Combined Cognitive Training and Vortioxetine Mitigates Age-Related Declines in Functional Brain Network Integrity.

OBJECTIVE: Age-related cognitive decline is common and potentially modifiable with cognitive training. Combining cognitive training with pro-cognitive medication offers an opportunity to modify brain networks to mitigate age-related cognitive decline. We tested the hypothesis that the efficacy of cognitive training could be amplified by combining it with vortioxetine, a pro-cognitive and pro-neuroplastic multimodal antidepressant. METHODS: We evaluated the effects of 6 months of computerized cognitive training plus vortioxetine (versus placebo) on resting state functional connectivity in older adults (age 65+) with age-related cognitive decline. We first evaluated the association of functional connectivity with age and cognitive performance (N = 66). Then we compared the effects of vortioxetine plus cognitive training versus placebo plus cognitive training on connectivity changes over the training period (n = 20). RESULTS: At baseline, greater age was significantly associated with lower within-network strength and network segregation, and poorer cognitive function. Cognitive training plus vortioxetine over 6 months positively impacted the relationship between age to mean network segregation. These effects were not observed in the placebo group. In contrast, vortioxetine did not modify the relationship of age to change in mean within-network strength. Exploratory analyses identified the cingulo-opercular network as the network most affected by cognitive training plus vortioxetine. CONCLUSION: This preliminary study provides evidence that combining cognitive training with pro-cognitive medication may modulate the effects of aging on functional brain networks. Results indicate that for older adults experiencing age-related cognitive decline, vortioxetine has a potentially beneficial effect on the correspondence between aging and functional brain network segregation. These results await replication in a larger sample.

The power of negative and positive episodic memories.

The power of episodic memories is that they bring a past moment into the present, providing opportunities for us to recall details of the experiences, reframe or update the memory, and use the retrieved information to guide our decisions. In these regards, negative and positive memories can be especially powerful: Life's highs and lows are disproportionately represented in memory, and when they are retrieved, they often impact our current mood and thoughts and influence various forms of behavior. Research rooted in neuroscience and cognitive psychology has historically focused on memory for negative emotional content. Yet the study of autobiographical memories has highlighted the importance of positive emotional memories, and more recently, cognitive neuroscience methods have begun to clarify why positive memories may show powerful relations to mental wellbeing. Here, we review the models that have been proposed to explain why emotional memories are long-lasting (durable) and likely to be retrieved (accessible), describing how in overlapping-but distinctly separable-ways, positive and negative memories can be easier to retrieve, and more likely to influence behavior. We end by identifying potential implications of this literature for broader topics related to mental wellbeing, education, and workplace environments.

Positive information facilitates response inhibition in older adults only when emotion is task-relevant.

Emotional information is integral to everyday life and impacts a variety of cognitive abilities including response inhibition, a critical skill for maintaining appropriate and flexible behaviour. However, reported effects of emotion on response inhibition are inconsistent in younger adults, and very limited in older adults. Effects of aging are especially relevant because emotion regulation improves with aging despite declining inhibitory control over neutral information. Across three studies, we assessed the impact of emotional facial expressions on response inhibition in younger and older adults while manipulating attention to task stimuli. Emotional faces (versus neutral faces) altered response inhibition only when task instructions required explicit attention to emotional attributes of the faces. When directly comparing fear faces to happy faces, both age groups had better response inhibition to happy faces. Age further influenced differences across conditions, in that happy faces enhanced response inhibition relative to neutral faces in older adults but not younger adults. Thus, emotional response inhibition for task-relevant (but not task-irrelevant) positive information is enhanced in late life compared to early adulthood. The present work extends the nascent literature on emotional response inhibition in aging, and proffers a framework to reconcile the mixed literature on this topic in younger adults.

Impact of Intensive Lifestyle Intervention on Neural Food Cue Reactivity: Action for Health in Diabetes Brain Ancillary Study.

OBJECTIVE: The Action for Health in Diabetes (Look AHEAD) research study was a randomized trial comparing the effects of an intensive lifestyle intervention (ILI) versus a diabetes support and education (DSE) control group in adults with type 2 diabetes and overweight or obesity. Functional magnetic resonance imaging was used to determine whether neural food cue reactivity differed for these groups 10 years after randomization. METHODS: A total of 232 participants (ILI, n = 125, 72% female; DSE, n = 107, 64% female) were recruited at three of the Look AHEAD sites for functional magnetic resonance imaging. Neural response to high-calorie foods compared with nonfoods was assessed in DSE versus ILI. Exploratory correlations were conducted within ILI to identify regions in which activity was associated with degree of weight loss. RESULTS: Voxel-wise whole-brain comparisons revealed greater reward-processing activity in left caudate for DSE compared with ILI and greater activity in attention- and visual-processing regions for ILI than DSE (P < 0.05, family-wise error corrected). Exploratory analyses revealed that greater weight loss among ILI participants from baseline was associated with brain activation indicative of increased cognitive control and attention and visual processing in response to high-calorie food cues (P < 0.001, uncorrected). CONCLUSIONS: These findings suggest there may be legacy effects of participation in a behavioral weight loss intervention, with reduced reward-related activity and enhanced attention or visual processing in response to high-calorie foods.

Objectively-assessed physical activity and weight change in young adults: a randomized controlled trial.

BACKGROUND: Reductions in physical activity (PA) are common throughout young adulthood and low PA is associated with weight gain. The SNAP Trial previously reported that two self-regulation approaches to weight gain prevention reduced weight gain over a 2-year period in 18-35 year olds. Presented here are secondary analyses examining changes in PA and the relationship between PA and weight change over 2 years. METHODS: 599 young adults (age: 27.4 ± 4.4 yrs.; BMI: 25.4 ± 2.6 kg/m2) were randomly assigned to 1 of 3 treatment arms: Small Changes (reduce calorie intake by 100 kcals/day & add 2000 steps/day), Large Changes (lose 2.3-4.5 kg initially & increase PA to ≥250 min/wk), or Self-guided (control condition). Small and Large Changes received 10, face-to-face group sessions (months 1-4), and two 4-week refresher courses each subsequent year. Body weight and PA were objectively-measured at baseline, 4 months, 1 and 2 years. Daily steps and bout-related moderate-to-vigorous intensity PA (MVPA: ≥3 METs, ≥10-min bouts) was calculated. RESULTS: Changes in bout-related MVPA and daily steps did not differ among treatment groups over the 2-year period (p's > 0.16). Collapsed across groups, participants gaining >1 lb. (n = 187; 39.6%) had smaller changes in bout-related MVPA at 4 months, 1 and 2 years relative to those maintaining or losing weight (≤1 lb. weight gain; n = 282, 60.4%, p's < 0.05). Averaged across time points, this difference equated to 47.8 min/week. Those gaining and not gaining >1 lb. did not differ on daily steps (p's > 0.10). Among participants engaging in ≥250 min/wk. of MVPA at 2 years (n = 181), 30% gained >1 lb. from baseline to 2 years, which was not different from those engaging in 150-250 min/wk. (n = 87; 36%; p = 0.40), but this percentage was significantly lower when compared to those engaging in <150 min/wk. (n = 176; 49%; p < 0.001). CONCLUSIONS: On average, PA differences were not observed between young adults assigned to small or large changes self-regulation interventions to prevent weight gain. Regardless of group assignment, higher levels of MVPA were associated with better weight gain prevention over 2 years. Our data suggest that achieving >150 min/week of MVPA is needed for weight gain prevention and that increasing MVPA, rather than steps, should be targeted. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01183689). Registered Aug 13, 2010.

The Effects of Experimental Manipulation of Sleep Duration on Neural Response to Food Cues.

Despite growing literature on neural food cue responsivity in obesity, little is known about how the brain processes food cues following partial sleep deprivation and whether short sleep leads to changes similar to those observed in obesity. We used functional magnetic resonance imaging (fMRI) to test the hypothesis that short sleep leads to increased reward-related and decreased inhibitory control-related processing of food cues.In a within-subject design, 30 participants (22 female, mean age = 36.7 standard deviation = 10.8 years, body mass index range 20.4-40.7) completed four nights of 6 hours/night time-in-bed (TIB; short sleep) and four nights of 9 hours/night TIB (long sleep) in random counterbalanced order in their home environments. Following each sleep condition, participants completed an fMRI scan while viewing food and nonfood images.A priori region of interest analyses revealed increased activity to food in short versus long sleep in regions of reward processing (eg, nucleus accumbens/putamen) and sensory/motor signaling (ie, right paracentral lobule, an effect that was most pronounced in obese individuals). Contrary to the hypothesis, whole brain analyses indicated greater food cue responsivity during short sleep in an inhibitory control region (right inferior frontal gyrus) and ventral medial prefrontal cortex, which has been implicated in reward coding and decision-making (false discovery rate corrected q = 0.05).These findings suggest that sleep restriction leads to both greater reward and control processing in response to food cues. Future research is needed to understand the dynamic functional connectivity between these regions during short sleep and whether the interplay between these neural processes determines if one succumbs to food temptation.