Alison Mary

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.

A geometric correction scheme for spatial leakage effects in MEG/EEG seed-based functional connectivity mapping

Spatial leakage effects are particularly confounding for seed‐based investigations of brain networks using source‐level electroencephalography (EEG) or magnetoencephalography (MEG). Various methods designed to avoid this issue have been introduced but are limited to particular assumptions about its temporal characteristics. Here, we investigate the usefulness of a model‐based geometric correction scheme (GCS) to suppress spatial leakage emanating from the seed location. We analyze its properties theoretically and then assess potential advantages and limitations with simulated and experimental MEG data (resting state and auditory‐motor task). To do so, we apply Minimum Norm Estimation (MNE) for source reconstruction and use variation of error parameters, statistical gauging of spatial leakage correction and comparison with signal orthogonalization. Results show that the GCS has a local (i.e., near the seed) effect only, in line with the geometry of MNE spatial leakage, and is able to map spatially all types of brain interactions, including linear correlations eliminated after signal orthogonalization. Furthermore, it is robust against the introduction of forward model errors. On the other hand, the GCS can be affected by local overcorrection effects and seed mislocation. These issues arise with signal orthogonalization too, although significantly less extensively, so the two approaches complement each other. The GCS thus appears to be a valuable addition to the spatial leakage correction toolkits for seed‐based FC analyses in source‐projected MEG/EEG data. Hum Brain Mapp 36:4604–4621, 2015.

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.

About the electrophysiological basis of resting state networks

Matthew Jon Brookes, Mark Woolrich, Henry Luckhoo, Darren Price, Joanne Hale, Mary Stephenson, Gareth Barnes, Stephen Smith, and Peter Morris Sir Peter Mansfield Magnetic Resonance Centre, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom, Oxford centre for human brain activity, University of Oxford, Oxford, Wellcome trust centre for neuroimaging, University College London, London, Oxford Centre for functional MRI of the brain, University of Oxford, Oxford

Selective modulations of attentional asymmetries after sleep deprivation

Pseudoneglect is a slight but consistent misplacement of attention toward the left visual field, commonly observed in young healthy subjects. This leftward attentional bias is thought to result from a right hemispheric dominance in visuospatial processing. Changes in endogenous levels of alertness may modulate attentional asymmetries and pseudoneglect in particular. In line with this hypothesis, it has been shown that sleep deprived shift-workers present a reversal of their attentional bias in a landmark (LDM) task (Manly, T., Dobler, V. B., Dodds, C. M., & George, M. A. (2005). Rightward shift in spatial awareness with declining alertness. Neuropsychologia, 43(12), 1721-1728). However, circadian disturbances and fatigue effects at the end of a shift work may have contributed to this reversal effect. In a first experiment, we show that sleep deprivation (SD) under controlled conditions does not markedly change the leftward bias, observable both at 21:00 and at 07:00 after SD. In a second experiment, we tested the hypothesis that a drastic reduction or inversion in the attentional bias would be present only when both the circadian drive for sleep propensity is maximal (i.e. around 05:00) and homeostatic sleep pressure is high. Thus participants were tested at 21:00 and under SD conditions at 05:00 and 09:00. Additionally, we used the greyscales (GS) task well-known to evidence a leftward bias in luminance judgments. Although results evidenced a consistent leftward bias both in the LDM and GS, we found a suppression of the leftward bias at the circadian nadir of alertness (05:00) after SD only for the GS, but not for the LDM. Noticeably, the leftward bias in the GS vanished at 05:00 after SD but reappeared at 09:00 despite continued SD, suggesting a predominant circadian influence on attentional asymmetries in the GS. Additionally, inter-sessions correlations evidenced a reproducible, consistent bias both in the LDM and GS, with no consistent relationship between the two tasks, suggesting independence of the neural networks subtending performance in LDM and GS. Overall, our results suggest that SD per se does not impede the leftward bias both in LDM and GS, whereas circadian-related variations in vigilance may impact attentional asymmetries in luminance judgments.

Accelerated long-term forgetting in aging and intra-sleep awakenings

The architecture of sleep and the functional neuroanatomical networks subtending memory consolidation processes are both modified with aging, possibly leading to accelerated forgetting in long-term memory. We investigated associative learning and declarative memory consolidation processes in 16 young (18–30 years) and 16 older (65–75 years) healthy adults. Performance was tested using a cued recall procedure at the end of learning (immediate recall), and 30 min and 7 days later. A delayed recognition test was also administered on day 7. Daily sleep diaries were completed during the entire experiment. Results revealed a similar percentage of correct responses at immediate and 30-min recall in young and older participants. However, recall was significantly decreased 7 days later, with an increased forgetting in older participants. Additionally, intra-sleep awakenings were more frequent in older participants than young adults during the seven nights, and were negatively correlated with delayed recall performance on day 7 in the older group. Altogether, our results suggest a decline in verbal declarative memory consolidation processes with aging, eventually leading to accelerated long-term forgetting indicating that increased sleep fragmentation due to more frequent intra-sleep awakenings in older participants contribute to the reported age-related decline in long-term memory retrieval. Our results highlight the sensitivity of long-term forgetting measures to evidence consolidation deficits in healthy aging.

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.

Sleep and memory consolidation: Motor performance and proactive interference effects in sequence learning

That post-training sleep supports the consolidation of sequential motor skills remains debated. Performance improvement and sensitivity to proactive interference are both putative measures of long-term memory consolidation. We tested sleep-dependent memory consolidation for visuo-motor sequence learning using a proactive interference paradigm. Thirty-three young adults were trained on sequence A on Day 1, then had Regular Sleep (RS) or were Sleep Deprived (SD) on the night after learning. After two recovery nights, they were tested on the same sequence A, then had to learn a novel, potentially competing sequence B. We hypothesized that proactive interference effects on sequence B due to the prior learning of sequence A would be higher in the RS condition, considering that proactive interference is an indirect marker of the robustness of sequence A, which should be better consolidated over post-training sleep. Results highlighted sleep-dependent improvement for sequence A, with faster RTs overnight for RS participants only. Moreover, the beneficial impact of sleep was specific to the consolidation of motor but not sequential skills. Proactive interference effects on learning a new material at Day 4 were similar between RS and SD participants. These results suggest that post-training sleep contributes to optimizing motor but not sequential components of performance in visuo-motor sequence learning.

Age‐related differences in practice‐dependent resting‐state functional connectivity related to motor sequence learning

Decreased neural plasticity is observed with healthy ageing in the primary sensorimotor (SM1) cortex thought to participate in motor learning and memory consolidation processes. In the present magnetoencephalography study, the post‐training reorganization of resting‐state functional connectivity (rsFC) and its relation with motor learning and early consolidation in 14 young (19–30 years) and 14 old (66–70 years) healthy participants were investigated. At the behavioral level, participants were trained on a motor sequence learning task then retested 20–30 min later for transient offline gains in performance. Using a sensorimotor seed‐based approach, rsFC relying on beta band power envelope correlation was estimated immediately before and 10 min after the learning episode. Post‐training changes in rsFC (from before to after learning) were correlated with motor learning performance and with the offline improvement in performance within the hour after learning. Young and old participants exhibited differential patterns of sensorimotor‐related rsFC, bearing specific relationships with motor learning and consolidation. Our findings suggest that rsFC changes following learning reflect the offline processing of the new motor skill and contribute to the early memory consolidation within the hour after learning. Furthermore, differences in post‐training changes in rsFC between young and old participants support the hypothesis that ageing modulates the neural circuits underlying the learning of a new motor skill and the early subsequent consolidation stages. Hum Brain Mapp 38:923–937, 2017.

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.