Caudate Lesions Research Articles

The caudate nucleus and acquisition of win-shift radial-maze behavior: Effect of exposure to the reinforcer during maze adaptation

Rats with lesions of the caudate nucleus or sham lesions were trained on a win-shift radial-maze task following one of two types of maze-adaptation trials. In one adaptation condition, rats were allowed to obtain food from maze arms on an unlimited basis for 5 min on 2 consecutive days prior to the start of win-shift food trials. In this maze-adaptation condition, rats with lesions of the caudate nucleus exhibited a transient impairment in the acquisition of win-shift behavior. In a second maze-adaptation condition, different groups of caudate or sham rats were allowed to explore an empty maze for 5 min on 2 consecutive days prior to the start of win-shift food trials. In this maze-adaptation condition, caudate rats were not impaired in the acquisition of win-shift behavior. The role of reinforcers may be one difference in the operating principles that distinguish between caudate-nucleus and hippocampal memory systems.

Subtotal lesions of the amygdala: The rostral central nucleus in passive avoidance and ulceration

Rats received small bilateral electrolytic or ibotenate lesions of the rostral part of the amygdaloid central (rACE) or lateral (rAL) nuclei, or caudal part of the basolateral nuclei (cBL), or electrolytic lesions of the dorsal hippocampus (HIPP). All groups were tested in a drinking passive avoidance (PA) task that appears less sensitive to deficits in acquisition/retention or activity/spatial perception than are many other PA tasks, and more specifically sensitive to deficits in generation of fear. Consistent with this interpretation, performance in the task was facilitated, not deficient, in the HIPP group. Electrolytic lesions of rAL produced a mild deficit in PA, but ibotenate lesions did not, and neither did the more caudal lesions of the cBL groups. Ibotenate lesions of rACE did produce a deficit in PA, consistent with views of a role of this part of the amygdala in fear. Electrolytic lesions of rACE produced a very profound PA deficit and also blocked the rapid development of gastric erosions by water-restraint stress, effects that were not found with ibotenate lesions in this location. This suggests a particular contribution of fibers passing through rACE to some of the more marked effects of electrolytic lesions of rostrodorsal portions of the amygdala.

Double dissociation of fornix and caudate nucleus lesions on acquisition of two water maze tasks: further evidence for multiple memory systems.

The present study examined the effect of lesions of the caudate nucleus or fimbria-fornix on the acquisition of two water maze tasks. In both tasks, two rubber balls with different visual patterns were used as platforms (i.e., cues). The "correct" cue was attached to a submerged rectangular platform and could be mounted by an animal to escape the water. The "incorrect" cue was attached to a thin round pedestal and could not be mounted. In a spatial version of the task, the correct cue was located in the same quadrant of the maze on all trials, whereas the visual pattern on the cue was varied from trial to trial. Lesions of the fornix, but not the caudate nucleus, impaired acquisition of this spatial task in relation to control animals. In a simultaneous visual discrimination version of the task, the correct cue on all trials was one with a specific visual pattern, and the spatial location of the correct cue was varied from trial to trial. Lesions of the caudate nucleus, but not the fornix, impaired acquisition of this visual discrimination task in relation to control animals. The double dissociation observed supports the hypothesis that the hippocampus and caudate nucleus are parts of systems that differ in the type of memory they mediate.

Double dissociation of fornix and caudate nucleus lesions on acquisition of two water maze tasks: Further evidence for multiple memory systems.

Double dissociation of fornix and caudate nucleus lesions on acquisition of two water maze tasks: Further evidence for multiple memory systems.

The Role of the Caudate in Nonmotor Behaviors in Huntington’s Disease

Neuropsychologic data suggest an important role for the caudate nucleus (CN) in behavioral impairments in Huntington's disease (HD). These include abnormalities in executive function, egocentric visuospatial representations, communication, and retrieval of declarative memories, changes in personality, and psychiatric disturbances. Animal paradigms of CN lesions support a role for the CN in some of these behaviors. Current theories of basal ganglia function add explanatory value to the role of the CN in these behaviors. A disconnection of the caudate from limbic structures, including the amygdala may account for many nonmotor behaviors observed in HD.

The role of the caudate in nonmotor behaviors in Huntington's disease.

Neuropsychologic data suggest an important role for the caudate nucleus (CN) in behavioral impairments in Huntington's disease (HD). These include abnormalities in executive function, egocentric visuospatial representations, communication, and retrieval of declarative memories, changes in personality, and psychiatric disturbances. Animal paradigms of CN lesions support a role for the CN in some of these behaviors. Current theories of basal ganglia function add explanatory value to the role of the CN in these behaviors. A disconnection of the caudate from limbic structures, including the amygdala may account for many nonmotor behaviors observed in HD.

The effect of selective brainstem or spinal cord lesions on treadmill locomotion evoked by stimulation of the mesencephalic or pontomedullary locomotor regions

The descending pathways from the brainstem locomotor areas were investigated by utilizing reversible cooling (to block synaptic or fiber transmission) and irreversible subtotal lesions of the brainstem or spinal cord (C2-C3 level). Experiments were conducted on decerebrate cats induced to walk on a treadmill by electrical stimulation of the brainstem. Locomotion produced by stimulation of the mesencephalic locomotor region (MLR) was not abolished by caudal brainstem lesions that isolated the lateral tegmentum or by extended rostral/caudal dorsal hemisections of the spinal cord. These results demonstrate that the MLR does not require a pathway projecting through the lateral tegmentum of the brainstem or the dorsal half of the spinal cord, as previously suggested (Mori et al., 1977, 1978b; Shik and Yagodnitsyn, 1978; Shik, 1983). Rather, the results indicate that the descending pathway originating from the MLR projects through the medial reticular formation (MedRF) and the ventral half of the spinal cord. Locomotion produced by stimulation of the pontomedullary locomotor region (PLR) was blocked by reversible cooling of either the MedRF or the ventrolateral funiculus of the spinal cord. In some cases, locomotion could be produced by stimulation of the PLR following extended dorsal hemisections of the spinal cord. These results demonstrate that the PLR can also produce locomotion by activation of cells in the MedRF that project caudally through the ventral half of the spinal cord. Stimulation of the PLR could also elicit locomotion following its surgical isolation from the MedRF of the brainstem. Furthermore, lesions of the dorsal spinal cord resulted in the loss of PLR-evoked locomotion in some, but not all, cases. Thus, an alternative projection of the PLR through the dorsal half of the spinal cord (Kazennikov et al., 1980, 1983a,b; Shik, 1983) cannot be ruled out. Overall, these results demonstrate that the PLR is not an essential component of the motor pathway originating from the MLR. The organizational scheme of "brainstem locomotor regions" is discussed in the context of recent information demonstrating a link between the sensory component of the trigeminal system and locomotor pathways (Noga et al., 1988).

Central nervous pathways underlying synchronization of human motor unit firing studied during voluntary contractions.

1. Motor unit firing has been studied during weak voluntary isometric contractions with pairs of needle electrodes in normal human subjects. 2. Pre- and post-stimulus time histograms of the firing time of firing of one event unit before and after the time of firing of another reference (stimulus) unit showed a clear central peak, indicative of synchronization. 3. Synchronization was seen in all the muscles studied. The mean strength of synchronization, expressed as the number of concomitant discharges of the two units as a proportion of the number of stimulus unit discharges, was 0.095 extra event unit spikes/reference unit spike (range 0.042-0.28) for first dorsal interosseous muscle, 0.016 extra event unit spikes per reference unit spike (range 0-0.043) for medial gastrocnemius and 0.056 extra event unit spikes per reference unit spike range 0.016-0.079) for tibialis anterior. 4. The mean duration of synchronization was 11.3 ms (range 5.0-21.0 ms) for first dorsal interosseous, 10.3 ms (range 3.5-21.7 ms) for medial gastrocnemious and 13.5 ms (range 3.0-25.0) for tibialis anterior. 5. Seven patients with radiographically and clinically identified central strokes were studied while they made weak voluntary isometric contractions. The duration of synchronization was significantly prolonged compared to that found in normal subjects. In these stroke patients the mean duration of synchronization on the affected side was longer than that seen in the normal subjects, and in first dorsal interosseous muscle was 35.4 ms (range 12.0-65.0 ms), in medial gastrocnemius was 21.3 ms (range 4.0-43.0 ms) and in tibialis anterior was 28.8 ms (range 14.0-49.0 ms). 6. The mean strength of synchronization of motor unit discharge was found to be greater in the stroke patients than that seen in the normal subjects for first dorsal interosseous muscle (0.161 extra event unit spikes per reference unit spike, range 0.017-0.391) and for medial gastrocnemius (0.030 extra event unit spikes per reference unit spike) but only significantly so when pooled data was compared. There was no difference in the strength of motor unit synchronization in tibialis anterior between stroke patients and normal subjects. 7. Broad duration synchronization among first dorsal interosseous motor units was also found in a patient with a rostral cervical spine lesion (total duration range 43-46 ms; n = 2), but not in a patient with a caudal (thoracic) spinal lesion.(ABSTRACT TRUNCATED AT 400 WORDS)

Lesioning of the Striatum Reverses Motor Asymmetry in the6‐Hydroxydopamine Rodent Model of Parkinsonism

In the rat several paradigms of grafting of adrenal medulla into the striatum were studied following the induction of a parkinsonian model, using a unilateral 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra . Direct autologous grafting of adrenal medulla into the caudate-putamen complex, a radiofrequency lesion of the striatum alone, and a radiofrequency lesion followed by delayed grafting of adrenal medulla were compared by analyzing rotational behavior. Direct grafting of adrenal medulla produced an overall reduction in apomorphine induced turning behavior by 43.5% when compared with controls. Radiofrequency lesioning of the striatum without graft showed the best improvement over control animals with a 92% reduction in the total number of rotations induced by apomorphine. Delayed grafting into the caudate lesion cavity also produced a dramatic reduction in motor asymmetry but did not improve the behavioral outcome over that of the lesion alone. Animals receiving only radiofrequency lesions exhibited a band of increased tyrosine hydroxylase like immunoreactivity bordering the lesion cavity. Graft survival was limited in the nonlesioned animals but appeared enhanced in the animals whose striatum was previously lesioned. Lesion location within the striatum influenced the behavioral outcome. Large reductions in apomorphine-induced rotations could result from small lesions of the dorso-lateral striatum. These findings indicate that selective destruction of the caudate-putamen complex without tissue transplantation produces a dramatic reduction in the motor asymmetry of 6-OHDA treated rats. Suggested explanations for the decrease in induced rotational behavior with radiofrequency lesions include a decrease in the number of striatal dopamine receptors following cell destruction and lesioninduced recovery of host dopaminergic afferents. Striatal damage in critical areas can reverse some of the motor behavior associated with the 6-OHDA model and needs to be considered when evaluating the effects of neural grafting in this model.

Changes in instrumentally and classically conditioned limb-flexion responses following inferior olivary lesions and olivocerebellar tractotomy in the cat

Lesions were placed in various parts of the inferior olivary nucleus and olivocerebellar tract in an attempt to define further the role of the inferior olive in the performance of a conditioned limb-flexion response (LFR) in cats. Thirty-two cats were trained to make an LFR using either classical or instrumental conditioning. The conditioned stimulus (CS) was a tone, and the unconditioned stimulus (US), a shock to the forelimb. Following training, lesions were placed in various parts of the inferior olivary nucleus in 20 animals (radio frequency lesions, 17; electrolytic lesions, 3). Midline section of the olivocerebellar tract was carried out in 12 animals. The degree of conditioned-response (CR) loss resulting from a given lesion was closely related to the precise locus of the lesion. Rostromedial olivary lesions, which included the spino- and cortico-olivary forelimb projection zones and the olivocerebellar projection area, resulted in varying degrees of CR loss (from partial to near total), deregulation of response latency, and a significant reduction of response amplitude. The CR deficit and degree of post-operative CR recovery were directly related to the extent of damage to this part of the rostromedial olive. Lesions restricted to the caudal olive or to caudal levels of the olivo-cerebellar tract resulted in no postoperative CR deficits. Animals with caudal lesions, however, showed more severe general motor deficits postoperatively than did those with rostromedial lesions and loss of the CR. Prolonged training of animals with the most complete CR deficits resulted in some relearning, but response patterns were typified by long-latency, low-amplitude CRs and a highly unstable response pattern.

Epidemiology of spinal cord lesions in Denmark

Denmark has a population of about 5.2 million. The rehabilitation of spinal cord injured (SCI) takes place in two specialised rehabilitation hospitals. The incidence of new traumatic SCI admitted to these hospitals in the period 1975-1984 was 9.2 per million per year. During this period 92 Danes with non-traumatic and 268 with newly sustained traumatic spinal cord lesions were admitted to the rehabilitation hospital in Hornboek, which uptake area corresponded to South and East Denmark and Greenland and the Faroe Islands. Among the traumatic SCI 47% were due to traffic accidents, 23% to falls to a level below, 8% to attempted suicides, 6% to shallow water diving, and 6% to sporting accidents. The number of SCI caused by traffic accidents was found to decrease coincidently with the introduction of general speed limits and compulsory seat belt wearing. The male/female ratio was for the traumatic SCI 3.3, which was significantly lower than in the preceding 10-year period. 40% of all traumatic SCI were sustained at 15-24 years of age, and 51% had tetraplegia. Traffic accidents gave rise to more cervical, and falls to more caudal lesions. 41% of the traumatic SCI had an improvement in their neurological status after their admission to the neurosurgical department until the discharge from the rehabilitation hospital. Those with incomplete lesions showed greater improvement than those with complete lesions regardless of the level. Complete cervical lesions had significant better remissions than complete thoracic/lumbar lesions.

Cortical, hippocampal, and striatal mediation of schedule-induced behaviors.

The sequential occurrence of licking, locomotor activity, entries into the food magazine (panel pressing), and nonreenforced lever pressing engendered by a periodic schedule of food presentation were measured in each 60-s interreenforcement interval in normal and brain-damaged rats. The development of these responses was measured over 20 days in different groups of food-deprived rats that had received aspirations of the hippocampus, small lesions of the cortex overlying the hippocampus (hippocampal-operated control group), decortication, or 6-hydroxy-dopamine lesions of the caudate nucleus or nucleus accumbens. All lesions produced distinctive patterns of change in the measured behaviors, and dissociations as well as similarities in their effects were evident. These results are discussed with respect to dissociations in the motor and motivational effects of the various lesions and in terms of contemporary hypotheses of schedule-induced behavior.

MAGNETIC BRAIN STIMULA AND IMMUNE RESPONSE IN THE RAT WITH LESIONED BRAIN STRUCTURES

Rats with electrolytic anterior hypothalamic lesions showed a suppressed Arthus reaction, delayed skin hypersensitivity, and antibody production at 7, 14 and 21 days after immunization with bovine serum albumin (BSA) in complete Freud's adjuvant (CFA). However, magnetic treatment of the brain of rats with anterior hypothalamic or caudate nucleus lesions increased both humoral and cellular sensitivity reactions. These data indicate that magnetic stimulation of the brain is capable of modulating immune functions.

Lesions of the caudate nucleus selectively impair “reference memory” acquisition in the radial maze

Groups of Long-Evans rats with bilateral lesions of the caudate nucleus, sham lesions, or no lesions were given one trial per day in an eight-arm radial maze. The same four maze arms were baited on each trial. The remaining four arms never contained food. Optimal performance required animals to enter each of the baited arms only once on each trial and to avoid entering the arms in the unbaited set. Rats with caudate lesions learned to enter each of the baited arms only once on each trial. However, these rats were severely impaired in learning to avoid entering the arms in the unbaited set. Implications for dual-memory theories are discussed.

Memory facilitation produced by dopamine agonists: Role of receptor subtype and mnemonic requirements

The role of dopamine (DA) receptor subtypes in the acquisition of two memory tasks in the 8-arm radial maze was examined. The receptors were manipulated with posttraining, subcutaneous injections of an indirect DA receptor agonist (D-amphetamine), a selective D2 receptor agonist (LY171555), and a selective D1 receptor agonist (SKF-38393). On a win-stay task (sensitive to caudate nucleus lesions) a light cue signalled the location of food in 4 randomly selected arms on each trial. Rats were given one trial per day and injected after training on day 5. D-Amphetamine (2.0 mg/kg) and LY171555 (2.0 mg/kg) improved performance relative to controls; however SKF-38393 (1–4 mg/kg) had no effect on the acquisition of win-stay behavior. On a win-shift task (sensitive to fornix/hippocampal lesions) a delay of 18 hr was imposed between the first 4 and second 4 choices; drugs were injected after the first 4 choices. D-Amphetamine (1.0 mg/kg) and LY171555 (2.0 mg/kg) significantly improved retention relative to controls. SKF-38393 (1–4 mg/kg) had no effect on win-shift retention. These results suggest that the memory-improving properties of DA agonists on tasks sensitive to both hippocampal and caudate lesions are mediated by the D2 receptor.

Differential effects of fornix and caudate nucleus lesions on two radial maze tasks: evidence for multiple memory systems

The present experiments were designed to examine the hypothesis that the mammalian brain contains anatomically distinct memory systems. Rats with bilateral lesions of caudate nucleus or fimbria-fornix and a control group were tested postoperatively on 1 of 2 versions of the radial maze task. In a standard win-shift version, each of the 8 arms of the maze was baited once, and the number of errors (revisits) in the first 8 choices of each trial was recorded. Fimbria-fornix rats were impaired in choice accuracy, while caudate animals were unimpaired relative to controls. Different groups of rats with similar lesions were tested on a newly developed win-stay version of the radial maze, in which the location of 4 randomly selected baited arms was signaled by a light at the entrance to each arm, and which required rats to revisit arms in which reinforcement had been previously acquired within a trial. Rats with fimbria-fornix lesions were superior to controls in choice accuracy on the win-stay radial maze task, while caudate animals were impaired relative to controls. The results demonstrate a double dissociation of the mnemonic functions of the hippocampus and caudate nucleus. Some implications of the presence of 2 memory systems in the mammalian brain are discussed.

Neurobehavioral changes associated with caudate lesions.

We report behavioral and cognitive characteristics of 12 patients with caudate nuclei lesions, 11 unilateral and one bilateral. These patients developed an acute behavioral change characterized by apathy, disinhibition, or a major affective disturbance. The pattern of personality change correlated with size and location of lesion within the caudate but not the laterality. Seven patients were further compared with matched controls on a series of neuropsychological tests. Their performance was impaired on tasks requiring planning and sequencing. They had short attention spans and decreased free recall of episodic and semantic items with good recognition memory scores. Similar behavioral and cognitive changes also occur in early Huntington's disease, frontal-lesioned patients, and caudate-lesioned animals, and correspond to disturbances of specific frontal-caudate circuits. These results implicate the caudate nuclei in mediating prefrontal behaviors and possibly in the conceptual integration of memories.

Blocking of morphine-induced locomotor hyperactivity by amygdaloid lesions in C57BL/6 mice

Bilateral lesions of the amygdaloid complex in C57BL/6 mice prevented the occurrence of morphine-induced hypermotility (running fit). This effect, that was different from that observed after hippocampal lesions but similar to that observed after caudate lesions, confirms the role of the basal ganglia catecholaminergic system in the development of the motor stimulation consecutive to the administration of this opiate receptor agonist.

Allocentric spatial and tactile memory impairments in rats with dorsal caudate lesions are affected by preoperative behavioral training.

Rats with caudate lesions and pretrained for 36 trials demonstrated impaired performance on the "reference memory" or invariant aspect of a 12-arm radial maze and normal performance on the "working memory" or variable aspect of the maze. Rats with caudate lesions and no pretraining were also impaired on an invariant tactile discrimination in a T maze, but they were not impaired on the variable goal-arm choice of the T maze. More extensive preoperative training ameliorated behavioral deficits of rats with caudate lesions in the T maze and radial arm maze. Results showed that behavioral impairment after damage to the caudate is not restricted to egocentric tasks as previously suggested, but the caudate seems to be involved in the initial acquisition of information that is invariant over many trials.

Allocentric spatial and tactile memory impairments in rats with dorsal caudate lesions are affected by preoperative behavioral training.

Rats with caudate lesions and pretrained for 36 trials demonstrated impaired performance on the "reference memory" or invariant aspect of a 12-arm radial maze and normal performance on the "working memory" or variable aspect of the maze. Rats with caudate lesions and no pretraining were also impaired on an invariant tactile discrimination in a T maze, but they were not impaired on the variable goal-arm choice of the T maze. More extensive preoperative training ameliorated behavioral deficits of rats with caudate lesions in the T maze and radial arm maze. Results showed that behavioral impairment after damage to the caudate is not restricted to egocentric tasks as previously suggested, but the caudate seems to be involved in the initial acquisition of information that is invariant over many trials.