Cortical-hippocampal functional connectivity during covert consolidation sub-serves associative learning: Evidence for an active “rest” state

Abstract

We studied modulation of undirected functional connectivity (uFC) in cortical-hippocampal sub-networks during associative learning. Nineteen healthy individuals were studied (fMRI acquired on a Siemens Verio 3T), and uFC was studied between nodes in a network of regions identified by standard activation models based on bivariate correlational analyses of time series data. The paradigm alternated between Memory Encoding, Rest and Retrieval. "Rest" intervals promoted covert consolidation. Over the task, performance was broadly separable into linear (Early) and asymptomatic (Late) regimes, with late performance reflecting successful memory consolidation. Significant modulation of uFC was observed during periods of covert consolidation. The sub-networks which were modulated constituted connections between frontal regions such as the dorsal prefrontal cortex (dPFC) and dorsal anterior cingulate cortex (dACC), the medial temporal lobe (hippocampus, HPC), the superior parietal cortex (SPC) and the fusiform gyrus (FG). uFC patterns were dynamic in that sub-networks modulated during Early learning (dACC ↔ SPC, dACC ↔ FG, dPFC ↔ HPC) were not identical to those modulated during Late learning (dACC ↔ HPC, dPFC ↔ FG, FG ↔ SPC). Covert consolidation exerts systematic effects, and these results add to emerging evidence for the constructive role of the brain's "resting state" in potentiating action.

From mathematics to medicine: A practical primer on topological data analysis (TDA) and the development of related analytic tools for the functional discovery of latent structure in fMRI data

“…These state representations readily permit the assessment of macroscopic brain network interactions that can be modelled using an array of mathematical or statistical models [ 25 , 26 ]. Thus, time series in the rest state can be treated as stochastic fluctuations, that may (or may not) loosely track structural connections between regions [ 27 , 28 ] and/or that may potentiate networks for cognitive or sensorimotor action [ 1 , 29 , 30 ]. Alternatively, state changes can be experimentally induced, using well-constructed tasks with systematically manipulated experimental conditions within them.…”

“…This application of the workflow results from fMRI data from a single healthy participant, collected during an associative learning task (all study procedures were approved by Wayne State University’s Institutional Review Board, and the participant gave informed written consent to participate in the fMRI procedures). Several studies from our group have used task-specific fMRI paradigms to study brain network dynamics induced by associative learning and memory [ 30 , 82 – 88 ]. Associative learning and memory are characterized by the acquisition of reliably co-occurring environmental contingencies [ 89 ].…”

“…The latter region is of particular interest given that it is strongly linked with meta-cognitive processing, sustained attention, and executive control [ 93 ], processes that are expected to be in play throughout the course of an associative memory paradigm. Details of the fMRI paradigm can be found elsewhere [ 30 ]; in brief, the task alternated between blocks of memory encoding (during which paired memoranda were presented for encoding, 27 s, 3 s/pair), post-encoding consolidation (27 s), cued-retrieval (during which memory for each of the 9 associated pairs was tested, 27 s, 3 s/pair), and post-retrieval consolidation (27 s). Eight iterations were employed (fMRI data were collected with a TR = 3s, 288 images acquired).…”

A multimodal study of a first episode psychosis cohort: potential markers of antipsychotic treatment resistance

“…GSH is a physiological reservoir for Glu through the GSH cycle [62], and a reduction in the ACC GSH level, as shown in the present study, implies not only redox imbalance but also glutamatergic neurotransmission imbalance [63] involving the ACC in TR patients. The brain regions underscored in the present study mediate multiple higher brain functions, including associative learning and memory, in which glutamatergic and non-dopaminergic neurotransmission play important roles [64, 65]. This may be one of the reasons why D2-targeted antipsychotics, regardless of first or second generation, may not work for TR patients.…”

“…The copyright holder for this preprint (which this version posted May 4, 2021. ; https://doi.org/10.1101/2021.05.03.442450 doi: bioRxiv preprint associative learning and memory, in which glutamatergic and non-dopaminergic neurotransmission play important roles [64,65]. This may be one of the reasons why D2-targeted antipsychotics, regardless of first or second generation, may not work for TR patients.…”