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Biomedical subjects

B Pillon

Publications and source records attributed to B Pillon.

At least 37 records · Page 2Linked to original sources

Bilateral subthalamic or pallidal stimulation for Parkinson's disease affects neither memory nor executive functions: a consecutive series of 62 patients.

There is a renewal of interest in surgical approaches including lesions and deep brain stimulation directed at motor subcorticofrontal loops. Bilateral lesioning presents a far greater risk of adverse effects, especially cognitive impairment. Furthermore, the main advantages of the stimulation procedure over lesioning are adaptability and reversibility of effects. The aim of this study was to assess the influence of bilateral stimulation of the subthalamic nucleus or internal globus pallidus on memory and executive functions in Parkinson's disease. Sixty-two patients were assessed before and after 3 to 6 months of chronic bilateral stimulation of the subthalamic nucleus (n = 49) or internal globus pallidus (n = 13). The neuropsychological tests used were the Mattis Dementia Rating Scale, the Grober and Buschke Verbal Learning Test, the Wisconsin Card Sorting Test, category and literal fluency, graphic and motor series, the Stroop Test, and the Trail Making Test. Mood was evaluated by the Beck Depression Inventory. Only 4 of 25 cognitive variables were affected by deep brain stimulation. Under stimulation, performance improved for Parts A and B of the Trail Making Test, but there was a deterioration in literal and total lexical fluency. There was also a mild but significant improvement in mood. It may therefore be concluded that stimulation of the subthalamic nucleus or internal globus pallidus does not change the overall cognitive performance in Parkinson's disease and does not greatly affect the functioning of subcorticofrontal loops involved in cognition in humans. This relative absence of cognitive impairment in bilateral deep brain stimulation is likely because of the accurate positioning of the electrodes, allowing the effects of stimulation to be confined to sensorimotor circuits.

Electric Stimulation↗

Acute and long-term administration of anticholinergics in Parkinson's disease: specific effects on the subcortico-frontal syndrome.

Parkinson's Disease (PD) is often associated with a subcortico-frontal syndrome (SCFS) that is mainly characterized by executive dysfunctions. The complete biochemistry of these dysfunctions remain misunderstood. Most studies have focused on the well-known nigro-striatal dopaminergic degenerations of PD, but a more satisfying understanding of the SCFS has come from the study of the cholinergic systems. We present here two new experiments carried out with long-term and acute anticholinergic treatments in PD. In the first experiment, the effects of a 2-week treatment with trihexyphenidyl were compared to those observed under placebo on a neuropsychological battery. Results showed that anticholinergic-induced deficits in PD were exclusively concerned with executive functions. In the second experiment, the effects of an acute subclinical dose of scopolamine were compared between normal controls and PD patients who were devoid of cognitive deficit on a subset of executive tasks. Results indicates that PD patients but not normal controls developed a transient SCFS for the duration of the drug action. In contrast to other populations with cholinergic depletions-such as Alzheimer's disease-cholinergic blockade in PD exacerbates specifically the SCFS. Such a discrepancy between these two neuropsychological profiles are discussed in terms of the specificity of the underlying cholinergic lesions.

Acute Disease↗

Specificity of memory deficits after right or left temporal lobectomy.

An impairment of verbal memory has consistently been associated with resection of the left dominant temporal lobe, whereas non-verbal memory deficits have been less reliably observed following resection of the right temporal lobe. Such a dissociation may be due to material-specific differences of processing between verbal and non-verbal information. Alternatively, the influence of the left and right limbic structures may vary according to the stage of memory processing. The aim of the study was to test these hypotheses by comparing verbal and spatial learning in patients with left or right temporal lobe resection for intractable epilepsy, using verbal and visuospatial memory tasks with the same design: control of encoding, multiple trial learning, free and cued recall, short and long delays. The results showed: (1) a similar pattern of learning and recall in the two groups; (2) a higher performance in spatial learning for patients with left temporal lobe resection and in verbal learning for patients with right temporal lobe resection; (3) material-specific effects characterized by a higher sensitivity to cues in the verbal domain and a better retention of information during delays in the spatial domain. These results suggest parallel processing of the two temporal lobes at the various memory stages, rather than an interaction between memory stage and side of the lesion similar to that already proposed for the frontal lobes. They also confirm a double dissociation between verbal/spatial information processing and side of temporal lobe resection.

Adult↗

At which steps of spatial working memory processing do striatofrontal circuits intervene in humans?

Striatofrontal circuits have been implicated in spatial working memory in non-human and human primates. To determine at which steps of information processing (stimulus encoding, storage or response programming) they intervene, we compared 32 levodopa-treated patients with idiopathic Parkinson's disease (PD) and 32 matched control subjects in a visuo-spatial pattern span paradigm. Our testing procedure allowed us to evaluate the influence of: (1) the type of encoding (controlled vs free); (2) the nature of interference during a 10 s delay (spatial vs verbal); and (3) response elaboration (reproduction vs error detection). As expected, the performance of control subjects was significantly better in controlled than in free encoding, in verbal than in spatial interference and in detection than in reproduction, clearly demonstrating the sensitivity of the procedure to these factors. Compared to controls, PD patients were impaired in all conditions and the severity of the deficit was significantly correlated with that observed in tests of executive functions. The global pattern of performance, however, was identical to that of controls. These data confirm the involvement of striatofrontal circuits in spatial working memory in humans and suggest that the executive working memory component intervenes at all steps of working memory processing.

Antiparkinson Agents↗

Distinct prefrontal activations in processing sequence at the sentence and script level: an fMRI study.

Neuropsychological studies have shown that the prefrontal cortex is important in planning and monitoring everyday behaviour. In this study, using functional magnetic resonance imaging (fMRI), we investigated whether specific prefrontal regions are involved in processing a sequence of actions. Subjects were required to perform two different tasks: Script-event order and Sentence-word order. Script sequence and word sequence processing were found to activate partially overlapping areas which are known to be implicated in language processing. In addition, the Script-task activated a large area in the dorsolateral prefrontal cortex (Brodmann area 6 and 8, BA 6 and 8), in both the left and right hemispheres, as well as the left supplementary motor area and left angular gyrus (BA 39). Our results suggest that these prefrontal areas may be more specifically involved in the process of analysing sequential links in the action domain.

Adult↗

Sensitivity to semantic cuing: an index of episodic memory dysfunction in early Alzheimer disease.

Alzheimer disease (AD) is characterized by episodic memory impairment. This study was aimed at assessing various aspects of episodic memory, and particularly sensitivity to semantic cuing, in patients with various degrees of cognitive deterioration, compared with normal elderly subjects. One hundred thirty-one patients, subdivided into four subgroups as a function of their Mini-Mental State Examination score, were included. All subjects, including 20 normal elderly subject, were given an episodic memory test with controlled encoding and selective reminding. The subgroups of patients were homogeneous in terms of free recall and recognition, but differed in terms of responsiveness to cuing by semantic categories corresponding to the to-be-remembered items. The data confirmed that a severe amnesic syndrome occurs very early in AD, even in a subgroup of patients who did not meet the criteria for dementia. The data indicated that free recall performance, characterized in all subgroups by a floor effect, is not likely to be an appropriate index in pharmacological trials. By contrast, sensitivity to semantic cuing seemed relatively preserved in the early stages, and decreased with the progression of the disease. This index would be the most sensitive index of episodic memory in AD.

Aged↗

[Fronto-temporal dementia: a clinical approach].

Although the existence of atrophy of the anterior part of the brain has been known for a long time (Pick, 1892), the interest for fronto-temporal dementias (DFT) is relatively recent. Several excellent reviews have been recently published on the topic (Gustafson, 1993; Neary and Snowden, 1996; Pasquier et al., 1998) and, for that reason, we only recall the main aspects of the disease to insist on some lesser known features, illustrated by original observations.

Aged↗

The effects of apomorphine on attentional processing in Parkinson's disease.

To ascertain whether variations in central dopaminergic transmission can differentially affect motor and cognitive processing, we studied the effects of apomorphine (APO) in 9 patients with Parkinson's disease (PD). The UPDRS motor scores and auditory event-related potentials (ERPs) obtained in the 'odd-ball' (OB) and in the 'covert orientation of attention' (COA) tasks were studied in the 'off' and in the 'on' state after an injection of APO. Although APO injection improved patients' motor status, it induced a significant increase in the latencies of the P2 and P3 ERP components in the OB. In the COA task, right-hand reaction times (RTs) were markedly shortened in the 'on' state while left hand RTs remained unchanged. The contrasting effects of dopaminergic stimulation on the motor performance and on some aspects of cognitive processing suggest the existence of complex interactions within pre- and postsynaptic brain dopamine receptors, and an intervention of segregated basal ganglia-prefrontal cortex loops in motor and cognitive behaviour.

Adult↗

Deficit in evaluating pre-determined sequences of script events in patients with Parkinson's disease.

The purpose of the present study was to assess how the striato-frontal system contributes to the manipulation of goal-directed actions. We studied a group of ten patients with Parkinson's disease (PD) in order to investigate which aspects of action knowledge processing are impaired and to define the conditions under which the deficits may occur. PD patients committed errors of sequence and inserted distractors in tasks that required them to order pre-determined events belonging to a given script in a typical sequence. Rather than attributing errors of event sequencing to a deficit of script "syntax" knowledge, we suggest that the difficulties manifested by PD patients were due to an impairment of a switching mechanism that is necessary for processing information in parallel.

Adult↗

Spatio-temporal working memory and frontal lesions in man.

The delayed-response paradigm is thought to be a marker of the activity of the dorsolateral convexity of primates' prefrontal cortex, as this procedure requires the activation of working memory processes. Although the role of the dorsolateral prefrontal cortex (DLPC) in working memory seems to be well established, much remains to be understood about the processes this structure actually controls: encoding domain-specific information, its retention in short-term memory, its monitoring in working memory, or its selection and retrieval when a specific response program is required. To clarify the role of the DLPC in delayed-response tasks in humans, a set of sequencing paradigms was designed which incorporates the dissociation of (1) spatial and temporal parameters, (2) recall and recognition processes, and (3) the presence or absence of a delay. Performance of a group of patients with DLPC lesions (n = 8) was compared to that of age-matched normal subjects (n = 8). To verify the specificity of the results obtained for the DLPC lesioned patients, the performance of patients with a temporal lobotomy was also studied (n = 10). A significant effect of the delay was observed only in patients with DLPC lesions, affecting both their spatial and spatio-temporal recall, whereas their spatio-temporal recognition was normal. These findings suggest that the DLPC plays a role in the retrieval of visuospatial information for guiding a response program.

Brain Injuries↗

Is impaired memory for spatial location in Parkinson's disease domain specific or dependent on 'strategic' processes?

Spatial memory has been found to be impaired in Parkinson's disease (PD). To determine the nature of the deficit, we compared the performance of'standard' levodopa-treated patients with PD to that of matched control subjects in different situations: (i) spatial versus verbal conditional associative learning; (ii) 'global' versus 'local' contextual encoding; (iii) pattern span and related supraspan learning. The relationship between dopaminergic depletion, which characterizes the disease, and the impaired memory processes was investigated by comparing the performance of 'de novo' not yet treated PD patients to that of matched control subjects. Both groups of PD patients were impaired in all situations requiring strategic processes, shared a decreased pattern span and had a normal visuospatial learning once the pattern span was taken into account. All these results suggest that the memory deficit for spatial location observed in PD results mainly from a disturbance of strategic processes and from decreased attentional resources, which may be due, at least in part, to the dopaminergic depletion and related striatofrontal dysfunction.

Aged↗

Are cognitive changes the first symptoms of Huntington's disease? A study of gene carriers.

BACKGROUND: Huntington's disease is a neurodegenerative disorder due to an excessive number of CAG repeats in the IT15 gene on chromosome 4. The first symptoms are typically choreic movements or psychiatric disorders, whereas global cognitive decline generally becomes obvious later. This study was aimed at detecting early subtle cognitive deficits in asymptomatic gene carriers. METHODS: As part of the testing procedure for predictive diagnosis of Huntington's disease, 91 asymptomatic at risk candidates had a neuropsychological examination, evaluating global efficiency, attention, memory (Wechsler memory scale and California verbal learning test), and executive functions. RESULTS: The groups of carriers (n=42) and non-carriers (n=49) differed only on a few memory variables. When we considered the group of gene carriers as a whole, significant correlations emerged between the number of CAG repeats and (a) performance on several tests of executive functions, and (b) performance on the hard pairs associates of the Wechsler memory scale. Further analysis of performance on this memory subtest led to the division of the group of carriers into two subgroups, without any overlap. The performance of subjects without cognitive deficits (n=32) was similar to that of non-carriers on all tests. The subjects with cognitive deficits (n=10) differed from both carriers without cognitive deficits and non-carriers over a wide array of variables measuring executive functions and memory. Moreover, qualitative aspects of the performance of carriers with cognitive deficits in the California verbal learning test closely resembled those of patients diagnosed as having Huntington's disease. CONCLUSION: This suggests that these subjects already have Huntington's disease, despite a total lack of motor and psychiatric signs. An ongoing follow up study is testing the prediction that they will develop the full range of symptoms of the disease earlier than carriers without cognitive deficits.

Adolescent↗

Clinicometabolic dissociation of cognitive functions and social behavior in frontal lobe lesions.

OBJECTIVE/BACKGROUND: Case studies suggest a dissociation between cognitive functions that have been impaired after damage to the dorsolateral prefrontal cortex and social skills disturbed when the ventromedial prefrontal areas are affected. Because this dissociation had not been confirmed in a clinical setting, clinicometabolic correlations were sought in 13 patients with various lesions of the prefrontal cortex. DESIGN/METHODS: The clinical assessment included extensive testing of executive functions and evaluation of behavioral abnormalities based on an informant questionnaire. Regional cerebral glucose metabolism (rCMRGlu) was measured with [l8F] fluorodeoxyglucose ([18F] FDG) and 31-slide high-resolution PET. RESULTS: Executive-function test performance was significantly correlated with rCMRGlu in the dorsolateral prefrontal cortex (Brodmann's areas 8, 9, 45, 46, and 47) and anterior cingulate cortex (Brodmann's areas 24 and 32). Behavioral scores were significantly correlated with rCMRGlu in the frontopolar (Brodmann's area 10) and orbitofrontal cortex (Brodmann's areas 11, 12, 13, and 14). CONCLUSION: These results show that impaired executive functions and serial skill deficits are associated with distinct metabolic patterns in patients with frontal lobe pathology. In agreement with activation studies in normal subjects, our data suggest the existence of a modular organization of the frontal cortex in humans, as previously reported in nonhuman primates.

Adult↗

Cognitive deficits in Parkinson's disease.

Neuropsychological investigations of patients with Parkinson's disease have shown specific impairments even in the early stages of the disease, which include deficit of behavioural regulation in sorting or planning tasks, defective use of memory stores, and impaired manipulation of internal representation of visuospatial stimuli. These deficits, reported in a disease which predominantly involves subcortical structures, have drawn attention to a potential role of the basal ganglia in cognitive processes. Given the modulatory role of the basal ganglia, these disorders might result from more fundamental deficits concerning the allocation of attentional resources, the temporal organization of behaviour, the maintenance of representations in working memory or the self-elaboration of internal strategies, all of which resemble dysfunctions of processes that are commonly considered to be controlled by the frontal lobes. This suggests a functional continuity or complementarity between the basal ganglia and association areas of the prefrontal cortex. The recent description in primates of segregated loops that interconnect discrete regions of the caudate nucleus to the dorsolateral and orbitofrontal regions of the prefrontal cortex via the thalamus may give some support to this hypothesis. Alternatively, degeneration of the ascending cholinergic and catecholaminergic neuronal systems may contribute, at least in part, to the occurrence of this frontal-lobe-like symptomatology associated with Parkinson's disease.

Aging↗

Memory for spatial location in 'de novo' parkinsonian patients.

A deficit in memory for spatial location was recently reported in typical non-demented parkinsonian patients ('standard'). Is this deficit related to dopamine depletion? Such an association would reinforce the suggestion that striato-frontal neuronal circuits are implicated in memory for item-specific spatial coordinates. To answer this question, we compared the performance of 10 recently diagnosed and not yet treated parkinsonian patients ('de novo'), in which the neurobiochemical deficit is considered to involve mainly the nigrostriatal dopaminergic system, to that of 14 controls matched for age, global cognitive efficiency and mood, on a visuospatial learning test. The task required little motor or constructive functions and was designed to allow control of encoding and comparison of free recall, cued recall and recognition. Compared to controls, 'de novo' patients displayed a lower performance in memory for visuospatial location of pictures, contrasting with relative preservation of verbal memory, perceptive visuospatial and executive functions. These results confirm the sensitivity of visuospatial memory even at an early stage of Parkinson's disease and suggest the implication of the nigrostriatal dopaminergic system, and associated striato-frontal neuronal circuits, in executive processes needed for spatial location learning.

Analysis of Variance↗

The mental representation of hand movements after parietal cortex damage.

Recent neuroimagery findings showed that the patterns of cerebral activation during the mental rehearsal of a motor act are similar to those produced by its actual execution. This concurs with the notion that part of the distributed neural activity taking place during movement involves internal simulations, but it is not yet clear what specific contribution the different brain areas involved bring to this process. Here, patients with lesions restricted to the parietal cortex were found to be impaired selectively at predicting, through mental imagery, the time necessary to perform differentiated finger movements and visually guided pointing gestures, in comparison to normal individuals and to a patient with damage to the primary motor area. These results suggest that the parietal cortex is important for the ability to generate mental movement representations.

Adult↗

Cognitive deficits in non-Alzheimer's degenerative diseases.

Although observed in various brain disorders, dementia is particularly frequent in neurodegenerative diseases. Alzheimer's disease is characterized by the association of progressive amnesia with either instrumental (aphasia, apraxia, agnosia) or behavioral (apathy, indifference, anosognosia) disorders, depending upon the location of the underlying neuronal lesions. By contrast, memory, linguistic, praxic, visuo-spatial or comportemental impairments are dissociated in more focal "lobar" atrophies, while planning and retrieval deficits predominate in movement disorders with dementia. Alzheimer's and non-Alzheimer's neurodegenerative diseases can therefore be distinguished insofar as the severity and location of the associated neuronal lesions differ. Dementia may be observed in various brain diseases, either vascular, metabolic, demyelinating, traumatic, infectious, inflammatory, neoplastic or hydrocephalus (Chui, 1989). It is particularly frequent in neurodegenerative diseases. The recent clinical description of focal lobar atrophies (Weintraub and Mesulam, 1993) and the analysis of cognitive impairment observed in diseases with movement disorders (Cummings and Benson, 1984) have changed the conception of dementia, that may no more be defined as a global deterioration of higher cortical functions. The relative specificity of the cognitive picture of each disease depends on the location of the underlying neuronal lesions. Together with other tools, such as the neurological examination or the functional imagery, the neuropsychological exam may contribute to characterize the clinical picture of a patient with non-Alzheimer's degenerative disease and therefore to determine a clinical diagnosis, that remains probable till the neuropathological confrontation.

Alzheimer Disease↗