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T W Robbins

Publications and source records attributed to T W Robbins.

At least 253 records · Page 14Linked to original sources
PubMed1992

Cognitive performance in multiple system atrophy.

The cognitive performance of a group of patients with multiple system atrophy (MSA) of striato-nigral predominance was compared with that of age and IQ matched control subjects, using three tests sensitive to frontal lobe dysfunction and a battery sensitive to memory and learning deficits in Parkinson's disease and dementia of the Alzheimer type. The MSA group showed significant deficits in all three of the tests previously shown to be sensitive to frontal lobe dysfunction. Thus, a significant proportion of patients from the MSA group failed an attentional set-shifting test, specifically at the stage when an extra-dimensional shift was required. They were also impaired in a subject-ordered test of spatial working memory. The MSA group showed deficits mostly confined to measures of speed of thinking, rather than accuracy, on the Tower of London task. These deficits were seen in the absence of consistent impairments in language or visual perception. Moreover, the MSA group showed no significant deficits in tests of spatial and pattern recognition previously shown to be sensitive to patients early in the course of probable Alzheimer's disease and only a few patients exhibited impairment on the Warrington Recognition Memory Test. There were impairments on other tests of visual memory and learning relative to matched controls, but these could not easily be related to fundamental deficits of memory or learning. Thus, on a matching-to-sample task the patients were impaired at simultaneous but not delayed matching to sample, whereas difficulties in a pattern-location learning task were more evident at its initial, easier stages. The MSA group showed no consistent evidence of intellectual deterioration as assessed from their performance on subtests of the Wechsler Adult Intelligence Scale (WAIS) and the National Adult Reading Test (NART). Consideration of individual cases showed that there was some heterogeneity in the pattern of deficits in the MSA group, with one patient showing no impairment, even in the face of considerable physical disability. The results show a distinctive pattern of cognitive deficits, unlike those previously seen using the same tests in patients with Parkinson's and Alzheimer's diseases, and suggesting a prominent frontal-lobe-like component. The implications for concepts of 'subcortical' dementia and 'fronto-striatal' cognitive dysfunction are considered.

Adult↗
PubMed1992

Fronto-striatal cognitive deficits at different stages of Parkinson's disease.

Groups of patients with idiopathic Parkinson's disease, either medicated or unmedicated, were compared with matched groups of normal controls on a computerized battery previously shown to be sensitive to frontal lobe dysfunction, including tests of planning, spatial working memory and attentional set-shifting. In a series of problems based on the 'Tower of London' test, medicated patients with Parkinson's disease were shown to be impaired in the amount of time spent thinking about (planning) the solution to each problem. Additionally, an impairment in terms of the accuracy of the solution produced on this test was only evident in those patients with more severe clinical symptoms and was accompanied by deficits in an associated test of spatial short-term memory. Medicated patients with both mild and severe clinical symptoms were also impaired on a related test of spatial working memory. In contrast, a group of patients who were unmedicated and 'early in the course' of the disease were unimpaired in all three of these tests. However, all three Parkinson's disease groups were impaired in the test of attentional set-shifting ability, although unimpaired in a test of pattern recognition which is insensitive to frontal lobe damage. These data are compared with those previously published from a group of young neurosurgical patients with localized excisions of the frontal lobes and are discussed in terms of the specific nature of the cognitive deficit at different stages of Parkinson's disease.

Aged↗
PubMed1992

Striatal graft-associated recovery of a lesion-induced performance deficit in the rat requires learning to use the transplant.

Peformance in a prelearned choice reaction time task was studied 6 months after surgery in rats with ibotenate-induced lesions of the striatum either with or without striatal grafts, and in sham-operated controls. The long postoperative interval allowed full transplant maturation and the establishment of appropriate connections by the transplants. The animals were trained prior to surgery on a visual choice reaction time task which requires that a movement is made away from stimuli signalling reward. The use of multiple measures allowed a thorough analysis of several aspects of the animals' performance. Whilst sham-operated control animals recovered normal (preoperative) performance rapidly, the lesioned animals had a severe performance deficit. Although the transplanted animals were initially at least as deficient in performance as the lesioned group, repeated testing led to an amelioration of the lesion-induced deficit according to two distinct measures of spatial bias and reaction time. On a third measure, latency to complete the lateralized movement, the grafted group were initially worse than the lesioned group but repeated testing resulted in significant recovery. These results suggest that postoperative training may help to optimize the efficacy of graft-induced recovery, and that animals may need to learn to use a transplant in order for it to confer functional benefit in complex prelearned tasks.

Journal Article↗
PubMed1992

Forebrain norepinephrine: role in controlled information processing in the rat.

A series of experiments examined the effects of 6-hydroxydopamine (6-OHDA)-induced depletion of forebrain norepinephrine (NE) on the performance of a visual detection (spatial localization) task. The behavioral paradigm used was an analogue of Leonard's 5-choice serial reaction time task for humans. The 6-OHDA lesion of the dorsal noradrenergic bundle (DNAB) produced a 98% depletion of the NE content in the neocortex, and a much smaller depletion (32%) of the NE content in the hypothalamus. As reported previously, performance of visual discrimination was unaffected by DNAB lesions, even when the discrimination was made more difficult by decreasing the intensity of the visual stimuli. However, the lesion produced a significant decrease in accuracy and a significant increase in omissions when a burst of loud white noise was presented just prior to the onset of the visual discriminanda. Similarly, a significant decrease in discriminative accuracy was produced in the rats with forebrain NE depletion by systemic administration of the psychomotor stimulant, d-amphetamine (0.2 to 0.8 mg/kg). In both of these experiments, the lesion-induced discrimination impairment was not magnified by reducing the brightness of the visual discriminanda, suggesting that the behavioral impairment was not caused by a decreased ability to detect the visual stimuli. In addition, the lesion impaired discriminative accuracy when the visual discriminanda were presented at an unpredictable rate. The implications of these behavioral impairments produced by forebrain NE depletion for theories of catecholamine involvement in attentional processes and arousal are discussed in terms of a possible role for the DNAB in controlled or "effortful" processing.

Acoustic Stimulation↗
PubMed1991

Dissociable roles of the ventral, medial and lateral striatum on the acquisition and performance of a complex visual stimulus-response habit.

The effects of discrete bilateral ibotenic acid lesions to 3 areas of striatum were examined on a conditional visual discrimination task involving temporal frequency (SLOW vs FAST flashes) that had previously been shown to be sensitive to the effects of dorsal striatal dopamine depletion. Two of the groups, namely, those with nucleus accumbens (ACC) and lateral caudate-putamen (LCP) lesions, were very disrupted in the acquisition of the task. The nature of the respective impairments of the 2 groups was dissociable, however. The performance of the ACC group could be improved either by manipulations of stimulus duration or inter-stimulus interval, implying an attentional deficit. In contrast, the rats with lesions of the LCP were not significantly improved by any of the behavioural challenges. Their performance was characterised by a bias to respond to the SLOW discriminandum. Under conditions of non-reward, the LCP group extinguished their responding at a similar rate to control rats whereas the ACC group were very much more persistent. Lesions of the medial caudate-putamen failed to affect any index of performance significantly. These data suggest that the LCP is necessary for the acquisition of arbitrary stimulus-response rules and that damage to an equivalent area in humans, such as in Huntington's disease, may explain deficits of procedural memory. The second part of the experiment investigated the effects of ACC lesions on established performance of the schedule. The lesioned group behaved identically to the ACC group that had been lesioned prior to acquisition, both in terms of accuracy and degree of persistence in extinction, further implying the role of attentional factors and inflexibility in the lesion-induced deficit.

Animals↗
PubMed1991

Telencephalic but not diencephalic noradrenaline depletion enhances behavioural but not endocrine measures of fear conditioning to contextual stimuli.

Three experiments investigated the effects of primarily cortical or hypothalamic noradrenaline depletion on aversive conditioning of explicit and contextual stimuli in rats. In Expt. 1, two groups of rats were trained to respond under a variable interval schedule for food reward. One group of rats subsequently received injections of 6-hydroxydopamine into the dorsal noradrenergic bundle, resulting in profound depletion of cortical noradrenaline; the second group received vehicle injections. All rats were exposed to 5 pairings of an auditory stimulus (CS) and footshock (UCS) in a distinctive environment (the dark chamber of a place preference apparatus). During testing in a separate, neutral environment, DNAB-lesioned rats suppressed responding for food reward, in the presence of the aversive CS, to a greater degree than controls. Lesioned rats also showed a greater aversion to the distinctive environment in which they were shocked. In contrast, plasma corticosterone concentrations, measured immediately following each of these behavioural tests, revealed no differences between DNAB-lesioned and control rats. Expt. 2 showed that the DNAB lesion did not affect habituation to the light chamber of the place preference apparatus used in Expt. 1. Expt. 3 showed that 6-OHDA injection into the ventral noradrenergic bundle component of the central tegmental tract, which damages primarily the noradrenergic innervation of hypothalamus, had no effect on either behavioural or endocrine responses to conditioned aversive, explicit or contextual cues. The results are discussed in relation to other reports of the effects of DNAB lesions on simple associative learning in an aversive context.

Animals↗
PubMed1991

Behavioural rigidity and rule-learning deficits following isolation-rearing in the rat: neurochemical correlates.

Isolation-reared rats were compared to those reared in social groups on the acquisition of a conditional visual discrimination (Expt. I), a simultaneous (simple) light/dark discrimination and serial reversal learning (Expt. II). In Expt. I, rats reared in social isolation made more errors during the acquisition of the conditional discrimination but did reach a level of accurate performance which was comparable with that of socially-reared rats. Discrimination performance in isolates was less disruptable by manipulations of the task requirements. Reducing the number of stimulus lights or the introduction of a distracting stimulus increased the number of errors committed by socially-reared rats but did not significantly affect accuracy in isolates. Performance in isolated rats was also remarkably resistant to changes in motivational variables. Isolates responded more frequently during conditions of extinction and were virtually unaffected by pre-feeding prior to testing. In Expt. II, isolation-reared rats were not impaired in the acquisition of a simultaneous discrimination but unlike socially-reared rats isolates failed to show improvement with successive reversals of this discrimination. Isolates exhibited stronger position habits than socially-reared rats following reversal of the contingencies. These results of these two experiments combined have demonstrated a specific impairment in rule learning in isolates. Isolated rats were not impaired on a simultaneous discrimination in which accurate performance can be achieved simply by approaching the stimulus associated with reinforcement, but performed worse than controls on both the conditional discrimination and on serial reversal learning, another form of conditional task. In both of these latter tasks each stimulus becomes equally associated with reward and therefore performance can be improved by learning a rule. Post-mortem neurochemical measurements made at the completion of Expt. II revealed selective alterations in dopaminergic, serotoninergic and cholinergic markers in isolated rats. Correlational analyses indicated specific relationships between neurochemical and behavioural measurements.

Animals↗
PubMed1991

Potentiation of the effects of reward-related stimuli by dopaminergic-dependent mechanisms in the nucleus accumbens.

Three experiments examined the behavioural, pharmacological and neural specificity of the previously reported potentiation of responding with conditioned reinforcement following intra-accumbens d-amphetamine, by studying the effects of intra-accumbens dopamine (DA) and noradrenaline, using an acquisition of a new response procedure. In experiment 1, the effects of intra-cerebral DA infusions (5, 20, 50 micrograms/2 microliters) were compared in four conditions: (i) intra-accumbens DA following positive pairing of the conditioned stimulus (CS) and water during training; (ii) as (i) but also following a systemic dose of the DA receptor antagonist alpha-flupenthixol; (iii) intra-accumbens DA following random pairing of the CS and water during training; and (iv) as (i) but with intra-caudate rather than intra-accumbens DA. The results showed that only with intra-accumbens DA in the positive pairing condition was there a significant dose-dependent increase in responding. In experiment 2, the effects of a higher range of doses (20, 100, 200 micrograms) and smaller infusion volume (5, 25, 50 micrograms/l microliters) of intra-accumbens DA were studied, in comparison with a similar range of doses (5, 25, 50 micrograms/l microliters) of intra-accumbens noradrenaline (NA). Only DA produced a selective, dose-dependent increase in responding with conditioned reinforcement. In experiment 3 neurotoxic lesions of the dorsal noradrenergic bundle (DNAB) using 6-hydroxydopamine producing profound (about 90%) depletion of cortical and nucleus accumbens NA levels had no effect on the increased responding with conditioned reinforcement produced by intra-accumbens d-amphetamine (3, 10, 30 micrograms/l microliters).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Extra-dimensional versus intra-dimensional set shifting performance following frontal lobe excisions, temporal lobe excisions or amygdalo-hippocampectomy in man.

Attentional "set" shifting was assessed in a group of 20 neurosurgical patients with localized excisions of the frontal lobes, a group of 20 patients with unilateral temporal lobe lesions and a group of 11 patients who had undergone amygdalo-hippocampus removal. These three patient groups were compared with groups of both young (age-matched) and elderly normal control volunteers on a computerized test of visual discrimination learning involving both an intra- and an extra-dimensional shift. The frontal lobe group were selectively impaired in their ability to shift response set to a previously irrelevant dimension but not to shift attention to new exemplars of a previously relevant dimension. A similar pattern was observed in the elderly group of normal control volunteers. By comparison, both the temporal lobe patients and the amygdalo-hippocampectomy patients were unimpaired in their ability to perform either shift, although both groups had significantly prolonged selection latencies at the extra-dimensional shift stage of the task. These data are compared to previous findings from patients with idiopathic Parkinson's disease and are discussed in terms of a specific attentional set shifting deficit following frontal lobe damage.

Adult↗
PubMed1991

Frontal lobe function in Korsakoff and non-Korsakoff alcoholics: planning and spatial working memory.

Groups of Korsakoff (KS) and non-Korsakoff alcoholics (ALC) and a group of normal volunteers, matched for age and verbal IQ, were tested on traditional neuropsychological tests of frontal lobe function and on computerized tests of planning (the Tower of London task) and spatial working memory. KS demonstrated deficits on the planning task which could not be explained by abnormalities of memory, including spatial span, or by visuoperceptive disturbances. KS were also impaired on the spatial working memory task, in part because of the failure to adopt an organized strategy. ALC exhibited fewer impairments which could not be attributed to deficits in either planning or spatial working memory. On Nelson's modified Wisconsin Card Sorting Task, KS and ALC achieved fewer categories than controls but only KS made perseverative errors. The data suggest that in the alcoholic Korsakoff's syndrome there is a specific disturbance of frontal-lobe function in addition to amnesia. The impairment seen in chronic alcoholics without Korsakoff's syndrome, on the other hand, do not reflect specific frontal dysfunction.

Adult↗
PubMed1991

Sensitization of amphetamine-stereotypy reduces plasma corticosterone: implications for stereotypy as a coping response.

The potential coping functions of amphetamine-induced stereotypy were investigated using a physiological index of stress or arousal, plasma corticosterone level. A series of five injections of d-amphetamine was used to enhance stereotyped behavior in control animals as well as in rats with bilateral dopamine-depleting lesions of the caudate-putamen. This regimen of amphetamine injections significantly increased stereotyped behavior and also reduced the normal elevation in corticosterone produced by treatment with d-amphetamine. This effect was apparent in both control and lesioned animals. These results support the hypothesis that amphetamine-induced stereotyped behavior functions to reduce stress or arousal and additionally suggest that this effect is largely independent of underlying dopaminergic mechanisms.

Adaptation, Psychological↗
PubMed1991

The basal forebrain-cortical cholinergic system: interpreting the functional consequences of excitotoxic lesions.

Ibotenic acid and kainic acid lesions of the basal forebrain induce profound deficits in performance on a wide variety of tasks involving discrimination learning and memory. These observations have been widely taken to reflect damage of cholinergic projections from the nucleus basalis magnocellularis (NBM) to the neocortex, and to provide an animal model of dementia. However, injections of the toxins quisqualic acid and, more recently, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) into the same site, which produce at least as extensive cholinergic cell loss, induce only marginal impairments on the same range of cognitive tasks. Further analysis suggests that the cholinergic regulation of the neocortex may influence specific aspects of discrimination learning and visual attention. Conversely, we propose that many of the functional consequences of ibotenic acid lesions on mnemonic tasks cannot be attributed to disruption of basal forebrain cholinergic systems, but may instead result from damage in the globus pallidus to corticostriatal output pathways.

Animals↗
PubMed1991

The basolateral amygdala-ventral striatal system and conditioned place preference: further evidence of limbic-striatal interactions underlying reward-related processes.

The effects on the expression of a conditioned place preference of bilateral, excitotoxic amino acid-induced lesions of the basolateral region of the amygdala, or the ventral striatum, or asymmetric, unilateral lesions of both structures were studied. The place preference was conditioned by exposing hungry rats to sucrose in a distinctive environment. Following acquisition, bilateral quisqualate-induced lesions of the basolateral amygdala, as well as bilateral quinolinate-induced lesions of the ventral striatum, abolished the conditioned place preference. Bilateral ventromedial, but not dorsolateral, quinolinate-induced caudate-putamen lesions attenuated the place preference. Combining a unilateral lesion of the basolateral amygdala with a contralateral lesion of the ventral striatum also disrupted the conditioned place preference. These data provide further support for the hypothesis that the basolateral amygdala and ventral striatum are important parts of a neural system subserving stimulus-reward associations.

Amygdala↗
PubMed1991

Dissociable effects on spatial maze and passive avoidance acquisition and retention following AMPA- and ibotenic acid-induced excitotoxic lesions of the basal forebrain in rats: differential dependence on cholinergic neuronal loss.

Excitotoxic lesions of the basal forebrain were made by infusing either alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) or ibotenic acid. Acquisition and performance of spatial learning in the Morris water maze, over a ten day, two trials per day, training regimen were unaffected by the AMPA-induced lesions which reduced cortical choline acetyltransferase activity by 70%. However, acquisition was significantly impaired in rats with ibotenic acid-induced lesions that reduced cortical choline acetyltransferase by 50%. Additionally, ibotenic acid-lesioned rats swam further than either sham or AMPA-lesioned rats, in the "training" quadrant during a probe trial, in which the escape platform was removed, suggesting a perseverative search strategy. Lesions induced with AMPA, but not ibotenate, significantly impaired the acquisition of "step-through" passive avoidance. Both AMPA- and ibotenate-induced lesions significantly impaired the 96 h retention of passive avoidance, but the effect of AMPA was greater on latency measures. Histological analysis revealed that AMPA infusions destroyed more choline acetyltransferase-immunoreactive neurons than did ibotenate infusions but, unlike ibotenate, spared the overlying dorsal pallidum and also parvocellular, non-choline acetyltransferase-immunoreactive neurons in the ventral pallidal/substantia innominata region of the basal forebrain. The impairment in acquisition of the water maze following ibotenate-induced basal forebrain lesions therefore appears unrelated to damage to cholinergic neurons of the nucleus basalis of Meynert and to depend instead on damage to pallidal and other neurons in this area. The AMPA- and perhaps also the ibotenate-induced impairment in the retention of passive avoidance appears to be more directly related to destruction of cholinergic neurons of the nucleus basalis. These data are discussed in the context of cortical cholinergic involvement in mnemonic processes.

Animals↗
PubMed1991

Complementary roles for the amygdala and hippocampus in aversive conditioning to explicit and contextual cues.

Experiment 1 investigated the effects of catecholaminergic deafferentation or cell body lesions of the amygdala on fear conditioning to explicit and contextual cues. Bilateral infusions of quinolinic acid mainly damaged neurons within the basolateral region of the amygdala. 6-Hydroxydopamine infusions at the same coordinates resulted in an 86% depletion of noradrenaline and a 63% depletion of dopamine from the amygdala, but had no effect on the concentration of 5-hydroxytryptamine. After recovery from surgery, lesioned rats and controls were exposed to pairings of an auditory (clicker) conditioned stimulus and (foot shock) unconditioned stimulus in a distinctive environment. During testing, rats with both 6-hydroxydopamine and cell body lesions showed severely impaired conditioning to explicit cues, compared with controls, indicated by their reduced suppression of drinking when the conditioned stimulus was introduced into a separate, lick-operant chamber. Neither lesion affected fear conditioning to contextual cues, measured as preference for a "safe" environment over the one in which they were shocked. In Experiment 2, rats received bilateral, ibotenic acid-induced lesions of the hippocampal formation. Lesioned rats and controls were again tested for aversive conditioning to explicit and contextual cues. Rats with cell body lesions of the hippocampus showed normal suppression of drinking in the presence of the conditioned stimulus, but were severely impaired in choosing the safe environment based on contextual cues alone. These results suggest a double dissociation of the effects of amygdala and hippocampal damage on fear conditioning to explicit and contextual cues.

Amygdala↗
PubMed1991

Response-related deficits following unilateral lesions of the medial agranular cortex of the rat.

Rats with lesions of the medial agranular frontal cortex (AGm) were tested for sensorimotor function. Spatial response bias and reaction time to lateralized visual targets were recorded in an automated test of visual reaction time. The same rats were also tested for somatosensory capacity and on a skilled reaching task. In all tasks, there was an ipsilateral response bias but no evidence of sensory neglect. In the visual reaction time task, initiation time was lengthened bilaterally. These deficits may parallel the effects on motor function after unilateral frontal cortical lesioning in primates. The results support the hypothesis that rat AGm contains a homologue of primate secondary motor cortex.

Afferent Pathways↗