Hichem Slama

Is the Addenbrooke's cognitive examination effective to detect frontotemporal dementia?

Abstract.We evaluated the Addenbrooke’s cognitive examination (ACE), a simple instrument to differentiate frontotemporal dementia (FTD) from Alzheimer’s disease (AD), in our dementia patients clinic population. The Verbal-Language/Orientation-Memory (VLOM) ratio, which compares its language and memory scores, determines whether FTD or AD is more likely. The ACE was translated into French with adaptation maintaining the number of words in the name and address learning and delayed recall test, and with cultural adaptation for the semantic memory. The 85 included subjects had no evidence of two or more organic pathologies, after at least six months of follow-up, and an MMSE score ≥ 20/30. Patients with cognitive impairment due to alcohol intake were excluded. The diagnosis of a specific dementing illness was based on the consensus of the neurologist and neuropsychologists in the team. Thereafter, another neurologist expert in dementia, blinded to the ACE result and to the diagnosis and treatment, reviewed all cases files and proposed a diagnosis. A diagnostic agreement was reached for 79 cases (92.9%) with 40 (50.6%) dementia: 25 AD (62.5 %), 9 FTD (22.5 %).We estimated that the sensitivity for detecting dementia of an ACE score ≤ 83/100 was 90% with a specificity of 64.1%. When the ACE score was ≤ 88/100, the sensitivity for diagnosing FTD of a VLOM ratio < 2.2 was 11.1% with a specificity of 88 % and the sensitivity for diagnosing AD of a VLOM ratio > 3.2 was 72%,with a specificity of 69.4%. We conclude that, when used as originally proposed, ACE is very accurate for the detection of dementia, but much less effective in discriminating the most common frontal variant of FTD.

Working Memory-Related Functional Brain Patterns in Never Medicated Children with ADHD

Attention Deficit/Hyperactivity Disorder (ADHD) is a pervasive neurodevelopmental disorder characterized by 3 clusters of age-inappropriate cardinal symptoms: inattention, hyperactivity and impulsivity. These clinical/behavioural symptoms are assumed to result from disturbances within brain systems supporting executive functions including working memory (WM), which refers to the ability to transiently store and flexibly manipulate task-relevant information. Ongoing or past medications, co-morbidity and differences in task performance are potential, independent confounds in assessing the integrity of cerebral patterns in ADHD. In the present study, we recorded WM-related cerebral activity during a memory updating N-back task using functional Magnetic Resonance Imaging (fMRI) in control children and never medicated, prepubescent children with ADHD but without comorbid symptoms. Despite similar updating performance than controls, children with ADHD exhibited decreased, below baseline WM-related activation levels in a widespread cortico-subcortical network encompassing bilateral occipital and inferior parietal areas, caudate nucleus, cerebellum and functionally connected brainstem nuclei. Distinctive functional connectivity patterns were also found in the ADHD in these regions, with a tighter coupling in the updating than in the control condition with a distributed WM-related cerebral network. Especially, cerebellum showed tighter coupling with activity in an area compatible with the brainstem red nucleus. These results in children with clinical core symptoms of ADHD but without comorbid affections and never treated with medication yield evidence for a core functional neuroanatomical network subtending WM-related processes in ADHD, which may participate to the pathophysiology and expression of clinical symptoms.

The French Addenbrooke’s Cognitive Examination Is Effective in Detecting Dementia in a French-Speaking Population

We evaluated the sensitivity and specificity of our French version of Addenbrooke’s cognitive examination (ACE) to detect dementia in our patient population. One hundred and fifty-eight cases were included in the study. In our patient series, the sensitivity for diagnosing dementia with a Mini-Mental State Examination (MMSE) score of ≤24/30 was 48.5%, the sensitivity of an MMSE score of ≤27/30 was 82.5% with a specificity of 72.1%, the sensitivity of an ACE score of ≤83/100 was 86.6% with a specificity of 70.5% and the sensitivity of an ACE score of ≤88/100 was 97.9% with a specificity of 59%. We conclude that the French version of the ACE is a very accurate test for the detection of dementia, and should be widely used in clinical practice.

Executive and attentional contributions to Theory of Mind deficit in attention deficit/hyperactivity disorder (ADHD)

Attention deficit/hyperactivity disorder (ADHD) in children has been associated with attentional and executive problems, but also with socioemotional difficulties possibly associated with deficits in Theory of Mind (ToM). Socioemotional problems in ADHD are associated with more negative prognoses, notably interpersonal, educational problems, and an increased risk of developing other psychiatric disorders that emphasize the need to clarify the nature of their ToM deficits. In this study, we hypothesized that ToM dysfunction in children with ADHD is largely attributable to their attentional and/or executive deficits. Thirty-one children with ADHD (8–12 years, IQ > 85) and 31 typically developing (TD) children were assessed using executive functions (inhibition, planning, and flexibility) and attentional tasks, as well as two advanced ToM tasks (Reading the Mind in the Eyes and Faux Pas) involving different levels of executive control. Children with ADHD performed more poorly than TD children in attentional, executive function, and ToM tasks. Linear regression analyses conducted in the ADHD group indicated that inhibition scores predicted performance on the “Faux Pas” task the best, while attention scores were the best for predicting performance on the Reading the Mind in the Eyes task. When controlled for inhibition and attentional variables, ToM performance in children with ADHD was actually similar to TD children. Contrarily, controlling for ToM scores did not normalize performance for inhibition and attentional tasks in children with ADHD. This unidirectional relationship suggests that deficits in the EF and attentional domains are responsible for ToM deficits in ADHD, which therefore may contribute to their socioemotional difficulties.

Cognitive Fatigue Facilitates Procedural Sequence Learning.

Enhanced procedural learning has been evidenced in conditions where cognitive control is diminished, including hypnosis, disruption of prefrontal activity and non-optimal time of the day. Another condition depleting the availability of controlled resources is cognitive fatigue (CF). We tested the hypothesis that CF, eventually leading to diminished cognitive control, facilitates procedural sequence learning. In a two-day experiment, 23 young healthy adults were administered a serial reaction time task (SRTT) following the induction of high or low levels of CF, in a counterbalanced order. CF was induced using the Time load Dual-back (TloadDback) paradigm, a dual working memory task that allows tailoring cognitive load levels to the individual’s optimal performance capacity. In line with our hypothesis, reaction times (RT) in the SRTT were faster in the high- than in the low-level fatigue condition, and performance improvement was higher for the sequential than the motor components. Altogether, our results suggest a paradoxical, facilitating impact of CF on procedural motor sequence learning. We propose that facilitated learning in the high-level fatigue condition stems from a reduction in the cognitive resources devoted to cognitive control processes that normally oppose automatic procedural acquisition mechanisms.

Grey matter volumes in treatment naïve vs. chronically treated children with attention deficit / hyperactivity disorder: a combined approach

Psychostimulants are the first-line treatment in attention deficit/hyperactivity disorder (ADHD), but their effects on brain development remain poorly understood. In particular, previous structural magnetic resonance imaging (sMRI) studies only investigated treatment effects on grey matter (GM) volumes in selected regions of interest (ROIs). In this study, voxel-based morphometry (VBM) was used to assess medication-related GM volume differences across the entire brain. Automated tracing measurements of selected ROIs were also obtained. Three groups (77 participants aged 7-to-13 year old) underwent MRI scans and were compared: never-medicated children with ADHD (n=33), medicated (methylphenidate) children with ADHD (n=20) and typically developing children (TD; n=24). Optimised VBM was used to investigate regional GM volumes, controlling for age and gender. Automated tracing procedures were also used to assess the average volume of the caudate nucleus, the amygdala and the nucleus accumbens. When compared to both medicated children with ADHD and TD children, never-medicated children with ADHD exhibited decreased GM volume in the insula and in the middle temporal gyrus. When compared to TD children, medicated children with ADHD had decreased GM volume in the middle frontal gyrus and in the precentral gyrus. Finally, ROI analyses revealed a significant association between duration of treatment and GM volume of the left nucleus accumbens in medicated children with ADHD. In conclusion, this study documents potential methylphenidate-related GM volume normalization and deviation in previously unexplored brain structures, and reports a positive association between treatment history and GM volume in the nucleus accumbens, a key region for reward-processing.

Afternoon Nap and Bright Light Exposure Improve Cognitive Flexibility Post Lunch

Beneficial effects of napping or bright light exposure on cognitive performance have been reported in participants exposed to sleep loss. Nonetheless, few studies investigated the effect of these potential countermeasures against the temporary drop in performance observed in mid-afternoon, and even less so on cognitive flexibility, a crucial component of executive functions. This study investigated the impact of either an afternoon nap or bright light exposure on post-prandial alterations in task switching performance in well-rested participants. Twenty-five healthy adults participated in two randomized experimental conditions, either wake versus nap (n=15), or bright light versus placebo (n=10). Participants were tested on a switching task three times (morning, post-lunch and late afternoon sessions). The interventions occurred prior to the post-lunch session. In the nap/wake condition, participants either stayed awake watching a 30-minute documentary or had the opportunity to take a nap for 30 minutes. In the bright light/placebo condition, participants watched a documentary under either bright blue light or dim orange light (placebo) for 30 minutes. The switch cost estimates cognitive flexibility and measures task-switching efficiency. Increased switch cost scores indicate higher difficulties to switch between tasks. In both control conditions (wake or placebo), accuracy switch-cost score increased post lunch. Both interventions (nap or bright light) elicited a decrease in accuracy switch-cost score post lunch, which was associated with diminished fatigue and decreased variability in vigilance. Additionally, there was a trend for a post-lunch benefit of bright light with a decreased latency switch-cost score. In the nap group, improvements in accuracy switch-cost score were associated with more NREM sleep stage N1. Thus, exposure to bright light during the post-lunch dip, a countermeasure easily applicable in daily life, results in similar beneficial effects as a short nap on performance in the cognitive flexibility domain with possible additional benefits on latency switch-cost scores.

Grey matter volume differences associated with gender in children with attention-deficit/hyperactivity disorder: A voxel-based morphometry study

Highlights • We studied gender effect on grey matter volumes in children with ADHD.• A gender-by-diagnosis interaction was found in the ventral Anterior Cingulate Gyrus.• This finding may underlie emotion dysregulation symptoms in ADHD.• Contribute to differences in symptoms profiles between boys and girls with ADHD.

Structural correlates of COMT Val158Met polymorphism in childhood ADHD: a voxel-based morphometry study.

Abstract Objectives. The Val158-allele of the catechol-O-methyltransferase (COMT) Val158Met (rs4680) functional polymorphism has been identified as a risk factor for antisocial behaviour in attention-deficit/hyperactivity disorder (ADHD). Here, we used voxel-based morphometry to investigate the effects of Val158Met polymorphism on grey matter (GM) volumes in a sample of 7–13-year-old children. Methods. MRI and genotype data were obtained for 38 children with combined-type ADHD and 24 typically developing (TD) children. Four regions of interest were identified: striatum, cerebellum, temporal lobe and inferior frontal gyrus (IFG). Results. When compared to TD children, those with ADHD had a significant decrease of GM volume in the IFG. Volume in this region was negatively correlated with ratings of hyperactivity/impulsivity symptoms. Furthermore, the smaller GM volume in the IFG was attributed to the presence of the Met158-allele, as only children with ADHD carrying a Met158-allele exhibited such decrease in the IFG. Children with ADHD homozygotes for the Val158-allele presented increased GM volume in the caudate nucleus when compared with TD children. Conclusions. This study provides the first evidence of a modulation of ADHD-related GM volume alterations by Val158Met in two key regions, possibly mediating the relationship between Val158Met polymorphism and antisocial behaviour in children with ADHD.

Placebo-suggestion modulates conflict resolution in the Stroop Task.

Here, we ask whether placebo-suggestion (without any form of hypnotic induction) can modulate the resolution of cognitive conflict. Naïve participants performed a Stroop Task while wearing an EEG cap described as a “brain wave” machine. In Experiment 1, participants were made to believe that the EEG cap would either enhance or decrease their color perception and performance on the Stroop task. In Experiment 2, participants were explicitly asked to imagine that their color perception and performance would be enhanced or decreased (non-hypnotic imaginative suggestion). We observed effects of placebo-suggestion on Stroop interference on accuracy: interference was decreased with positive suggestion and increased with negative suggestion compared to baseline. Intra-individual variability was also increased under negative suggestion compared to baseline. Compliance with the instruction to imagine a modulation of performance, on the other hand, did not influence accuracy and only had a negative impact on response latencies and on intra-individual variability, especially in the congruent condition of the Stroop Task. Taken together, these results demonstrate that expectations induced by a placebo-suggestion can modulate our ability to resolve cognitive conflict, either facilitating or impairing response accuracy depending on the suggestion’s contents. Our results also demonstrate a dissociation between placebo-suggestion and non-hypnotic imaginative suggestion.