Aging and Alzheimer's disease have dissociable effects on local and regional medial temporal lobe connectivity.

Functional disruption of the medial temporal lobe-dependent networks is thought to underlie episodic memory deficits in aging and Alzheimer's disease. Previous studies revealed that the anterior medial temporal lobe is more vulnerable to pathological and neurodegenerative processes in Alzheimer's disease. In contrast, cognitive and structural imaging literature indicates posterior, as opposed to anterior, medial temporal lobe vulnerability in normal aging. However, the extent to which Alzheimer's and aging-related pathological processes relate to functional disruption of the medial temporal lobe-dependent brain networks is poorly understood. To address this knowledge gap, we examined functional connectivity alterations in the medial temporal lobe and its immediate functional neighbourhood-the Anterior-Temporal and Posterior-Medial brain networks-in normal agers, individuals with preclinical Alzheimer's disease and patients with Mild Cognitive Impairment or mild dementia due to Alzheimer's disease. In the Anterior-Temporal network and in the perirhinal cortex, in particular, we observed an inverted 'U-shaped' relationship between functional connectivity and Alzheimer's stage. According to our results, the preclinical phase of Alzheimer's disease is characterized by increased functional connectivity between the perirhinal cortex and other regions of the medial temporal lobe, as well as between the anterior medial temporal lobe and its one-hop neighbours in the Anterior-Temporal system. This effect is no longer present in symptomatic Alzheimer's disease. Instead, patients with symptomatic Alzheimer's disease displayed reduced hippocampal connectivity within the medial temporal lobe as well as hypoconnectivity within the Posterior-Medial system. For normal aging, our results led to three main conclusions: (i) intra-network connectivity of both the Anterior-Temporal and Posterior-Medial networks declines with age; (ii) the anterior and posterior segments of the medial temporal lobe become increasingly decoupled from each other with advancing age; and (iii) the posterior subregions of the medial temporal lobe, especially the parahippocampal cortex, are more vulnerable to age-associated loss of function than their anterior counterparts. Together, the current results highlight evolving medial temporal lobe dysfunction in Alzheimer's disease and indicate different neurobiological mechanisms of the medial temporal lobe network disruption in aging versus Alzheimer's disease.

Aging and Alzheimer's Disease Have Dissociable Effects on Medial Temporal Lobe Connectivity.

Functional disruption of the medial temporal lobe-dependent networks is thought to underlie episodic memory deficits in aging and Alzheimer's disease. Previous studies revealed that the anterior medial temporal lobe is more vulnerable to pathological and neurodegenerative processes in Alzheimer's disease. In contrast, cognitive and structural imaging literature indicates posterior, as opposed to anterior, medial temporal lobe vulnerability in normal aging. However, the extent to which Alzheimer's and aging-related pathological processes relate to functional disruption of the medial temporal lobe-dependent brain networks is poorly understood. To address this knowledge gap, we examined functional connectivity alterations in the medial temporal lobe and its immediate functional neighborhood - the Anterior-Temporal and Posterior-Medial brain networks - in normal agers, individuals with preclinical Alzheimer's disease, and patients with Mild Cognitive Impairment or mild dementia due to Alzheimer's disease. In the Anterior-Temporal network and in the perirhinal cortex, in particular, we observed an inverted 'U-shaped' relationship between functional connectivity and Alzheimer's stage. According to our results, the preclinical phase of Alzheimer's disease is characterized by increased functional connectivity between the perirhinal cortex and other regions of the medial temporal lobe, as well as between the anterior medial temporal lobe and its one-hop neighbors in the Anterior-Temporal system. This effect is no longer present in symptomatic Alzheimer's disease. Instead, patients with symptomatic Alzheimer's disease displayed reduced hippocampal connectivity within the medial temporal lobe as well as hypoconnectivity within the Posterior-Medial system. For normal aging, our results led to three main conclusions: (1) intra-network connectivity of both the Anterior-Temporal and Posterior-Medial networks declines with age; (2) the anterior and posterior segments of the medial temporal lobe become increasingly decoupled from each other with advancing age; and, (3) the posterior subregions of the medial temporal lobe, especially the parahippocampal cortex, are more vulnerable to age-associated loss of function than their anterior counterparts. Together, the current results highlight evolving medial temporal lobe dysfunction in Alzheimer's disease and indicate different neurobiological mechanisms of the medial temporal lobe network disruption in aging vs. Alzheimer's disease.

Comparison of epicardial adipose tissue volume quantification between ECG-gated cardiac and non-ECG-gated chest computed tomography scans.

BACKGROUND: This study investigated accuracy and consistency of epicardial adipose tissue (EAT) quantification in non-ECG-gated chest computed tomography (CT) scans. METHODS: EAT volume was semi-automatically quantified using a standard Hounsfield unit threshold (- 190, - 30) in three independent cohorts: (1) Cohort 1 (N = 49): paired 120 kVp ECG-gated cardiac non-contrast CT (NCCT) and 120 kVp non-ECG-gated chest NCCT; (2) Cohort 2 (N = 34): paired 120 kVp cardiac NCCT and 100 kVp non-ECG-gated chest NCCT; (3) Cohort 3 (N = 32): paired non-ECG-gated chest NCCT and chest contrast-enhanced CT (CECT) datasets (including arterial phase and venous phase). Images were reconstructed with the slice thicknesses of 1.25 mm and 5 mm in the chest CT datasets, and 3 mm in the cardiac NCCT datasets. RESULTS: In Cohort 1, the chest NCCT-1.25 mm EAT volume was similar to the cardiac NCCT EAT volume, while chest NCCT-5 mm underestimated the EAT volume by 7.5%. In Cohort 2, 100 kVp chest NCCT-1.25 mm were 13.2% larger than 120 kVp cardiac NCCT EAT volumes. In Cohort 3, the chest arterial CECT and venous CECT dataset underestimated EAT volumes by ~ 28% and ~ 18%, relative to chest NCCT datasets. All chest CT-derived EAT volumes were similarly associated with significant coronary atherosclerosis with cardiac CT counterparts. CONCLUSION: The 120 kVp non-ECG-gated chest NCCT-1.25 mm images produced EAT volumes comparable to cardiac NCCT. Chest CT EAT volumes derived from consistent imaging settings are excellent alternatives to the cardiac NCCT to investigate their association with coronary artery disease.

Investigating the effects of healthy cognitive aging on brain functional connectivity using 4.7 T resting-state functional magnetic resonance imaging.

Functional changes in the aging human brain have been previously reported using functional magnetic resonance imaging (fMRI). Earlier resting-state fMRI studies revealed an age-associated weakening of intra-system functional connectivity (FC) and age-associated strengthening of inter-system FC. However, the majority of such FC studies did not investigate the relationship between age and network amplitude, without which correlation-based measures of FC can be challenging to interpret. Consequently, the main aim of this study was to investigate how three primary measures of resting-state fMRI signal-network amplitude, network topography, and inter-network FC-are affected by healthy cognitive aging. We acquired resting-state fMRI data on a 4.7 T scanner for 105 healthy participants representing the entire adult lifespan (18-85 years of age). To study age differences in network structure, we combined ICA-based network decomposition with sparse graphical models. Older adults displayed lower blood-oxygen-level-dependent (BOLD) signal amplitude in all functional systems, with sensorimotor networks showing the largest age differences. Our age comparisons of network topography and inter-network FC demonstrated a substantial amount of age invariance in the brain's functional architecture. Despite architecture similarities, old adults displayed a loss of communication efficiency in our inter-network FC comparisons, driven primarily by the FC reduction in frontal and parietal association cortices. Together, our results provide a comprehensive overview of age effects on fMRI-based FC.

Involvement of hippocampal subfields and anterior-posterior subregions in encoding and retrieval of item, spatial, and associative memories: Longitudinal versus transverse axis.

The functional role of the hippocampal formation in episodic memory has been studied using functional magnetic resonance imaging (fMRI) for many years. The hippocampus can be segmented into three major anteroposterior sections, called head, body and tail, and into the Cornu Ammonis (CA), dentate gyrus (DG), and subiculum (Sub) subfields based on its transverse axis. However, the exact role of these subregions and subfields in memory processes is less understood. In the present study we combined ultra-high-resolution structural Magnetic Resonance Imaging (MRI) at 4.7 T with an event-related high-resolution fMRI paradigm based on the 'Designs' subtest of the Wechsler Memory Scale to investigate how the hippocampal subfields and longitudinal subregions are involved in encoding and retrieval of item, spatial, and associative memories. Our results showed that during memory encoding, regardless of the type of memory being learned, all subregions and all subfields were active. During the retrieval phase, on the other hand, we observed an anterior to posterior gradient in hippocampal activity for all subfields and all types of memory. Our findings also confirmed presence of an anterior to posterior gradient in hippocampal activity during spatial learning. Comparing subfield activities to each other revealed that the DG was more active than the CA1-3 and Sub during both encoding and retrieval. Finally, our results showed that for every subfield, encoding vs. retrieval activity differences were larger in the hippocampal head than in the hippocampal body and tail. Furthermore, these encoding vs. retrieval activity differences were similar in all subfields, highlighting the importance of studying both the longitudinal and transverse axis specialization simultaneously. Current findings further elucidate the structure-function relationship between the human hippocampus and episodic memory.

Amygdala subnuclei and healthy cognitive aging.

Amygdala is a group of nuclei involved in the neural circuits of fear, reward learning, and stress. The main goal of this magnetic resonance imaging (MRI) study was to investigate the relationship between age and the amygdala subnuclei volumes in a large cohort of healthy individuals. Our second goal was to determine effects of the apolipoprotein E (APOE) and brain-derived neurotrophic factor (BDNF) polymorphisms on the amygdala structure. One hundred and twenty-six healthy participants (18-85 years old) were recruited for this study. MRI datasets were acquired on a 4.7 T system. Amygdala was manually segmented into five major subdivisions (lateral, basal, accessory basal nuclei, and cortical, and centromedial groups). The BDNF (methionine and homozygous valine) and APOE genotypes (ε2, homozygous ε3, and ε4) were obtained using single nucleotide polymorphisms. We found significant nonlinear negative associations between age and the total amygdala and its lateral, basal, and accessory basal nuclei volumes, while the cortical amygdala showed a trend. These age-related associations were found only in males but not in females. Centromedial amygdala did not show any relationship with age. We did not observe any statistically significant effects of APOE and BDNF polymorphisms on the amygdala subnuclei volumes. In contrast to APOE ε2 allele carriers, both older APOE ε4 and ε3 allele carriers had smaller lateral, basal, accessory basal nuclei volumes compared to their younger counterparts. This study indicates that amygdala subnuclei might be nonuniformly affected by aging and that age-related association might be gender specific.

Comparison of epicardial adipose tissue radiodensity threshold between contrast and non-contrast enhanced computed tomography scans: A cohort study of derivation and validation.

BACKGROUND AND AIMS: Epicardial adipose tissue (EAT) volume derived from contrast enhanced (CE) computed tomography (CT) scans is not well validated. We aim to establish a reliable threshold to accurately quantify EAT volume from CE datasets. METHODS: We analyzed EAT volume on paired non-contrast (NC) and CE datasets from 25 patients to derive appropriate Hounsfield (HU) cutpoints to equalize two EAT volume estimates. The gold standard threshold (-190HU, -30HU) was used to assess EAT volume on NC datasets. For CE datasets, EAT volumes were estimated using three previously reported thresholds: (-190HU, -30HU), (-190HU, -15HU), (-175HU, -15HU) and were analyzed by a semi-automated 3D Fat analysis software. Subsequently, we applied a threshold correction to (-190HU, -30HU) based on mean differences in radiodensity between NC and CE images (ΔEATrd = CE radiodensity - NC radiodensity). We then validated our findings on EAT threshold in 21 additional patients with paired CT datasets. RESULTS: EAT volume from CE datasets using previously published thresholds consistently underestimated EAT volume from NC dataset standard by a magnitude of 8.2%-19.1%. Using our corrected threshold (-190HU, -3HU) in CE datasets yielded statistically identical EAT volume to NC EAT volume in the validation cohort (186.1 ±â€¯80.3 vs. 185.5 ±â€¯80.1 cm3, Δ = 0.6 cm3, 0.3%, p = 0.374). CONCLUSIONS: Estimating EAT volume from contrast enhanced CT scans using a corrected threshold of -190HU, -3HU provided excellent agreement with EAT volume from non-contrast CT scans using a standard threshold of -190HU, -30HU.

Differential vulnerability of hippocampal subfields and anteroposterior hippocampal subregions in healthy cognitive aging.

In the present study, we investigated whether hippocampal subfields (cornu ammonis 1-3, dentate gyrus, and subiculum) and anteroposterior hippocampal subregions (head, body, and tail) follow the same trajectory with age using structural magnetic resonance imaging. We recruited 129 healthy volunteers, aged 18-85 years. Structural magnetic resonance imaging scans were acquired on a 4.7T system. Hippocampal subfields and subregions were manually segmented using reliable volumetric protocols. We found that all effects of age on the hippocampal volumes were nonlinear and were mainly found in the hippocampal body, while the hippocampal head and the tail volumes were not associated with age. The total subiculum and the total dentate gyrus volumes were associated with age, while the total cornu ammonis 1-3 was not. Significant associations with age for the cornu ammonis 1-3 and the dentate gyrus volumes were present only in the hippocampal body, while the subiculum volumes were associated with age throughout the entire hippocampus. Subiculum volumes were more negatively related to age in men than in women.

Amygdala subnuclei response and connectivity during emotional processing.

The involvement of the human amygdala in emotion-related processing has been studied using functional magnetic resonance imaging (fMRI) for many years. However, despite the amygdala being comprised of several subnuclei, most studies investigated the role of the entire amygdala in processing of emotions. Here we combined a novel anatomical tracing protocol with event-related high-resolution fMRI acquisition to study the responsiveness of the amygdala subnuclei to negative emotional stimuli and to examine intra-amygdala functional connectivity. The greatest sensitivity to the negative emotional stimuli was observed in the centromedial amygdala, where the hemodynamic response amplitude elicited by the negative emotional stimuli was greater and peaked later than for neutral stimuli. Connectivity patterns converge with extant findings in animals, such that the centromedial amygdala was more connected with the nuclei of the basal amygdala than with the lateral amygdala. Current findings provide evidence of functional specialization within the human amygdala.

A functional neuroimaging case study of Meares-Irlen syndrome/visual stress (MISViS).

The aim of this study is to evaluate the data from a participant in a reading study who had a diagnosis of Meares-Irlen syndrome/visual stress (MISViS). MISViS is characterised by visual distortions and somatic issues, which are remediated using coloured filters. The authors present a case study providing descriptive neurobiological comparisons of MISViS versus a control group. The study involved eleven English language speakers who participated in behavioural and neuroimaging versions of a language experiment with varied proportions of regular and exception words. Behavioural measures included accuracy and response times. Neuroimaging was conducted using a 1.5T Siemens Sonata MRI. The MISViS participant's data were removed from the overall experiment and analysed as a case study. Impulse response functions (IRFs) and percentage of active voxels were extracted from four regions of interest: BAs 17, 18, 19, and the postcentral gyrus (PG) and two control regions (BA6 and left BA45). The results indicated that significant differences existed between the control group and the MISViS participant for IRF intensity in two regions (BA6 and PG) and percentage of active voxels in four regions (BA17, BA19, PG, and BA6). No significant differences occurred in left BA45 for either variable of interest. No significant differences were found for behavioural measures. In conclusion, our findings offer one of the first neurobiological descriptions of differences in IRF intensity and percentage of active voxels in visual and somatosensory cortex during a language experiment for a participant with MISViS in the absence of migraine compared to controls.