[Age-related cognitive impairment: conceptual changes and diagnostic strategies]. / Troubles cognitifs liés au vieillissement: évolution récente des concepts et stratégies diagnostiques.

The actual field of dementia encompasses also the pre-symptomatic phase, which may evolve for decades. Early detection and appropriate diagnosis decrease patient's and family's anxiety, improve patient's global care and allow better legal patient's protection. General Practitioners have at hand several available tools to screen a neurocognitive disorder, with up to 80% of sensitivity and specificity, to complete their clinical evaluation. An accurate diagnosis requires then a complete medical, neurological neuropsychological and neuroradiological evaluation in a Memory Clinic. Other investigations, such as functional cerebral imagery and spinal tap can be critical in unusual situations. Despite mood improvement after diagnostic announcement, increased suicidal risk in the 3 first months should be screened.

Experience-based Auditory Predictions Modulate Brain Activity to Silence as do Real Sounds.

Interactions between stimuli's acoustic features and experience-based internal models of the environment enable listeners to compensate for the disruptions in auditory streams that are regularly encountered in noisy environments. However, whether auditory gaps are filled in predictively or restored a posteriori remains unclear. The current lack of positive statistical evidence that internal models can actually shape brain activity as would real sounds precludes accepting predictive accounts of filling-in phenomenon. We investigated the neurophysiological effects of internal models by testing whether single-trial electrophysiological responses to omitted sounds in a rule-based sequence of tones with varying pitch could be decoded from the responses to real sounds and by analyzing the ERPs to the omissions with data-driven electrical neuroimaging methods. The decoding of the brain responses to different expected, but omitted, tones in both passive and active listening conditions was above chance based on the responses to the real sound in active listening conditions. Topographic ERP analyses and electrical source estimations revealed that, in the absence of any stimulation, experience-based internal models elicit an electrophysiological activity different from noise and that the temporal dynamics of this activity depend on attention. We further found that the expected change in pitch direction of omitted tones modulated the activity of left posterior temporal areas 140-200 msec after the onset of omissions. Collectively, our results indicate that, even in the absence of any stimulation, internal models modulate brain activity as do real sounds, indicating that auditory filling in can be accounted for by predictive activity.

High and low stimulus-driven conflict engage segregated brain networks, not quantitatively different resources.

Task-irrelevant information is constantly present in our environment and may interfere with the processing of the information necessary to achieve goal-directed behavior. While task goals determine which information must be suppressed, the demand for inhibitory control depends on the strength of the interference induced by incoming, task-irrelevant information. Whether the same or distinct inhibitory processes are engaged to suppress various degrees of interference from task-irrelevant information remains largely unresolved. We investigated this question by manipulating the strength of the conflict induced by automatic word reading in a classical color Stroop task. High conflict was induced by presenting words in participant's native language and low conflict by presenting words in a less familiar language. Behavioral performance and electrical neuroimaging analyses of event-related potentials to the words were analyzed following a two-by-two within-subject design with factors conflict strength (high; low) and color word/word ink congruency (congruent; incongruent). Behaviorally, we observed a significant conflict strength × congruency driven by a smaller Stroop effect in the low- than high conflict condition. Electrophysiologically, we observed a significant conflict strength × congruency interaction at the topographic level during the period of the N450 components, indicative of the engagement of distinct configurations of brain networks. No such interaction was found at the level of response strength. Electrical sources analyses localized the topographic effect within the anterior cingulate cortex and basal ganglia, left middle frontal and occipital areas. We interpret our results in terms of qualitatively distinct executive mechanisms for reactive inhibitory control in conditions of high versus low stimulus-driven conflict.

Inter- and intrahemispheric dissociations in ideomotor apraxia: a large-scale lesion-symptom mapping study in subacute brain-damaged patients.

Pantomimes of object use require accurate representations of movements and a selection of the most task-relevant gestures. Prominent models of praxis, corroborated by functional neuroimaging studies, predict a critical role for left parietal cortices in pantomime and advance that these areas store representations of tool use. In contrast, lesion data points to the involvement of left inferior frontal areas, suggesting that defective selection of movement features is the cause of pantomime errors. We conducted a large-scale voxel-based lesion-symptom mapping analyses with configural/spatial (CS) and body-part-as-object (BPO) pantomime errors of 150 left and right brain-damaged patients. Our results confirm the left hemisphere dominance in pantomime. Both types of error were associated with damage to left inferior frontal regions in tumor and stroke patients. While CS pantomime errors were associated with left temporoparietal lesions in both stroke and tumor patients, these errors appeared less associated with parietal areas in stroke than in tumor patients and less associated with temporal in tumor than stroke patients. BPO errors were associated with left inferior frontal lesions in both tumor and stroke patients. Collectively, our results reveal a left intrahemispheric dissociation for various aspects of pantomime, but with an unspecific role for inferior frontal regions.

Cognition and psychopathology in nonagenarians and centenarians living in geriatric nursing homes in Switzerland: a focus on anosognosia.

BACKGROUND: The number of nonagenarians and centenarians is rising dramatically, and many of them live in nursing homes. Very little is known about psychiatric symptoms and cognitive abilities other than memory in this population. This exploratory study focuses on anosognosia and its relationship with common psychiatric and cognitive symptoms. METHODS: Fifty-eight subjects aged 90 years or older were recruited from geriatric nursing homes and divided into five groups according to Mini-Mental State Examination scores. Assessment included the five-word test, executive clock-drawing task, lexical and categorical fluencies, Anosognosia Questionnaire-Dementia, Neuropsychiatric Inventory, and Charlson Comorbidity Index. RESULTS: Subjects had moderate cognitive impairment, with mean ± SD Mini-Mental State Examination being 15.41 ± 7.04. Anosognosia increased with cognitive impairment and was associated with all cognitive domains, as well as with apathy and agitation. Subjects with mild global cognitive decline seemed less anosognosic than subjects with the least or no impairment. Neither anosognosia nor psychopathological features were related to physical conditions. CONCLUSIONS: Anosognosia in oldest-old nursing home residents was mostly mild. It was associated with both cognitive and psychopathological changes, but whether anosognosia is causal to the observed psychopathological features requires further investigation.

Electrical neuroimaging during auditory motion aftereffects reveals that auditory motion processing is motion sensitive but not direction selective.

Following prolonged exposure to adaptor sounds moving in a single direction, participants may perceive stationary-probe sounds as moving in the opposite direction [direction-selective auditory motion aftereffect (aMAE)] and be less sensitive to motion of any probe sounds that are actually moving (motion-sensitive aMAE). The neural mechanisms of aMAEs, and notably whether they are due to adaptation of direction-selective motion detectors, as found in vision, is presently unknown and would provide critical insight into auditory motion processing. We measured human behavioral responses and auditory evoked potentials to probe sounds following four types of moving-adaptor sounds: leftward and rightward unidirectional, bidirectional, and stationary. Behavioral data replicated both direction-selective and motion-sensitive aMAEs. Electrical neuroimaging analyses of auditory evoked potentials to stationary probes revealed no significant difference in either global field power (GFP) or scalp topography between leftward and rightward conditions, suggesting that aMAEs are not based on adaptation of direction-selective motion detectors. By contrast, the bidirectional and stationary conditions differed significantly in the stationary-probe GFP at 200 ms poststimulus onset without concomitant topographic modulation, indicative of a difference in the response strength between statistically indistinguishable intracranial generators. The magnitude of this GFP difference was positively correlated with the magnitude of the motion-sensitive aMAE, supporting the functional relevance of the neurophysiological measures. Electrical source estimations revealed that the GFP difference followed from a modulation of activity in predominantly right hemisphere frontal-temporal-parietal brain regions previously implicated in auditory motion processing. Our collective results suggest that auditory motion processing relies on motion-sensitive, but, in contrast to vision, non-direction-selective mechanisms.

Glossolalia and Aphasia: Related but Different Worlds.

The word glossolalia, also referred to as "speaking in tongues," originates from the Greek "glossa" which means "language" and "Lalia" which means "speak." It simply means to talk language. On a linguistic perspective, glossolalia is characterized by almost no recognizable words or semantic content, apart from biblical words and phrases, with an overrepresentation of a small phonemes number, accelerated speech output, and modification of accents and melody. Its phonemic properties have been said to resemble those of the language(s) of the speaker. It is generally a voluntary intimate communication act associated with religious spiritual thoughts, although it has also been described in mental disorders. Glossolalia state is a special mental state, completely different from aphasia. Aphasia is characterized by some phonological and grammatical rules; however, these are related to neurolinguistics and not to developmental principles. Unlike aphasia, glossolalia is not associated with central nervous system affection. There is, however, a psychiatric type of glossolalia, which, although similar in terms of phenomenology, is probably a different phenomenon. A common thought is that there is a linguistic trend, whose basic component is a stream of speech. This stream is suggested to use early-acquired rules of phonation, adapted according to socially meaningful values and attitudes, in an unconscious way. Therefore, the act of glossolalia is out of the "glossolalists" control. It would appear, therefore, that there is a broad spectrum of anomalous speech, of which religious glossolalia is only one manifestation. The aim of this chapter is to understand the mental state of glossolalia in comparison to aphasia in the light of neurolinguistic and psychiatric features. Moreover, we tried to highlight the underlying brain network. Pilot neuroscientific data suggest that it is associated with a deactivation of the cognitive system and an activation of some parts of the mirror neuron networks.

Effects of Prefrontal Transcranial Direct Current Stimulation on Lexical Access in Chronic Poststroke Aphasia.

BACKGROUND: A successful interplay between prefrontal and domain-specific language areas is critical for language processing. Previous studies involving people with aphasia have shown that executive control processes might act on lexical-semantic representations during retrieval. Modulating the prefrontal control network by means of noninvasive brain stimulation might, therefore, improve lexical access in people with aphasia. OBJECTIVE: The present study investigates the effects of prefrontal transcranial direct current stimulation (tDCS) on lexical access in chronic poststroke aphasia. METHODS: We report data of 14 participants with chronic poststroke aphasia. We used a sham-tDCS (S-tDCS) controlled and double-blind within-subjects design. Performances in picture naming, verbal fluency, and word repetition were assessed immediately after stimulation. RESULTS: As compared with S-tDCS, anodal tDCS (A-tDCS) improved verbal fluency as well as the speed of naming high frequency words, but not word repetition. CONCLUSION: The results of our study suggest that the brain network dedicated to lexical retrieval processing can be facilitated by A-tDCS over the left dorsolateral prefrontal cortex. This finding supports the notion that strengthening executive control functions after stroke could complement speech and language-focused therapy.

Analysis of CYP1B1 Gene Mutations in Patients with Primary Congenital Glaucoma.

Primary congenital glaucoma (PCG) is the most common type of infantile glaucoma, yet it remains a relatively rare disease, because the disease is often transmitted in an autosomal recessive pattern. However, PCG occurs up to 10 times more frequently in certain ethnic and geographical groups where consanguineous relationships are common. The aim of this study was to investigate the distribution of mutations in the cytochrome P450 1B1 gene ( CYP1B1 ) in patients with PCG among different populations around the world from 2011 until May 2016. We referred to the electronic databases, such as Medline, Clinicalkey, Scopus, and ScienceDirect, to search for articles that were published in this area. Nineteen records were included in this qualitative synthesis. CYP1B1 mutations were assessed in 1,220 patients with PCG and identified in 41.6% of them. According to these studies, 99 mutations including 60 novel mutations were found. Nonsignificant difference in the sex ratio has been reported. This current review shows that consanguinity plays an important role in the PCG pathogenesis and transmission; however, sporadic mutations have been found in some cases. A difference in penetrance was highlighted by some mutations. The CYP1B1 mutations were mostly found in the Middle East and the Maghreb with a rate of 64.8 and 54.4%, respectively, followed by Europe (34.7%), Asia (21.3%), and finally the United States (14.9%). Founder mutations in different geographical areas have been discovered. For instance, the p.Gly61Glu, p.Arg390His, p.Gly61Glu, c.4,339delG, p.E387Lys, and p.Val320Leu were considered founder mutations for Iran/Saudi Arabia, Pakistan, Lebanon, Morocco, Europe, and Vietnam/South Korea, respectively. Many common mutations in different countries were found, such as in Morocco, where its mutations were similar to seven other countries. These findings suggest that the ethnic differences and the geographical distribution of PCG give us a large CYP1B1 mutation pattern. Genetic tests looking for founder and common mutations should be the first step in genetic screening for patients with PCG.

Partly segregated cortico-subcortical pathways support phonologic and semantic verbal fluency: A lesion study.

Verbal fluency refers to the ability to generate as many words as possible in a limited time interval, without repetition and according to either a phonologic (each word begins with a given letter) or a semantic rule (each word belongs to a given semantic category). While current literature suggests the involvement of left fronto-temporal structures in fluency tasks, whether the same or distinct brain areas are necessary for each type of fluency remains unclear. We tested the hypothesis for an involvement of partly segregated cortico-subcortical structures between phonologic and semantic fluency by examining with a voxel-based lesion symptom mapping approach the effects of brain lesions on fluency scores corrected for age and education level in a group of 191 unselected brain-damaged patients with a first left or right hemispheric lesion. There was a positive correlation between the scores to the two types of fluency, suggesting that common mechanisms underlie the word generation independent of the production rule. The lesion-symptom mapping revealed that lesions to left basal ganglia impaired both types of fluency and that left superior temporal, supramarginal and rolandic operculum lesions selectively impaired phonologic fluency and left middle temporal lesions impaired semantic fluency. Our results corroborate current neurocognitive models of word retrieval and production, and refine the role of cortical-subcortical interaction in lexical search by highlighting the common executive role of basal ganglia in both types of verbal fluency and the preferential involvement of the ventral and dorsal language pathway in semantic and phonologic fluency, respectively.