Biomedical subjects

H J Sagar

Publications and source records attributed to H J Sagar.

At least 37 records · Page 2Linked to original sources

PubMed1994

Slowed central processing in simple and go/no-go reaction time tasks in Parkinson's disease.

Studies of cognition and motor control have independently suggested that patients with Parkinson's disease show deficits in both attentional control and the preprogramming of movement. However, few studies have examined directly the involvement of cognitive processes in the origin of their slowed response. We examined the performance of 100 Parkinson's disease patients on simple reaction time (SRT) and a series of go/no-go cross-modality choice reaction time (CRT) tasks, in which motor response was constant; correct positive responses required attention to a progressively increasing number of dimensions of visual and auditory stimuli. The results showed that Parkinson's disease patients became increasingly impaired in response speed as choice complexity increased. Slowed response speed in Parkinson's disease involved two factors: (i) a 'perceptuomotor' factor which was constant across conditions and independent of choice complexity. Depression affected this factor selectively and independently of confounding associations with impoverished motor control; (ii) a 'cognitive-analytical' factor, which played an increasingly important role as complexity of choice increased. The characteristics of the relationship between response latency and cognitive complexity indicate that the deficit was due to a constant proportional slowing in cognitive speed across all SRT and CRT conditions. A cognitive deficit affecting the monitoring of stimulus-response compatibility may contribute to delayed response in Parkinson's disease. This cognitive-analytical deficit is present in early, untreated cases and, in contrast to perceptuomotor processes, is weakly related to depression.

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PubMed1994

The role of the striatum in motor learning: dissociations between isometric motor control processes in Parkinson's disease.

Studies of Parkinson's disease (PD) have been used to support the hypothesis that the striatum serves procedural learning but interpretation of the results is confounded by extra-striate pathology and coincidental non-procedural cognitive deficits. The motor deficit of PD involves particularly internally cued movement, without visual feedback, because of disruption to frontostriatal circuits. Thus, we used a non-visual isometric task as a sensitive measure of motor learning in early non-demented patients with PD and examined the effects of dopamine replacement. The PD group showed disproportionate under-shooting of the target but normal motor learning. Learning correlated with some cognitive measures but not clinical motor disability or depression. Treatment had no effect on performance, despite clinical improvement. The results indicate dissociations between motor control processes resulting from striatal pathology. Putaminal circuits are involved in force generation and prediction but not critically in motor learning.

Basal Ganglia↗

PubMed1993

Encoding ability is preserved in amnesia: evidence from a direct test of encoding.

The encoding ability of 17 amnesics of mixed aetiology and 17 matched normal controls was assessed directly using a novel procedure. On two separate occasions, subjects were shown 60 complex drawings each containing six pictures. On one occasion each drawing was shown for 6 sec, and on the other occasion it was shown for 25 sec. Immediately after presentation of each drawing subjects were asked a single unpredictable question about picture colours, location, size or semantic category. Amnesics performed normally in the 6-sec exposure condition indicating that all of the tested kinds of information were encoded at a normal rate. Performance in this condition correlated with short-term, but not long-term memory in the amnesics indicating that it depended largely on encoding and short-term memory. However, the amnesics were impaired in the 25-sec condition where performance should have depended on (long-term) memory abilities at which they were impaired. The results are inconsistent with available encoding deficit accounts of amnesia.

Adult↗

PubMed1993

Short-term memory and temporal ordering in early Parkinson's disease: effects of disease chronicity and medication.

Studies of Parkinson's disease (PD) have shown impaired temporal ordering but interpretation may be confounded by task requirements and the effects of medication. We examined item recognition and recency discrimination in PD in relation to treatment and performance on other tests. Patients showed increased response latency and impaired recency discrimination only at short retention intervals. The deficits were greater in chronically medicated patients but treatment with levodopa, bromocriptine or anticholinergic drugs did not affect performance of newly diagnosed cases. The short-term memory deficits correlated with scores on tests of working memory, attention and executive function. These results do not indicate a generalised temporal ordering deficit in PD but suggest that much of the cognitive impairment in the disorder arises from attentional deficits affecting short-term and working memory.

Adult↗

PubMed1993

Encoding deficits in untreated Parkinson's disease.

Short-term memory deficits are prominent in untreated Parkinson's Disease (PD) and speed of central processing is known to be abnormal. To investigate the relationship between these findings, a modification of the Brown-Peterson paradigm was given to newly diagnosed, untreated patients and healthy control subjects (HCS). The PD patients were impaired under conditions of long stimulus exposure but not when study time was short. Although patients displayed deficits in immediate recall, they were more impaired at longer test delays. They achieved fewer encoding operations per unit time, resulting in a divergence of group performance with increasing duration of stimulus exposure. Performance in the PD group did not associate with motor disability, disease duration or rating of depression. These results are discussed in terms of a unifying reduced central processing deficit that is evident in PD but is independent of physical symptoms.

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PubMed1993

Incidental and intentional recall in Parkinson's disease: an account based on diminished attentional resources.

The recall of common objects and their spatial location was examined in 65 patients with Parkinson's disease (PD) under conditions in which available attentional resources were manipulated by secondary task demands. PD patients were impaired at item recall particularly under intentional learning conditions but were unimpaired at recall of spatial location. These findings were similar in newly diagnosed, untreated cases as well as patients who had suffered with the disease for an average of 9.6 years. Test performance was not improved by levodopa therapy, despite it benefiting motor control, and was not impaired by anticholinergic medication. Item recall correlated significantly with other memory measures (particularly tasks of working memory) but only weakly with indices of physical disability and traditional frontal-lobe measures. Spatial recall, by contrast, correlated with memory quotient but no other cognitive measure and depression and disease duration failed to correlate significantly with performance on either recall task. These results are attributed to a deficit in attentional resources in PD that impairs performance most markedly for tasks and conditions that make the greatest demands upon effort.

Adult↗

PubMed1993

Alternating fluency in Parkinson's disease. An evaluation of the attentional control theory of cognitive impairment.

One theory for the pattern of cognitive impairment associated with Parkinson's disease is that deficits are apparent only on tasks which rely on the internal control of attention, which in turn is assumed to place heavy demands on limited attentional resources. This theory is evaluated in the present study by examining the performance of Parkinson's disease subjects and matched healthy control subjects on a series of fluency tasks. In one condition, subjects were required to generate exemplars under standard verbal fluency instructions, i.e. either to a single letter or a single semantic category. In a related condition, subjects had to generate exemplars alternately using two fluency probes, which could either be from the same domain, i.e. letter-letter or category-category, or from different domains, i.e. category-letter. The requirement to alternate between fluency probes presumably places greater demands on internal attentional control mechanisms, and in a yoked condition, subjects were given external cue cards to minimize these extra demands. Overall, there was no evidence that Parkinson's disease subjects had a basic fluency deficit, nor were they impaired when required to alternate between probes of the same domain. A specific deficit did emerge, however, for the mixed alternating condition (i.e. category-letter), in which Parkinson's disease subjects produced significantly more perseverative errors and had a significantly lower output. The former of these was reversible by the provision of external cue cards, but the overall output was unchanged. These data do not support the theory of internal attentional control, at least as a general theory of cognitive impairment in Parkinson's disease. To explain the observed pattern, we propose that Parkinson's disease is associated with: (i) a deficit in inhibitory attentional processes, and (ii) an impairment in the maintenance of those internal representations which control action.

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PubMed1992

Different effects of dopaminergic and anticholinergic therapies on cognitive and motor function in Parkinson's disease. A follow-up study of untreated patients.

The cognitive performance of a group of 82 newly diagnosed patients with Parkinson's disease who had never been treated was reassessed approximately 4 mths after randomization to one of three monotherapies (levodopa, bromocriptine or anticholinergic drugs). Dopaminergic and anticholinergic treatments both led to improvement in motor control but their effects upon cognitive performance dissociated. Anticholinergic drugs produced impairment in processes underlying the immediate registration of information whilst dopaminergic therapy produced improvement on a task dependent on working memory and cognitive sequencing. Other cognitive measures showed no change on treatment. The deficits that were affected by cholinergic and dopaminergic modulation are those that were most compromised in the early, untreated state in Parkinson's disease. The data support the notion that cognitive impairment in Parkinson's disease is multifactorial in origin: short-term memory processes are served by both dopaminergic and cholinergic subcortico-frontal systems but much of the cognitive impairment of Parkinson's disease is independent of this subcortical neurochemical pathology and may be due to early neuronal dysfunction within the cerebral cortex.

Adult↗

PubMed1992

A component analysis of the generation and release of isometric force in Parkinson's disease.

Paradigms of isometric force control allow study of the generation and release of movement in the absence of complications due to disordered visuomotor coordination. The onset and release of isometric force in Parkinson's disease (PD) was studied, using computerised determinants of latency of response and rate of force generation and release. Components of isometric force control were related to measures of cognitive, affective and clinical motor disability. The effects of treatment were determined by longitudinal study of de novo patients. Patients with PD showed impairment in latency and rate of force change for movement release as well as onset. Rate of force change correlated with depression, clinical motor disability and memory quotient but latency showed no correlation with any of these measures. Treatment improved rate of force release, in concert with clinical motor disability, but not latency. These results suggest dissociations between latency and rate of force change that may be linked to different neurochemical deficits. Further, they demonstrate akinetic deficits in force release that argue against the "neural energy hypothesis" of akinesia.

Bromocriptine↗

PubMed1992

Cognitive components of reaction time in Parkinson's disease.

Studies of reaction time in Parkinson's disease (PD) have suggested a selective deficit in simple reaction time (SRT), compared with choice reaction time (CRT). This finding has been interpreted as a deficit in motor preprogramming but could involve other factors, such as attentional focussing and stimulus predictability. Moreover, not all studies show the same selective deficit, possibly because of differences in patient selection and treatment effects. The neurochemical basis of RT deficits in PD remains unclear. Accordingly, the contribution of cognitive factors to impaired RT was assessed in a large group of PD patients, including early untreated cases, and performance was examined in relation to clinical variables and the effect of treatment in longitudinal study. Motor output was constant in both SRT and CRT tasks. In the SRT task, all stimuli required a response; in the CRT task, subjects were required to respond to only one of the two possible stimuli. Attentional focussing on SRT was examined by variation of the interval between cue and stimulus; effects of stimulus uncertainty were evaluated from a comparison of SRT and CRT; temporal predictability of the stimulus was examined from a comparison of conditions in which the interval between warning signal and imperative stimulus was constant or variable. The PD patients showed similar deficits in SRT and CRT, but normal effects of cue-stimulus interval and temporal predictability. Reaction time correlated with measures of global cognitive capacity and frontal-lobe function, as well as motor disability. Treatment had no effect on SRT or CRT, despite clinical benefit. These findings indicate that RT deficits in PD are not due to impaired attentional focussing or stimulus predictability but are compatible with a deficit in higher-order processes concerned with the orientation of both cognitive and motor responses to a stimulus. These processes are not substantially dopamine-dependent but may be served by non-dopaminergic neurotransmission.

Antiparkinson Agents↗

PubMed1991

The role of magnetic stimulation in the diagnosis of multiple sclerosis.

Magnetic stimulation was used to measure motor conduction time (MCT) between head and neck, and head and lumbar region, as well as amplitude of the motor evoked potential (MEP) in normal subjects and patients with multiple sclerosis (MS). Patients with definite MS had significantly longer MCTs and smaller amplitude MEPs than normal subjects when recording from arm and leg muscles. In a comparison with visual evoked potential (VEP) recordings, head to neck MCTs were abnormal less often than VEPs, and VEPs detected more silent lesions. Recording from leg as well as arm muscles significantly increased the yield of abnormal MCT measurements. The detection of silent lesions in the patients with definite MS was improved, but there was no improvement in the non-definite cases. Amplitude measurements provided very little extra diagnostic information over MCT measurements alone and did not improve the detection of silent lesions. Interside MCT differences yielded extra abnormalities when recording from the arms but not the legs. Interside MCT abnormalities increased the detection of silent lesions in both the definite and non-definite categories. It was concluded that the majority of useful diagnostic information in patients with MS should be obtainable from bilateral MCT (head to neck) measurements, together with estimation of interside MCT differences. However, VEP recording is a better diagnostic test for MS than MEP recording as more silent lesions are detected. This may be because MCT abnormalities tend to reflect the degree of pyramidal disability.

Adult↗

PubMed1991

The role of magnetic stimulation as a quantifier of motor disability in patients with multiple sclerosis.

Magnetic stimulation was used to measure motor conduction time (MCT) between head and neck in a prospective longitudinal study of patients with multiple sclerosis (MS) and normal subjects. MCT measurements showed a high degree of reproducibility in normal subjects and patients with stable MS. In patients with definite MS, there was significant positive correlation between MCT and motor disability. In patients treated with steroids for relapse of MS, there was significant shortening of MCT following treatment in those who clinically improved, but not in those who were clinically unchanged. In a smaller group of patients followed for 3 months, MCT changes tended to mirror the clinical pattern. Magnetic stimulation should prove a useful tool for the quantification of motor disability, and monitoring the response to new treatments in MS.

Adrenal Cortex Hormones↗

PubMed1991

Normal release from proactive interference in untreated patients with Parkinson's disease.

The relationship of release from proactive interference (PI) to set-shifting, explicit free recall and language remains controversial. We tested 56 patients with Parkinson's disease (PD) who had never received medication and 37 matched normal control subjects on a test of PI release based on semantic category. The PD group showed normal PI release but impaired word recall. PI release was independent of impaired Wisconsin card-sorting test performance, language production, explicit memory, overall cognitive status and severity of depression. The results indicate dissociation between ability to benefit from semantic stimulus properties and processes of explicit memory, set-shifting and expressive language.

Attention↗

PubMed1991

Double dissociation of short-term and long-term memory for nonverbal material in Parkinson's disease and global amnesia. A further analysis.

The traditional concept of memory disorder is deficiency of the long-term (LTM) but not short-term (STM) component of memory. STM impairment with LTM sparing is seldom reported. The present study investigated STM and LTM for nonverbal material in three neurological conditions associated with memory impairment: bilateral medial temporal lobe lesions (patient H.M.), Parkinson's disease (PD) and Alzheimer's disease (AD). Subjects received 3 tests of nonverbal memory: forward block span, immediate and delayed recall of the Wechsler Memory Scale drawings, and immediate and delayed recognition of abstract designs. Compared with the normal control group, the patient groups displayed different patterns of sparing and loss of the two components of memory: in PD, only STM was impaired; in medial temporal lobe amnesia, only LTM was impaired; and in AD, STM and LTM were both impaired. The contrasting patterns of sparing and loss of STM and LTM in PD and global amnesia were present for both recognition and recall. These results provide evidence that STM and LTM are dissociable processes and are served by separate neurological systems: STM depends upon intact corticostriatal systems, whereas LTM depends upon intact medial temporal lobe systems.

Aged↗

PubMed1991

Cognitive impairment in early, untreated Parkinson's disease and its relationship to motor disability.

Current knowledge of cognitive dysfunction in Parkinson's disease (PD) has largely been obtained from studies of chronically treated patients in whom effects of disease chronicity, treatment, depression and dementia are confounding factors. Studies of untreated patients have examined few cognitive domains and relationships between cognition, depression and motor disability have been incompletely explored. Accordingly, we studied 60 consecutive patients with newly diagnosed, untreated, idiopathic PD and 37 matched, healthy control subjects; no subject had clinical dementia or depression. All subjects received tests of specific processes of memory and cognition, including working memory, verbal and non-verbal short- and long-term memory, language, visuospatial capacity, set-formation and shifting and sequencing. Patients also received quantitative global clinical measures of severity of dementia, depression and motor disability. The PD group as a whole showed deficits in immediate recall of verbal material, language production and semantic fluency, set-formation, cognitive sequencing and working memory and visuomotor construction. However, this group was unimpaired in immediate memory span, long-term forgetting, naming, comprehension and visual perception. Language deficits and more severe frontal lobe impairments were confined to those PD patients scoring abnormally on a Mini Mental State examination. Motor disability correlated strongly with severity of depression but weakly with cognitive impairment. Cognitive sequencing, set-formation and set-shifting deficits tended to associate with depression, but otherwise there was no association between cognition and depression. The results indicate dissociation of cognition and motor control in early PD which suggests that cognitive dysfunction is largely independent of frontostriatal dopamine deficiency underlying motor disability. Some, but not all, of the frontal lobe deficits of chronic disease are detectable in early, untreated PD. The pathogenesis of the cognitive deficits shown here appears to involve extrastriatal dopamine systems or non-dopaminergic pathology. Longitudinal study is necessary to determine whether increasing disease duration exacerbates the early cognitive deficits and affects new cognitive domains, in addition to producing increasing motor disability.

Adult↗

PubMed1990

Abnormalities of central motor conduction in Parkinson's disease.

The new technique of magnetic stimulation was used to measure amplitude of the motor evoked potential (MEP) recorded from abductor digiti minimi whilst stimulating at the head, and motor conduction time (MCT) between head and neck. Bilateral studies were made in 12 normal subjects and 56 patients with Parkinson's disease. The amplitudes of the MEPs were significantly larger (P less than 0.05) in the patients (mean 1.6 mV, SD 1.4) compared with the normal subjects (mean 0.9 mV, SE 0.6). MCTs were significantly shorter (P less than 0.001) in patients (mean 8.1 ms, SD 1.3) compared with the normal subjects (mean 9.4 ms, SD 1.2). Although the pathophysiological basis of these changes has not been determined, they provide objective measurements which may be clinically valuable in monitoring therapy.

Central Nervous System↗

PubMed1990

Recency and frequency discrimination in the amnesic patient H.M.

Temporal contextual memory and event memory were compared across retention intervals in the patient H.M. who is amnesic following bilateral medial temporal lobectomy. Memory for temporal context was assessed using verbal and nonverbal recency discrimination tasks and a frequency task in which subjects made discriminations between words repeated 1, 3 or 5 times. The tests evaluated event memory under parallel conditions by two-choice content recognition tasks. In both recency and frequency tests, H.M. showed above-chance and often normal temporal contextual memory under conditions of impaired and even chance-level content recognition. These results show that temporal contextual memory does not require intact content recognition and is independent of medial temporal lobe structures. Furthermore, the amnesia of bilateral medial temporal lobe resection does not manifest primary loss of temporal contextual memory.

Amnesia↗

PubMed1989

Different cognitive profiles on standard behavioral tests in Parkinson's disease and Alzheimer's disease.

Patients with Parkinson's disease (PD) displayed a different pattern of cognitive deficit from patients with dementia resulting from Alzheimer's disease (AD). Specifically, PD patients, whether or not impaired on a mental status examination, had deficient Picture Arrangement but normal Vocabulary test scores whereas AD patients were impaired on both measures. Furthermore, PD patients with impaired mental status examination scores showed a deficit in set formation on Picture Arrangement not seen in the AD patients. Finally, when recent memory performance, as measured by the Wechsler Memory Scale, was predicted from an estimated IQ, 71% of PD patients who had normal mental status examination scores were seen to have at least a mild memory impairment.

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