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

OBJECTIVE: We 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. METHODS: Six 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. RESULTS: DBS 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. CONCLUSION: DBS 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.

A survey of neuroscience courses for predoctoral dental students.

Course directors of the seventeen neuroscience courses offered in U.S. dental schools were surveyed. Information was obtained about the course organization, topics covered, and the amount of didactic and nondidactic instruction for sixteen neuroscience courses, which included four courses that combined medical and dental student instruction. The courses averaged 51.4 contact hours with a range of 11 to 110 hours. Approximately 75 percent of time was for didactic instruction. Most courses emphasized neuroanatomy, electrochemical cell signaling, and the somatic sensory system, including specific lectures on pain sensation. The majority of courses also included several lectures on topics dealing with motor control and the limbic and the autonomic systems, whereas limited time was allocated to topics concerned with higher cortical functions. The nondidactic instruction typically included neuroanatomy laboratories and group discussions of the relation between lesions of sensory and motor pathways and neurological signs. The establishment of guidelines for neuroscience could encourage dental schools to provide a strong basic science foundation in neuroscience.

Teaching physiology to predoctoral dental students.

A survey was sent to the physiology course directors of the fifty-three dental schools in the continental United States. Information was collected regarding the type of instructional arrangements, course content and emphasis, and amount and type of nondidactic instruction. Responses were obtained for forty-eight courses, all of which covered the core topics of physiology, although twelve schools taught neurophysiology as part of a neuroscience course. Combined medical and dental student (MS+DS) courses used six to fourteen hours of nondidactic instruction per core topic, whereas the courses taught by dental school-(DS-B) or medical school-based instructors used 0.5 to 2.6 hours per topic. Courses combining dental students with other nonmedical professional students used mainly didactic instruction. While most dental school physiology courses continue to rely on traditional didactic instruction, a few schools integrate physiology with other basic science and clinical courses, include problem-solving exercises, and offer advanced physiological topics during the clinical years. Consequently, there is considerable potential for change in predoctoral physiology instruction.

A survey of predoctoral dental basic pharmacology education.

A survey of fifty-one of the fifty-three dental schools in the continental United States provided information about pharmacology curriculum content and time allocation. Most dental schools offer a traditional didactic course in basic pharmacology, with about 50 percent of the medical school-based (MSB) and 75 percent of the dental school-based (DSB) programs providing additional pharmacology material in other basic and clinical courses. The four combined medical-dental (M-D) student courses have more hours of instruction, clinical conferences and reviews, and number of instructors than either the dental school- or medical school-based courses. DSB and MSB pharmacology courses were similar in most regards, with a relatively low compliance with the current curriculum guidelines. The DSB and MSB courses provided more time for neuropharmacology and less time for agents related to various organ systems than the M-D courses. There is considerable potential to improve pharmacology instruction by expanding the inclusion of pharmacology in other courses, increasing the number of clinical conferences and discussions, and offering problem-based-learning sessions.

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

OBJECTIVES: To test the hypotheses that Parkinson's 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 Parkinson's 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 Parkinson's disease with fluctuations in motor responses to levodopa were tested while off and on. RESULTS: During the off state, patients with Parkinson's 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: Parkinson's 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.

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.

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.

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.

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.

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.

Patterns of intersection among climbing fiber receptive fields.

Peripheral receptive fields of climbing fiber responses from the anterior lobe of the cat display large intersections and distinct organizations. Receptive fields of the extremities and face have boundaries that follow the lines of a grid. Receptive fields of the tail and ventral trunk and some of the receptive fields on the extremities form concentric sets, which can be completely ordered by inclusion. Receptive fields along the spine form a chain, which indicates rostrocaudal position. Such regularities among the intersections, especially in the grid organization, allow the receptive fields to encode combinations and alternative combinations of skin locations as a pianist might distinguish chords rather than notes.

Representations of the body surface by climbing fiber responses in the dorsal paraflocculus of the cat.

Mechanical stimulation elicited climbing fiber responses in 22% of the 377 Purkinje cells isolated in the dorsal paraflocculus of cats anesthetized with sodium pentobarbital. The responsive units were not evenly distributed throughout the dorsal paraflocculus. In the posterior division, 37% (65/177) of the cells had climbing fiber responses elicited by tactile stimulation, whereas in the lateral and accessory divisions the units were mainly unresponsive to tactile stimulation. Eleven of the 174 cells were responsive to tactile stimulation in the lateral division and only one climbing fiber response was driven in the 26 cells isolated in the accessory division. The climbing fiber representation was mainly of the ipsilateral forelimb and hindlimb with only a few responses representing the face. About half of the hindlimb representation was encountered in a patch located in the most medial part of the posterior division. No consistent location was identified between animals for the rest of the representations, which were intermingled among unresponsive units. The receptive fields of the majority of the forepaw and hindpaw representation included areas of the lateral toes; only a few responses represented the medial parts of the paw.

Relationship of parasagittal bands of acetylcholinesterase activity to the climbing fiber representation.

The organization of the somatosensory representation by the climbing fiber system was correlated to parasagittal zones in the vermis, which were demarcated by the parasagittal banding pattern of acetylcholinesterase (AChE) activity. Extracellular recordings were made of climbing fiber responses that were elicited by tactile stimulation in anesthetized cats. After the climbing fiber representation was mapped physiologically, the cerebellum was histologically processed for AChE activity. The lateral edge of the lateral AChE banding coincided with the junction between a medial vermis (zones A and X) where 82% of the units were unresponsive and the lateral vermis (zone B) where 72% of the climbing fiber responses represented areas of the body surface.

Somatosensory representation of the cerebellar climbing fiber system in the rat.

The climbing fiber responses of 542 Purkinje cells were isolated in the vermal and intermediate zones of lobules II to VI of the rat cerebellum. Mechanical stimulation successfully elicited 53% of the isolated climbing fiber responses, whereas the remaining units were unresponsive to any stimulation employed. Of the units elicited by the stimulation, 34% required cutaneous and 66% required deep stimulation. Some proportion of the representation of each body region required either cutaneous or deep stimulation. The hind-limb had the largest representation and accounted for 55% (160/288) of the units. In contrast, the forelimb was only represented by 10% of the units, the tail by 16%, the face by 11% and the remaining 6% of the units by surface regions of the spine, chest and abdomen. On the basis of their proportional representation of body regions, 3 different cortical areas were distinguished: (1) a medial vermis, which consisted predominantly of unresponsive units; (2) a lateral vermis, which included representations of the extremities, trunk and tail; and (3) the intermediate zone, where the only representation of the face was evident. Within each area, the representations formed a disjunctive pattern of irregularly shaped patches and areas of overlap. In comparison with the climbing fiber organization of the cat, the medial vermal unresponsive zone and the patch-like representations of various body surfaces in the rat were similar to the cat, but the proportional representation of various body surfaces and effective stimulus modality were different, which may reflect morphological and behavioral differences between the species.

Somatosensory representation of the climbing fiber system in the rostral intermediate cerebellum.

The fine grain organization of the climbing fiber (CF) representation for the intermediate cortex of lobules III, IV, and Va was examined. Data were obtained from cats anesthetized with sodium pentobarbital. Through extracellular recording techniques, CF responses were identified in 814 Purkinje cells; 74% were elicited by mechanical stimulation of various body surfaces. Of the CF responses elicited by stimulation, 60% involved the ipsilateral hindlimb, 36% represented parts of the forelimb, and only 4% represented areas of the face, tail, or abdomen. Hindlimb representation predominated in lobules III and IV, and forelimb representation was mainly confined to lobule Va. No distinct parasagittal zones that involved all three lobules were identified. In general, the organization for most sublobules could be best described as a mixture of patches of forelimb or hindlimb representations. Within the patches there was considerable diversity of receptive field types, particularly for the extremities. The receptive fields involving the distal phalanges were generally smaller than those for the proximal areas, but a range in field sizes was evident for both distal and proximal regions. More than half of either the forelimb or the hindlimb representation was limited to the distal paw areas; the two middle toes received the most frequent representation. Representations of the proximal limb areas were generally centered around either the wrist or the heel, or around the elbow or knee, but many of these receptive fields also extended to the phalanges. The multiple representation of various areas of forelimb and hindlimb throughout the rostral intermediate cortex was consistent with the type of organization that had been identified in other regions of the anterior lobe, although each cortical area contained a unique proportional CF representation of various body areas.

Allometric characteristics of the developing inferior olivary nucleus of the kitten.

The allometric characteristics of the inferior olivary complex were studied in 13 kittens, which ranged in age from 39 to 125 days gestation (parturition = 62 days). The date of conception was known for 8 of the specimens whereas only the date of birth was known for the other 5 kittens. Each brain stem was serially sectioned and every tenth section was stained with cresyl-echt violet. The volume of the complete inferior olivary complex showed a curvilinear increase, with an 8% per day growth rate postnatally. The neuron diameter also showed greater increase postnatally. The diameter reached adult range by 1 month postnatally. The neuron population exhibited both prenatal and postnatal changes. There was a 35% cell decrease from 75,800 estimated cells at 49 days to 49,140 at parturition; this was followed by a 33% increase to 73,700 estimated cells by 73 days after which the population was within the adult range. The neuron density demonstrated more than a 70% decrease prenatally. This quantitative analysis of the kitten's inferior olivary complex indicates that a transient population of olivary neurons exists prenatally and that considerable maturation of olivary complex occurs postnatally.

Topographic features of climbing fiber input in the rostral vermal cortex of the cat cerebellum.

The topographic organization of the climbing fiber (CF) responses was mapped in the rostral vermal cortex (lobules III, IV, and Va) of the cerebellum. Extracellular, single-unit recordings were obtained from 699 Purkinje cells in cats anesthetized with sodium pentobarbital. Approximately 72% of the CF responses were elicited by low-threshold or deep tactile stimulation, whereas the remaining units were unresponsive to any peripheral stimulation. On the basis of response characteristics, the vermal cortex was separated into an approximately 1-mm-wide medial zone and a 1 to 1.5-mm-wide lateral zone. The medial zone contained many unresponsive cells, except along the midline, where about 35% of the CF responses were elicited by deep stimulation at the base of the tail. The majority (78%) of the CF responses within the lateral vermal cortex represented various areas of the hindpaw, although representations of the forepaw (8%), tail (4%), and chin (0.6%), as well as unresponsive units (10%), were evident. The lateral vermal cortex contained a mediolateral topography of different receptive fields, although the topography was not sharply defined or equally displayed in all animals. The medial part of the lateral zone contained a representation of the ipsilateral forelimb in lobules IV and Va; the middle part had a representation of the medial or the lateral half of the hindpaw; and the lateral portion of the zone had an extensive representation of the distal hindpaw. The CF responses with similar receptive fields were often found in patches, which in some areas were arranged in layers from the inner to the outer areas of the sublobules. A particular body surface may be represented in multiple patches and in different lobules. Activation of the majority of CF responses within a sublobule may occur only during selected behaviors.

Organization of climbing fiber input from mechanoreceptors to lobule V vermal cortex of the cat.

The somatotopic organization of the climbing fiber (CF) projections to the vermal cortex of lobule V of the cat was revealed by low threshold natural stimulation of mechanoreceptors. Extracellular single-unit recordings were made from 554 Purkinje cells in cats anesthetized with sodium pentobarbital. Forty-nine percent of the CF responses were elicited by cutaneous stimulation of the forelimb (62%), hindlimb (25%), or upper back and neck (13%). The topographical arrangement consisted of a 1 mm wide medial zone and a 1-1.5 mm wide lateral zone. In the medial zone, the CF responses were mainly nonresponsive to any cutaneous stimulation except in the caudomedial portion of the lobule where the upper back, neck or ears were represented in a narrow parasagittally oriented strip. The lateral zone contained a mixture of CF responses representing projections from different portions of the ipsilateral forelimb and hindlimb. Although CF responses connected with the forepaw or hindpaw predominated throughout all parts of the lateral zone, the more medial portions of this zone contained larger receptive fields involving the more proximal areas of the limb whereas the lateral part of the zone had smaller receptive fields representing the distal regions, particularly the ventral forepaw surface. Cells with similar receptive fields were often grouped together, but adjacent skin areas were not necessarily represented in adjacent cortical patches. Thus, the cutaneous projections to this lobule terminated in a patchy or mosaic fashion.

Localization of cutaneously elicited climbing fiber responses in lobule V of the monkey cerebellum.

The somatotopic organization of climbing fibers (CF) elicited by natural stimulation was determined for the intermediate zone of lobule V of Macaca fascicularis. In monkeys anesthetized with sodium pentobarbital, extracellular recordings of single Purkinje cells with CF responses were evaluated by gentle taps to the body and by computer-controlled punctate stimuli. Of the 311 Purkinje cells studied, 53% had CF responses elicited by cutaneous stimulation whereas the remaining cells were unresponsive. The entire ipsilateral, dorsal surface of the forelimb, face, and the oral cavity were represented in the intermediate zone. The topographic organization consisted of three 1.5-3 mm wide parasagittal bands of cells: a forelimb band medially, then a face band, and an unresponsive zone laterally. Most receptive fields in the forelimb band involved portions of the wrist, hand, and digits, although shoulder, arm, and forearm were also represented. The receptive fields of the hand usually included more than 1 digit and only a few fields contained the thumb. Most responses in the face band were elicited by stimulation of areas innervated by the mandibular division of the trigeminal nerve, although some responses were produced by stimulating areas related to the ophthalmic and maxillary divisions and to the anterior cutaneous nerve. Cells with similar receptive fields tended to be grouped together. The somatotopic CF organization of the monkey differed in many ways from the arrangement in the cat.