Jean-Marie Annoni

Cognitive dysfunction in HIV patients despite long-standing suppression of viremia.

Objective:To determine the prevalence of cognitive complaints and HIV-associated neurocognitive disorders (HANDs) in a cohort of aviremic HIV-positive patients. To evaluate the relevance of the HIV dementia scale to detect HANDs. Design:Assessment of HANDs with neuropsychological tests. Methods:Two hundred HIV-infected patients with undetectable HIV-1 RNA concentrations in the plasma, no history of major opportunistic infection of the central nervous system in the past 3 years, no current use of intravenous drugs, and no major depression answered a questionnaire designed to elicit cognitive complaints. Cognitive functions of 50 complaining and 50 noncomplaining HIV-positive patients were assessed. Results:Patients had undetectable HIV-1 RNA concentrations for a median time of 48 months (range 3.2–136.6). The prevalence of cognitive complaints was 27%. The prevalence of HANDs was 84% among patients with cognitive complaints (asymptomatic neurocognitive impairment 24%, mild neurocognitive disorders 52%, and HIV-associated dementia 8%) and 64% among noncomplainers (asymptomatic neurocognitive impairment 60%, mild neurocognitive disorders 4%, and HIV-associated dementia 0%; P < 0.001). A score of 14 points or less on the HIV dementia scale yielded a positive predictive value of HANDs of 92% in complainers and 82% in noncomplainers. Conclusion:The prevalence of HANDs is high even in long-standing aviremic HIV-positive patients. However, HANDs without functional repercussion in daily life (asymptomatic neurocognitive impairment) is the most frequent subtype observed. In this population, the HIV dementia scale with a cutoff of 14 points or less seems to provide a useful tool to screen for the presence of HANDs.

Variability of fMRI Activation During a Phonological and Semantic Language Task in Healthy Subjects

Assessing inter‐individual variability of functional activations is of practical importance in the use of functional magnetic resonance imaging (fMRI) in a clinical context. In this fMRI study we addressed this issue in 30 right‐handed, healthy subjects using rhyme detection (phonologic) and semantic categorization tasks. Significant activations, found mainly in the left hemisphere, concerned the inferior frontal gyrus, the superior/middle temporal gyri, the prefrontal cortex, the inferior parietal lobe, the superior parietal lobule/superior occipital gyrus, the pre‐central gyrus, and the supplementary motor area. Intensity/spatial analysis comparing activations in both tasks revealed an increased involvement of frontal regions in the semantic task and of temporo‐parietal regions in the phonologic task. The frequency of activation analyzed in nine regional subdivisions revealed a high inter‐subject variability but showed that the most frequently activated regions were the inferior frontal gyrus and the prefrontal cortex. Laterality indices, strongly lateralizing in both tasks, were slightly higher in the semantic (0.76 ± 0.19) than the phonologic task (0.66 ± 0.27). Frontal dominance indices (a measure of frontal vs. posterior left hemisphere dominance) indicated more robust frontal activations in the semantic than the phonologic task. Our study allowed the characterization of the most frequently involved foci in two language tasks and showed that the combination of these tasks constitutes a suitable tool for determining language lateralization and for mapping major language areas. Hum. Brain Mapping 23:140–155, 2004.

The Neural Cost of the Auditory Perception of Language Switches: An Event-Related Functional Magnetic Resonance Imaging Study in Bilinguals

One of the most remarkable abilities of bilinguals is to produce and/or to perceive a switch from one language to the other without any apparent difficulty. However, several psycholinguistic studies indicate that producing, recognizing, and integrating a linguistic code different from the one in current use may entail a processing cost for the speaker/listener. Up to now, the underlying neural substrates of perceiving language switches are unknown. In the present study, we investigated the neural mechanisms of language switching during auditory perception in bilinguals. Event-related functional magnetic resonance imaging was performed in 12 early, highly proficient Italian/French bilinguals, who were more exposed to their second language. Subjects had to listen to narratives containing “switched passages” that could either respect (i.e., regular switches) or violate (i.e., irregular switches) the constituents of sentence structure. The results indicate that switching engages an extensive neural network, including bilateral prefrontal and temporal associative regions. Moreover, a clear dissociation is observed for the types of switches. Regular switches entail a pattern of brain activity closely related to lexical processing, whereas irregular switches engage brain structures involved in syntactic and phonological aspects of language processing. Noteworthy, when switching into the less-exposed language, we observed the selective engagement of subcortical structures and of the anterior cingulate cortex, putatively involved in cognitive and executive control. This suggests that switching into a less-exposed language requires controlled processing resources. This pattern of brain activity may constitute an important neural signature of language dominance in bilinguals.

Long-term effects of cannabis on brain structure.

The dose-dependent toxicity of the main psychoactive component of cannabis in brain regions rich in cannabinoid CB1 receptors is well known in animal studies. However, research in humans does not show common findings across studies regarding the brain regions that are affected after long-term exposure to cannabis. In the present study, we investigate (using Voxel-based Morphometry) gray matter changes in a group of regular cannabis smokers in comparison with a group of occasional smokers matched by the years of cannabis use. We provide evidence that regular cannabis use is associated with gray matter volume reduction in the medial temporal cortex, temporal pole, parahippocampal gyrus, insula, and orbitofrontal cortex; these regions are rich in cannabinoid CB1 receptors and functionally associated with motivational, emotional, and affective processing. Furthermore, these changes correlate with the frequency of cannabis use in the 3 months before inclusion in the study. The age of onset of drug use also influences the magnitude of these changes. Significant gray matter volume reduction could result either from heavy consumption unrelated to the age of onset or instead from recreational cannabis use initiated at an adolescent age. In contrast, the larger gray matter volume detected in the cerebellum of regular smokers without any correlation with the monthly consumption of cannabis may be related to developmental (ontogenic) processes that occur in adolescence.

Theory of mind tasks and executive functions: A systematic review of group studies in neurology

A growing number of studies have been addressing the relationship between theory of mind (TOM) and executive functions (EF) in patients with acquired neurological pathology. In order to provide a global overview on the main findings, we conducted a systematic review on group studies where we aimed to (1) evaluate the patterns of impaired and preserved abilities of both TOM and EF in groups of patients with acquired neurological pathology and (2) investigate the existence of particular relations between different EF domains and TOM tasks. The search was conducted in Pubmed/Medline. A total of 24 articles met the inclusion criteria. We considered for analysis classical clinically accepted TOM tasks (first- and second-order false belief stories, the Faux Pas test, Happes stories, the Mind in the Eyes task, and Cartoons tasks) and EF domains (updating, shifting, inhibition, and access). The review suggests that (1) EF and TOM appear tightly associated. However, the few dissociations observed suggest they cannot be reduced to a single function; (2) no executive subprocess could be specifically associated with TOM performances; (3) the first-order false belief task and the Happes story task seem to be less sensitive to neurological pathologies and less associated to EF. Even though the analysis of the reviewed studies demonstrates a close relationship between TOM and EF in patients with acquired neurological pathology, the nature of this relationship must be further investigated. Studies investigating ecological consequences of TOM and EF deficits, and intervention researches may bring further contributions to this question.

Chronic posttraumatic stress symptoms after nonsevere stroke

Objective: To determine whether posttraumatic stress disorder (PTSD)–related symptoms were present 1 year after a nonsevere stroke and, if so, to examine the relationship between PSTD, coexisting cognitive variables, and infarct localization Methods: The authors assessed 49 patients using standard measures of memory, trauma experience, neurologic deficit, depression, anxiety, and PTSD. Results: Fifteen (31%) patients had significant PTSD symptoms on the Impact of Event Scale (IES > 30). PTSD-like syndrome was independent of neurologic impairment, peristroke amnesia, long-term memory impairment, nosognosia, hypochondriac preoccupations, and physical pain during hospitalization, but was more frequent in women, less educated patients, and patients with more negative appraisals of the stroke experience. Intrusions were increased after basal ganglia strokes, suggesting that the re-experiencing phenomena may be modulated by frontosubcortical pathways. Conclusions: Posttraumatic stress disorder symptoms seem frequent in patients with nonsevere stroke and were associated with the subjective intensity of the stroke experience and accompanied by a depressive and anxious state.

Pure representational neglect after right thalamic lesion

After a right thalamic stroke, an 86‐year‐old man presented an acute pure left representational neglect in the absence of any perceptual neglect. On spatial mental imagery tasks, the patient systematically omitted items located on his left side, but only when a vantage point was given. This suggests that (1) pure representational neglect is not just a residual finding after recovery from global (perceptual and representational) neglect; (2) space representation can be coded by two independent processes: in viewer‐centered or world‐based (allocentric) coordinates; and (3) the right thalamus serves as a relay in the processing of spatial visual imagery.

Classifying minimally disabled multiple sclerosis patients from resting state functional connectivity

Multiple sclerosis (MS), a variable and diffuse disease affecting white and gray matter, is known to cause functional connectivity anomalies in patients. However, related studies published to-date are post hoc; our hypothesis was that such alterations could discriminate between patients and healthy controls in a predictive setting, laying the groundwork for imaging-based prognosis. Using functional magnetic resonance imaging resting state data of 22 minimally disabled MS patients and 14 controls, we developed a predictive model of connectivity alterations in MS: a whole-brain connectivity matrix was built for each subject from the slow oscillations (<0.11 Hz) of region-averaged time series, and a pattern recognition technique was used to learn a discriminant function indicating which particular functional connections are most affected by disease. Classification performance using strict cross-validation yielded a sensitivity of 82% (above chance at p<0.005) and specificity of 86% (p<0.01) to distinguish between MS patients and controls. The most discriminative connectivity changes were found in subcortical and temporal regions, and contralateral connections were more discriminative than ipsilateral connections. The pattern of decreased discriminative connections can be summarized post hoc in an index that correlates positively (ρ=0.61) with white matter lesion load, possibly indicating functional reorganisation to cope with increasing lesion load. These results are consistent with a subtle but widespread impact of lesions in white matter and in gray matter structures serving as high-level integrative hubs. These findings suggest that predictive models of resting state fMRI can reveal specific anomalies due to MS with high sensitivity and specificity, potentially leading to new non-invasive markers.

Poststroke fatigue following minor infarcts: A prospective study

Objective: To explore the potential relationship between fatigue following strokes and poststroke mood, cognitive dysfunction, disability, and infarct site and to determine the predictive factors in the development of poststroke fatigue (PSF) following minor infarcts. Methods: Ninety-nine functionally active patients aged less than 70 years with a first, nondisabling stroke (NIH Stroke Scale score ≤6 in acute phase and ≤3 after 6 months, modified Rankin Scale score ≤1 at 6 months) were assessed during the acute phase and then at 6 (T1) and 12 months (T2) after their stroke. Scores in the Fatigue Assessment Inventory were described and correlated to age, gender, neurologic and functional impairment, lesion site, mood scores, neuropsychological data, laboratory data, and quality of life at T1 and T2 using a multivariate logistic regression analysis in order to determine which variables recorded at T1 best predicted fatigue at T2. Result: As many as 30.5% of the patients at T1 and 34.7% at T2 (11.6% new cases between T1 and T2) reported fatigue. At both 6 and 12 months, there was a significant association between fatigue and a reduction in professional activity. Attentional-executive impairment, depression, and anxiety levels remained associated with PSF throughout this time period, underlining the critical role of these variables in the genesis of PSF. There was no significant association between the lesion site and PSF. Conclusion: This study suggests that attentional and executive impairment, as well as depression and anxiety, may play a critical role in the development of PSF.

Brain activity during observation and motor imagery of different balance tasks: An fMRI study

After immobilization, patients show impaired postural control and increased risk of falling. Therefore, loss of balance control should already be counteracted during immobilization. Previously, studies have demonstrated that both motor imagery (MI) and action observation (AO) can improve motor performance. The current study elaborated how the brain is activated during imagination and observation of different postural tasks to provide recommendations about the conception of non-physical balance training. For this purpose, participants were tested in a within-subject design in an fMRI-scanner in three different conditions: (a) AO + MI, (b) AO, and (c) MI. In (a) participants were instructed to imagine themselves as the person pictured in the video whereas in (b) they were instructed simply to watch the video. In (c) subjects closed their eyes and kinesthetically imagined the task displayed in the video. Two tasks were evaluated in each condition: (i) static standing balance and (ii) dynamic standing balance (medio-lateral perturbation). In all conditions the start of a new trial was indicated every 2 sec by a sound. During AO + MI of the dynamic task, participants activated motor centers including the putamen, cerebellum, supplementary motor area, premotor cortices (PMv/d) and primary motor cortex (M1). MI showed a similar pattern but no activity in M1 and PMv/d. In the SMA and cerebellum, activity was generally higher in the dynamic than in the static condition. AO did not significantly activate any of these brain areas. Our results showed that (I) mainly AO + MI, but also MI, activate brain regions important for balance control; (II) participants display higher levels of brain activation in the more demanding balance task; (III) there is a significant difference between AO + MI and AO. Consequently, best training effects should be expected when participants apply MI during AO (AO + MI) of challenging postural tasks.