Skill learning induces changes in estimates of gray matter volume (GMV) in the human brain, commonly detectable with magnetic resonance imaging (MRI). Rapid changes in GMV estimates while executing tasks may however confound between- and within-subject differences. Fluctuations in arterial blood flow are proposed to underlie this apparent task-related tissue plasticity. To test this hypothesis, we acquired multiple repetitions of structural T₁-weighted and functional blood-oxygen level-dependent (BOLD) MRI measurements from 51 subjects performing a finger-tapping task (FTT; á 2 min) repeatedly for 30–60 min. Estimated GMV was decreased in motor regions during FTT compared with rest. Motor-related BOLD signal changes did not overlap nor correlate with GMV changes. Nearly simultaneous BOLD signals cannot fully explain task-induced changes in T₁-weighted images. These sensitive and behavior-related GMV changes pose serious questions to reproducibility across studies, and morphological investigations during skill learning can also open new avenues on how to study rapid brain plasticity.

The objective of this study is to introduce a new quantitative data-driven analysis (QDA) framework for the analysis of resting-state fMRI (R-fMRI) and use it to investigate the effect of adult age on resting-state functional connectivity (RFC). Whole-brain R-fMRI measurements were conducted on a 3T clinical MRI scanner in 227 healthy adult volunteers (N = 227, aged 18–76 years old, male/female = 99/128). With the proposed QDA framework we derived two types of voxel-wise RFC metrics: the connectivity strength index and connectivity density index utilizing the convolutions of the cross-correlation histogram with different kernels. Furthermore, we assessed the negative and positive portions of these metrics separately. With the QDA framework we found age-related declines of RFC metrics in the superior and middle frontal gyri, posterior cingulate cortex (PCC), right insula and inferior parietal lobule of the default mode network (DMN), which resembles previously reported results using other types of RFC data processing methods. Importantly, our new findings complement previously undocumented results in the following aspects: (1) the PCC and right insula are anti-correlated and tend to manifest simultaneously declines of both the negative and positive connectivity strength with subjects’ age; (2) separate assessment of the negative and positive RFC metrics provides enhanced sensitivity to the aging effect; and (3) the sensorimotor network depicts enhanced negative connectivity strength with the adult age. The proposed QDA framework can produce threshold-free and voxel-wise RFC metrics from R-fMRI data. The detected adult age effect is largely consistent with previously reported studies using different R-fMRI analysis approaches. Moreover, the separate assessment of the negative and positive contributions to the RFC metrics can enhance the RFC sensitivity and clarify some of the mixed results in the literature regarding to the DMN and sensorimotor network involvement in adult aging.

Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12–87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS—or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.

To investigate the impact of adult age on the brain functional connectivity, whole-brain resting-state functional magnetic resonance imaging (R-fMRI) data were acquired on a 3T clinical MRI scanner in a cohort of 227, right-handed, native Swedish-speaking, healthy adult volunteers (N=227, aged 18-74 years old, male/female=99/128). The dataset is mainly consisted of a younger (18-30 years old n=124, males/females=51/73) and elderly adult (n=76, 60-76 years old, males/females=35/41) subgroups. The dataset was analyzed using a new data-driven analysis (QDA) framework. With QDA two types of threshold-free voxel-wise resting-state functional connectivity (RFC) metrics were derived: the connectivity strength index (CSI) and connectivity density index (CDI), which can be utilized to assess the brain changes in functional connectivity associated with adult age. The dataset can also be useful as a reference to identify abnormal changes in brain functional connectivity resulted from neurodegenerative or neuropsychiatric disorders.

Normal adult aging is associated with decline in some socioemotional abilities, such as the ability to recognize emotions in others, and age-related neurobiological processes may contribute to these deficits. There is increasing evidence that the neuropeptide oxytocin plays a key role in social cognition, including emotion recognition. The mechanisms through which oxytocin promotes emotion recognition are not well understood yet, and particularly in aging. In a randomized, double-blind, placebo-controlled within-subjects design, we investigated the extent to which a single dose of 40 IU of intranasal oxytocin facilitates emotion recognition in 40 younger (M = 24.90 yrs., SD = 2.97, 48% women) and 40 older (M = 69.70 yrs., SD = 2.99, 55% women) men and women. During two fMRI sessions, participants viewed dynamic positive and negative emotional displays. Preliminary analyses show that younger participants recognized positive and negative emotions more accurately than older participants (p < .001), with this behavioral effect not modulated by oxytocin. In the brain data, however, we found an age x treatment interaction in medial prefrontal cortex (xyz [14, 14, 6], p = .007) and superior temporal gyrus (xyz [53, 9, 2], p = .031). In particular, oxytocin (vs. placebo) reduced activity in these regions for older participants, while it enhanced activity in these regions for younger participants. In line with previous research, these findings support the notion that the effects of oxytocin vary by context and individual factors (e.g., social proficiency, age).

Aging is associated with complex biological changes that can be accelerated, slowed, or even temporarily reversed by biological and non-biological factors. This article focuses on the link between biological aging, psychological stressors, and mental illness. Rather than comprehensively reviewing this rapidly expanding field, we highlight challenges in this area of research and propose potential strategies to accelerate progress in this field. This effort requires the interaction of scientists across disciplines - including biology, psychiatry, psychology, and epidemiology; and across levels of analysis that emphasize different outcome measures - functional capacity, physiological, cellular, and molecular. Dialogues across disciplines and levels of analysis naturally lead to new opportunities for discovery but also to stimulating challenges. Some important challenges consist of 1) establishing the best objective and predictive biological age indicators or combinations of indicators, 2) identifying the basis for inter-individual differences in the rate of biological aging, and 3) examining to what extent interventions can delay, halt or temporarily reverse aging trajectories. Discovering how psychological states influence biological aging, and vice versa, has the potential to create novel and exciting opportunities for healthcare and possibly yield insights into the fundamental mechanisms that drive human aging.

We are currently lacking clinically useful predictors of treatment response in common psychiatric disorders. Non-invasive and increasingly accessible neuroimaging techniques like functional magnetic resonance imaging (fMRI) could be a useful tool. In contrast to the conventional approach investigating the brain’s average responses, the brain’s signal variability could be a better estimate of the brain’s dynamic operations (Garrett et al., 2010, 2015). In addition, telomere attrition is a hallmark of cellular aging and shorter telomeres have been reported in mood and anxiety disorders. Telomere shortening is counteracted by the enzyme telomerase and cellular protection is also provided by the antioxidant enzyme glutathione peroxidase (GPx). Here, we investigate if baseline BOLD-fMRI signal variability, and indices of cellular protection, predicts social anxiety disorder patient’s response to internet-delivered cognitive behavior therapy. Forty-six patients with social anxiety disorder (SAD) were scanned twice with a 3 Tesla fMRI before initiating CBT. Treatment outcome was assessed the Liebowitz Social Anxiety Scale (self-report). 1) BOLD-fMRI acquisition was performed while passively viewing emotional faces flashing on the screen for 80 seconds. Raw BOLD-fMRI data was implemented in an Independent Component Analysis in order to manually denoise images by carefully remove noise from neural signal. Across time, each voxel’s standard deviation was calculated and used as an index of variability. Multivariate partial least squares regression models were used for second level analysis. 2) Telomerase activity and telomere length were measured in peripheral blood mononuclear cells and GPx activity in plasma. Significant latent level brain scores, and baseline analytes were implemented in linear regressions with LSAS-SR change score as the outcome. Results will be presented and discussed.

The neuropeptide oxytocin plays a prominent role in social and emotional cognition. Findings suggest that intranasal oxytocin administration facilitates emotion recognition in humans, but individual and contextual differences may have moderating effects. A major caveat in this line of work is its predominant focus on young males, which limits current knowledge and generalizability across gender. To uncover potential gender effects, the present study included 32 men (mean age 45.78, sd. 22.87) and 39 women (mean 47.87, sd. 22.59). Utilizing a randomized, double-blind, placebo-controlled, within-subjects design, participants self-administered a single-dose of 40 IUs intranasal oxytocin 40 minutes prior to completion of a dynamic emotion recognition task in the MRI scanning. The task paradigm used positive and negative stimuli from the Geneva Multimodal Emotion Portrayals Core Set. Preliminary analyses show that oxytocin induced dorsomedial prefrontal cortex (dmPFC) activity reductions during exposure to negative (relative to positive) stimuli in women, while dmPCF activity was increased under this condition in men. We observed no effect of sex in the behavioral data, however, the results show a similar trend as in brain data. We speculate that the effects of oxytocin on brain activity during emotion recognition may be related to emotion-regulatory and mentalization processes. The observed gender-differential modulatory role of oxytocin raises concern of a bias in the previous oxytocin literature on emotion recognition and associated brain activity by neglecting women in the examination. Next, we will determine the role of age effects on gender-bytreatment interactions, as well as consider modality of the emotion stimulus presentation.  

This study presents findings about the effectiveness of two computerized training-programs for emotion recognition accuracy that were evaluated in a double-blind randomized controlled study with repeated measures design. Both trainings are effective in training emotion recognition accuracy. The trainings and results are presented in detail and practical implications are discussed.

Telomere attrition is a hallmark of cellular aging and shorter telomeres have been reported in mood and anxiety disorders. Telomere shortening is counteracted by the enzyme telomerase and cellular protection is also provided by the antioxidant enzyme glutathione peroxidase (GPx). Here, telomerase, GPx, and telomeres were investigated in 46 social anxiety disorder (SAD) patients in a within-subject design with repeated measures before and after cognitive behavioral therapy. Treatment outcome was assessed by the Liebowitz Social Anxiety Scale (self-report), administered three times before treatment to control for time and regression artifacts, and posttreatment. Venipunctures were performed twice before treatment, separated by 9 weeks, and once posttreatment. Telomerase activity and telomere length were measured in peripheral blood mononuclear cells and GPx activity in plasma. All patients contributed with complete data. Results showed that social anxiety symptom severity was significantly reduced from pretreatment to posttreatment (Cohen’s d = 1.46). There were no significant alterations in telomeres or cellular protection markers before treatment onset. Telomere length and telomerase activity did not change significantly after treatment, but an increase in telomerase over treatment was associated with reduced social anxiety. Also, lower pretreatment telomerase activity predicted subsequent symptom improvement. GPx activity increased significantly during treatment, and increases were significantly associated with symptom improvement. The relationships between symptom improvement and putative protective enzymes remained significant also after controlling for body mass index, sex, duration of SAD, smoking, concurrent psychotropic medication, and the proportion of lymphocytes to monocytes. Thus, indices of cellular protection may be involved in the therapeutic mechanisms of psychological treatment for anxiety.