Emmanuel J. Barbeau

Evaluation of visual recognition memory in MCI patients

Background: Neurofibrillary tangles seen early in Alzheimer disease (AD) initially appear in a subregion of the perirhinal cortex. In the monkey, damage to the perirhinal cortex impairs performance on visual recognition memory tasks. The authors evaluated impairment of visual recognition memory as a potential early diagnostic marker of AD. Methods: The authors developed a visual delayed matching-to-sample task (DMS48) designed to assess visual recognition memory in humans. Twenty-three patients fulfilling the criteria of amnestic mild cognitive impairment (MCI) (mean Mini-Mental State Examination [MMSE]: 26.6, SD = 1.6) were recruited. All underwent a full neuropsychological evaluation, which included the Free and Cued Selective Reminding (FCSR) test. Their performance was compared with that of 10 patients with mild AD, 20 patients with moderate AD, 20 patients with Parkinson disease (PD), and 40 age-matched controls. Results: Control subjects and patients with PD performed close to ceiling. Patients with mild AD had very low scores, while patients with moderate AD answered at random. MCI patients obtained scores that were between those of control subjects and patients with mild AD (78%, SD = 16%). MCI patients who failed on the DMS48 had lower scores on free recall (p < 0.05) and received less benefit from cueing (p < 0.01) on the FCSR than the other MCI, suggesting a profile of genuine memory impairment related to medial temporal lobe lesions. Conclusion: The DMS48, a test of visual recognition memory, is impaired early in the course of patients with MCI. Further studies are necessary to determine whether the evaluation of visual recognition memory may contribute to the identification of patients with AD.

The cognitive and neural expression of semantic memory impairment in mild cognitive impairment and early Alzheimer's disease

Semantic deficits in Alzheimers disease have been widely documented, but little is known about the integrity of semantic memory in the prodromal stage of the illness. The aims of the present study were to: (i) investigate naming abilities and semantic memory in amnestic mild cognitive impairment (aMCI), early Alzheimers disease (AD) compared to healthy older subjects; (ii) investigate the association between naming and semantic knowledge in aMCI and AD; (iii) examine if the semantic impairment was present in different modalities; and (iv) study the relationship between semantic performance and grey matter volume using voxel-based morphometry. Results indicate that both naming and semantic knowledge of objects and famous people were impaired in aMCI and early AD groups, when compared to healthy age- and education-matched controls. Item-by-item analyses showed that anomia in aMCI and early AD was significantly associated with underlying semantic knowledge of famous people but not with semantic knowledge of objects. Moreover, semantic knowledge of the same concepts was impaired in both the visual and the verbal modalities. Finally, voxel-based morphometry analyses revealed that semantic impairment in aMCI and AD was associated with cortical atrophy in the anterior temporal lobe (ATL) region as well as in the inferior prefrontal cortex (IPC), some of the key regions of the semantic cognition network. These findings suggest that the semantic impairment in aMCI may result from a breakdown of semantic knowledge of famous people and objects, combined with difficulties in the selection, manipulation and retrieval of this knowledge.

Cortical stimulation study of the role of rhinal cortex in déjà vu and reminiscence of memories

Objective: To study the role of perirhinal (PC) and entorhinal cortices (EC) in dreamy state symptoms (déjà vu and reminiscence of scenes). These phenomena have been attributed to functional alteration of memory networks supported by the medial temporal lobes, principally involving the amygdala and hippocampus. The role of sub-hippocampal structures (EC and PC) in inducing these phenomena has not previously been addressed. Methods: The authors studied the symptoms evoked by direct electrical stimulations of PC and EC in comparison with those obtained after stimulation of the amygdala and hippocampus. Stimulations were performed in a group of 24 patients with epilepsy, during stereoelectroencephalographic (SEEG) recordings in the setting of presurgical evaluation. All patients had electrodes that sampled the rhinal cortices, amygdala, and hippocampus. Results: A total of 280 stimulations were analyzed. Entorhinal and perirhinal stimulations induced classic mesial temporal lobe responses (emotional, dysautonomic) but also more specific responses, particularly the déjà vu phenomenon and reminiscence of scenes. Such déjà vu or déjà vécu type responses were produced proportionately more often by stimulation of the EC than by stimulation of the amygdala and hippocampus. In particular, déjà vu was associated with stimulation of the EC and reminiscence of memories with PC stimulation. Conclusion: This study strongly suggests that experiential symptoms are largely dependent upon functional modification of the physiology of the rhinal cortices.

Ultra-Rapid Sensory Responses in the Human Frontal Eye Field Region

Most of what we know about the human frontal eye field (FEF) is extrapolated from studies in animals. There is ample evidence that this region is crucial for eye movements. However, evidence is accumulating that this region also plays a role in sensory processing and that it belongs to a “fast brain” system. We set out to investigate these issues in humans, using intracerebral recordings in patients with drug-refractory epilepsy. Event-related potential recordings were obtained from 11 epileptic patients from within the FEF region while they passed a series of visual and auditory perceptual tests. No eye movement was required. Ultra-rapid responses were observed, with mean onset latencies at 24 ms after stimulus to auditory stimuli and 45 ms to visual stimuli. Such early responses were compatible with cortical routes as assessed with simultaneous recordings in primary auditory and visual cortices. Components were modulated very early by the sensory characteristics of the stimuli, in the 30–60 ms period for auditory stimuli and in the 45–60 ms period for visual stimuli. Although the frontal lobes in humans are generally viewed as being involved in high-level cognitive processes, these results indicate that the human FEF is a remarkably quickly activated multimodal region that belongs to a network of low-level neocortical sensory areas.

Patterns of semantic memory impairment in Mild Cognitive Impairment

Although the semantic memory impairment has been largely documented in Alzheimers disease, little is known about semantic memory in the preclinical phase of the disease (Mild Cognitive Impairment). The purpose of this study was to document the nature of semantic breakdown using a battery of tests assessing different aspects of conceptual knowledge: knowledge about common objects, famous people and famous public events. Results indicate that all domains of semantic memory were impaired in MCI individuals but knowledge about famous people and famous events was affected to a greater extent than knowledge about objects. This pattern of results suggests that conceptual entities with distinctive and unique properties may be more prone to semantic breakdown in MCI. In summary, results of this study support the view that genuine semantic deficits are present in MCI. It could be useful to investigate the etiological outcome of patients failing or succeeding at such tests.

Profile of memory impairment and gray matter loss in amnestic mild cognitive impairment

The present study assessed the patterns of cortical gray matter (GM) loss in patients with amnestic mild cognitive impairment (aMCI) with distinct profiles of memory impairment, i.e. aMCI patients failing on both recall and recognition memory vs. aMCI patients showing impaired recall but preserved recognition memory. This distinction is usually not taken into account in studies on aMCI and the aim of the present study was to assess whether this distinction is useful. Twenty-eight aMCI patients and 28 matched controls subjects were included. All aMCI patients failed a recall memory task (inclusion criteria). All underwent a visual recognition memory task (DMS48). However, 12 succeeded on this task while 16 failed. Relative gray matter (GM) loss was measured using voxel-based morphometry. When comparing aMCI patients to controls regardless of the profile of memory impairment, GM loss was found in temporal, parietal and frontal areas. However, in aMCI patients with preserved recognition (but impaired recall), GM loss was confined to frontal areas. This contrasted with GM loss in the right medial temporal lobe and bilateral temporo-parietal regions in aMCI patients with impaired recall and recognition memory, a pattern of GM loss usually described in early AD. We conclude that different profiles of memory impairment in aMCI patients are associated with distinct patterns of GM loss.

Basal functional connectivity within the anterior temporal network is associated with performance on declarative memory tasks

Spontaneous fluctuations in the blood oxygenation level-dependent (BOLD) signal, as measured by functional magnetic resonance imaging (fMRI) at rest, exhibit a temporally coherent activity thought to reflect functionally relevant networks. Antero-mesial temporal structures are the site of early pathological changes in Alzheimers disease and have been shown to be critical for declarative memory. Our study aimed at exploring the functional impact of basal connectivity of an anterior temporal network (ATN) on declarative memory. A heterogeneous group of subjects with varying performance on tasks assessing memory was therefore selected, including healthy subjects and patients with isolated memory complaint, amnestic Mild Cognitive Impairment (aMCI) and mild Alzheimers disease (AD). Using Independent Component Analysis on resting-state fMRI, we extracted a relevant anterior temporal network (ATN) composed of the perirhinal and entorhinal cortex, the hippocampal head, the amygdala and the lateral temporal cortex extending to the temporal pole. A default mode network and an executive-control network were also selected to serve as control networks. We first compared basal functional connectivity of the ATN between patients and control subjects. Relative to controls, patients exhibited significantly increased functional connectivity in the ATN during rest. Specifically, voxel-based analysis revealed an increase within the inferior and superior temporal gyrus and the uncus. In the patient group, positive correlations between averaged connectivity values of ATN and performance on anterograde and retrograde object-based memory tasks were observed, while no correlation was found with other evaluated cognitive measures. These correlations were specific to the ATN, as no correlation between performance on memory tasks and the other selected networks was found. Taken together, these findings provide evidence that basal connectivity inside the ATN network has a functional role in object-related, context-free memory. They also suggest that increased connectivity at rest within the ATN could reflect compensatory mechanisms that occur in response to early pathological insult.

The right temporal lobe variant of frontotemporal dementia : Cognitive and neuroanatomical profile of three patients.

The right temporal variant of frontotemporal lobar degeneration (Rtv-FTLD) is a focal degenerative condition affecting predominantly the right temporal lobe. The aim of this study was to further characterize the profile of cognitive impairment and the neuroanatomical basis of Rtv-FTLD patients without behavioural disturbances. A group of three patients with this syndrome had a detailed neuropsychological assessment, along with Voxel-Based Morphometry (VBM) of their brain to determine location of cortical atrophy. VBM analyses showed a pattern of atrophy that was predominant in the right hemisphere and concerned primarily the right anterior temporal lobe region. Patients carried out a test of famous people in which their ability to recognize, name and provide semantic information about famous persons from their faces, their voices and their names was investigated. They all showed a severe defect in recognizing, naming and identifying famous people irrespective of modality. Therefore, their inability to recognize famous people resulted from a multimodal defect (semantic). These results highlight the semantic nature of the defect, and suggest that the anterior right temporal lobe may have a prominent role in processing person-based semantic knowledge. This study helps in further understanding the neuropsychological profile of patients with Rtv-FTLD.

Neuropsychological outcome after a first symptomatic ischaemic stroke with 'good recovery'

Background:  Neuropsychological impairment after stroke when no motor, sensory or language deficits are left remains understudied. The primary aim of this study was to assess neuropsychological outcome in a specific population of patients after a first symptomatic stroke without previous cognitive decline and with a good motor, linguistic, and functional recovery (i.e. ‘good outcome’). The secondary aims were to identify the profile of this potential impairment and relations between brain lesions and neuropsychological outcome.

Extent and neural basis of semantic memory impairment in mild cognitive impairment.

An increasing number of studies indicate that semantic memory is impaired in mild cognitive impairment (MCI). However, the extent and the neural basis of this impairment remain unknown. The aim of the present study was: 1) to evaluate whether all or only a subset of semantic domains are impaired in MCI patients; and 2) to assess the neural substrate of the semantic impairment in MCI patients using voxel-based analysis of MR grey matter density and SPECT perfusion. 29 predominantly amnestic MCI patients and 29 matched control subjects participated in this study. All subjects underwent a full neuropsychological assessment, along with a battery of five tests evaluating different domains of semantic memory. A semantic memory composite Z-score was established on the basis of this battery and was correlated with MRI grey matter density and SPECT perfusion measures. MCI patients were found to have significantly impaired performance across all semantic tasks, in addition to their anterograde memory deficit. Moreover, no temporal gradient was found for famous faces or famous public events and knowledge for the most remote decades was also impaired. Neuroimaging analyses revealed correlations between semantic knowledge and perirhinal/entorhinal areas as well as the anterior hippocampus. Therefore, the deficits in the realm of semantic memory in patients with MCI is more widespread than previously thought and related to dysfunction of brain areas beyond the limbic-diencephalic system involved in episodic memory. The severity of the semantic impairment may indicate a decline of semantic memory that began many years before the patients first consulted.