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This study investigated the impact of Alzheimer׳s disease (AD) on conjunctive and relational binding in episodic memory. Mild AD patients and controls had to remember item–color associations by imagining color either as a contextual association (relational memory) or as a feature of the item to be encoded (conjunctive memory). Patients׳ performance in each condition was correlated with cerebral metabolism measured by FDG-PET. The results showed that AD patients had an impaired capacity to remember item–color associations, with deficits in both relational and conjunctive memory. However, performance in the two kinds of associative memory varied independently across patients. Partial Least Square analyses revealed that poor conjunctive memory was related to hypometabolism in an anterior temporal-posterior fusiform brain network, whereas relational memory correlated with metabolism in regions of the default mode network. These findings support the hypothesis of distinct neural systems specialized in different types of associative memory and point to heterogeneous profiles of memory alteration in Alzheimer׳s disease as a function of damage to the respective neural networks.

Typical Alzheimer's disease (AD) is characterized by an impaired form of associative memory, recollection, that includes the controlled retrieval of associations. In contrast, familiarity-based memory for individual items may sometimes be preserved in the early stages of the disease. This is the first study that directly examines whole-brain regional activity during one core aspect of the recollection function: associative controlled episodic retrieval (CER), contrasted to item familiarity in AD patients. Cerebral activity related to associative CER and item familiarity in AD patients and healthy controls (HCs) was measured with functional magnetic resonance imaging during a word-pair recognition task to which the process dissociation procedure was applied. Some patients had null CER estimates (AD-), whereas others did show some CER abilities (AD+), although significantly less than HC. In contrast, familiarity estimates were equivalent in the three groups. In AD+, as in controls, associative CER activated the inferior precuneus/posterior cingulate cortex (PCC). When performing group comparisons, no region was found to be significantly more activated during CER in HC than AD+ and vice versa. However, during associative CER, functional connectivity between this region and the hippocampus, the inferior parietal and dorsolateral prefrontal cortex (DLPFC) was significantly higher in HC than in AD+. In all three groups, item familiarity was related to activation along the intraparietal sulcus (IPS). In conclusion, whereas the preserved automatic detection of an old item (without retrieval of accurate word association) is related to parietal activation centred on the IPS, the inferior precuneus/PCC supports associative CER ability in AD patients, as in HC. However, AD patients have deficient functional connectivity during associative CER, suggesting that the residual recollection function in these patients might be impoverished by the lack of some recollection-related aspects such as autonoetic quality, episodic details and verification.

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.

Contains fulltext : 168981.pdf (Publisher’s version ) (Closed access) Resting-state functional connectivity analysis has become a widely used method for the investigation of human brain connectivity and pathology. The measurement of neuronal activity by functional MRI, however, is impeded by various nuisance signals that reduce the stability of functional connectivity. Several methods exist to address this predicament, but little consensus has yet been reached on the most appropriate approach. Given the crucial importance of reliability for the development of clinical applications, we here investigated the effect of various confound removal approaches on the test-retest reliability of functional-connectivity estimates in two previously defined functional brain networks. Our results showed that gray matter masking improved the reliability of connectivity estimates, whereas denoising based on principal components analysis reduced it. We additionally observed that refraining from using any correction for global signals provided the best test–retest reliability, but failed to reproduce anti-correlations between what have been previously described as antagonistic networks. This suggests that improved reliability can come at the expense of potentially poorer biological validity. Consistent with this, we observed that reliability was proportional to the retained variance, which presumably included structured noise, such as reliable nuisance signals (for instance, noise induced by cardiac processes). We conclude that compromises are necessary between maximizing test-retest reliability and removing variance that may be attributable to non-neuronal sources. 22 p.

Item does not contain fulltext Little is known about how several functions are organized or how putative subregions are coupled with wider brain networks in the human right PMd. To address these issues, we performed connectivity-based parcellation (CBP) based on PMd voxels' coactivations yielded by meta-analytic connectivity modeling (MACM). We additionally search for a similar cluster solution with CBP based on resting-state functional connectivity (RSFC) and probabilistic diffusion tractography. MACM and RSFC assessed FC of the MACM-CBP-derived subregions while functional characterization revealed their behavioral associations. This procedure showed that the right PMd could be divided into five distinct clusters highlighting a cognitive-motor gradient along a rostro-caudal axis including a rostral cluster functionally interacting with prefrontal cortex in supporting high-level cognitive processes and a caudal cluster closely integrated with the motor system. MACM-CBP also revealed a ventral cluster, whose functional profile fits the concept of an eye field, and a dorsal cluster, preferentially hand-related and connected to both cognitive and motor regions. Finally, MACM-CBP yielded a central cluster showing a mixed behavioral profile and FC to parietal regions of the dorsal attention network. Thus, our results showed that the right PMd may be considered as a functional mosaic formed by five subregions. 1 p.

Item does not contain fulltext Recently, we functionally characterized five right dorsal premotor (PMdr) subregions (identified by coactivation based parcellation) by quantitative forward and reverse inference based on a wide range of task-based activation studies (Genon et al, in prep.). We found that the rostral subregion was associated to high-level cognitive tasks, the caudal one to motor functions, the dorsal one to hand-movements, the ventral one to visual functions while the central one showed a heterogeneous profile. Here, we aimed to reinforce and complement this characterization by using correlations between brain morphology and standard neuropsychological tests in two independent large datasets, which were matched for age, gender, education, depression and handedness (Forschungszentrum Jülich [FZJ, n=87, age range: 21-71] and Nathan Kline Institute [NKI; 135: 20-75]). T1 images were processed with the VBM8 toolbox (Friston using linear and non-linear modulation). The five PMdr subregions were used as regions of interest (ROIs), from which regional gray matter volume (GMV) was extracted. We performed partial correlations to examine correlation between each ROI GMV and neuropsychological test performance when controlling for confounding effects of age, education and handedness. To further examine the reliability of correlation, we also performed the analyses in 1000 subsamples of 30 randomly selected subjects within each sample individually. Our analyses yielded generally low correlation coefficients of which only few were statistically significant even at a lenient threshold of p < .05, uncorrected for multiple testing. Notably, a considerable number of correlations showed an inverse relationship between test performance and brain structure, i.e., higher performance was associated with lower GMV. In addition, the patterns of correlations were inconsistent across samples in magnitude, significance and direction. Finally, subsampling revealed that the pattern of correlations that could be observed varied widely when analyses were based on randomly drawn small samples. Our correlational approach, relating GMV and performance across a wide range of standard neuropsychological tests in two large population-based samples did not corroborate the profiles previously revealed using functional decoding based on fMRI-activations. On the one hand, these findings suggest that the functional specialization of some cortical regions, as highlighted by fMRI studies, does not necessarily imply a significant covariance of their actual structure with related standard task performance across individuals in the healthy population. That is, a cognitive-morphologic approach based on healthy interindividual differences may not mirror functional characterization revealed by activation studies in some brain regions. On the other hand, the fact that we found (all kinds of) significant associations in the smaller, randomly assembled subsamples also highlights the high likelihood of spurious findings when performing such correlation analyses in small samples as prevalent in current neuroimaging studies. 2 p.

Item does not contain fulltext Meta-analytic techniques allow cognitive neuroscientists to pool large amounts of data across many individual task-based functional neuroimaging experiments. These methods have been aided by the introduction of online databases such as Brainmap.org or Neurosynth.org, which collate peak activation coordinates obtained from thousands of published studies. Findings from meta-analytic studies typically include brain regions which are consistently activated across studies for specific contrasts, investigating cognitive or clinical hypotheses. These regions can be subsequently used as the basis for seed-based connectivity analysis, or formally compared to neuroimaging data in order to help interpret new findings. To facilitate such approaches, we have developed a new online repository of meta-analytic neuroimaging results, named the Archive of Neuroimaging Meta-analyses (ANIMA). The ANIMA platform consists of an intuitive online interface for querying, downloading, and contributing data from published meta-analytic studies. Additionally, to aid the process of organizing, visualizing, and working with these data, we present an open-source desktop application called Volume Viewer. Volume Viewer allows users to easily arrange imaging data into composite stacks, and save these sessions as individual files, which can also be uploaded to the ANIMA database. The application also allows users to perform basic functions, such as computing conjunctions between images, or extracting regions-of-interest or peak coordinates for further analysis. The introduction of this new resource will enhance the ability of researchers to both share their findings and incorporate existing meta-analytic results into their own research. 2 p.

International audience; In human cognition, self and memory processes strongly interact, as evidenced by the memory advantage for self-referential materials [Self-Reference Effect (SRE) and Self-Reference Recollection Effect (SRRE)]. The current study examined this interaction at the behavioural level and its neural correlates in patients with Alzheimer's disease (AD). Healthy older controls (HC) and AD patients performed trait-adjectives judgements either for self-relevance or for other-relevance (encoding phase). In a first experiment, the encoding and subsequent yes–no recognition phases were administrated in a Magnetic Resonance Imaging (MRI) scanner. Brain activation as measured by functional MRI (fMRI) was examined during self-relevance judgements and anatomical images were used to search for correlation between the memory advantage for self-related items and grey matter density (GMD). In a second experiment, participants described the retrieval experience that had driven their recognition decisions (familiarity vs recollective experience). The behavioural results revealed that the SRE and SRRE were impaired in AD patients compared to HC participants. Furthermore, verbal reports revealed that the retrieval of self-related information was preferentially associated with the retrieval of contextual details, such as source memory in the HC participants, but less so in the AD patients. Our imaging findings revealed that both groups activated the medial prefrontal cortex (MPFC) at encoding during self-relevance judgements. However, the variable and limited memory advantage for self-related information was associated with GMD in the lateral prefrontal cortex in the AD patients, a region supporting high-order processes linking self and memory. These findings suggest that even if AD patients engage MPFC during self-referential judgements, the retrieval of self-related memories is qualitatively and quantitatively impaired in relation with altered high-order processes in the lateral PFC.

et al., in press). In a recent study, we suggested that selfreferential processing at encoding is related to the engagement of the ventromedial prefrontal cortex (VMPFC) in AD patients as it is in healthy older people, whereas reduced and variable SRE in AD patients is related to grey matter volume reduction in the lateral prefrontal cortex (LPFC) across the middle and superior frontal gyri (Genon et al., in press). In a relevant commentary on our study, Irish (in press) insightfully raised the issue of the medial temporal lobe and posterior cingulate cortex (PCC)’s role in the impaired interaction between self andmemory in AD patients. Indeed, given

International audience; The present experiment aimed to investigate age differences in the neural correlates of familiarity and recollection, while keeping performance similar across age groups by varying task difficulty. Twenty young and 20 older adults performed an episodic memory task in an event-related functional magnetic resonance imaging (fMRI) design. At encoding, participants were presented with pictures, either once or twice. Then, they performed a recognition task, with a Remember/Know paradigm. A similar performance was observed for the two groups in the Easy condition for recollection and in the Hard condition for familiarity. Imaging data revealed the classic recollection-related and familiarity-related networks, common to young and older groups. In addition, we observed that some activity related to recollection (left frontal, left temporal, left parietal cortices and left parahippocampus) and familiarity (bilateral anterior cingulate, right frontal gyrus and left superior temporal gyrus) was reduced in older compared to young adults. However, for recollection processes only, older adults additionally recruited the right precuneus, possibly to successfully compensate for their difficulties, as suggested by a positive correlation between recollection and precuneus activity.

Introduction Genetic variability related to the catechol-O-methyltransferase (COMT) gene (Val 158 Met polymorphism) has received increasing attention as a possible modulator of cognitive control functions. Methods In an event-related functional magnetic resonance imaging (fMRI) study, a modified version of the Stroop task was administered to three groups of 15 young adults according to their COMT Val 158 Met genotype [Val/Val (VV), Val/Met (VM) and Met/Met (MM)]. Based on the theory of dual mechanisms of control ( Braver et al., 2007 ), the Stroop task has been built to induce proactive or reactive control processes according to the task context. Results Behavioral results did not show any significant group differences for reaction times but Val allele carriers individuals are less accurate in the processing of incongruent items. fMRI results revealed that proactive control is specifically associated with increased activity in the anterior cingulate cortex (ACC) in carriers of the Met allele, while increased activity is observed in the middle frontal gyrus (MFG) in carriers of the Val allele. Conclusion These observations, in keeping with a higher cortical dopamine level in MM individuals, support the hypothesis of a COMT Val 158 Met genotype modulation of the brain regions underlying proactive control, especially in frontal areas as suggested by Braver et al.

Recognition memory can rely on recollection (recall of the details from the encoding episode) and familiarity (feeling that some information is old without any recollection). In Alzheimer's disease (AD), where there is a clear deficit of recollection, the evidence regarding familiarity is mixed, with some studies showing preserved familiarity and others reporting impairment. The current study examined whether recognition memory performance can be improved in AD when the use of familiarity is facilitated by the salience of processing fluency due to an earlier encounter with the information. Fifteen AD patients and 16 healthy controls performed a verbal recognition memory task where the salience of fluency was manipulated by means of letters overlap. Studied and unstudied words were constituted of either two separate sets of letters (no-overlap condition, high fluency salience) or the same set of letters (overlap condition, low fluency salience). The results showed that, although performance was globally poorer in AD patients than in the controls, both groups performed significantly better in the no-overlap condition than in the overlap condition. This suggests that AD patients benefited as much as the controls from the salience of fluency. 8 9 10 11 12 13 14 15 16 17

REFERENCES Daselaar SM, Fleck MS, Dobbins IG, Madden DJ, and Cabeza R. 2006. Effects of healthy aging on hippocampal and rhinal memory functions: An event-related fMRI study. Cerebral Cortex. 16: 1771-1782. Davidson PSR and Glisky EL. 2002. Neuropsychological correlates of recollection and familiarity in normal aging. Cognitive, Affective, and Behavioral Neuroscience. 2 : 174-186. Morcom AM, Li J, and Rugg MD. 2007. Age Effects on the Neural Correlates of Episodic Retrieval: Increased Cortical Recruitment with Matched Performance. Cerebral Cortex. 17: 2491-506. Yonelinas AP. 2002. The nature of recollection and familiarity: a review of 30 years of research. Journal of Memory and Language. 46: 441-517.

Typical Alzheimer's disease (AD) is characterized by an impaired form of associative memory, recollection, that includes the controlled retrieval of associations. In contrast, familiarity-based memory for individual items may sometimes be preserved in the early stages of the disease. This is the first study that directly examines whole-brain regional activity during one core aspect of the recollection function: associative controlled episodic retrieval (CER), contrasted to item familiarity in AD patients. Cerebral activity related to associative CER and item familiarity in AD patients and healthy controls (HCs) was measured with functional magnetic resonance imaging during a word-pair recognition task to which the process dissociation procedure was applied. Some patients had null CER estimates (AD-), whereas others did show some CER abilities (AD+), although significantly less than HC. In contrast, familiarity estimates were equivalent in the three groups. In AD+, as in controls, associative CER activated the inferior precuneus/posterior cingulate cortex (PCC). When performing group comparisons, no region was found to be significantly more activated during CER in HC than AD+ and vice versa. However, during associative CER, functional connectivity between this region and the hippocampus, the inferior parietal and dorsolateral prefrontal cortex (DLPFC) was significantly higher in HC than in AD+. In all three groups, item familiarity was related to activation along the intraparietal sulcus (IPS). In conclusion, whereas the preserved automatic detection of an old item (without retrieval of accurate word association) is related to parietal activation centred on the IPS, the inferior precuneus/PCC supports associative CER ability in AD patients, as in HC. However, AD patients have deficient functional connectivity during associative CER, suggesting that the residual recollection function in these patients might be impoverished by the lack of some recollection-related aspects such as autonoetic quality, episodic details and verification.

Introduction Un deficit en memoire episodique est caracteristique dans la maladie d’Alzheimer (AD) et chez les patients âges presentant une alteration cognitive legere (MCI). Cette alteration peut s’expliquer par un deficit d’acquisition et/ou un deficit de consolidation. Toutefois, les modifications cerebrales responsables de ces deficits ne sont pas encore parfaitement elucidees. L’objectif de notre etude etait de mettre en relation le profil d’apprentissage deficitaire de ces patients avec leur metabolisme cerebral au repos. Methode L’epreuve du California Verbal Learning Test (CVLT) a ete administree a 51 patients AD, 18 patients MCI qui sont restes stables (suivi longitudinal de 18 mois, MCI-S), 16 patients MCI qui ont developpe la maladie d’Alzheimer (MCI-C) durant les 18 mois de suivi et 12 participants de controle. La mesure d’acquisition est la proportion moyenne de gain a travers les 5 essais d’apprentissage du CVLT. La mesure de consolidation est la proportion totale de pertes a travers ces 5 essais. La mesure du metabolisme cerebral au repos a ete effectuee en tomographie par emission de positions (18FDG-TEP). Les mesures de correlation cognitivometabolique ont ete realisees au moyen du logiciel SPM8 (p non-corrige avec hypothese a priori Resultats Les groupes AD et MCI-C ont un gain moyen moindre que les groupes MCI-S et controles. L’ampleur du gain inter-essais est positivement correlee a l’activite metabolique au niveau de l’hippocampe posterieur chez les patients AD, a l’activite parietale inferieure chez les patients MCI-S, et a l’activite frontale posterieure dans le groupe controle. Par ailleurs, le groupe AD presente plus de pertes inter-essais que les trois autres groupes. Toutefois, aucune correlation significative apparait entre le total des pertes inter-essais et le metabolisme cerebral. Discussion Ces donnees suggerent que les patients AD, meme a un stade tres precoce (MCI-C) presentent un deficit d’acquisition de l’information. Ce deficit pourrait etre soustendu par des perturbations metaboliques dans le reseau d’apprentissage fronto-parietal et hippocampique. Il existe de plus un deficit de consolidation inter-essais specifique aux patients AD mais ce deficit n’est correle a aucune region cerebrale au seuil statistique utilise.

Regional connectivity-based parcellation (rCBP) is a widely used procedure for investigating the structural and functional differentiation within a region of interest (ROI) based on its long-range connectivity. No standardized software or guidelines currently exist for applying rCBP, making the method only accessible to those who develop their own tools. As such, there exists a discrepancy between the laboratories applying the procedure each with their own software solutions, making it difficult to compare and interpret the results. Here, we outline an rCBP procedure accompanied by an open source software package called CBPtools. CBPtools is a Python (version 3.5+) package that allows users to run an extensively evaluated rCBP analysis workflow on a given ROI. It currently supports two modalities: resting-state functional connectivity and structural connectivity based on diffusion-weighted imaging, along with support for custom connectivity matrices. Analysis parameters are customizable and the workflow can be scaled to a large number of subjects using a parallel processing environment. Parcellation results with corresponding validity metrics are provided as textual and graphical output. Thus, CBPtools provides a simple plug-and-play, yet customizable way to conduct rCBP analyses. By providing an open-source software we hope to promote reproducible and comparable rCBP analyses and, importantly, make the rCBP procedure readily available. Here, we demonstrate the utility of CBPtools using a voluminous data set on an average compute-cluster infrastructure by performing rCBP on three ROIs prominently featured in parcellation literature. Electronic supplementary material The online version of this article (10.1007/s00429-020-02046-1) contains supplementary material, which is available to authorized users.

Algorithmic biases that favor majority populations pose a key challenge to the application of machine learning for precision medicine. Here, we assessed such bias in prediction models of behavioral phenotypes from brain functional magnetic resonance imaging. We examined the prediction bias using two independent datasets (preadolescent versus adult) of mixed ethnic/racial composition. When predictive models were trained on data dominated by white Americans (WA), out-of-sample prediction errors were generally higher for African Americans (AA) than for WA. This bias toward WA corresponds to more WA-like brain-behavior association patterns learned by the models. When models were trained on AA only, compared to training only on WA or an equal number of AA and WA participants, AA prediction accuracy improved but stayed below that for WA. Overall, the results point to the need for caution and further research regarding the application of current brain-behavior prediction models in minority populations.