Item familiarity and controlled associative retrieval in Alzheimer's disease: An fMRI study

in Cortex : A Journal Devoted to the Study of the Nervous System & Behavior (in press)

Brain metabolic dysfunction in Capgras syndrome during Alzheimer’s disease: a positron emission tomography study

Poster (2013, June)

The neural correlates of recollection and familiarity during aging

Poster (2013)

The role of memory traces quality in directed forgetting: A comparison of young and elderly participants using the item procedure

Poster (2013)

An intervention study on physical activity and cognitive functioning in people with Parkinson’s disease

Poster (2013)

Exploration of the mechanisms underlying the ISPC effect: Evidence from behavioral and neuroimaging data

in Neuropsychologia (2013), 51

The item-specific proportion congruent (ISPC) effect in a Stroop task – the observation of reduced interference for color words mostly presented in an incongruent color – has attracted growing interest ... [more ▼]

The item-specific proportion congruent (ISPC) effect in a Stroop task – the observation of reduced interference for color words mostly presented in an incongruent color – has attracted growing interest since the original study by Jacoby (2003). Two mechanisms have been proposed to explain the effect: associative learning of contingencies and item-specific control through word reading modulation. Both interpretations have received empirical support from behavioral data. Therefore, the aim of this study was to investigate the responsible mechanisms of the ISPC effect with the classic two-item sets design using fMRI. Results showed that the ISPC effect is associated with increased activity in the anterior cingulate (ACC), dorsolateral prefrontal (DLPFC), and inferior and superior parietal cortex. Importantly, behavioral and fMRI analyses specifically addressing the respective contribution of associative learning and item-specific control mechanisms brought support for the contingency learning account of the ISPC effect. Results are discussed in reference to task and procedure characteristics that may influence the extent to which item-specific control and/or contingency learning contribute to the ISPC effect. [less ▲]

Verbal learning in Alzheimer’s disease and mild cognitive impairment:fine-grained acquisition and short-delay consolidation performance and neural correlates

in Neurobiology of Aging (2013), 34

The aim of this study was to examine correlations between acquisition and short-delay consolidation and brain metabolism at rest measured by fluorodeoxyglucose positron emission tomography (FDG-PET) in 44 ... [more ▼]

The aim of this study was to examine correlations between acquisition and short-delay consolidation and brain metabolism at rest measured by fluorodeoxyglucose positron emission tomography (FDG-PET) in 44 Alzheimer’s disease (AD) patients, 16 patients with mild cognitive impairment (MCI) who progressed to dementia (MCI-AD), 15 MCI patients who remained stable (MCI-S, 4–8 years of follow-up), and 20 healthy older participants. Acquisition and short-delay consolidation were calculated respectively as mean gained (MG) and lost (ML) access to items of the California Verbal Learning Task. MG performance suggests that acquisition is impaired in AD patients even at predementia stage (MCI-AD). ML performance suggests that short-delay consolidation is deficient only in confirmed AD patients. Variations in acquisition performance in control participants are related to metabolic activity in the anterior parietal cortex, an area supporting task-positive attentional processes. In contrast, the acquisition deficit is related to decreased activity in the lateral temporal cortex, an area supporting semantic processes, in patients at an early stage of AD and is related to metabolic activity in the hippocampus, an area supporting associative processes, in confirmed AD patients. [less ▲]

Does processing speed protect from age-related decline in cognitive control?

in Frontiers in Human Neuroscience (2012, October 27)

Age-related difficulties have been reported on proactive control whereas reactive control seems to remain intact (Braver, Gray, & Burgess, 2007; Braver, 2012). This study investigated the potential ... [more ▼]

Age-related difficulties have been reported on proactive control whereas reactive control seems to remain intact (Braver, Gray, & Burgess, 2007; Braver, 2012). This study investigated the potential influence of speed of processing abilities on the age-related decline in proactive control. We used a working memory recognition paradigm involving proactive or reactive cognitive control by manipulating the interference level across items. 80 young adults (18-29 years old) and 80 healthy older adults (60-89 years old) were included. The main results revealed significant effects of age on sensitivity to interference. As expected, reactive control performance remained intact with aging (similar interference effect in the two groups). In contrast, we observed a larger interference effect in the proactive condition in aging. Finally, when the groups are matched according to their processing speed (assessed by the Code task of the WAIS III, with both younger and older adults having a score comprised between 60 and 93), the effect of age on sensitivity to interference disappeared. In other words, when younger and older adults had similar speed of processing abilities, no age-related proactive control decline was observed. In conclusion, beyond the fact that this study confirms the selective age-related decline in proactive control, it also indicates that speed of processing, a measure considered as reflecting the integrity of cognitive functioning during aging (Salthouse, 1996), influences the efficiency of proactive control in that population. [less ▲]

Evidence for a role of a cortico-subcortical network for automatic and unconscious motor inhibition of manual responses

in PLoS ONE (2012)

It is now clear that non-consciously perceived stimuli can bias our decisions. Although previous researches highlighted the importance of automatic and unconscious processes involved in voluntary action ... [more ▼]

It is now clear that non-consciously perceived stimuli can bias our decisions. Although previous researches highlighted the importance of automatic and unconscious processes involved in voluntary action, the neural correlates of such processes remain unclear. Basal ganglia dysfunctions have long been associated with impairment in automatic motor control. In addition, a key role of the medial frontal cortex has been suggested by administrating a subliminal masked prime task to a patient with a small lesion restricted to the supplementary motor area (SMA). In this task, invisible masked arrows stimuli were followed by visible arrow targets for a left or right hand response at different interstimuli intervals (ISI), producing a traditional facilitation effect for compatible trials at short ISI and a reversal inhibitory effect at longer ISI. Here, by using fast event-related fMRI and a weighted parametric analysis, we showed BOLD related activity changes in a cortico-subcortical network, especially in the SMA and the striatum, directly linked to the individual behavioral pattern. This new imaging result corroborates previous works on subliminal priming using lesional approaches. This finding implies that one of the roles of these regions was to suppress a partially activated movement below the threshold of awareness. [less ▲]

Influence of sleep homeostasis and circadian rhythm on waking EEG oscillations during a constant routine

Poster (2012, September)

Introduction & Objectives Human sleep and wake EEG oscillations are modulated by complex non-additive interaction between homeostatic and circadian processes. Quantitative analysis of EEG data, during ... [more ▼]

Introduction & Objectives Human sleep and wake EEG oscillations are modulated by complex non-additive interaction between homeostatic and circadian processes. Quantitative analysis of EEG data, during extended wakefulness, indicate that its frequency-specificity is influenced by both factors, such that low-frequencies (<8Hz) increase with time spent awake (1), thus more homeostatically-driven, while alpha activity undergoes a clear circadian modulation (2). Interindividual differences in sleep-wake regulation in young volunteers are associated with the variable-number tandem-repeat (VNTR) polymorphism in the coding region of the circadian clock gene PERIOD3 (PER3). Individuals homozygous for the longer allele of PER3 (PER35/5) were reported to generate more slow wave activity during NREM sleep and theta activity during wakefulness, relative to individuals with the shorter allele (PER34/4). However, the phase and amplitude of circadian markers do not differ between these genotypes (3). Here we tested the hypothesis if fluctuations in the dynamics of waking EEG frequency-specificity are modulated by a polymorphism in the clock gene PER3, under 42h of sustained wakefulness. Materials and Methods Population. A total of 400 young men and women were recruited, from whom DNA samples and questionnaire data were collected. On the basis of their PER3 polymorphism, 35 healthy young volunteers (age: 19-26 y; 17 females) were recruited, out of which twelve were PER35/5 and twenty-three PER34/4 homozygotes, and matched by age, gender, level of education, chronotype and IQ at the group level. Study protocol. The laboratory part of this study began in the evening of day 1 until day 5 (Fig. 1). During the first 2 nights (habituation and baseline), volunteers followed one out of two possible sleep-wake schedules (00:00-08:00 or 01:00-09:00). Thereafter, participants underwent approximately 42 hours of sustained wakefulness under constant routine (CR) conditions (semi-recumbent position, dim light <5 lux, no time-of-day information), and a subsequent recovery sleep episode. EEG recordings. Continuous EEG measurements with 9 EEG channels (F3, Fz, F4, C3, Cz, C4, Pz, O1, O2) were performed throughout the CR. Waking EEG was recorded every 2-h, during a modified version of the Karolinska Drowsiness Test (KDT) (4). Data presented here pertain to the last 60-sec of KDT, during which subjects were instructed to relax, to fixate a dot displayed on a screen ca. 75cm and to try to suppress blinks. After re-referencing to mean mastoids, recordings were scored using Rechtschaffen criteria. The 1-min EEGs during the KDT were manually and visually scored for artifacts (eye blinks, body movements, and slow eye movements) offline by 2 independent observers. The absolute EEG power density was then calculated for artifact-free 2-s epochs in the frequency range of 0.5 to 20 Hz , overlapping by 1 second using the pwelch function in MATLAB (7.5.0). For data reduction, power density of artifact-free 2-s epochs was averaged over 20-s epochs. Statistics. Waking EEG delta (0.75-4.5Hz), theta (4.75-7.75Hz) and alpha (8-12.0Hz) power density computed on Central derivation (Cz) were analyzed with a mixed-model analysis of variance (PROC Mixed), with main factors “elapsed time awake” and “genotype” (PER34/4 and PER35/5), and the interaction of these two factors. All p-values derived from r-ANOVAs were based on Huynh-Feldt's (H-F) corrected degrees of freedom (p<0.05). Multiple comparisons were performed using Tukey-Kramer test. Theoretical coefficients for the homeostatic sleep pressure (derived from a quasi-linear function) and the circadian oscillation (24-hour period sine wave) were used in a multiple regression model to predict delta, theta and alpha activity during the CR. Prior to multiple regression analysis, data were normalized according to PROC Transreg, in order to derive the best normalization method for linear and non-linear datasets. Results. Delta activity Analysis of delta activity yielded a significant main effect of “elapsed time awake” (F=5.31; p < 0.0001), albeit no significant effects for “genotype” (F=0.01; p = 0.94) nor for the interaction of these factors (F=0.85; p = 0.65). The multiple regression model revealed a significant regression (R² = 0.0433 Adj. R² = 0.0404; F = 15.24; p <0.0001), for the homeostat (p < 0.0001 ) and circadian (p = 0.0006) coefficients. Theta activity Analysis of theta activity yielded a significant main effect of “elapsed time awake” (F= 12.2; p < 0.0001), although no significant effects for “genotype” (F= 0.1; p = 0.70) nor for the interaction of these factors (F= 0.67; p = 0.86). The multiple regression model revealed a significant regression (R²= 0.072 Adj. R² =0.069; F= 26.36; p <0.0001), for the homeostat (p < 0.0001 ) and circadian (p < 0.0001 ) coefficients. Alpha activity Analysis of alpha activity yielded a significant main effect of “elapsed time awake”(F=3.43; p < 0.0001), although no significant effects for “genotype” (F = 0.01; p = 0.92) nor for the interaction of these factors (F= 1.23; p = 0.22). The multiple regression model revealed a significant regression (R²=0.052; Adj. R²=0.05; F =18.63; p <0.0001), for the homeostat (p = 0.0012) and for the circadian (p < 0.0001) coefficients. Conclusion Our results indicate that fluctuations in the dynamics of waking EEG activity are modulated by the circadian and homeostatic processes, although the magnitude of these differences are not underlined by a polymorphism in the clock gene PER3. REFERENCES 1. Cajochen C, Brunner DP, Kräuchi K, Graw P, Wirz-Justice A. Power density in theta/alpha frequencies of the waking EEG progressively increases during sustained wakefulness. Sleep. 1995, 10:890-894. 2. Cajochen C, Wyatt JK, Czeisler CA, Dijk DJ.Separation of circadian and wake duration-dependent modulation of EEG activation during wakefulnessNeuroscience. 2002, 114:1047-60. 3. Viola AU, Archer SN, James LM, Groeger JA, Lo JC, Skene DJ, von Schantz M, Dijk DJ PER3 polymorphism predicts sleep structure and waking performance. Curr Biol 2007,17:613–618. 4. Gillberg M, Kecklund G, Akerstedt T. Relations between performance and subjective rating of sleepiness during a night awake. Sleep 1994, 17:236-241. ACKNOWLEDGEMENTS & SPONSORS Cyclotron Research Centre (CRC) ; Belgian National Funds of Scientific Research (FNRS) ; Actions de Recherche Concertées (ARC, ULg) – Fondation Médicale Reine Elisabeth (FMRE) ; Walloon Excellence in Lifesciences and Biotechnology (WELBIO) ; Wellcome Trust ; Biotechnology and Biological Sciences Research Council (BBSRC) [less ▲]