Randomized controlled trial evaluating the temporal effects of high‐intensity exercise on learning,short‐term and long‐term memory,and prospective memory

The broader purpose of this study was to examine the temporal effects of high‐intensity exercise on learning, short‐term and long‐term retrospective memory and prospective memory. Among a sample of 88 young adult participants, 22 were randomized into one of four different groups: exercise before learning, control group, exercise during learning, and exercise after learning. The retrospective assessments (learning, short‐term and long‐term memory) were assessed using the Rey Auditory Verbal Learning Test. Long‐term memory including a 20‐min and 24‐hr follow‐up assessment. Prospective memory was assessed using a time‐based procedure by having participants contact (via phone) the researchers at a follow‐up time period. The exercise stimulus included a 15‐min bout of progressive maximal exertion treadmill exercise. High‐intensity exercise prior to memory encoding (vs. exercise during memory encoding or consolidation) was effective in enhancing long‐term memory (for both 20‐min and 24‐h follow‐up assessments). We did not observe a differential temporal effect of high‐intensity exercise on short‐term memory (immediate post‐memory encoding), learning or prospective memory. The timing of high‐intensity exercise may play an important role in facilitating long‐term memory.     

High‐resolution investigation of memory‐specific reinstatement in the hippocampus and perirhinal cortex

Episodic memory involves remembering the details that characterize a prior experience. Successful memory recovery has been associated with the reinstatement of brain activity patterns in a number of sensory regions across the cortex. However, how the hippocampus and surrounding medial temporal lobe (MTL) cortex contribute to this process is less clear. Models of episodic memory posit that hippocampal pattern reinstatement, also referred to as pattern completion, may mediate cortical reinstatement during retrieval. Empirical evidence of this process, however, remains elusive. Here, we use high‐resolution fMRI and encoding‐retrieval multi‐voxel pattern similarity analyses to demonstrate for the first time that the hippocampus, particularly right hippocampal subfield CA1, shows evidence of reinstating individual episodic memories. Furthermore, reinstatement in perirhinal cortex (PrC) is also evident. Critically, we identify distinct factors that may mediate the cortical reinstatement in PrC. First, we find that encoding activation in PrC is related to later reinstatement in this region, consistent with the theory that encoding strength in the regions that process the memoranda is important for later reinstatement. Conversely, retrieval activation in right CA1 was correlated with reinstatement in PrC, consistent with models of pattern completion. This dissociation is discussed in the context of the flow of information into and out of the hippocampus during encoding and retrieval, respectively. © 2016 Wiley Periodicals, Inc.     

Parallel prefrontal pathways reach distinct excitatory and inhibitory systems in memory‐related rhinal cortices

To investigate how prefrontal cortices impinge on medial temporal cortices we labeled pathways from the anterior cingulate cortex (ACC) and posterior orbitofrontal cortex (pOFC) in rhesus monkeys to compare their relationship with excitatory and inhibitory systems in rhinal cortices. The ACC pathway terminated mostly in areas 28 and 35 with a high proportion of large terminals, whereas the pOFC pathway terminated mostly through small terminals in area 36 and sparsely in areas 28 and 35. Both pathways terminated in all layers. Simultaneous labeling of pathways and distinct neurochemical classes of inhibitory neurons, followed by analyses of appositions of presynaptic and postsynaptic fluorescent signal, or synapses, showed overall predominant association with spines of putative excitatory neurons, but also significant interactions with presumed inhibitory neurons labeled for calretinin, calbindin, or parvalbumin. In the upper layers of areas 28 and 35 the ACC pathway was associated with dendrites of neurons labeled with calretinin, which are thought to disinhibit neighboring excitatory neurons, suggesting facilitated hippocampal access. In contrast, in area 36 pOFC axons were associated with dendrites of calbindin neurons, which are poised to reduce noise and enhance signal. In the deep layers, both pathways innervated mostly dendrites of parvalbumin neurons, which strongly inhibit neighboring excitatory neurons, suggesting gating of hippocampal output to other cortices. These findings suggest that the ACC, associated with attention and context, and the pOFC, associated with emotional valuation, have distinct contributions to memory in rhinal cortices, in processes that are disrupted in psychiatric diseases. J. Comp. Neurol. 521:4260–4283, 2013. © 2013 Wiley Periodicals, Inc.     

Hippocampal hemispheric and long‐axis differentiation of stimulus content during episodic memory encoding and retrieval: An activation likelihood estimation meta‐analysis

While there is ample evidence that the hippocampus is functionally heterogeneous along its longitudinal axis, there is still no consensus regarding its exact organization. Whereas spatial memory tasks frequently engage the posterior hippocampus, the regions engaged during episodic memory are more varying and may depend on the specific nature of the stimuli. Here, we investigate the effect of stimulus content on the location of hippocampal recruitment during episodic memory encoding and retrieval of pictorial and verbal material with a meta‐analysis approach, using activation likelihood estimation and restricting the analysis to the hippocampus. Verbal material was associated with left‐lateralized anterior activation, compared to pictorial material that recruited a more posterior aspect of the hippocampus, primarily within the right hemisphere. This effect held for encoding of both single items and item–item associations but was less clear during retrieval. The findings lend further support to a functional subdivision of the hippocampus along its longitudinal axis and indicate that the content of episodic memories is one factor that determines the location of hippocampal recruitment. © 2015 Wiley Periodicals, Inc.     

Physical activity and inflammation: effects on gray‐matter volume and cognitive decline in aging

Physical activity has been positively associated with gray‐matter integrity. In contrast, pro‐inflammatory cytokines seem to have negative effects on the aging brain and have been related to dementia. It was investigated whether an inactive lifestyle and high levels of inflammation resulted in smaller gray‐matter volumes and predicted cognitive decline across 6 years in a population‐based study of older adults (n = 414). Self‐reported physical activity (fitness‐enhancing, health‐enhancing, inadequate) was linked to gray‐matter volume, such that individuals with inadequate physical activity had the least gray matter. There were no overall associations between different pro‐and anti‐inflammatory markers (IL‐1β, IL‐6, IL‐10, IL‐12p40, IL‐12p70, G‐CSF, and TNF‐α) and gray‐matter integrity. However, persons with inadequate activity and high levels of the pro‐inflammatory marker IL‐12p40 had smaller volumes of lateral prefrontal cortex and hippocampus and declined more on the Mini‐Mental State Examination test over 6 years compared with physically inactive individuals with low levels of IL‐12p40 and to more physically active persons, irrespective of their levels of IL‐12p40. These patterns of data suggested that inflammation was particularly detrimental in inactive older adults and may exacerbate the negative effects of physical inactivity on brain and cognition in old age. Hum Brain Mapp 37:3462–3473, 2016. © 2016 Wiley Periodicals, Inc.     

Low‐intensity daily walking activity is associated with hippocampal volume in older adults

Hippocampal atrophy is associated with memory impairment and dementia and serves as a key biomarker in the preclinical stages of Alzheimer's disease. Physical activity, one of the most promising behavioral interventions to prevent or delay cognitive decline, has been shown to be associated with hippocampal volume; specifically increased aerobic activity and fitness may have a positive effect on the size of the hippocampus. The majority of older adults, however, are sedentary and have difficulty initiating and maintaining exercise programs. A modestly more active lifestyle may nonetheless be beneficial. This study explored whether greater objectively measured daily walking activity was associated with larger hippocampal volume. We additionally explored whether greater low‐intensity walking activity, which may be related to leisure‐time physical, functional, and social activities, was associated with larger hippocampal volume independent of exercise and higher‐intensity walking activity. Segmentation of hippocampal volumes was performed using Functional Magnetic Resonance Imaging of the Brain's Software Library (FSL), and daily walking activity was assessed using a step activity monitor on 92, nondemented, older adult participants. After controlling for age, education, body mass index, cardiovascular disease risk factors, and the Mini Mental State Exam, we found that a greater amount, duration, and frequency of total daily walking activity were each associated with larger hippocampal volume among older women, but not among men. These relationships were specific to hippocampal volume, compared with the thalamus, used as a control brain region, and remained significant for low‐intensity walking activity, independent of moderate‐ to vigorous‐intensity activity and self‐reported exercise. This is the first study, to our knowledge, to explore the relationship between objectively measured daily walking activity and hippocampal volume in an older adult population. Findings suggest the importance of examining whether increasing nonexercise, lifestyle physical activities may produce measurable cognitive benefits and affect hippocampal volume through molecular pathways unique to those related to moderate‐intensity exercise. © 2014 Wiley Periodicals, Inc.     

Effects of overnight fasting on working memory‐related brain network: An fMRI study

Glucose metabolism serves as the central source of energy for the human brain. Little is known about the effects of blood glucose level (BGL) on higher‐order cognitive functions within a physiological range (e.g., after overnight fasting). In this randomized, placebo‐controlled, double blind study, we assessed the impact of overnight fasting (14h) on brain activation during a working memory task. We sought to mimic BGLs that occur naturally in healthy humans after overnight fasting. After standardized periods of food restriction, 40 (20 male) healthy participants were randomly assigned to receive either glucagon to balance the BGL or placebo (NaCl). A parametric fMRI paradigm, including 2‐back and 0‐back tasks, was used. Subclinically low BGL following overnight fasting was found to be linked to reduced involvement of the bilateral dorsal midline thalamus and the bilateral basal ganglia, suggesting high sensitivity of those regions to minimal changes in BGLs. Our results indicate that overnight fasting leads to physiologically low levels of glucose, impacting brain activation during working memory tasks even when there are no differences in cognitive performance. Hum Brain Mapp 36:839–851, 2015. © 2014 Wiley Periodicals, Inc.     

Age‐related differences in practice‐dependent resting‐state functional connectivity related to motor sequence learning

Decreased neural plasticity is observed with healthy ageing in the primary sensorimotor (SM1) cortex thought to participate in motor learning and memory consolidation processes. In the present magnetoencephalography study, the post‐training reorganization of resting‐state functional connectivity (rsFC) and its relation with motor learning and early consolidation in 14 young (19–30 years) and 14 old (66–70 years) healthy participants were investigated. At the behavioral level, participants were trained on a motor sequence learning task then retested 20–30 min later for transient offline gains in performance. Using a sensorimotor seed‐based approach, rsFC relying on beta band power envelope correlation was estimated immediately before and 10 min after the learning episode. Post‐training changes in rsFC (from before to after learning) were correlated with motor learning performance and with the offline improvement in performance within the hour after learning. Young and old participants exhibited differential patterns of sensorimotor‐related rsFC, bearing specific relationships with motor learning and consolidation. Our findings suggest that rsFC changes following learning reflect the offline processing of the new motor skill and contribute to the early memory consolidation within the hour after learning. Furthermore, differences in post‐training changes in rsFC between young and old participants support the hypothesis that ageing modulates the neural circuits underlying the learning of a new motor skill and the early subsequent consolidation stages. Hum Brain Mapp 38:923–937, 2017. © 2016 Wiley Periodicals, Inc.     

The influence of aerobic fitness on cerebral white matter integrity and cognitive function in older adults: Results of a one‐year exercise intervention

Cerebral white matter (WM) degeneration occurs with increasing age and is associated with declining cognitive function. Research has shown that cardiorespiratory fitness and exercise are effective as protective, even restorative, agents against cognitive and neurobiological impairments in older adults. In this study, we investigated whether the beneficial impact of aerobic fitness would extend to WM integrity in the context of a one‐year exercise intervention. Further, we examined the pattern of diffusivity changes to better understand the underlying biological mechanisms. Finally, we assessed whether training‐induced changes in WM integrity would be associated with improvements in cognitive performance independent of aerobic fitness gains. Results showed that aerobic fitness training did not affect group‐level change in WM integrity, executive function, or short‐term memory, but that greater aerobic fitness derived from the walking program was associated with greater change in WM integrity in the frontal and temporal lobes, and greater improvement in short‐term memory. Increases in WM integrity, however, were not associated with short‐term memory improvement, independent of fitness improvements. Therefore, while not all findings are consistent with previous research, we provide novel evidence for correlated change in training‐induced aerobic fitness, WM integrity, and cognition among healthy older adults. Hum Brain Mapp 34:2972–2985, 2013. © 2012 Wiley Periodicals, Inc.     

Antenatal depression: a rationale for studying exercise

Background: Major depressive disorder (MDD) in pregnancy or antenatal depression poses unique treatment challenges and has serious consequences for mothers, unborn babies, and families when untreated. This review presents current knowledge on exercise during pregnancy, antidepressant effects of exercise, and the rationale for the specific study of exercise for antenatal depression. Method: A systematic literature review was performed using English language articles published in Medline, PsycINFO, CINAHL, and the Cochrane Library from 1985 to January 2010. Results: There is a broad literature supporting the antidepressant effects of exercise, but a paucity of studies specifically for antenatal depression. A small number of observational studies have reported that regular physical activities improve self‐esteem and reduce symptoms of anxiety and depression during pregnancy. To date, there have not been randomized controlled studies of exercise for the treatment of MDD in pregnant women. Conclusions: Systematic studies are needed to assess exercise as a treatment alternative for MDD during pregnancy. In consideration of the benefits of exercise for the mother and baby, and the burden of depression, studies are needed to determine the role of exercise for pregnant women with depression. Depression and Anxiety 28:234–242,2011. © 2010 Wiley‐Liss, Inc.     

Neural activity during working memory encoding,maintenance, and retrieval: A network‐based model and meta‐analysis

It remains unclear whether and to what extent working memory (WM) temporal subprocesses (i.e., encoding, maintenance, and retrieval) involve shared or distinct intrinsic networks. To address this issue, I constructed a model of intrinsic network contributions to different WM phases and then evaluated the validity of the model by performing a quantitative meta‐analysis of relevant functional neuroimaging data. The model suggests that the transition from the encoding to maintenance and to retrieval stages involves progressively decreasing involvement of the dorsal attention network (DAN), but progressively increasing involvement of the frontoparietal control network (FPCN). Separate meta‐analysis of each phase effect and direct comparisons between them yielded results that were largely consistent with the model. This evidence included between‐phase double dissociations that were consistent with the model, such as encoding > maintenance contrast showing some DAN, but no FPCN, regions, and maintenance > encoding contrast showing the reverse, that is, some FPCN, but no DAN, regions. Two closely juxtaposed regions that are members of the DAN and FPCN, such as inferior frontal junction versus caudal prefrontal cortex and superior versus inferior intraparietal sulcus, showed a high degree of functional differentiation. Although all regions identified in the present study were already identified in previous WM studies, this study uniquely enhances our understating of their roles by clarifying their network membership and specific associations with different WM phases.