Biology subjects

Eisenstein, T.

Publications and source records attributed to Eisenstein, T..

4 recordsLinked to original sources

bioRxiv2023

Increased cortical inhibition immediately following brief motor memory reactivation supports reconsolidation and overnight offline learning gains

Practicing motor skills stabilizes and strengthens motor memories by repeatedly reactivating and reconsolidating them. The conventional view, by which a repetitive practice is required for substantially improving skill performance, has been recently challenged by behavioral experiments, in which even brief reactivations of the motor memory have led to significant improvements in skill performance. However, the mechanisms which facilitate brief reactivation-induce skill improvements remain elusive. While initial memory consolidation has been repeatedly associated with increased neural excitation and dis-inhibition, reconsolidation has been shown to involve a poorly-understood mixture of both excitatory and inhibitory alterations. Here, we followed a three-day reactivation-reconsolidation framework, to examine whether the excitatory/inhibitory mechanisms which underlie brief reactivation and repetitive practice differ. Healthy volunteers practiced a motor sequence learning task using either brief reactivation or repetitive practice and were assessed using ultra-high field (7T) magnetic resonance spectroscopy at the primary motor cortex (M1). We found that increased inhibition (GABA concentrations) and decreased excitation/inhibition (glutamate/GABA ratios) immediately following the brief reactivation were associated with overnight offline performance gains. These gains were on-par with those exhibited following repetitive practice, where no correlations with inhibitory or excitatory changes were observed. Our findings suggest that brief reactivation and repetitive practice depend on fundamentally different neural mechanisms, and that early inhibition - and not excitation - is particularly important in supporting the learning gains exhibited by brief reactivation.

neuroscience↗

bioRxiv2022

Early excitatory and inhibitory modifications in the motor cortex following skill learning support motor memory consolidation and cortical plasticity overnight

The learning of new motor skills constitutes an inseparable part of our lives. Motor consolidation refers to the offline processing of motor memories following the acquisition of new motor skills. The animal literature suggests that the primary motor cortex (M1) plays a key role in motor memory consolidation, and structural and functional plasticity in M1 following motor consolidation have been demonstrated. However, the mechanisms supporting motor memory consolidation and plasticity in the human M1 are not well understood. Initial human neuroimaging studies show that the initial stages of motor learning in humans are accompanied by short-term temporal dynamics of the brains main excitatory and inhibitory neurotransmitters - Glutamate (Glu) and GABA - in M1, but it remains unclear how these relate to the question of motor memory consolidation. Here, we show that early Glu and GABA modifications in M1 following motor skill learning may play vital roles in supporting motor memory consolidation and neural plasticity that take place over longer time scales. Using a multimodal magnetic resonance approach implemented on ultra-high field 7T scanner in healthy young adults (n=36), we found increased Glu and decreased GABA in M1 during the initial offline period following learning to support consolidation-related local and inter-regional functions of M1, such as motor memory reactivation and increased functional connectivity with the striatum. These neurochemical changes also correlated with overnight structural and functional plasticity expressed as increased M1 grey matter volume and functional connectivity, while Glu modifications also correlated with adaptive behavior, as reflected by improvements in skill performance. Our results provide intriguing microscale mechanistic evidence to the potential distinctive roles of Glu and GABA in promoting motor memory consolidation and plasticity in the human M1. They also highlight a role for early neurochemical modifications to memory consolidation and plasticity in the human brain and may hold important clinical implications in rehabilitative settings such as in stroke and brain injury.

neuroscience↗

bioRxiv2021

Physically active lifestyle is associated with attenuation of hippocampal dysfunction in healthy older adults

Alterations in hippocampal function have been shown in older adults, expressed as changes in hippocampal activity and connectivity. While hippocampal activation during memory demands have been demonstrated to decrease with age, some older individuals present increased activity, or hyperactivity, of the hippocampus which is associated with increased neuropathology and poorer memory function. In addition, lower functional coherence between the hippocampus and core hubs of the default mode network (DMN), namely the posteromedial and medial prefrontal cortices, as well as increased local intrahippocampal connectivity, were also demonstrated in cognitively intact older adults. Aerobic exercise has been shown to elicit neuroprotective effects on hippocampal structure and vasculature in aging, and improvements in maximal aerobic capacity (MAC) have been suggested to mediate these exercise-related effects. However, how these lifestyle factors relate to hippocampal function is not clear. Fifty-two cognitively intact older adults (age 65-80) have been recruited and divided into physically active (n=29) or non-active (n=23) groups based on their aerobic activity lifestyle habits. Participants underwent resting-state as well as task-based fMRI experiments which included an associative memory encoding paradigm followed by a post-scan memory recognition test. In addition, forty-four participants also performed cardiopulmonary exercise tests to evaluate MAC. While both groups demonstrated increased anterior hippocampal activation during memory encoding, physically active lifestyle was associated with significantly lower activity level and higher memory performance in the recognition task. In addition, the physically active group also demonstrated higher functional connectivity of the anterior and posterior hippocampi with the core hubs of the DMN, and lower local intra-hippocampal connectivity within and between hemispheres. MAC was negatively associated with hippocampal activation level and demonstrated positive correlation with hippocampal-DMN connectivity. According to these findings, aerobically active lifestyle may be associated with attenuation of hippocampal dysfunction in cognitively healthy older adults.

neuroscience↗

bioRxiv2020

Grey and White Matter Pathways Underlying the Relationship Between Aerobically Active Lifestyle, Cardiorespiratory Function, and Episodic Memory in the Aging Human Brain

Aging is associated with structural alterations of the hippocampus, a key region in episodic memory processes. Aerobic activity and maximal aerobic capacity (MAC), a key measure of cardiorespiratory function and a physiological adaptation of aerobic exercise, have been associated with biological and cognitive resilience of the brain. However, investigations of their relationship with the hippocampus in humans had resulted with inconsistent findings. This study aimed to investigate the relationship between lifestyles aerobic activity and MAC and hippocampal grey and white matter structure, as well as episodic memory performance in cognitively healthy older adults. In addition, we examined the relationship between aerobic activity and MAC, and cerebrovascular pathology expressed as white matter lesions (WML). Next, we used a regression-based mediation analysis to examine possible biological pathways which may underlie the relationship between MAC and hippocampal volume, which was demonstrated in previous works, and was confirmed in the current study. Fifty cognitively healthy older adults (70.92 {+/-} 3.9 years) were divided into aerobically active (n=27) and non-active (n=23) groups, and performed structural and diffusion MRI. Forty-two participants were also evaluated for MAC. Aerobically active lifestyle and higher MAC were associated with increased hippocampal volume and microstructural integrity, as well as increased fornix microstructural integrity, and lower WML burden (p<.05). In addition, both factors were correlated with increased episodic memory performance (p<.05). Mediation analysis revealed two pathways potentially mediating the relationship between MAC, hippocampal volume, and episodic memory - a white matter pathway consisted of WML and fornix microstructure, and grey matter pathway including hippocampal microstructure. These findings shed light on possible neurobiological mechanisms that could potentially underlie the neuroprotective effect of cardiorespiratory function and aerobic physical activity on hippocampal macrostructure and memory function in the aging human brain.

neuroscience↗