Sarah Genon

Differential effects of aging on the neural correlates of recollection and familiarity.

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.

Modulating effect of COMT genotype on the brain regions underlying proactive control process during inhibition.

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.

The Right Dorsal Premotor Mosaic: Organization, Functions, and Connectivity

Abstract The right dorsal premotor cortex (PMd) of humans has been reported to be involved in a broad range of motor and cognitive functions. We explored the basis of this behavioral heterogeneity by performing a connectivity‐based parcellation using meta‐analytic approach applied to PMd coactivations. We compared our connectivity‐based parcellation results with parcellations obtained through resting‐state functional connectivity and probabilistic diffusion tractography. Functional connectivity profiles and behavioral decoding of the resulting PMd subregions allowed characterizing their respective behavior profile. These procedures divided the right PMd into 5 distinct subregions that formed a cognitive‐motor gradient along a rostro‐caudal axis. In particular, we found 1) a rostral subregion functionally connected with prefrontal cortex, which likely supports high‐level cognitive processes, such as working memory, 2) a central subregion showing a mixed behavioral profile and functional connectivity to parietal regions of the dorsal attention network, and 3) a caudal subregion closely integrated with the motor system. Additionally, we found 4) a dorsal subregion, preferentially related to hand movements and connected to both cognitive and motor regions, and 5) a ventral subregion, whose functional profile fits the concept of an eye movement‐related field. In conclusion, right PMd may be considered as a functional mosaic formed by 5 subregions.

Item familiarity and controlled associative retrieval in Alzheimer’s disease: an fMRI study.

Typical Alzheimers 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.

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

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 Alzheimers 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.

Resting-state test-retest reliability of a priori defined canonical networks over different preprocessing steps

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.

ANIMA: A data-sharing initiative for neuroimaging meta-analyses.

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.

The heterogeneity of the left dorsal premotor cortex evidenced by multimodal connectivity-based parcellation and functional characterization

ABSTRACT Despite the common conception of the dorsal premotor cortex (PMd) as a single brain region, its diverse connectivity profiles and behavioral heterogeneity argue for a differentiated organization of the PMd. A previous study revealed that the right PMd is characterized by a rostro‐caudal and a ventro‐dorsal distinction dividing it into five subregions: rostral, central, caudal, ventral and dorsal. The present study assessed whether a similar organization is present in the left hemisphere, by capitalizing on a multimodal data‐driven approach combining connectivity‐based parcellation (CBP) based on meta‐analytic modeling, resting‐state functional connectivity, and probabilistic diffusion tractography. The resulting PMd modules were then characterized based on multimodal functional connectivity and a quantitative analysis of associated behavioral functions. Analyzing the clusters consistent across all modalities revealed an organization of the left PMd that mirrored its right counterpart to a large degree. Again, caudal, central and rostral modules reflected a cognitive‐motor gradient and a premotor eye‐field was found in the ventral part of the left PMd. In addition, a distinct module linked to abstract cognitive functions was observed in the rostro‐ventral left PMd across all CBP modalities, implying greater differentiation of higher cognitive functions for the left than the right PMd.

Neural correlates of successful memory retrieval in aging: Do executive functioning and task difficulty matter?

The current experiment aimed to explore age differences in brain activity associated with successful memory retrieval in older adults with different levels of executive functioning, at different levels of task demand. Memory performance and fMRI activity during a recognition task were compared between a young group and two older groups characterized by a low (old-low group) vs. high (old-high group) level of executive functioning. Participants first encoded pictures, presented once (Hard condition) or twice (Easy condition), and then completed a recognition memory task. Old-low adults had poorer memory performance than the two other groups, which did not differ, in both levels of task demands. In the Easy condition, even though older adults demonstrated reduced activity compared to young adults in several regions, they also showed additional activations in the right superior frontal gyrus and right parietal lobule (positively correlated to memory accuracy) for the old-high group and in the right precuneus (negatively correlated to memory accuracy), right anterior cingulate gyrus and right supramarginal gyrus for the old-low group. In the Hard condition, some regions were also more activated in the young group than in the older groups. Vice versa, old-high participants demonstrated more activity than either the young or the old-low group in the right frontal gyrus, associated with more accurate memory performance, and in the left frontal gyrus. In sum, the present study clearly showed that age differences in the neural correlates of retrieval success were modulated by task difficulty, as suggested by the CRUNCH model, but also by interindividual variability, in particular regarding executive functioning.

Enhancing the Salience of Fluency Improves Recognition Memory Performance in Mild Alzheimer's Disease

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 Alzheimers 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.