Is the HM story only a "remote memory"? Some facts about hippocampus and memory in humans.

In this review, we argue that a number of current data support the notion that the hippocampal formations play an important role in episodic memory in humans. We will focus on data gathered from three topics within this field: (1) the neuropsychological study of memory in degenerative diseases, which provides striking dissociations of processes, as a function of the location of cerebral lesions and of their functional consequences; (2) the description of patients' memory difficulties after unilateral medial temporal lobectomy. Given the visuo-verbal dissociation, we may anticipate that the study of the effects of such lesions may help in the understanding of the role of the hippocampus in memory, in terms of: (i) the stage of memory processing where the hippocampus is really involved (encoding, consolidation and/or retrieval); (ii) the specificity of the impairments as a function of the nature (verbal vs. visuo-spatial) of the to-be-remembered material; (3) recent evidence from imaging studies: (i) the morphological approach, which provides interesting information with the study of correlations between the volumes of diverse cerebral regions-particularly the volume of the hippocampus-and episodic memory performance and other cognitive measures; (ii) metabolic studies, using PET scan, which were first designed for correlational analyses between performance in episodic memory tasks and glucose utilization at rest in diverse regions of interest, such as the hippocampal formations; (iii) activation studies with PET and functional MRI, which are actually more straightforward, since they allow correlations between the metabolism in regions of interest and performance on line (e.g. during encoding or retrieval of information). In our view, inasmuch as such different approaches-degenerative diseases, lesions or imagery-provide convergent information, they give renewed weight to the notion according to which the hippocampal formations are critically concerned in episodic memory processes.

The role of dorsolateral prefrontal cortex in the preparation of forthcoming actions: an fMRI study.

The dorsolateral prefrontal cortex (DLPFC) plays a key role in working memory (WM). Yet its precise contribution (the storage, manipulation and/or utilization of information for the forthcoming response) remains to be determined. To test the hypothesis that the DLPFC is more involved in the preparation of actions than in the maintenance of information in short-term memory (STM), we undertook a functional magnetic resonance imaging investigation in normal subjects performing two delayed response tasks (matching and reproduction tasks) in a visuospatial task sequence (presentation, delay, response). In the two tasks, the presentation and delay phases were similar, but the expected response was different: in the matching task, subjects had to indicate whether a visuospatial sequence matched the sequence presented before the delay period; in the reproduction task, subjects had to reproduce the sequence and, therefore, to mentally organize their response during the delay. Using a fMRI paradigm focusing on the delay period, we observed a significant DLPFC activation when subjects were required to mentally prepare a sequential action based on the information stored in STM. When subjects had only to maintain a visuospatial stimulus in STM, no DLPFC activation was found. These results suggest that a parietal-premotor network is sufficient to store visuospatial information in STM whereas the DLPFC is involved when it is necessary to mentally prepare a forthcoming sequential action based on the information stored in STM.

[Procedural learning and Parkinson disease: implication of striato-frontal loops]. / Apprentissage procédural et maladie de Parkinson: implication des boucles striato-frontales.

OBJECTIVE: To investigate procedural learning in non demented patients with idiopathic Parkinson's disease (PD). BACKGROUND: Experimental evidence implicate the basal ganglia in procedural learning. Selective impairment has more recently been described in patients with frontal lesions. METHODS: The performance of 20 demented patients and 15 matched normal controls was studied in the serial reaction time task (SRTT). Performance on procedural task was further compared with that of 9 normal controls and with patients' performance on tests assessing explicit memory, executive functions and global efficiency. RESULTS: The group of patients with PD showed impaired procedural learning. The difference of response time between the repeated and the non-repeated blocks was smaller in PD when compared to controls. Subsequent analyses separated PD patients into two subgroups according to their performance on SRTT, measured by the rebound effect. PD patients whose learning was normal differed from PD patients whose learning was impaired on performance in tests sensitive to frontal lobe dysfunction. CONCLUSION: These results confirm the implication of the striatum in procedural learning and suggest that performance on cognitive procedural learning depends on the striato-frontal circuits.

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.

["Boxer's dementia" without motor signs]. / "Démence pugilistique" sans signes moteurs.

BACKGROUND: The neurological complications related to boxing include dementia. Boxer's dementia is generally associated with severe motor impairment. CASE REPORT: A former professional boxer presented dementia with no motor signs. The diagnostic discussion was based on clinical observations, and neuropsychological and supplementary explorations, and eliminated all other etiological hypotheses. DISCUSSION: This case draws attention to the possibility of cognitive disorders without motor impairment in the neurological complications of boxing.

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.

[Dementia and memory: morphologic imagery with MRI]. / Démences et mémoires: imagerie morphologique par IRM.

Modern imaging techniques, and notably magnetic resonance imaging (MRI) enable an increasingly precise exploration of primary degenerative dementias. The main contribution of imaging is to demonstrate lesion localizations which confirm the degenerative nature of the observed disorders, contributing to an understanding of the correlation between clinical signs and causal lesions. The development of techniques quantifying cerebral volume which can be applied to an analysis of small structures such as the hippocampus coupled with a better understanding of primary degenerative dementias allow more specific study of the atrophy than could be obtained with a global assessment of ventricular dilatation. More recently, the development of MRI methods studying brain perfusion open the way for noninvasive exploration of perfusion anomalies in these patients.

Coupled temporal memories in Parkinson's disease: a dopamine-related dysfunction.

Dysfunction of the basal ganglia and the brain nuclei interconnected with them leads to disturbances of movement and cognition, including disordered timing of movement and perceptual timing deficits. Patients with Parkinson's disease (PD) were studied in temporal reproduction tasks. We examined PD patients when brain dopamine (DA) transmission was impaired (OFF state) and when DA transmission was reestablished, at the time of maximal clinical benefit following administration of levodopa + apomorphine (ON state). Patients reproduced target times of 8 and 21 sec trained in blocked trials with the peak interval procedure, which were veridical in the ON state, comparable to normative performance by healthy young and aged controls (Experiment 1). In the OFF state, temporal reproduction was impaired in both accuracy and precision (variance). The 8-sec signal was reproduced as longer and the 21-sec signal was reproduced as shorter than they actually were (Experiment 1). This "migration" effect was dependent upon training of two different durations. When PD patients were trained on 21 sec only (Experiment 2), they showed a reproduction error in the long direction, opposite to the error produced under the dual training condition of Experiment 1. The results are discussed as a mutual attraction between temporal processing systems, in memory and clock stages, when dopaminergic regulation in the striatum is dysfunctional.

The influence of semantic and perceptual encoding on recognition memory in Alzheimer's disease.

Previous results from a population of patients with Alzheimer's disease (Dalla Barba and Goldblum, 1996) demonstrated that the ability of patients to make a semantic association between two items was significantly and positively correlated to their performance on a yes/no recognition task for the same items and that patients who were impaired on the semantic task did significantly worse on the recognition task than patients who were unimpaired on the semantic task. These findings gave support to a hierarchical model of organization of human memory in which episodic memory depends on the integrity of semantic memory. The present study further investigates the relationship between semantic memory deficits and episodic recognition memory in 15 patients with Alzheimer's disease and 15 controls, as a function of their semantic and perceptual encoding abilities and of their cognitive impairment in other domains. The results confirmed the previous findings and showed that, although patients heavily relied on perceptual analysis, this type of encoding did not enhance their recognition memory. Correlations analyses showed that some patients who were not impaired in the semantic association, but with particularly low scores on a verbal fluency task presented with a pattern, in recognition memory tasks, that suggests a possible early involvement of frontal lobes in this subgroup of patients.

Priming for new associations in normal aging and in mild dementia of the Alzheimer type.

Recent data suggest that patients with Alzheimer's disease (AD) are able to show perceptual priming and, to some extent, conceptual priming for material which has preexisting representations in memory, and that normal elderly subjects are able to automatically activate pre-existing representations in both perceptual and conceptual priming tasks. An important question concerns the capacity of showing priming for materials without pre-existing representations in memory in normal and pathological aging. In order to address this issue, 20 patients with mild AD, 20 elderly controls and 20 young controls subjects were assessed with a paradigm of priming for new verbal associations. Neither the patients nor the normal elderly subjects demonstrated priming effects for new associations, while young subjects showed significant priming effects. These results suggest that the absence of priming for new verbal associations is attributable more to an effect of aging than to a specific effect of Alzheimer's disease.

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.

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.

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.

Memory for spatial location is affected in Parkinson's disease.

Are the striato-frontal neuronal circuits implicated in learning of item-specific spatial coordinates? To answer this question, we compared the performance of 20 patients with Parkinson's disease to that of 14 controls matched for age, global cognitive efficiency and mood, on a visuo-spatial learning task with little involvement of motor and constructive functions, allowing control of encoding and comparison of free recall, cued recall and recognition. Compared to controls, patients showed a severe memory impairment for visuo-spatial location of pictures, contrasting with relative preservation of verbal memory, and mild difficulties in perceptive visuo-spatial and executive functions. These results implicate striato-frontal neuronal circuits in memory for spatial location.

Cross-form priming in normal aging and in mild dementia of the Alzheimer type.

Twenty patients at early stages of Alzheimer's disease (AD), 20 elderly control subjects and 20 young subjects completed a cross-form priming task, followed by a free recall task. Results show that patients with mild AD display priming effects, and that these priming effects are strictly comparable to those obtained by elderly and young control subjects. Moreover, while the patients' performances are normal in the implicit part of the task, they are massively impaired in the explicit free recall task. These results don't support the hypothesis of a dissociation of performances between identification tasks and generation tasks in Alzheimer's disease, and show that conceptual priming can be observed at early stages of the disease, despite semantic memory impairments.

The neuropsychological pattern of corticobasal degeneration: comparison with progressive supranuclear palsy and Alzheimer's disease.

The pattern of cortical and subcortical neuropathologic lesions in corticobasal degeneration (CBD) should predict a specific cognitive profile in this disease. To characterize this profile and to determine its specificity by comparison with progressive supranuclear palsy (PSP) and senile dementia of the Alzheimer's type (SDAT), we used an extensive neuropsychological battery assessing global efficiency, executive functions, various tests of encoding and retrieval, dynamic motor organization, and upper limb praxis. We compared the performance of patients with CBD (n = 15) with that of controls (n = 19) matched for age and education, and with that of patients with PSP and SDAT (15 in each group), matched for severity of dementia and depression. Patients with CBD showed: (1) a moderate global deterioration; (2) a dysexecutive syndrome similar to that of patients with PSP and more severe than in SDAT; (3) explicit learning deficits, without retention difficulties and easily compensated by using the same semantic cues at encoding and retrieval as in PSP; this was in contrast with SDAT where cued recall and recognition were also impaired; (4) disorders of dynamic motor execution (temporal organization, bimanual coordination, control, and inhibition) similar to those of patients with PSP and not in SDAT; (5) asymmetric praxis disorders (posture imitation, symbolic gesture execution, and object utilization) that were not observed in PSP or SDAT. Patients with CBD show a specific neuropsychological pattern associating a dysexecutive syndrome, likely due to degeneration of the basal ganglia and prefrontal cortex, and asymmetric praxis disorders, which might be related to premotor and parietal lobe lesions. This neuropsychological profile may help to distinguish this condition clinically from other neurodegenerative diseases.

[Deficits in memory retrieval: an argument in favor of frontal subcortical dysfunction in depression]. / Les troubles de la récupération mnésique: un argument en faveur d'un dysfonctionnement des structures sous-cortico-frontales dans la dépression.

UNLABELLED: While numerous studies have objective quantitative and qualitative deficits of memory in depressed patients, the mechanisms of these impairments are not well established. The study reported here was designed to assess encoding and retrieval processes in depression and to define the specific nature of memory failure associated with this disorder. METHODS: Ten inpatients with major depression responding to DSM III-R criteria and ten normal controls were included in this study. All subjects were assessed with a neuropsychological battery including: a) subtests of Weschsler memory scale (digit span, logical memory); b) verbal fluency (letter); c) two tasks assessing executive functions (cognitive estimate, Nelson's test); d) two explicit tasks of verbal learning (California Verbal Learning Test and Grober & Buschke's procedure) which measure memory performance in various conditions of encoding (incidental vs controlled) and of recollection (free recall, cued recall and recognition). Severity of depression was assessed with the MADRS and the Retardation Rating Scale for Depression. RESULTS: Although there was no difference between patients and controls on digit span and logical memory tasks, depressed patients exhibited a deficit in verbal learning with CVLT and Grober & Buschke's procedure. On California Verbal Learning Test, depressive subjects performed poorly in free recall and demonstrated poor consistency. Patients show free recall improvement across trials 1 or 5 and this learning effect didn't differ from controls. Score of patients and controls on cued recall and recognition were at the same level. Grober & Buschke's procedure confirmed these results. Despite a control of encoding processes during the initial presentation of the words, free recall measure revealed significant difference between groups. Like controls, patients recalled almost all items when semantic cues was provided and their recognition results showed a ceiling effect. Consistency indexes of free recall and cued recall differed significantly between groups. Verbal fluency and frontal tasks didn't allow to distinguish the depressive patients from controls. DISCUSSION: Depressive subjects exhibited a deficit in free recall and poor consistency while cued recall and recognition were normal. Patient's results in free recall are characterized by difficulties in planning and in maintaining retrieval strategies. These findings suggest that memory failure in depression could reflect an impairment in retrieval processes depending on executive functions controlled by the subcortical structures.

Memory disorders in probable Alzheimer's disease: the role of hippocampal atrophy as shown with MRI.

Magnetic resonance based volumetric measures of hippocampal formation, amygdala (A), caudate nucleus (CN), normalised for total intracranial volume (TIV), were analysed in relation to measures of cognitive deterioration and specific features of memory functions in 18 patients with probable Alzheimer's disease. Neuropsychological examination included the mini mental state examination (MMSE), the Mattis dementia rating scale (DRS), tests of executive functions, assessment of language abilities and praxis, the Wechsler memory scale (WMS), the California verbal learning test (CVLT) and the Grober and Buschke test. The volume of the hippocampal formation (HF/TIV) was correlated with specific memory variables: memory quotient and paired associates of the WMS; intrusions and discriminability at recognition for the Grober and Buschke test. By contrast, except for intrusions, no correlations were found between memory variables and the volume of amygdala (A/TIV). No correlations were found between the volume of caudate nuclei (CN/TIV) and any neuropsychological score. The volume of the hippocampal formation was therefore selectively related to quantitative and qualitative aspects of memory performance in patients with probable Alzheimer's disease.

Neuropsychological pattern of striatonigral degeneration: comparison with Parkinson's disease and progressive supranuclear palsy.

To study the neuropsychological pattern of striatonigral degeneration (SND), 14 consecutive patients with probable SND were submitted to an extensive battery of neuropsychological tests. Compared with controls the performance of patients with SND was impaired on category and phonemic fluency, frontal behaviours, trail making test A and B, and free recall of the Grober and Buschke test, but normal on the revised WAIS verbal scale, Raven 47 coloured progressive matrices, Wechsler memory scale, California verbal learning test, Wisconsin card sorting test, and the Stroop interference condition. The performance of patients with SND was also compared with that of 14 patients with Parkinson's disease and 14 patients with progressive supranuclear palsy (PSP) matched for age at onset, duration of disease, severity of intellectual deterioration, and depression. The results showed that the dysexecutive syndrome of SND is similar to that of Parkinson's disease and less severe than in PSP.