Interactions between physical exercise, associative memory, and genetic risk for Alzheimer's disease.

The ε4 allele of the APOE gene heightens the risk of late onset Alzheimer's disease. ε4 carriers, may exhibit cognitive and neural changes early on. Given the known memory-enhancing effects of physical exercise, particularly through hippocampal plasticity via endocannabinoid signaling, here we aimed to test whether a single session of physical exercise may benefit memory and underlying neurophysiological processes in young ε3 carriers (ε3/ε4 heterozygotes, risk group) compared with a matched control group (homozygotes for ε3). Participants underwent fMRI while learning picture sequences, followed by cycling or rest before a memory test. Blood samples measured endocannabinoid levels. At the behavioral level, the risk group exhibited poorer associative memory performance, regardless of the exercising condition. At the brain level, the risk group showed increased medial temporal lobe activity during memory retrieval irrespective of exercise (suggesting neural compensatory effects even at baseline), whereas, in the control group, such increase was only detectable after physical exercise. Critically, an exercise-related endocannabinoid increase correlated with task-related hippocampal activation in the control group only. In conclusion, healthy young individuals carrying the ε4 allele may present suboptimal associative memory performance (when compared with homozygote ε3 carriers), together with reduced plasticity (and functional over-compensation) within medial temporal structures.

A single session of moderate intensity exercise influences memory, endocannabinoids and brain derived neurotrophic factor levels in men.

Regular physical exercise enhances memory functions, synaptic plasticity in the hippocampus, and brain derived neurotrophic factor (BDNF) levels. Likewise, short periods of exercise, or acute exercise, benefit hippocampal plasticity in rodents, via increased endocannabinoids (especially anandamide, AEA) and BDNF release. Yet, it remains unknown whether acute exercise has similar effects on BDNF and AEA levels in humans, with parallel influences on memory performance. Here we combined blood biomarkers, behavioral, and fMRI measurements to assess the impact of a single session of physical exercise on associative memory and underlying neurophysiological mechanisms in healthy male volunteers. For each participant, memory was tested after three conditions: rest, moderate or high intensity exercise. A long-term memory retest took place 3 months later. At both test and retest, memory performance after moderate intensity exercise was increased compared to rest. Memory after moderate intensity exercise correlated with exercise-induced increases in both AEA and BNDF levels: while AEA was associated with hippocampal activity during memory recall, BDNF enhanced hippocampal memory representations and long-term performance. These findings demonstrate that acute moderate intensity exercise benefits consolidation of hippocampal memory representations, and that endocannabinoids and BNDF signaling may contribute to the synergic modulation of underlying neural plasticity mechanisms.

Effect of acute physical exercise on motor sequence memory.

Acute physical exercise improves memory functions by increasing neural plasticity in the hippocampus. In animals, a single session of physical exercise has been shown to boost anandamide (AEA), an endocannabinoid known to promote hippocampal plasticity. Hippocampal neuronal networks encode episodic memory representations, including the temporal organization of elements, and can thus benefit motor sequence learning. While previous work established that acute physical exercise has positive effects on declarative memory linked to hippocampal plasticity mechanisms, its influence on memory for motor sequences, and especially on neural mechanisms underlying possible effects, has been less investigated. Here we studied the impact of acute physical exercise on motor sequence learning, and its underlying neurophysiological mechanisms in humans, using a cross-over randomized within-subjects design. We measured behavior, fMRI activity, and circulating AEA levels in fifteen healthy participants while they performed a serial reaction time task before and after a short period of exercise (moderate or high intensity) or rest. We show that exercise enhanced motor sequence memory, significantly for high intensity exercise and tending towards significance for moderate intensity exercise. This enhancement correlated with AEA increase, and dovetailed with local increases in caudate nucleus and hippocampus activity. These findings demonstrate that acute physical exercise promotes sequence learning, thus attesting the overarching benefit of exercise to hippocampus-related memory functions.

Human Discrimination and Categorization of Emotions in Voices: A Functional Near-Infrared Spectroscopy (fNIRS) Study.

Functional Near-Infrared spectroscopy (fNIRS) is a neuroimaging tool that has been recently used in a variety of cognitive paradigms. Yet, it remains unclear whether fNIRS is suitable to study complex cognitive processes such as categorization or discrimination. Previously, functional imaging has suggested a role of both inferior frontal cortices in attentive decoding and cognitive evaluation of emotional cues in human vocalizations. Here, we extended paradigms used in functional magnetic resonance imaging (fMRI) to investigate the suitability of fNIRS to study frontal lateralization of human emotion vocalization processing during explicit and implicit categorization and discrimination using mini-blocks and event-related stimuli. Participants heard speech-like but semantically meaningless pseudowords spoken in various tones and evaluated them based on their emotional or linguistic content. Behaviorally, participants were faster to discriminate than to categorize; and processed the linguistic faster than the emotional content of stimuli. Interactions between condition (emotion/word), task (discrimination/categorization) and emotion content (anger, fear, neutral) influenced accuracy and reaction time. At the brain level, we found a modulation of the Oxy-Hb changes in IFG depending on condition, task, emotion and hemisphere (right or left), highlighting the involvement of the right hemisphere to process fear stimuli, and of both hemispheres to treat anger stimuli. Our results show that fNIRS is suitable to study vocal emotion evaluation, fostering its application to complex cognitive paradigms.

Effect of cerebral vasomotion during physical exercise on associative memory, a near-infrared spectroscopy study.

Regular physical exercise has been shown to benefit neurocognitive functions, especially enhancing neurogenesis in the hippocampus. However, the effects of a single exercise session on cognitive functions are controversial. To address this issue, we measured hemodynamic changes in the brain during physical exercise using near-infrared spectroscopy (NIRS) and investigated related effects on memory consolidation processes. Healthy young participants underwent two experimental visits. During each visit, they performed an associative memory task in which they first encoded a series of pictures, then spent 30-min exercising or resting, and finally were asked to recall the picture associations. We used NIRS to track changes in oxygenated hemoglobin concentration over the prefrontal cortex during exercise and rest. To characterize local tissue oxygenation and perfusion, we focused on low frequency oscillations in NIRS, also called vasomotion. We report a significant increase in associative memory consolidation after exercise, as compared to after rest, along with an overall increase in vasomotion. Additionally, performance improvement after exercise correlated positively with power in the neurogenic component (0.02 to 0.04 Hz) and negatively with power in the endothelial component (0.003 to 0.02 Hz). Overall, these results suggest that changes in vasomotion over the prefrontal cortex during exercise may promote memory consolidation processes.

A nap to recap or how reward regulates hippocampal-prefrontal memory networks during daytime sleep in humans.

Sleep plays a crucial role in the consolidation of newly acquired memories. Yet, how our brain selects the noteworthy information that will be consolidated during sleep remains largely unknown. Here we show that post-learning sleep favors the selectivity of long-term consolidation: when tested three months after initial encoding, the most important (i.e., rewarded, strongly encoded) memories are better retained, and also remembered with higher subjective confidence. Our brain imaging data reveals that the functional interplay between dopaminergic reward regions, the prefrontal cortex and the hippocampus contributes to the integration of rewarded associative memories. We further show that sleep spindles strengthen memory representations based on reward values, suggesting a privileged replay of information yielding positive outcomes. These findings demonstrate that post-learning sleep determines the neural fate of motivationally-relevant memories and promotes a value-based stratification of long-term memory stores.

Interaction Between Hippocampus and Cerebellum Crus I in Sequence-Based but not Place-Based Navigation.

To examine the cerebellar contribution to human spatial navigation we used functional magnetic resonance imaging and virtual reality. Our findings show that the sensory-motor requirements of navigation induce activity in cerebellar lobules and cortical areas known to be involved in the motor loop and vestibular processing. By contrast, cognitive aspects of navigation mainly induce activity in a different cerebellar lobule (VIIA Crus I). Our results demonstrate a functional link between cerebellum and hippocampus in humans and identify specific functional circuits linking lobule VIIA Crus I of the cerebellum to medial parietal, medial prefrontal, and hippocampal cortices in nonmotor aspects of navigation. They further suggest that Crus I belongs to 2 nonmotor loops, involved in different strategies: place-based navigation is supported by coherent activity between left cerebellar lobule VIIA Crus I and medial parietal cortex along with right hippocampus activity, while sequence-based navigation is supported by coherent activity between right lobule VIIA Crus I, medial prefrontal cortex, and left hippocampus. These results highlight the prominent role of the human cerebellum in both motor and cognitive aspects of navigation, and specify the cortico-cerebellar circuits by which it acts depending on the requirements of the task.

Temporal order memory assessed during spatiotemporal navigation as a behavioral cognitive marker for differential Alzheimer's disease diagnosis.

Episodic memory impairment is a hallmark for early diagnosis of Alzheimer's disease. Most actual tests used to diagnose Alzheimer's disease do not assess the spatiotemporal properties of episodic memory and lead to false-positive or -negative diagnosis. We used a newly developed, nonverbal navigation test for Human, based on the objective experimental testing of a spatiotemporal experience, to differentially Alzheimer's disease at the mild stage (N = 16 patients) from frontotemporal lobar degeneration (N = 11 patients) and normal aging (N = 24 subjects). Comparing navigation parameters and standard neuropsychological tests, temporal order memory appeared to have the highest predictive power for mild Alzheimer's disease diagnosis versus frontotemporal lobar degeneration and normal aging. This test was also nonredundant with classical neuropsychological tests. As a conclusion, our results suggest that temporal order memory tested in a spatial navigation task may provide a selective behavioral marker of Alzheimer's disease.

Developmental time course of the acquisition of sequential egocentric and allocentric navigation strategies.

Navigation in a complex environment can rely on the use of different spatial strategies. We have focused on the employment of "allocentric" (i.e., encoding interrelationships among environmental cues, movements, and the location of the goal) and "sequential egocentric" (i.e., sequences of body turns associated with specific choice points) strategies during navigation. To investigate the developmental pattern of these two strategies in school-aged children, we used a virtual reality paradigm in which the spontaneous or imposed use of both strategies could be assessed. Our results showed an increase in spontaneous use of the allocentric strategy and also an increase in reliance on environmental landmarks with age. Although a majority of the children spontaneously used the sequential egocentric strategy, all age groups performed above chance when the allocentric strategy was imposed. Altogether, our findings suggest that young children are able to employ an allocentric strategy but that the nature of this allocentric strategy changes progressively in a complex cognitive representation between 5 and 10 years of age.

Lateralized human hippocampal activity predicts navigation based on sequence or place memory.

The hippocampus is crucial for both spatial navigation and episodic memory, suggesting that it provides a common function to both. Here we adapt a spatial paradigm, developed for rodents, for use with functional MRI in humans to show that activation of the right hippocampus predicts the use of an allocentric spatial representation, and activation of the left hippocampus predicts the use of a sequential egocentric representation. Both representations can be identified in hippocampal activity before their effect on behavior at subsequent choice-points. Our results suggest that, rather than providing a single common function, the two hippocampi provide complementary representations for navigation, concerning places on the right and temporal sequences on the left, both of which likely contribute to different aspects of episodic memory.

Sequential egocentric strategy is acquired as early as allocentric strategy: Parallel acquisition of these two navigation strategies.

At least two main cognitive strategies can be used to solve a complex navigation task: the allocentric or map-based strategy and the sequential egocentric or route-based strategy. The sequential egocentric strategy differs from a succession of independent simple egocentric responses as it requires a sequential ordering of events, possibly sharing functional similarity with episodic memory in this regard. To question the possible simultaneous encoding of sequential egocentric and allocentric strategies, we developed a paradigm in which these two strategies are spontaneously used or imposed. Our results evidenced that sequential egocentric strategy can be spontaneously acquired at the onset of the training as well as allocentric strategy. Allocentric and sequential egocentric strategies could be used together within a trial, and bidirectional shifts (between trials) were spontaneously performed during the training period by 30% of the participants. Regardless of the strategy used spontaneously during the training, all participants could execute immediate shifts to the opposite non previously used strategy when this strategy was imposed. Altogether, our findings suggest that subjects acquire different types of spatial knowledge in parallel, namely knowledge permitting allocentric navigation as well as knowledge permitting sequential egocentric navigation.