Progressive limb ataxia following inferior olive lesions.

Cerebellar climbing fibres originate in the inferior olive (IO). Temporary IO inactivation produces movement deficits. Does permanent inactivation produce similar deficits and, if so, do they recover? The excitotoxin, kainic acid, was injected into the rostral IO of three cats. Behaviour was measured during reaching and locomotion. Two cats were injected during the reaching task. Within minutes, grasping became difficult and the trajectories of the reaches showed higher arcing than normally seen. During locomotion, both cats showed head and trunk deviation to the injected side, walking paths curved to the injected side, and the paws were lifted higher than normal. Limbs contralateral to the injections became rigid. Within 1 day, posture had normalized, locomotion was unsteady and high lifting of the paws had reversed to a tendency to drag the dorsum of the paws. Passive body movement produced vestibular signs. Over a few days, locomotion normalized and vestibular signs disappeared. Reach trajectories were normal but grasping deficits persisted. Over the first week, the amplitude of limb lift during reaching and locomotion began to increase. The increase continued over time and, after several months, limb movements became severely ataxic. The effects followed the somatotopy of the rostral IO: a loss of cells in medial rostral IO only affected the forelimb, whereas a loss of cells in medial and lateral IO affected both forelimb and hindlimb. Deficits produced by IO lesions involve multiple mechanisms; some recover rapidly, some appear stable, and some worsen over time. The nature of the progressive deficit suggests a gradual loss of Purkinje cell inhibition on cerebellar nuclear cells.

Is orientation-specific color adaptation in human vision due to edge detectors, afterimages, or "dipoles"?

After one looks alternately at red vertical and green horizontal stripes, vertical and horizontal white stripes appear greenish and pink, respectively. This color aftereffect might imply that contour-detecting cells participate in human vision, or might simply be due to afterimages. A procedure that precludes afterimages still yields aftereffects, but sensory units less complex than edge detectors could be responsible.

Velocity signals related to hand movements recorded from red nucleus neurons in monkeys.

Neural activity of the red nucleus was studied in monkeys trained to operate devices requiring shoulder, elbow, wrist, hand, or finger movements. Single cell activity was more closely related to movements of the hand and fingers than to movements of the other joints. Discharge consistently preceded movements by a constant time interval; duration of discharge was highly correlated with the duration of movement; and discharge rate was highly correlated with movement velocity. These data suggest a role for the rubrospinal pathway in the initiation and control of hand movements.

Somatosensory properties of the inferior olive of the cat.

We examined the somatosensory properties of 391 neurons in the inferior olive in 20 cats that were anesthetized with barbiturate or decerebrated. A response consisted of a single spike with a variable number of wavelets followed by a long refractory period. Neurons responsive to natural somatosensory stimuli were recorded in all olivary subdivisions. The dorsal accessory olive (DAO) contained the highest proportion of responsive units (96%), compared with 66% for the medial accessory olive (MAO) and 43% for the principal olivary (PO) nucleus. Within the rostral DAO we found a refined cutaneous map of the entire contralateral body surface. In the caudal DAO responsiveness to manipulation of deep tissues became prominent, and both individual limbs and bilateral pairs were represented. In the medial region of the PO responsiveness to taps predominated and bilaterally symmetrical fields were frequent. The lateral PO was unresponsive under the conditions of these experiments. The MAO was distinguished by a greater complexity of receptive field and by a preponderance of deep over cutaneous modality. The lateral part of caudal MAO contained cells with interesting spatial patterns of excitation and inhibition, whereas most cells in the rostral MAO had purely excitatory fields. A teleceptive area receiving visual and auditory input was recognized in the medial MAO and nearby structures such as the dorsal cap. Contact and proprioceptive signals arriving via climbing fibers may provide the cerebellum with information necessary to relate the body to external objects.

Somatotopic alignment between climbing fiber input and nuclear output of the cat intermediate cerebellum.

The rostral dorsal accessory olive (rDAO) contains a detailed somatosensory map of the entire contralateral body surface. The rDAO projects to the anterior interpositus nucleus (NIA) directly as well as indirectly by way of Purkinje cells in cerebellar cortex. NIA maintains a topographic relation to different levels of the spinal cord through a relay in the magnocellular red nucleus (RNm) and, thus, contains a motor somatotopy. By using bidirectional transport of WGA-HRP, we demonstrate that the sensory somatotopy of rDAO aligns with the motor somatotopy of NIA. It is likely that rDAO information supplied to the cerebellum from a specific part of the body is used to influence movements restricted to that same body part.

Limb specific connections of the cat magnocellular red nucleus.

Afferent and efferent connections of the limb specific divisions of the cat magnocellular red nucleus (RNm) were traced using the bidirectional transport of wheatgerm agglutinin-horseradish peroxidase complex (WGA-HRP). Injection sites within forelimb or hindlimb RNm regions were identified by microelectrode recording and confirmed by the position of labeled rubrospinal terminals. Additional injections into structures that project to, or receive input from, RNm confirmed the somatotopic organization of these pathways. The forelimb region of RNm receives input from the posteriolateral part of the anterior interpositus nucleus (NIA) and the intermediate part of the posterior interpositus nucleus (NIP). The hindlimb region of RNm receives input from anteriomedial NIA and medial NIP. Terminals of NIA cells densely fill all of RNm, but terminals of NIP cells form a half shell on the medial, ventral, and posterior borders of RNm without encroaching on RNm's lateral edge or central core. Forelimb and hindlimb RNm are reciprocally connected with the caudal cuneate and gracile nuclei respectively. There is little or no input to RNm from the medial or lateral cerebellar nuclei. Forelimb RNm, which also contains a face representation, projects to the lateral reticular nucleus, cell group f of the inferior vestibular nucleus, the facial nucleus, the main sensory nucleus of the trigeminal nerve, the caudal cuneate nucleus, the parvicellular reticular formation, and cervical segments of the spinal cord. A few fibers from forelimb RNm project directly to motor neurons in the lower cervical cord. Hindlimb RNm projects to only the lateral reticular nucleus, gracile nucleus, and lower spinal segments. Forelimb and hindlimb RNm project to different regions of the lateral reticular nucleus with some overlap.

Organization of ascending pathways to the forelimb area of the dorsal accessory olive in the cat.

The purpose of these experiments was to define the topography of cuneate and spinal projections to the forelimb representation in the rostral dorsal accessory olive (rDAO). We were interested in determining whether the spinal and cuneate inputs constitute a homogeneous afferent source, and whether there is evidence that they serve different functional roles. We were also interested in determining whether the somatotopy of rDAO is the result of a point-to-point projection from its afferent sources, or whether the projection suggests a reorganization of afferents at the olive. Single unit recording was used to identify specific regions of rDAO, and the topography of inputs to the identified regions was determined by using wheat germ agglutinin-horseradish peroxidase (WGA-HRP) as a tracer. The results from retrograde tracing were confirmed by using WGA-HRP as an anterograde tracer from input sources. The cuneate and spinal neurons providing input to rDAO constitute two distinct neural populations. One consists of cells in the caudal cuneate nucleus and lamina VI of the rostral two cervical segments, the other consists of cells in the rostral cuneate nucleus. The cells in the caudal cuneate nucleus and the rostral cervical segments are large, multipolar neurons that form a single column of rDAO input cells. The column of cells projects to the contralateral rDAO in a topographic fashion with rostral regions of the column projecting to rostral rDAO, which contains cells that respond to somatosensory stimulation of the contralateral shoulder, trunk, and proximal forelimb. Caudal regions of the column project to caudal rDAO, which contains cells that respond to stimulation of the distal forelimb. Despite this topography, there is a large degree of overlap in the terminations from neighboring regions of the input column, indicating that a major reorganization occurs at the rDAO. The projection from the rostral cuneate nucleus arises from small neurons that project bilaterally to rDAO, and the input from the rostral cuneate nucleus lacks a clear topography. We propose that input from the cell column is responsible for the somatosensory sensitivity of rDAO neurons, whereas input from rostral cuneate is most likely modulatory, probably inhibitory, in nature.

Selective projections from the cat red nucleus to digit motor neurons.

Classical studies of the cat rubrospinal tract describe dense terminations in spinal laminae V-VII and an absence of any significant projection to lamina IX. In contrast, our recent studies, utilizing the anterograde transport of wheat germ agglutinin conjugated with horseradish peroxidase, have demonstrated a consistent and circumscribed area of label in lamina IX at caudal cervical segments. The present study was undertaken to determine the distribution of rubrospinal terminals among motor neurons in lamina IX as well as to identify the likely target muscles of those motor neurons located near rubrospinal terminals. We injected wheat germ agglutinin-horseradish peroxidase into the red nucleus and unconjugated horseradish peroxidase into selected forearm muscles of the same side of the body. The locations of rubrospinal terminals showing anterograde label on one side of the spinal cord could then be compared with the locations of motor neurons showing retrograde label on the opposite side of the cord. The results demonstrated a clear focus of rubrospinal terminals in the lateral and dorsal portions of the ventral horn beginning at C8 and extending through rostral T1. No other segments of the spinal cord showed a focus of rubrospinal terminations in lamina IX. Retrogradely labeled motor neurons from the muscle injections showed that the rubrospinal terminals overlap extensively with motor neuronal pools supplying distal forearm muscles. Several lines of evidence indicate that the terminals are from rubrospinal fibers and are not due to transneuronal transport.

Construction of a reach-to-grasp.

Reaching out to grasp an object requires the coordinated action of many different areas of the brain. Each area probably makes a unique contribution to the control of limb movement. We have studied the discharge of interpositus, the output nucleus of intermediate cerebellum, and magnocellular red nucleus, which connects interpositus to the spinal cord. The neurons in these areas discharge at high rates only if a hand movement is included with the reach, and discharge pattern is similar regardless of reach direction. Therefore, interpositus and magnocellular red nucleus are involved primarily in grasp control during the reach-to-grasp; other areas must be controlling the reach. Several other areas of the brain, including the reticular formation, rostral mesencephalon, superior colliculus and motor cortex, are active during reaching. The output from these descending systems converges on interneurons at spinal level C1 and C2 which, in turn, project to level C6, where motor neurons innervating shoulder muscles are located. We hypothesize that reach control is achieved by the convergence of multiple descending pathways onto a complex spinal interneuronal system.

Activity of primate magnocellular red nucleus related to hand and finger movements.

Single cells were recorded in the magnocellular red nucleus (RNm) of two cynomolgus monkeys using tungsten microelectrodes. The first monkey was trained to press finger switches and to operate a push-pull device. Comparison of responses while operating the two devices demonstrated a strong distal bias. The finger device elicited large modulations in discharge (greater than or equal to 50 impulses/s) in 75% of the sampled neurons. Most cells fired optimally during thumb switch operation, but also fired vigorously in association with other switch operations. The left motor cortex was removed from the second monkey 18 months prior to microelectrode recording. Cells in the cortically denervated RNm discharged vigorously in association with grouped finger movements that opened and closed the affected right hand. These results coupled with our previous findings suggest that the RNm is preferentially linked to distal limb muscles, and the primary role of the forelimb zone may be to control coordinated hand function including grouped movements of the fingers.

Functional and anatomic differentiation between parvicellular and magnocellular regions of red nucleus in the monkey.

Single unit recording in awake monkeys was used to search for functional differences between the two divisions of the red nucleus, and anatomical tracing of WGA-HRP was used to investigate inputs to the two divisions. We studied a total of 323 units in 4 red nuclei of two monkeys. Recording sites were identified in histological sections by the locations of lesions and the reconstruction of electrode tracks. Of the units in the RNm 98.5% discharged in high frequency bursts during movement. Only 52% showed reliable responses to somatosensory stimulation, and the responses observed were weaker than the movement-related discharge. None of the units recorded in the RNp showed strong movement-related discharge, and 51% were completely unresponsive during both motor and sensory tests. A dorsolateral group of medium-sized cells that overlaps the rostral half of the main RNm and the caudal pole of RNp appears to represent an extension of the magnocellular region. Retrograde transport of WGA-HRP indicated that some of these cells are rubrospinal neurons. Furthermore, the discharge properties of dorsolateral neurons are like the main RNm neurons, except for lower discharge rates and smaller spike amplitudes. Mouth movements are strongly represented in the dorsolateral region. Anterograde transport of WGA-HRP from the motor cortex demonstrated dense terminal label in RNp as contrasted with light label in RNm. Retrograde transport of WGA-HRP from RNm labeled many more cells in the cerebellar interpositus nucleus than in motor cortex. We concluded that input to RNm from the cerebellum is the likely source of the strong movement-related activity recorded from cells in the RNm. The absence of appreciable movement-related activity in parvicellular red nucleus provides a clear functional distinction between this division and the magnocellular division of the red nucleus.

Receptive fields of single cells from the face zone of the cat rostral dorsal accessory olive.

Natural stimulation was used to map the receptive fields of single cells recorded from the rostral medial portion of the dorsal accessory olive (rDAO) and the subjacent principal olive (PO) of the barbiturate anesthetized cat. Previous reports indicated a somatotopic mapping of the entire contralateral body within the rDAO which included a small face zone and a larger zone with a very precise map for the limbs. While concentrating on the face zone of the rDAO we confirmed the previously reported somatotopy (face: rostral and medial; forelimb: caudal and medial; hindlimb; caudal and lateral; and trunk: rostal and lateral) and found a somatotopy within, and adjacent to, the face zone. At the border between rDAO regions representing forelimb and face, cells with forelimb fields were found to lie dorsally to cells with facial fields. Within the rDAO face region, cells with large facial fields lie dorsally to cells with small facial fields. In both cases, the more ventral cells lie in the ventral lamella of the PO, which suggests a functional as well as physical continuity between rDAO and the ventral lamella of the PO. We therefore conclude that the face zone in the rDAO and the face zone in the PO form one continuous and complete map of the face with an orderly progression of receptive fields. Furthermore, we have found that stimulation of the red nucleus can inhibit rDAO cells with facial receptive fields just as it does cells with receptive fields from the rest of the body.

A sensitive low artifact TMB procedure for the demonstration of WGA-HRP in the CNS.

A TMB reaction with increased sensitivity and lower artifact can be obtained by dividing the Mesulam reaction into two stages. Use of the modified reaction with HRP conjugated wheat germ agglutinin (WGA-HRP) yields a powerful technique for anterograde and retrograde tracing.

Decussation of hind-limb and fore-limb fibers in the monkey corticospinal tract: relevance to cruciate paralysis.

Cruciate paralysis is a clinical entity in which patients with trauma to the anterior cervicomedullary junction present with weakness of the upper extremity greater than that of the lower extremity. The underlying mechanism of this paralysis is commonly thought to be selective damage affecting the upper-extremity nerve fibers in the pyramidal decussation. The authors examined the anatomical basis of cruciate paralysis in six New World squirrel monkeys and two Old World cynomolgus monkeys. No evidence for a differential decussation of fore-limb and hind-limb fibers was found. Thus, there is no obvious anatomical explanation for cruciate palsy. The results do suggest two alternative explanations for cruciate paralysis: 1) selective damage to neural areas involving the internuncial cells, the central gray area, and the cuneate nucleus, or 2) injury to the ventral corticospinal tract.

Psychological morbidity following laryngectomy: a pilot study.

This study evaluated the nature and extent of problems faced by patients following discharge from hospital following laryngectomy. Semi-structured interviews investigated the practical and psychological concerns of a cohort of laryngectomy patients in a district general hospital. A number of simple practical measures can be employed to reduce early hospital re-admission following laryngectomy. Psychological morbidity is an important cause of low quality of life following laryngectomy. Formal psychological treatment could be of benefit in the management of these patients.