the climbing fiber receptive fields from either the anterior lobe or the crus IIp were unique to the region, whereas the majority of the receptive fields of responses from the PML were encountered in one or both of the other regions. Overlapping all face receptive fields from each of the three regions revealed that the receptive fields were differentially focused on or around the cornea, nose, or chin. In the anterior lobe, the face receptive fields mainly included the chin (43%) and the glabrous tip of the nose (40%), but few included the cornea (1%). In the PML, the receptive fields included the cornea (24%) and the chin (58%), but none included the nose. In the crus IIp, the cornea was included in the greatest number (37%) of receptive fields, whereas the nose and the chin were included equally (24%). The different sets of climbing fiber receptive fields in each of the three regions afforded the regions differing abilities to distinguish among complex patterns of stimuli, depending on the portion of the face stimulated.

Somatosensory climbing fiber responses in the caudal posterior vermis of the cat cerebellum

Tactile stimulation of the body surface elicited climbing fiber responses in 5% of the 839 Purkinje cells recorded in the caudal posterior vermis (lobules VII-IX) of cats anesthetized with sodium pentobarbital. The cells responsive to tactile stimulation were mainly encountered around the prepyramidal fissure between lobules VIIb and VIIIa. This region was characterized by responses representing only selective areas of the ipsilateral face, forepaw, hindlimb, or proximal tail-pelvic territory. Climbing fiber responses representing the face and forepaw were encountered more laterally and those representing the proximal tail-pelvic area more medially. Tactile representations of the body surface are located within the same cortical domain as other climbing fiber inputs, which suggests that the caudal posterior vermis is a multifunctional region of the cerebellum.

Distribution of Acetylcholinesterase in the Granular Layer of the Cerebellum of the Rhesus Monkey (Macaca mulatta)

A nonuniform distribution of acetylcholinesterase (AChE) activity was identified in the granular layer of the cerebellum in rhesus monkeys. The distribution of darkly AChE-stained clumps in the granular layer was determined for each lobule of the vermis and the lateral cortex. The vermis contained a greater density of AChE reaction product than the lateral cortex. In the vermis, lobules IX and X had significantly the highest level of activity, followed by lobules VII and VIII, which were significantly higher than lobules II-VI. In the lateral cortex, the flocculus had the highest level of the AChE activity, followed by crus I and the dorsal paraflocculus, which had significantly higher levels than the remaining lobules. The high levels of AChE activity in the flocculonodular lobe and lobule IX may correspond to cholinergic mossy fiber transmission, but the high levels of AChE activity in other cerebellar regions probably involve noncholinergic functions. The significance of the nonuniform AChE distribution is not yet known, but may correspond to regional differences in neuronal or metabolic activity in the cerebellum that occur in conjunction with specific behaviors.