Altered default mode network connectivity in adolescents with post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is characterized by intrusions, re-experiencing, avoidance and hyperarousal. These symptoms might be linked to dysfunction in core neurocognitive networks subserving self-referential mental processing (default mode network, DMN), detection of salient stimuli (salience network, SN) and cognitive dysfunction (central executive network, CEN). Resting state studies in adolescent PTSD are scarce and findings are inconsistent, probably due to differences in patient symptom severity. Resting state brain activity was measured in 14 adolescents with severe PTSD and 24 age-matched controls. Seed-based connectivity analyses were used to examine connectivity between the DMN and the whole brain, including regions from other networks (SN and CEN). The relationships of network properties with symptom dimensions (severity, anxiety and depression) and episodic memory were also examined. Analyses revealed decreased within-DMN connectivity (between PCC and occipital cortex) in patients compared to controls. Furthermore, within-DMN connectivity (between PCC and hippocampus) correlated negatively with symptom dimensions (severity and anxiety), while increased connectivity (DMN-SN and DMN-CEN) correlated positively with episodic memory measures. These abnormal network properties found in adolescent PTSD corroborate those previously reported in adult PTSD. Decreased within-DMN connectivity and disrupted DMN-SN and DMN-CEN coupling could form the basis for intrusive trauma recollection and impaired episodic autobiographical recall in PTSD.

Distinct influence of specific versus global connectivity on the different Alzheimer's disease biomarkers.

See Franzmeier and Dyrba (doi:10.1093/brain/awx304) for a scientific commentary on this article. Recent findings suggest that the topography and propagation of lesions in Alzheimer's disease are related to functional connectivity, either showing that regions of high global connectivity are more vulnerable or that lesions propagate neuron-to-neuron from a starting area called the epicentre, thus involving specific connectivity. However, the relative influence of specific and global connectivity and their differential impact on the three main neuroimaging biomarkers of the disease (atrophy, hypometabolism and amyloid-ß deposition) have never been investigated to date. Forty-two healthy elderly subjects and 35 amyloid-ß positive amnestic mild cognitive impairment and Alzheimer's disease patients underwent resting-state functional MRI, anatomical T1-weighted MRI, 18F-fluorodeoxyglucose-PET and florbetapir-PET scans. All patients also underwent follow-up T1-weighted MRI, 18F-fluorodeoxyglucose-PET and florbetapir-PET scans 18 months later to assess the lesion propagation. The epicentre was defined per modality as the most altered region at baseline in patients compared to controls. Maps of global and specific functional connectivity were computed from the resting-state functional MRI data of the healthy elderly subjects. Global connectivity corresponds to the connectivity strength of each grey matter area with the rest of the brain (i.e. all other grey matter areas) while specific connectivity refers to the connectivity of a single specific brain region (the epicentre) with the rest of the brain (i.e. all other brain regions). Maps of baseline alterations and propagation were computed for grey matter atrophy, hypometabolism and amyloid-ß deposition in patients. Regression analyses were performed across the 239 brain regions to assess the links between global or specific functional connectivity in healthy elderly subjects and Alzheimer's disease-related baseline disruptions or alteration propagation. Atrophy at baseline was predicted by specific connectivity and inversely correlated with global connectivity, while hypometabolism and amyloid-ß deposition were positively influenced by both global and specific connectivity. Regarding longitudinal changes, atrophy spread in regions with high specific connectivity while hypometabolism propagated in areas showing high global connectivity. This is the first study to show that global connectivity has an opposite relationship with atrophy versus hypometabolism and amyloid-ß deposition, suggesting that the high level of functional connectivity found in hubs exerts a differential influence on these Alzheimer's disease lesions. These results sustain the hypotheses of higher vulnerability of hubs to hypometabolism and amyloid-ß deposition versus transneuronal propagation of atrophy from the epicentre to connected regions, in Alzheimer's disease. Global and specific connectivity exert a differential influence on, and provide complementary information to predict, the topography of Alzheimer's disease lesions and their propagation.

Association between educational attainment and amyloid deposition across the spectrum from normal cognition to dementia: neuroimaging evidence for protection and compensation.

The brain mechanisms underlying the effect of intellectual enrichment may evolve along the normal aging Alzheimer's disease (AD) cognitive spectrum and may include both protective and compensatory mechanisms. We assessed the association between early intellectual enrichment (education, years) and average cortical florbetapir standardized uptake value ratio as well as performed voxel-wise analyses in a total of 140 participants, including cognitively normal older adults, mild cognitive impairment (MCI), and AD patients. Higher education was associated with lower cortical florbetapir positron emission tomography (florbetapir-PET) uptake, notably in the frontal lobe in normal older adults, but with higher uptake in frontal, temporal, and parietal regions in MCI after controlling for global cognitive status. No association was found in AD. In MCI, we observed an increased fluorodeoxyglucose positron emission tomography (FDG-PET) uptake with education within the regions of higher florbetapir-PET uptake, suggesting a compensatory increase. Early intellectual enrichment may be associated with protection and compensation for amyloid beta (Aß) deposition later in life, before the onset of dementia. Previous investigations have been controversial as regard to the effects of intellectual enrichment variables on Aß deposition; the present findings call for approaches aiming to evaluate mechanisms of resilience across disease stages.

Intrinsic connectivity of hippocampal subfields in normal elderly and mild cognitive impairment patients.

Hippocampal connectivity has been widely described but connectivity specificities of hippocampal subfields and their changes in early AD are poorly known. The aim of this study was to highlight hippocampal subfield networks in healthy elderly (HE) and their changes in amnestic patients with mild cognitive impairment (aMCI). Thirty-six HE and 27 aMCI patients underwent resting-state functional MRI scans. Specific intrinsic connectivity of bilateral CA1, SUB (subiculum), and CA2/3/4/DG was identified in HE (using seeds derived from manually delineation on high-resolution scans) and compared between HE and aMCI. Compared to the other subfields, CA1 was more strongly connected to the amygdala and occipital regions, CA2/3/4/DG to the left anterior cingulate cortex, temporal, and occipital regions, and SUB to the angular, precuneus, putamen, posterior cingulate, and frontal regions. aMCI patients showed reduced connectivity within the SUB network (with frontal and posterior cingulate regions). Our study highlighted for the first time three specific and distinct hippocampal subfield functional networks in HE, and their alterations in aMCI. These findings are important to understand AD specificities in both cognitive deficits and lesion topography, given the role of functional connectivity in these processes. Hum Brain Mapp 38:4922-4932, 2017. © 2017 Wiley Periodicals, Inc.

Subjective cognitive decline in cognitively normal elders from the community or from a memory clinic: Differential affective and imaging correlates.

INTRODUCTION: Subjective cognitive decline (SCD) could indicate preclinical Alzheimer's disease, but the existing literature is confounded by heterogeneous approaches to studying SCD. We assessed the differential cognitive, affective, and neuroimaging correlates of two aspects of SCD: reporting high cognitive difficulties on a self-rated questionnaire versus consulting at a memory clinic. METHODS: We compared 28 patients from a memory clinic with isolated SCD, 35 community-recruited elders with similarly high levels of self-reported cognitive difficulties, and 35 community-recruited controls with low self-reported cognitive difficulties. RESULTS: Increased anxiety and amyloid ß deposition were observed in both groups with high self-reported difficulties, whereas subclinical depression and (hippocampal) atrophy were specifically associated with medical help seeking. Cognitive tests showed no group differences. DISCUSSION: These results further validate the concept of SCD in both community- and clinic-based groups. Yet, recruitment methods influence associated biomarkers and affective symptomatology, highlighting the heterogeneous nature of SCD depending on study characteristics.

Relationships between sleep quality and brain volume, metabolism, and amyloid deposition in late adulthood.

Recent studies in mouse models of Alzheimer's disease (AD) and in humans suggest that sleep disruption and amyloid-beta (Aß) accumulation are interrelated, and may, thus, exacerbate each other. We investigated the association between self-reported sleep variables and neuroimaging data in 51 healthy older adults. Participants completed a questionnaire assessing sleep quality and quantity and underwent positron emission tomography scans using [18F]florbetapir and [18F]fluorodeoxyglucose and an magnetic resonance imaging scan to measure Aß burden, hypometabolism, and atrophy, respectively. Longer sleep latency was associated with greater Aß burden in prefrontal areas. Moreover, the number of nocturnal awakenings was negatively correlated with gray matter volume in the insular region. In asymptomatic middle-aged and older adults, lower self-reported sleep quality was associated with greater Aß burden and lower volume in brain areas relevant in aging and AD, but not with glucose metabolism. These results highlight the potential relevance of preserving sleep quality in older adults and suggest that sleep may be a factor to screen for in individuals at risk for AD.

Connectivity Disruption, Atrophy, and Hypometabolism within Posterior Cingulate Networks in Alzheimer's Disease.

The posterior cingulate cortex (PCC) is a critical brain network hub particularly sensitive to Alzheimer's disease (AD) and can be subdivided into ventral (vPCC) and dorsal (dPCC) regions. The aim of the present study was to highlight functional connectivity (FC) disruption, atrophy, and hypometabolism within the ventral and dorsal PCC networks in patients with amnestic mild cognitive impairment (aMCI) or AD. Forty-three healthy elders (HE) (68.7 ± 6 years), 34 aMCI (73.4 ± 6.8 years) and 24 AD (70.9 ± 9.1 years) patients underwent resting-state functional MRI, anatomical T1-weighted MRI and FDG-PET scans. We compared FC maps obtained from the vPCC and dPCC seeds in HE to identify the ventral and dorsal PCC networks. We then compared patients and HE on FC, gray matter volume and metabolism within each network. In HE, the ventral PCC network involved the hippocampus and posterior occipitotemporal and temporoparietal regions, whereas the dorsal PCC network included mainly frontal, middle temporal and temporoparietal areas. aMCI patients had impaired ventral network FC in the bilateral hippocampus, but dorsal network FC was preserved. In AD, the ventral network FC disruption had spread to the left parahippocampal and angular regions, while the dorsal network FC was also affected in the right middle temporal cortex. The ventral network was atrophied in the bilateral hippocampus in aMCI patients, and in the vPCC and angular regions as well in AD patients. The dorsal network was only atrophied in AD patients, in the dPCC, bilateral supramarginal and temporal regions. By contrast, hypometabolism was already present in both the vPCC and dPCC networks in aMCI patients, and further extended to include the whole networks in AD patients. The vPCC and dPCC connectivity networks were differentially sensitive to AD. Atrophy and FC disruption were only present in the vPCC network in aMCI patients, and extended to the dPCC network in AD patients, suggesting that the pathology spreads from the vPCC to the dPCC networks. By contrast, hypometabolism seemed to follow a different route, as it was present in both networks since the aMCI stage, possibly reflecting not only local disruption but also distant synaptic dysfunction.

Brain structural, functional, and cognitive correlates of recent versus remote autobiographical memories in amnestic Mild Cognitive Impairment.

Deficits in autobiographical memory appear earlier for recent than for remote life periods over the course of Alzheimer's disease (AD). The present study aims to further our understanding of this graded effect by investigating the cognitive and neural substrates of recent versus remote autobiographical memories in patients with amnestic Mild Cognitive Impairment (aMCI) thanks to an autobiographical fluency task. 20 aMCI patients and 25 Healthy elderly Controls (HC) underwent neuropsychological tests assessing remote (20-to-30 years old) and recent (the ten last years) autobiographical memory as well as episodic and semantic memory, executive function and global cognition. All patients also had a structural MRI and an FDG-PET scan. Correlations were assessed between each autobiographical memory score and the other tests as well as grey matter volume and metabolism. Within the aMCI, performances for the remote period correlated with personal semantic memory and episodic memory retrieval whereas performances for the recent period only correlated with episodic memory retrieval. Neuroimaging analyses revealed significant correlations between performances for the remote period and temporal pole and temporo-parietal cortex volumes and anterior cingulate gyrus metabolism, while performances for the recent period correlated with hippocampal volume and posterior cingulate, medial prefrontal and hippocampus metabolism. The brain regions related with the retrieval of events from the recent period showed greater atrophy/hypometabolism in aMCI patients compared to HC than those involved in remote memories. Recall of recent memories essentially relies on episodic memory processes and brain network while remote memories also involve other processes such as semantic memory. This is consistent with the semanticization of memories with time and may explain the better resistance of remote memory in AD.

Musical practice and cognitive aging: two cross-sectional studies point to phonemic fluency as a potential candidate for a use-dependent adaptation.

Because of permanent use-dependent brain plasticity, all lifelong individuals' experiences are believed to influence the cognitive aging quality. In older individuals, both former and current musical practices have been associated with better verbal skills, visual memory, processing speed, and planning function. This work sought for an interaction between musical practice and cognitive aging by comparing musician and non-musician individuals for two lifetime periods (middle and late adulthood). Long-term memory, auditory-verbal short-term memory, processing speed, non-verbal reasoning, and verbal fluencies were assessed. In Study 1, measures of processing speed and auditory-verbal short-term memory were significantly better performed by musicians compared with controls, but both groups displayed the same age-related differences. For verbal fluencies, musicians scored higher than controls and displayed different age effects. In Study 2, we found that lifetime period at training onset (childhood vs. adulthood) was associated with phonemic, but not semantic, fluency performances (musicians who had started to practice in adulthood did not perform better on phonemic fluency than non-musicians). Current frequency of training did not account for musicians' scores on either of these two measures. These patterns of results are discussed by setting the hypothesis of a transformative effect of musical practice against a non-causal explanation.