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T W Robbins

Publications and source records attributed to T W Robbins.

At least 19 recordsLinked to original sources

Drug discrimination learning in rats with excitotoxic lesions of nucleus basalis and ventral globus pallidus.

Rats can readily acquire conditional discriminations in which mixtures of drugs serve as compound internal discriminative stimuli. Excitotoxic lesions in the region of the nucleus basalis have been shown to impair the acquisition of conditional discriminations based upon external visual stimuli, but nothing was known about their effects on discrimination of internal stimuli. A baseline of undiscriminated bar-pressing for food reinforcers was established prior to surgery. Lesions were made by infusing either ibotenic or quisqualic acid bilaterally into the basal forebrain (the ibotenate-induced lesions had been shown previously to impair cortical cholinergic function and to produce non-specific damage). After surgery, rats were trained to discriminate effects of drug mixtures using a standard, two-bar operant conditioning procedure. The ibotenate, but not the quisqualate, lesion impaired the acquisition of a discrimination of a mixture of (+)-amphetamine plus pentobarbitone, while neither lesion impaired acquisition with a mixture of (-)-nicotine plus midazolam. The ibotenate lesions also reduced overall rates of responding in both experiments. Thus, the deficit in the acquisition of drug discrimination in rats with ibotenate lesions had some pharmacological specificity, but could not be related easily to disturbances in neocortical cholinergic function. In comparisons with other published data, the results suggest a possible dichotomy in the processing of interoceptive and external information in the basal forebrain, a major target of ventral striatal overflow.

Animals

Social isolation increases the density of [125I]omega-conotoxin GVIA binding sites in the rat frontal cortex and caudate nucleus.

Rats were reared from weaning either in isolation or in social groups for 12 weeks. Potential isolation-related changes in L- and N-type voltage-sensitive calcium channels (VSCCs) were assessed by the in vitro binding of [3H]isradipine (100 pM) and [125I]omega-conotoxin GVIA (4 pM) to membranes prepared from three discrete central nervous system regions: frontal cortex, caudate nucleus and hippocampus. The [3H]isradipine binding was generally not affected by isolation. However, [125I]omega-conotoxin GVIA binding was significantly higher in frontal cortex (52%) and caudate nucleus (75%) of isolated rats when compared with socially reared controls. The increased [125I]omega-conotoxin GVIA binding reflected an elevated density of binding sites without an alteration of receptor affinity. The possible contribution of an increased density of neuronal N-VSCCs (as labeled with [125I]omega-conotoxin GVIA) to the behavioral and neurochemical changes observed in 'isolation syndrome' is discussed.

Animals

Attentional functions of the forebrain cholinergic systems: effects of intraventricular hemicholinium, physostigmine, basal forebrain lesions and intracortical grafts on a multiple-choice serial reaction time task.

Degeneration of the cholinergic magnocellular neurons in the basal forebrain and their cortical projections is a major feature of the neuropathology of Alzheimer's disease. In the present study, two experiments examined the disruptive effects on visual attentional performance of two different manipulations that reduce central cholinergic function. In Expt. I, pharmacological manipulation of the cholinergic system was investigated using icv administration of hemicholinium (HC-3), a high affinity choline uptake blocker, administered either alone or in conjunction with the anticholinesterase, physostigmine. The results revealed impairments in the ability of the rats to localize brief visual targets in a serial reaction time task, as shown in particular by a reduction in choice accuracy and lengthening of the latency to respond correctly to the visual stimulus. Cholinergic specificity was supported by the reversal of these behavioural impairments by pre-treatment with the anticholinesterase, physostigmine. In Expt. II, quisqualate-induced lesions of the basal forebrain produced behavioural deficits at 3 weeks post-lesion surgery similar to those observed following icv infusion of HC-3. In an attempt to restore the extrinsic cortical cholinergic innervation by reinnervation of the deafferented cortex, embryonic basal forebrain cholinergic cells were transplanted into the cortex of lesioned animals. After three months recovery, impairments in performance on the baseline schedule of the task were no longer apparent in lesioned animals. However, behavioural deficits, observed predominantly as a lengthening of correct response latency, could be reinstated in the lesioned animals by interpolation of distracting bursts of white noise during each trial, and this deficit was ameliorated by the cholinergic grafts. Furthermore, a non-specific effect of both cholinergic and non-cholinergic grafts in controlling the increase in perseverative time-out responses which occurred as a result of the basal forebrain lesion was consistently observed. These results suggest that cholinergic dysfunction can produce deficits in visual attention which can be ameliorated by cholinergic treatments such as physostigmine or cholinergic-rich cortical grafts. These data provide support for a role for the basal forebrain-neocortical cholinergic projection in attentional function.

Acetylcholine

L-dopa withdrawal in Parkinson's disease selectively impairs cognitive performance in tests sensitive to frontal lobe dysfunction.

A group of ten patients with idiopathic Parkinson's disease (PD) was tested on a series of automated tests of learning, memory, planning and attention whilst either on or off L-dopa medication. Controlled withdrawal of L-dopa interfered with aspects of performance on three of the tests that had previously been shown to be sensitive to frontal lobe dysfunction; a spatial working memory task, the Tower of London planning test, and a visual discrimination paradigm that also included intra- and extra-dimensional shift tests of selective attention. More specifically, errors were increased in the spatial working memory test, and both the accuracy and latency of thinking were impaired. Thinking time was significantly slowed following L-dopa withdrawal, even though the possible contaminating effects on motor slowing were fully controlled by a yoked control procedure. Nine out of ten patients reached a further stage of the visual discrimination, set-shifting paradigm when on, rather than off, L-dopa medication. Spatial span was also impaired off medication, but there were no effects of L-dopa withdrawal on tests of pattern and spatial recognition memory, simultaneous and delayed matching to sample or visuospatial conditional associative learning. Comparisons with a large control group confirmed previous findings that PD is associated with deficits on the majority of these tests. The results are discussed in terms of the fronto-striatal, dopamine dependent nature of some of the cognitive deficits found in PD, but the apparent dopamine-independent nature of deficits in other aspects of cognitive functioning, notably in tests of visual recognition memory and associative learning.

Brain Diseases

Disruptive effects of muscimol infused into the basal forebrain on conditional discrimination and visual attention: differential interactions with cholinergic mechanisms.

The behavioral effects of GABAergic manipulation of the basal forebrain were investigated using two behavioral tasks, which previous studies have shown to yield dissociable effects following quisqualate-induced lesions of the basal forebrain: a five-choice serial reaction time task, involving approaching the location of a brief visual stimulus that is associated with reward; and a conditional visual discrimination task, requiring retrieval of information about a discriminative stimulus that stays constant over time. Following acquisition of the tasks, chronic guide cannulae were stereotaxically implanted into the basal forebrain. Those animals trained on the conditional visual discrimination task showed a dose-dependent reduction in choice accuracy and a lengthening of latency to respond correctly to the visual stimulus following administration of the GABA-A agonist, muscimol (1, 2, 3 ng/microliters/hem). While certain of these deficits, for example response latency, could be restored to control levels by co-administration of the GABA-A antagonist, bicuculline, none of the behavioural impairments could be significantly attenuated by systemic by systemic co-administration of the cholinesterase inhibitor, physostigmine (0.05, 0.1, 0.2 mg/kg, IP). Similarly, a dose dependent effect of muscimol (1, 1.5, 2 ng/microliters/hem) on choice accuracy and correct response latency was observed on performance of the five-choice attentional task. However, in contrast to the conditional task, significant attenuation of the impairment in choice accuracy was obtained following administration of physostigmine (0.05 and 0.1 mg/kg). Attenuation of muscimol-induced deficits by administration of bicuculline was also observed. It is therefore evident that although manipulation of GABAergic activity in the region of the basal forebrain produces profound deficits in different tasks of cognitive function, only some of these may be due to modulation of the magnocellular cholinergic projection to the neocortex.

Animals

Differential effects of mesocortical, mesolimbic, and mesostriatal dopamine depletion on spontaneous, conditioned, and drug-induced locomotor activity.

Groups of rats with 6-hydroxydopamine (6-OHDA) lesions of either the medial prefrontal cortex (PFC), nucleus accumbens (NAC), or caudate putamen (CPu) were given daily tests for locomotor activity in photocell cages while food deprived. Two separate groups of NAC-lesioned rats were prepared with either large [NACT (90% NAC dopamine depletion)] or partial [NACP (67% NAC dopamine depletion)] lesions. NACT rats were spontaneously hypoactive whereas NACP rats were hyperactive compared with sham-operated controls. PFC-lesioned rats were also hyperactive compared to their respective controls. Spontaneous locomotor activity in CPu-lesioned rats did not differ from shams. When daily food supplements were paired with the photocell cages, all subjects developed a conditioned locomotor response. During the first few days of conditioning, the response to this conditioning procedure was markedly greater in the NACP group whereas the response in the NACT group was unaffected initially and actually enhanced during the latter days of testing. The locomotor response to the conditioning procedure was unaffected in either the PFC- or CPu-lesioned groups. Both the NACT and NACP lesions attenuated the locomotor response to 1.5 mg/kg d-amphetamine sulphate IP, and the NACT group showed a supersensitive response to 0.1 mg/kg apomorphine HCl SC. PFC or CPu 6-OHDA lesions did not alter the response to either drug. These results differentiate the role of PFC, NAC, and CPu dopamine in spontaneous, conditioned, and drug-induced locomotor activity and further implicate dopaminergic mechanisms of the NAC in the magnitude of the behavioural response to incentive stimuli.

3,4-Dihydroxyphenylacetic Acid

Dopaminergic and serotonergic function following isolation rearing in rats: study of behavioural responses and postmortem and in vivo neurochemistry.

This series of experiments compared isolation-reared and socially reared rats for their locomotor activity, behavioural stereotypy, and monoamine function both postmortem and in vivo using intracerebral dialysis. In Experiment 1, isolates showed an altered time course of locomotor activity following d-amphetamine sulphate (AMPH) administration (0.5, 2.0, 3.0, or 5.0 mg/kg, SC). Isolation-reared rats also showed increased sensitivity to the sedative effects of a low dose of apomorphine hydrochloride (0.1 mg/kg) but did not differ from social controls following higher doses of the drug (0.5, 1.5, or 3.0 mg/kg, SC). Isolates showed a decrease in the intensity of apomorphine-induced stereotyped behaviours but no change in stereotypy induced by AMPH. In Experiment 2, isolates had higher postmortem dopamine (DA) concentrations and an altered asymmetry in DA function in the medial prefrontal cortex (PFC) but not in the nucleus accumbens (NAC) or caudate putamen (CPu). Isolated rats also had a lower 5-hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT) ratio in the NAC (but not in the PFC or CPu) compared to controls. Experiment 3 used intracerebral dialysis to examine monoamine function in vivo following isolation rearing. Isolates showed greater increases in extracellular DA and greater decreases in DOPAC in response to 2 mg/kg AMPH SC in both the NAC and CPu. There were no apparent differences in the perfusate concentrations of either dopamine (DA), dihydroxyphenylacetic acid (DOPAC), or homovanillic acid (HVA) prior to drug administration. However, consistent with the results of Experiment 2, isolates had a reduced basal perfusate concentration of 5-HIAA from the NAC but not from the CPu. Experiment 4 measured postsynaptic DA function in CPu tissue slices following isolation. Isolation rearing did not affect cAMP accumulation in response to stimulation of D1 DA receptors by DA (0, 2.7, 9, or 30 microM). In addition, isolation rearing did not affect the coupling between D1 and D2 receptors, as measured by the increase in cAMP accumulation with 1 microM 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1 H-3-benzazepin (SK&F 38393) and its reduction by 10 microM quinperole hydrochloride (LY 171555). These results are discussed in terms of the possible relationship between these neurochemical findings and the behavioural disturbances following isolation rearing of rats.

3,4-Dihydroxyphenylacetic Acid

A specific form of cognitive rigidity following excitotoxic lesions of the basal forebrain in marmosets.

The effects of N-methyl-D-aspartate-induced lesions of the basal forebrain were studied on performance of a series of visual discrimination tests that examined a range of cognitive functions in the marmoset. These included the ability to attend to the various dimensional properties of stimuli and to use just one of these properties in order to solve a discrimination (intra-dimensional shift); to switch attention from one dimension to another (extra-dimensional shift); to learn the reinforcement value of specific exemplars within a dimension (new learning); and to relearn their reinforcement value following reversal of the reward contingencies (serial reversals). Lesions of the basal forebrain did not impair the ability either to attend selectively to the dimensional properties of the stimuli or to switch attention from one dimension to the other. However, the lesion did affect various aspects of associative learning including a transient impairment of new learning and a marked disruption of serial reversal learning. The reversal deficit could be characterised as a tendency to perseverate on the previously correct stimulus and as a failure to to show the formation of a reversal learning set. In addition, the lesion prevented disruption of performance of a well-learned discrimination when novel exemplars from the irrelevant dimension were introduced (probe test). It is suggested that the functional effects of the basal forebrain lesion reflect impaired learning of stimulus-reward associations and behavioural rigidity. The finding, however, that there was no effect of the lesion on attentional set-shifting suggests that any loss of inhibitory control was specific to the level of stimulus-response or stimulus-reward associations, inhibitory control at the level of attentional selection remaining intact. The similarity of the effects of damage to the basal forebrain to those seen following damage to the orbitofrontal cortex and the amygdala are discussed in the context of the close anatomical and functional relationships that exist among these three structures.

Animals

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

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

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

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

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

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

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

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