Martin Lepage

Stress, memory, and the hippocampus: can't live with it, can't live without it

Since the 1968s discovery of receptors for stress hormones (corticosteroids) in the rodent hippocampus, a tremendous amount of data has been gathered on the specific and somewhat isolated role of the hippocampus in stress reactivity. The hippocampal sensitivity to stress has also been extended in order to explain the negative impact of stress and related stress hormones on animal and human cognitive function. As a consequence, a majority of studies now uses the stress-hippocampus link as a working hypothesis in setting up experimental protocols. However, in the last decade, new data were gathered showing that stress impacts on many cortical and subcortical brain structures other than the hippocampus. The goal of this paper is to summarize the four major arguments previously used in order to confirm the stress-hippocampus link, and to describe new data showing the implication of other brain regions for each of these previously used arguments. The conclusion of this analysis will be that scientists should gain from extending the impact of stress hormones to other brain regions, since hormonal functions on the brain are best explained by their modulatory role on various brain structures, rather than by their unique impact on one particular brain region.

A new two-photon-sensitive block copolymer nanocarrier.

Easily disrupted: Micelles of a new amphiphilic block copolymer that bear coumarin groups are sensitive to near infrared light by two-photon absorption of the chromophore. Disruption of the micelles under irradiation at 794 nm results in release of both photocleaved coumarin and encapsulated nile red from the hydrophobic core of micelle into aqueous solution, which results in opposing changes in fluorescence emission intensity.

The Bank of Standardized Stimuli (BOSS), a New Set of 480 Normative Photos of Objects to Be Used as Visual Stimuli in Cognitive Research

There are currently stimuli with published norms available to study several psychological aspects of language and visual cognitions. Norms represent valuable information that can be used as experimental variables or systematically controlled to limit their potential influence on another experimental manipulation. The present work proposes 480 photo stimuli that have been normalized for name, category, familiarity, visual complexity, object agreement, viewpoint agreement, and manipulability. Stimuli are also available in grayscale, blurred, scrambled, and line-drawn version. This set of objects, the Bank Of Standardized Stimuli (BOSS), was created specifically to meet the needs of scientists in cognition, vision and psycholinguistics who work with photo stimuli.

Distributed self in episodic memory: neural correlates of successful retrieval of self-encoded positive and negative personality traits

Words processed with reference to the self are generally better remembered than words processed in semantic terms. An account of this phenomenon, labeled the Self Reference Effect (SRE), is that the self promotes elaboration and organization of encoded information. Although a few neuroimaging studies associated self-referential encoding with activations of the medial prefrontal cortex, no previous study has investigated the neural correlates of remembering emotional words encoded in an SRE paradigm. The main goal of this study was to define with fMRI the neural correlates of the successful retrieval of negative and positive personality traits encoded in a self-referential mode. Functional MRI scans were acquired for 11 subjects as they recognized positive and negative emotional personality traits adjectives encoded in a self-referential condition, a semantic condition and in a phonemic condition. The correct recognition of self-encoded personality traits engaged dorso-medial prefrontal cortex and lateral prefrontal regions, premotor cortex, parietal and occipital cortex, caudate and cerebellum. The specific recognition of self-encoded negative personality traits involved greater neural activation in the right extra-striate region than the recognition of positive personality traits. Our fMRI findings suggest that specific processes may operate at both encoding and retrieval to subserve the SRE. Unlike self-encoding, the retrieval of personality traits is modulated by the valence of the stimuli with greater activation for negative words. Our results indicate that personally relevant words may signal important emotional clues and support the notion of a widely distributed set of brain regions involved in maintaining the concepts of self.

Individual differences in trait anhedonia: a structural and functional magnetic resonance imaging study in non-clinical subjects

Anhedonia, the reduced capacity to gain pleasure from pleasurable experiences, is a key symptom of major depression and schizophrenia. Reduced hedonic capacity can also be measured as an enduring trait in non-clinical subjects. Such altered hedonic capacity is likely the result of a basic neuropsychophysiological dysfunction and a vulnerability marker that potentially precedes and contributes to the liability of developing psychiatric disorders. The characterization of the structural and functional neural correlates of trait anhedonia in non-clinical individuals may provide new insights for the early detection of such psychiatric diseases. Twenty-nine non-clinical subjects were scanned at the Montreal Neurological Institute. Trait anhedonia was measured using the Chapman Revised Physical Anhedonia Scale. Semi-automated and automated structural MRI segmentation techniques were used to explore structural correlates of trait anhedonia. Seventeen of the 29 subjects also underwent a functional imaging task where responses to the viewing of affective stimuli were examined to identify the functional correlates of trait anhedonia. Trait anhedonia was inversely related to anterior caudate volume, but positively related to ventromedial prefrontal cortex activity during the processing of positive information. These findings may reflect a specific kind of vulnerability for the development of psychiatric affective disorders and suggest that trait anhedonia may be linked to a volumetric reduction in the basal ganglia and to a prefrontal functional abnormality during hedonic processing.

IL-1 Receptor Antagonist Protects against Placental and Neurodevelopmental Defects Induced by Maternal Inflammation

The precise role of maternal bacterial infection and inflammation occurring at the end of gestation is a controversial matter. Although it is recognized as an independent risk factor for neurodevelopmental diseases such as cerebral palsy, mental deficiency, and autism, it remains unclear whether it is causal or simply associated with the diseases. In this study, we demonstrate that IL-1 plays a key role in mediating severe placental damage and neurodevelopmental anomalies in offspring. Our results show that end of gestation exposure of pregnant rats to systemic microbial product (LPS) triggers placental inflammation and massive cell death, fetal mortality, and both forebrain white matter and motor behavioral alterations in the offspring. All these effects are alleviated by the coadministration of IL-1 receptor antagonist with LPS, suggesting a possible protective treatment against human placental and fetal brain damage.

Cognitive and clinical moderators of recognition memory in schizophrenia: a meta-analysis

Recognition memory performance in schizophrenia has been shown to vary greatly across studies. To identify the conditions under which recognition memory is significantly impaired, we used a meta-analytic strategy to quantify the moderating effects of several cognitive and clinical variables. Eighty-four studies (from 1965 to July 2003) provided recognition memory data for both a schizophrenia and control group. The overall group comparison for recognition memory yielded a significant mean weighted effect size of d=0.76. Material specificity was the most significant cognitive variable found, with patients exhibiting greater impairment for figural than verbal recognition. A yes-no recognition format and auditory encoding also led to significantly greater effect sizes for recognition memory relative to forced-choice recognition tests and visual encoding, respectively. Furthermore, the effect size for recognition memory as measured by false alarm was smaller than the effect size as measured by hit rate or by d-prime and its related measures. Among clinical variables that were associated with higher effect sizes, chronicity was the most significant, but different trends linking poor performance to negative symptoms and general symptomatology were also observed. Thus, a recognition memory deficit moderated by both cognitive and clinical variables is clearly present in schizophrenia.

Multi-atlas segmentation of the whole hippocampus and subfields using multiple automatically generated templates

INTRODUCTION Advances in image segmentation of magnetic resonance images (MRI) have demonstrated that multi-atlas approaches improve segmentation over regular atlas-based approaches. These approaches often rely on a large number of manually segmented atlases (e.g. 30-80) that take significant time and expertise to produce. We present an algorithm, MAGeT-Brain (Multiple Automatically Generated Templates), for the automatic segmentation of the hippocampus that minimises the number of atlases needed whilst still achieving similar agreement to multi-atlas approaches. Thus, our method acts as a reliable multi-atlas approach when using special or hard-to-define atlases that are laborious to construct. METHOD MAGeT-Brain works by propagating atlas segmentations to a template library, formed from a subset of target images, via transformations estimated by nonlinear image registration. The resulting segmentations are then propagated to each target image and fused using a label fusion method. We conduct two separate Monte Carlo cross-validation experiments comparing MAGeT-Brain and basic multi-atlas whole hippocampal segmentation using differing atlas and template library sizes, and registration and label fusion methods. The first experiment is a 10-fold validation (per parameter setting) over 60 subjects taken from the Alzheimers Disease Neuroimaging Database (ADNI), and the second is a five-fold validation over 81 subjects having had a first episode of psychosis. In both cases, automated segmentations are compared with manual segmentations following the Pruessner-protocol. Using the best settings found from these experiments, we segment 246 images of the ADNI1:Complete 1Yr 1.5 T dataset and compare these with segmentations from existing automated and semi-automated methods: FSL FIRST, FreeSurfer, MAPER, and SNT. Finally, we conduct a leave-one-out cross-validation of hippocampal subfield segmentation in standard 3T T1-weighted images, using five high-resolution manually segmented atlases (Winterburn et al., 2013). RESULTS In the ADNI cross-validation, using 9 atlases MAGeT-Brain achieves a mean Dices Similarity Coefficient (DSC) score of 0.869 with respect to manual whole hippocampus segmentations, and also exhibits significantly lower variability in DSC scores than multi-atlas segmentation. In the younger, psychosis dataset, MAGeT-Brain achieves a mean DSC score of 0.892 and produces volumes which agree with manual segmentation volumes better than those produced by the FreeSurfer and FSL FIRST methods (mean difference in volume: 80 mm(3), 1600 mm(3), and 800 mm(3), respectively). Similarly, in the ADNI1:Complete 1Yr 1.5 T dataset, MAGeT-Brain produces hippocampal segmentations well correlated (r>0.85) with SNT semi-automated reference volumes within disease categories, and shows a conservative bias and a mean difference in volume of 250 mm(3) across the entire dataset, compared with FreeSurfer and FSL FIRST which both overestimate volume differences by 2600 mm(3) and 2800 mm(3) on average, respectively. Finally, MAGeT-Brain segments the CA1, CA4/DG and subiculum subfields on standard 3T T1-weighted resolution images with DSC overlap scores of 0.56, 0.65, and 0.58, respectively, relative to manual segmentations. CONCLUSION We demonstrate that MAGeT-Brain produces consistent whole hippocampal segmentations using only 9 atlases, or fewer, with various hippocampal definitions, disease populations, and image acquisition types. Additionally, we show that MAGeT-Brain identifies hippocampal subfields in standard 3T T1-weighted images with overlap scores comparable to competing methods.

A face to remember: emotional expression modulates prefrontal activity during memory formation.

Emotion can exert a modulatory role on episodic memory. Several studies have shown that negative stimuli (e.g., words, pictures) are better remembered than neutral ones. Although facial expressions are powerful emotional stimuli and have been shown to influence perception and attention processes, little is known about their effect on memory. We used functional magnetic resonance imaging (fMRI) in humans to investigate the effects of expression (happy, neutral, and fearful) on prefrontal cortex (PFC) activity during the encoding of faces, using a subsequent memory effect paradigm. Our results show that activity in right PFC predicted memory for faces, regardless of expression, while a homotopic region in the left hemisphere was associated with successful encoding only for faces with an emotional expression. These findings are consistent with the proposed role of right dorsolateral PFC in successful encoding of nonverbal material, but also suggest that left DLPFC may be a site where integration of memory and emotional processes occurs. This study sheds new light on the current controversy regarding the hemispheric lateralization of PFC in memory encoding.

Performance Evaluation of the LabPET APD-Based Digital PET Scanner

The LabPETTM is a fully digital avalanche photodiode (APD) based PET scanner designed for state-of-the- art molecular and genomic imaging of small animals. Two versions of the scanner were evaluated, having 3.75 (LabPET4) and 7.5 cm axial FOV (LabPET8). The detectors are made of 2x2x10/12 mm3 LYSO and LGSO crystals assembled in phoswich pairs read out by an APD. After digital crystal identification, the average energy resolution is 24 plusmn 6% for LYSO and 25 plusmn 6% for LGSO. The scanner overall timing resolution is 6.6 ns for LYSO/LYSO and 10.7 ns for LGSO/LGSO coincidences after coarse timing alignment. The FBP reconstructed tangential/radial resolution is 1.3/1.4 mm FWHM (2.5/2.4 mm FWTM) at the FOV center and remains below 2.1 mm FWHM (3.6 mm FWTM) within the central 4-cm diameter FOV. MLEM reconstruction of a micro resolution phantom provided clear separation of the 1.35 mm spots and fair identification of 1 mm spots. With an energy window of 250-650 keV, the sensitivity is 1.1% for LabPET4 and 2.1% for LabPET8. The imaging capabilities of the scanner are demonstrated with in vivo images of rats and mice.