Emotional recognition across the adult lifespan: Effects of age, sex, cognitive empathy, alexithymia traits, and amygdala subnuclei volumes.

The ability to recognize others' emotions is vital to everyday life. The goal of this study was to assess which emotions show age-related decline in recognition accuracy of facial emotional expressions across the entire adult lifespan and how this process is related to cognitive empathy (Theory of Mind [ToM]), alexithymia traits, and amygdala subnuclei volumes in a large cohort of healthy individuals. We recruited 140 healthy participants 18-85 years old. Facial affect processing was assessed with the Penn Emotion Recognition task (ER40) that contains images of the five basic emotions: Neutral, Happy, Sad, Angry, and Fearful. Structural magnetic resonance imaging (MRI) datasets were acquired on a 4.7T MRI system. Structural equation modeling was used to test the relationship between studied variables. We found that while both sexes demonstrated age-related reduction in recognition of happy emotions and preserved recognition of sadness, male participants showed age-related reduction in recognition of fear, while in female participants, age-related decline was linked to recognition of neutral and angry facial expressions. In both sexes, accurate recognition of sadness negatively correlated with alexithymia traits. On the other hand, better ToM capabilities in male participants were associated with improvement in recognition of positive and neutral emotions. Finally, none of the observed age-related reductions in emotional recognition were related to amygdala and its subnuclei volumes. In contrast, both global volume of amygdala and its cortical and centromedial subnuclei had significant direct effects on recognition of sad images.

Diffusion tensor imaging of superficial prefrontal white matter in healthy aging.

The prefrontal cortex (PFC) is a heterogenous structure that is highly susceptible to the effects of aging. Few studies have investigated age effects on the superficial white matter (WM) contained within the PFC using in-vivo magnetic resonance imaging (MRI). This study used diffusion tensor imaging (DTI) tractography to examine the effects of age, sex, and intracranial volume (ICV) on superficial WM within specific PFC subregions, and to model the relationships with age using higher order polynomial regression modelling. PFC WM of 140 healthy individuals, aged 18-85, was segmented into medial and lateral orbitofrontal, medial prefrontal, and dorsolateral prefrontal subregions. Differences due to age in microstructural parameters such as fractional anisotropy (FA), axial and radial diffusivities, and macrostructural measures of tract volumes, fiber counts, average fiber lengths, and average number of fibers per voxel were examined. We found that most prefrontal subregions demonstrated age effects, with decreases in FA, tract volume, and fiber counts, and increases in all diffusivity measures. Age relationships were mostly non-linear, with higher order regressions chosen in most cases. Declines in PFC FA began at the onset of adulthood while the greatest changes in diffusivity and volume did not occur until middle age. The effects of age were most prominent in medial tracts while the lateral orbitofrontal tracts were less affected. Significant effects of sex and ICV were also observed in certain parameters. The patterns mostly followed myelination order, with late-myelinating prefrontal subregions experiencing earlier and more pronounced age effects, further supporting the frontal theory of aging.

Selective Effects of Healthy Cognitive Aging and Catechol-O-Methyl Transferase Polymorphism on Limbic White Matter Tracts.

Introduction: The cingulum bundle and uncinate fasciculus are major limbic white matter tracts involved in emotion, memory, and cognition. The main goal of the present study was to investigate the relationship between age and structural properties of the uncinate fasciculus and the cingulum bundle using diffusion tensor imaging (DTI) tractography in a large cohort of healthy individuals. The second goal was to determine the effects of the catechol-O-methyl transferase (COMT) gene polymorphism on the DTI measurements of these white matter tracts. Methods: We recruited 140 healthy participants (18-85 years old). DTI data sets were acquired on a 1.5T magnetic resonance imaging system. The rostral, dorsal, and parahippocampal cingulum, as well as uncinate fasciculus, were delineated using deterministic tractography. Fractional anisotropy (FA), mean (MD), radial (RD), and axial (AD) diffusivities, tract volume, linear (Cl), planar (Cp), and spherical (Cs) tensor shapes were calculated. The COMT polymorphism (methionine homozygous vs. valine carriers) was determined using single nucleotide polymorphism. Results: We found that age was negatively associated with FA, but positively associated with MD and RD for the rostral cingulum, dorsal cingulum, and the uncinate fasciculus but not for the parahippocampal cingulum. Furthermore, individuals with the COMT methionine homozygous had higher FA and lower MD, RD, AD, and Cs values in the right rostral cingulum compared with the valine carriers across the entire adult life span. Discussion: This study indicates that limbic tracts might be nonuniformly affected by healthy aging, and the methionine homozygous genotype might be associated with micro/macro white matter properties of the right rostral cingulum.

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.

The associations of the BDNF and APOE polymorphisms, hippocampal subfield volumes, and episodic memory performance across the lifespan.

In this study, we explored the associations between the brain derived neurotrophic factor (BDNF) and the apolipoprotein E (APOE) polymorphisms and hippocampal subfields in 127 healthy participants (18-85 years). MRI datasets were collected on a 4.7 T system. Participants were administered the Wechsler Memory Scale to evaluate episodic memory function. Significant associations of both polymorphisms were present only in older adults (≥50 years). BDNF polymorphism was associated with larger dentate gyrus volumes within the anterior hippocampus (head) in Met-carriers compared to Val/Val homozygotes. We found that in Met-carriers total hippocampal volume predicted performance on visuospatial memory tasks. APOE polymorphism was associated with larger total hippocampal volume, especially in cornu ammonis 1-3 and subiculum in APOE ɛ2 carriers compared to both ɛ4 and ɛ3 carriers, while APOE ɛ3 and ɛ4 carriers did not differ from each other. APOE polymorphism was associated with better performance on visuospatial memory tasks in APOE ε2 carriers in comparison to ε4 carriers.

Diffusion tensor imaging of the corpus callosum in healthy aging: Investigating higher order polynomial regression modelling.

Previous diffusion tensor imaging (DTI) studies confirmed the vulnerability of corpus callosum (CC) fibers to aging. However, most studies employed lower order regressions to study the relationship between age and white matter microstructure. The present study investigated whether higher order polynomial regression modelling can better describe the relationship between age and CC DTI metrics compared to lower order models in 140 healthy participants (ages 18-85). The CC was found to be non-uniformly affected by aging, with accelerated and earlier degradation occurring in anterior portion; callosal volume, fiber count, fiber length, mean fibers per voxel, and FA decreased with age while mean, axial, and radial diffusivities increased. Half of the parameters studied also displayed significant age-sex interaction or intracranial volume effects. Higher order models were chosen as the best fit, based on Bayesian Information Criterion minimization, in 16 out of 23 significant cases when describing the relationship between DTI measurements and age. Higher order model fits provided different estimations of aging trajectory peaks and decline onsets than lower order models; however, a likelihood ratio test found that higher order regressions generally did not fit the data significantly better than lower order polynomial or linear models. The results contrast the modelling approaches and highlight the importance of using higher order polynomial regression modelling when investigating associations between age and CC white matter microstructure.

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.

In vivo quantification of amygdala subnuclei using 4.7 T fast spin echo imaging.

The amygdala (AG) is an almond-shaped heterogeneous structure located in the medial temporal lobe. The majority of previous structural Magnetic Resonance Imaging (MRI) volumetric methods for AG measurement have so far only been able to examine this region as a whole. In order to understand the role of the AG in different neuropsychiatric disorders, it is necessary to understand the functional role of its subnuclei. The main goal of the present study was to develop a reliable volumetric method to delineate major AG subnuclei groups using ultra-high resolution high field MRI. 38 healthy volunteers (15 males and 23 females, 21-60 years of age) without any history of medical or neuropsychiatric disorders were recruited for this study. Structural MRI datasets were acquired at 4.7 T Varian Inova MRI system using a fast spin echo (FSE) sequence. The AG was manually segmented into its five major anatomical subdivisions: lateral (La), basal (B), accessory basal (AB) nuclei, and cortical (Co) and centromedial (CeM) groups. Inter-(intra-) rater reliability of our novel volumetric method was assessed using intra-class correlation coefficient (ICC) and Dice's Kappa. Our results suggest that reliable measurements of the AG subnuclei can be obtained by image analysts with experience in AG anatomy. We provided a step-by-step segmentation protocol and reported absolute and relative volumes for the AG subnuclei. Our results showed that the basolateral (BLA) complex occupies seventy-eight percent of the total AG volume, while CeM and Co groups occupy twenty-two percent of the total AG volume. Finally, we observed no hemispheric effects and no gender differences in the total AG volume and the volumes of its subnuclei. Future applications of this method will help to understand the selective vulnerability of the AG subnuclei in neurological and psychiatric disorders.

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.