High-field mid-infrared pulses derived from frequency domain optical parametric amplification.

We present a novel, to the best of our knowledge, approach for scaling the peak power of mid-infrared laser pulses with few-cycle duration and carrier-to-envelope phase stabilization. Using frequency domain optical parametric amplification (FOPA), selective amplification is performed on two spectral slices of broadband pulses centered at 1.8 µm wavelength. In addition to amplification, the Fourier plane is used for specific pulse shaping to control both the relative polarization and the phase/delay between the two spectral slices of the input pulses. At the output of the FOPA, intrapulse difference frequency generation provides carrier-envelope phase stabilized two-cycle pulses centered at 9.5 µm wavelength with 25.5 µJ pulse energy. The control of the carrier-envelope phase is demonstrated through the dependence of high-harmonic generation in solids. This architecture is perfectly adapted to be scaled in the future to high average and high peak powers using picosecond ytterbium laser technologies.

Unawareness of memory impairment and behavioral abnormalities in patients with Alzheimer's disease: relation to professional health care burden.

OBJECTIVES: The present study investigates the impact of unawareness of deficit (anosognosia) in patients with Alzheimer's disease upon professional health care burden. DESIGN: Cross-sectional study with a consecutive clinical sample from an Alzheimer day-care hospital in France. SUBJECTS: 65 patients with probable AD, aged from 75 to 94 years old, consecutively admitted at the Alzheimer Day Hospital to complete a program of cognitive stimulation and psychosocial rehabilitation. MEASUREMENTS: Each patient was submitted to a standardized evaluation including clinical investigation, cerebral imagery, and neuropsychological assessment. Anosognosia of memory deficit and anosognosia of behavioral disturbances were measured as the "discrepancy scores" between patients' self-reports and family member ratings of patient memory performance and behavioral disturbances. Professional health care burden was assessed with the Professional Health Care Dementia Burden Index (PCDBI; maximal score: 12), designed for this study. Multiple linear regressions were used to examine the correlations between the PCDBI and the severity of anosognosia. RESULTS: The findings showed a significant positive correlation between the PCDBI and both anosognosia of memory impairment and behavioral abnormalities (both p at least less than 0.05). However, there was no significant correlation between the severity of the burden and the severity of cognitive decline or functional impairment (both p at least>0.05). CONCLUSION: Anosognosia in Alzheimer disease patients has a negative impact upon the professional caregivers' burden over and above the cognitive deficit and the functional impairments.

[French adaptation of the Hopkins Verbal Learning Test]. / Adaptation française du <>.

INTRODUCTION: A number of tests are currently used in clinical and research settings for the assessment of patients with memory deficits. Among them, the Hopkins Verbal Learning Test (HVLT) is particularly appropriate for the longitudinal follow-up of patients with memory disorders because it exists in six parallel forms, and therefore avoids the risk of learning effect at retest. Since a test with these characteristics is not available in French, we decided to adapt a French version of the HVLT. METHODS: 180 normal subjects participated in the study. Their mean age was 41 years (SD=11), and they had had on average 12 years of schooling (SD=3). The subjects were randomly divided into 6 groups of 30 subjects. One of the six forms of the French version of the HVLT was administered orally to each group of subjects. Each form consisted of a list of 12 words belonging to 3 different semantic categories. For the construction of the French version of the HVLT, we adopted the same procedure as used in the original version of the test taking into account the French lexical and semantic characteristics of the items. In the first part of the test, the list was administered three times to the subjects. Following each administration, subjects were asked for an immediate free recall. Twenty minutes later, used for intercurrent tasks, subjects were asked for a delayed free recall, which was immediately followed by a recognition memory task. In this task, subjects listened to a list of 24 words, 12 belonging to the studied list and 12 were distractors; the subjects were asked to recognize the 12 studied words. RESULTS: The subjects' performance was equivalent in the six forms of the test, except for the immediate recall of Form 3 (which was excluded from the test). No significant difference emerged in free recall, delayed free recall, and recognition across the five remaining forms of the test. CONCLUSION: Our study provides a useful tool for the longitudinal evaluation of patients with memory impairment and may become the test of reference in European longitudinal clinical trials. The French adaptation of the HVLT represents only a first step, because it needs to be standardized, in order to provide norms, and validated, in order to provide values of sensitivity and specificity.

Confabulation, but not executive dysfunction discriminate AD from frontotemporal dementia.

We examined confabulation and performance on frontal/executive tasks in Alzheimer's disease (AD) patients and patients with a diagnosis of probable frontotemporal dementia (FTD). Twenty-two patients with probable AD, 10 patients with probable FTD and 32 normal control subjects entered the study. Executive functions were assessed with the Modified Card Sorting test; a verbal fluency test; the Cognitive Estimation test; and the Stroop test. Confabulations were assessed with a modified version of the Confabulation Battery. The Confabulation Battery included 10 questions tapping each of the following domains: Episodic Memory (memories of personal past episodes), Semantic Memory (knowledge of famous facts and famous people), and Personal Future (personal plans). The results revealed that both AD patients and FTD patients were clearly and equally impaired on tests of executive functions. Both patients' groups confabulated across the three tasks of the Confabulation Battery, but FTD patients confabulated significantly more than AD patients on Episodic Memory and Personal Future. The results failed to provide any evidence of a correlation between the performance on frontal/executive tasks and the tendency to produce confabulatory reports. According to our results, confabulation, more than a deficit of frontal/executive functions, discriminate between AD and FTD. Therefore, screening for confabulation and, possibly, for other types of memory distortions may constitute a useful additional clinical tool in order to discriminate AD from FTD.

Memory deficits and retrieval processes in ALS.

Subtle neuropsychological deficits have been described in patients affected by amyotrophic lateral sclerosis (ALS) without dementia. Overall, selective impairment in memory function has been reported, but the source of memory impairment in ALS has yet to be defined. We performed neuropsychological screening in 20 ALS patients. Semantic encoding and post-encoding cue effects on the retrieval of word lists were investigated in the ALS patients and normal controls. Severity of memory impairment was correlated to cerebral blood perfusion detected by single photon emission computed tomography (SPECT). ALS patients showed moderate impairments in frontal and memory tests. Short-term memory was normal, while serial position retrieval of word lists with normal recency effect but poor primacy effect showed long-term memory deficit. ALS patients performed better in cued encoding than in cued post-encoding recall condition. In the cued post-encoding condition, the primacy effect in word list recall improved significantly in controls, but not in ALS patients, as compared with both the free recall and cued encoding conditions. SPECT hypoperfusion was observed in frontal and temporal areas in ALS patients. ALS patients showed a long-term memory deficit which did not improve in cued post-encoding condition as it does for controls. We hypothesize abnormal retrieval processes related to frontal lobe dysfunction which entails difficulties in generating stable long-memory traces at encoding.

Retest effects and cognitive decline in longitudinal follow-up of patients with early HD.

OBJECTIVE: To assess the natural progression of cognitive impairment in Huntington's disease (HD) and to reveal factors that may mask this progression. BACKGROUND: Although numerous cross-sectional studies reported cognitive deterioration at different stages of the disease, progressive cognitive deterioration has been, up to now, difficult to demonstrate in neuropsychological longitudinal studies. METHODS: The authors assessed 22 patients in early stages of HD at yearly intervals for 2 to 4 years (average, 31.2 +/- 10 months), using a comprehensive neuropsychological battery based on the Core Assessment Program for Intracerebral Transplantation in Huntington's Disease (CAPIT-HD). RESULTS: The authors observed a significant decline in different cognitive functions over time: these involved primarily attention and executive functions but also involved language comprehension, and visuospatial immediate memory. Episodic memory impairment that was already present at the time of enrollment did not show significant decline. The authors found a significant retest effect at the second assessment in many tasks. CONCLUSION: Many attention and executive tasks adequately assess the progression of the disease at an early stage. For other functions, the overlapping of retest effects and disease progression may confuse the results. High interindividual and intraindividual variability seem to be hallmarks of the disease.

Motor and cognitive improvements in patients with Huntington's disease after neural transplantation.

BACKGROUND: Huntington's disease is a neurodegenerative disease of genetic origin that mainly affects the striatum. It has severe motor and cognitive consequences and, up to now, no treatment. Motor and cognitive functions can be restored in experimental animal models by means of intrastriatal transplantation of fetal striatal neuroblasts. We explored whether grafts of human fetal striatal tissue could survive and have detectable effects in five patients with mild to moderate Huntington's disease. METHODS: After 2 years of preoperative assessment, patients were grafted with human fetal neuroblasts into the right striatum then, after a year, the left striatum. Final results were assessed 1 year later on the basis of neurological, neuropsychological, neurophysiological, and psychiatric tests. The results obtained were compared with those of a cohort of 22 untreated patients at similar stages of the disease who were followed up in parallel. Repeated magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning with fluorine-18-labelled fluorodeoxyglucose was also done to assess metabolic activity. FINDINGS: The final PET-scan assessment showed increased metabolic activity in various subnuclei of the striatum in three of five patients, contrasting with the progressive decline recorded in the two other patients in the series, as seen in patients with untreated Huntington's disease. Small areas of even higher metabolic activity, coregistering with spherical hyposignals on MRI were also present in the same three patients, suggesting that grafts were functional. Accordingly, motor and cognitive functions were improved or maintained within the normal range, and functional benefits were seen in daily-life activities in these three patients, but not in the other two. INTERPRETATION: Fetal neural allografts could be associated with functional, motor, and cognitive improvements in patients with Huntington's disease.

Confabulation in a patient with fronto-temporal dementia and a patient with Alzheimer's disease.

This paper describes two patients, O.I. and B.Y., with a confabulatory syndrome. O.I. was diagnosed with probable fronto-temporal dementia, whereas B.Y. met the criteria for probable Alzheimer's disease. O.I., but not B.Y., was impaired on tests of frontal/executive functions, and performed better than B.Y. on clinical tests of memory. Both patients confabulated in episodic/autobiographical memory tasks and in personal future planning tasks. B.Y. confabulated also in a semantic memory task. It is argued that the pattern of confabulation and the cognitive profile shown by the two patients is explained better by the hypothesis proposed by Dalla Barba and co-workers (Dalla Barba et al., 1997b) than by current theories of confabulation.

[Neuropsychological aspects of Alzheimer's disease]. / La neuropsychologie de la maladie d'Alzheimer.

This analysis is centered on the study of cognitive disorders in Alzheimer's Disease (AD), mainly for major neuropsychological functions. We insist on the heterogeneity of the clinical picture especially in the early stages of the illness, when deficits of episodic memory and executive functions are prevalent. We consider that studying early stages of the illness is necessary to delineate the diagnostic signs, to validate the new therapeutic experiments, to predict stages of decline.

Memory and language in neurodegenerative diseases.

This article reviews recent studies concerning memory and language disorders in Alzheimer's disease and other neurodegenerative conditions. It shows how different memory and language subcomponents may differentially be impaired in different neurodegenerative diseases and at different stages of the same disease.

Cortical networks implicated in semantic and episodic memory: common or unique?

While previous functional neuroimaging studies have shown that semantic and episodic memory tasks activate different cortical regions, they never compared regional cerebral blood flow (rCBF) patterns associated with semantic and episodic memory within the same experimental design. In this study, we used H2(15)O PET to study subjects in the course of semantic and episodic memory tasks. rCBF was measured in 9 normal volunteers during a resting baseline condition and two cognitive tasks. In the semantic categorisation task subjects heard a list of concrete words and had to respond to words belonging to the "animals" or "food" category. In the episodic recognition task subjects heard a list of concrete words, half "old", i.e. belonging to the list of the semantic categorisation task, and half "new", i.e. presented for the first time. Subjects had to respond to the "old" words. Both tasks were compared to a resting condition. Statistical analysis was performed with Statistical Parametric Mapping (SPM). Compared to the resting condition, the semantic tasks, activated the superior temporal gyri bilaterally, the left frontal cortex, and right premotor cortex. The episodic tasks activated the left superior temporal gyrus, the frontal cortex bilaterally, and the right inferior parietal cortex. Compared to the episodic memory tasks, the semantic memory tasks activated the superior temporal/insular cortex bilaterally and the right premotor cortex. Compared to the semantic memory tasks, the episodic memory tasks activated the right frontal cortex. These results suggest that cortical networks implicated in semantic and episodic memory show both common and unique regions, with the right prefrontal cortex being the neural correlate specific of episodic remembering.

Right-side neglect in Alzheimer's disease.

Unilateral neglect--the inability to pay attention to events occurring on one side of space--usually occurs for left-side events after focal right-hemisphere damage. We report a 73-year-old woman with probable AD and no evidence of focal brain lesions who showed signs of right-side neglect and extinction. Neglect was more severe after 1 year. Neuroimaging techniques demonstrated an asymmetry of cortical involvement, with cortical atrophy and hypoperfusion predominant in the left posterior regions. Unilateral neglect should be assessed systematically in AD.

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.

Temporal gradient in confabulation.

We report on a patient, PL, who developed an amnesic confabulatory syndrome following heart arrest. PL's confabulation occurred both in episodic and semantic memory tasks. In a task in which she was asked to identify photographs of people and events highly familiar to her, a temporal gradient on her performance emerged. Confabulation was massive for the recognition of photographs from the eighties and decreased consistently for the recognition of photographs representing people and events from earlier decades. Correct responses, in contrast, were distributed according to an opposite pattern. Correct recognition was very high for photographs from the fifties but consistently decreased for photographs from the following decades. These results are discussed in terms of the co-occurrence and interaction of preserved awareness of the personal past and impaired ability to access less stable memories. These results also suggest that memories are not stored randomly but according to a temporal criterion that presumably reflects the relative strength and stability of stored episodic memories.

Multiple-domain dissociation between impaired visual perception and preserved mental imagery in a patient with bilateral extrastriate lesions.

A brain-damaged patient is described whose pattern of performance provides insight into both the functional mechanisms and the neural structures involved in visual mental imagery. The patient became severely agnosic, alexic, achromatopsic and prosopagnosic following bilateral brain lesions in the temporo-occipital cortex. However, her mental imagery for the same visual entities that she could not perceive was perfectly preserved. This clear-cut dissociation held across all the major domains of high-level vision: object recognition, reading, colour and face processing. Our findings, together with other reports on domain-specific dissociations and functional brain imaging studies, provide evidence to support the view that visual perception and visual mental imagery are subserved by independent functional mechanisms, which do not share the same cortical implementation. In particular, our results suggest that mental imagery abilities need not be mediated by early visual cortices.

G.B. Vico, precursor of cognitive neuropsychology? The first reported case of noun-verb dissociation following brain damage.

The first case of selective impairment in retrieving verbs in comparison to nouns, following brain damage, was reported in 1744 by the Neapolitan philosopher G. B. Vico. He considered such observation experimental evidence of the correctness of his theory on mental organization of language, thus anticipating the methods of cognitive neuropsychology.

Remembering and knowing the past: a case study of isolated retrograde amnesia.

We describe a patient, RM, who suddenly became amnesic for premorbid autobiographic events in the absence of any known precipitating event. Learning abilities as well as semantic knowledge were normal. Knowledge of famous facts and persons was good, although not perfect. Whether RM suffered from organic or psychogenic isolated retrograde amnesia (IRA) could not be established on the basis of available clinical and neuropsychological elements. Regardless of its aetiology, RM's case respects the boundaries between semantic and episodic memory and so gives further support to the distinction between these two memory systems.

Recognition memory and recollective experience in Alzheimer's disease.

The phenomenal experience that accompanies the recognition of a previously presented stimulus seems to take at least two distinct forms. Recognition can occur when the stimulus evokes some specific experience in which the stimulus was previously involved, or, alternatively, when the stimulus gives rise only to feeling of familiarity without any recollective experience. These two kinds of conscious awareness can be measured in laboratory conditions by "remember" and "know" responses. A "remember" response indicates that recognising the stimulus brings back to mind some conscious recollection of its prior occurrence, whereas a "know" response indicates that recognising the stimulus is not accompanied by any conscious recollection of its prior occurrence. In the experiments reported here the relationship between recognition memory and conscious experience in Alzheimer's disease (AD) patients was investigated. The purpose of the experiments was to compare "remember" measures of conscious awareness in free recognition and forced-choice recognition memory for words and unfamiliar faces. The point of the experiments was to see whether AD patients' performance might be associated with a decrease in the relative incidence of "remember" responses as compared to normal controls (NC), and whether there was an effect of experimental material (words versus faces) on recognition performance and on recollective experience. In both experiments AD patients produced significantly fewer correct responses and fewer "remember" responses for correctly recognised items than NC. By contrast AD patients produced the same proportion of "know" responses to target items as compared to NC in all recognition conditions, with the exception of forced-choice recognition of faces where they gave more "know" responses to target faces than NC. These results are consistent with the assumption that recognition memory may entail two processes, only one of which gives rise to conscious recollection, and they suggest that an impairment of conscious recollection is responsible for the poor performance of AD patients in recognition memory. Implications of these findings for current theories of retrieval are discussed.