Evaluating methods for measuring background connectivity in slow event-related functional magnetic resonance imaging designs.

INTRODUCTION: Resting-state functional magnetic resonance imaging (fMRI) is widely used for measuring functional interactions between brain regions, significantly contributing to our understanding of large-scale brain networks and brain-behavior relationships. Furthermore, idiosyncratic patterns of resting-state connections can be leveraged to identify individuals and predict individual differences in clinical symptoms, cognitive abilities, and other individual factors. Idiosyncratic connectivity patterns are thought to persist across task states, suggesting task-based fMRI can be similarly leveraged for individual differences analyses. METHOD: Here, we tested the degree to which functional interactions occurring in the background of a task during slow event-related fMRI parallel or differ from those captured during resting-state fMRI. We compared two approaches for removing task-evoked activity from task-based fMRI: (1) applying a low-pass filter to remove task-related frequencies in the signal, or (2) extracting residuals from a general linear model (GLM) that accounts for task-evoked responses. RESULT: We found that the organization of large-scale cortical networks and individual's idiosyncratic connectivity patterns are preserved during task-based fMRI. In contrast, individual differences in connection strength can vary more substantially between rest and task. Compared to low-pass filtering, background connectivity obtained from GLM residuals produced idiosyncratic connectivity patterns and individual differences in connection strength that more resembled rest. However, all background connectivity measures were highly similar when derived from the low-pass-filtered signal or GLM residuals, indicating that both methods are suitable for measuring background connectivity. CONCLUSION: Together, our results highlight new avenues for the analysis of task-based fMRI datasets and the utility of each background connectivity method.

Bridging Big Data: Procedures for Combining Non-equivalent Cognitive Measures from the ENIGMA Consortium.

Investigators in neuroscience have turned to Big Data to address replication and reliability issues by increasing sample sizes, statistical power, and representativeness of data. These efforts unveil new questions about integrating data arising from distinct sources and instruments. We focus on the most frequently assessed cognitive domain - memory testing - and demonstrate a process for reliable data harmonization across three common measures. We aggregated global raw data from 53 studies totaling N = 10,505 individuals. A mega-analysis was conducted using empirical bayes harmonization to remove site effects, followed by linear models adjusting for common covariates. A continuous item response theory (IRT) model estimated each individual's latent verbal learning ability while accounting for item difficulties. Harmonization significantly reduced inter-site variance while preserving covariate effects, and our conversion tool is freely available online. This demonstrates that large-scale data sharing and harmonization initiatives can address reproducibility and integration challenges across the behavioral sciences.

Differential Functional Connectivity along the Long Axis of the Hippocampus Aligns with Differential Role in Memory Specificity and Generalization.

The hippocampus contributes to both remembering specific events and generalization across events. Recent work suggests that information may be represented along the longitudinal axis of the hippocampus at varied levels of specificity: detailed representations in the posterior hippocampus and generalized representations in the anterior hippocampus. Similar distinctions are thought to exist within neocortex, with lateral prefrontal and lateral parietal regions supporting memory specificity and ventromedial prefrontal and lateral temporal cortices supporting generalized memory. Here, we tested whether functional connectivity of anterior and posterior hippocampus with cortical memory regions is consistent with these proposed dissociations. We predicted greater connectivity of anterior hippocampus with putative generalization regions and posterior hippocampus with putative memory specificity regions. Furthermore, we tested whether differences in connectivity are stable under varying levels of task engagement. Participants learned to categorize a set of stimuli outside the scanner, followed by an fMRI session that included a rest scan, passive viewing runs, and category generalization task runs. Analyses revealed stronger connectivity of ventromedial pFC to anterior hippocampus and of angular gyrus and inferior frontal gyrus to posterior hippocampus. These differences remained relatively stable across the three phases (rest, passive viewing, category generalization). Whole-brain analyses further revealed widespread cortical connectivity with both anterior and posterior hippocampus, with relatively little overlap. These results contribute to our understanding of functional organization along the long axis of the hippocampus and suggest that distinct hippocampal-cortical connections are one mechanism by which the hippocampus represents both individual experiences and generalized knowledge.

Cognitive Reserve Protects Against Memory Decrements Associated With Neuropathology in Traumatic Brain Injury.

OBJECTIVE: To evaluate whether cognitive reserve (CR) moderates the relationship between neuropathology and cognitive outcomes after traumatic brain injury (TBI). SETTING: Outpatient research organization. PARTICIPANTS: Patients with complicated mild (n = 8), moderate (n = 9), and severe (n = 44) TBI. DESIGN: Prospective, cross-sectional study. MAIN MEASURES: Cognitive reserve was estimated using a test of word reading (Wechsler Test of Adult Reading). Diffusion tensor imaging (functional anisotropy) was used to quantify neuropathology. Neuropsychological test scores were submitted to principal components analyses to create cognitive composites for memory, attention, executive function, and processing speed domains. RESULTS: At lower levels of neuropathology, people with higher CR exhibited better memory than those with lower CR. This benefit diminished as neuropathology increased and disappeared at the highest levels of neuropathology. Cognitive reserve ceased exerting a protective effect at premorbid intelligence levels below average. CONCLUSION: Cognitive reserve may differentially protect some cognitive domains against neuropathology relative to others. A clinical cutoff below which CR is no longer protective, together with a possible neuropathology ceiling effect, may be instructive for prognostication and clinical decision-making in cognitive rehabilitation.

Functional connectivity between memory and reward centers across task and rest track memory sensitivity to reward.

External motivation, such as a promise of future monetary reward for remembering an event, can affect which events are remembered. Reward-based memory modulation is thought to result from encoding and post-encoding interactions between dopaminergic midbrain, signaling reward, and hippocampus and parahippocampal cortex, supporting episodic memory. We asked whether hippocampal and parahippocampal interactions with other reward-related regions are related to reward modulation of memory and whether such relationships are stable over time. Individuals' memory sensitivity to reward was measured using a monetary incentive encoding task in which a cue indicated potential monetary reward (penny, dime, or dollar) for remembering an upcoming object pair. Functional connectivity between memory and reward regions was measured before, during, and following the task. Reward-related regions of interest were generated using a meta-analysis of existing studies on reward and included ventral striatum, medial and orbital prefrontal cortices and anterior cingulate cortex, in addition to midbrain. The results showed that connectivity between memory and reward regions tracked individual differences in reward modulation of memory, irrespective of when connectivity was measured. Connectivity patterns of anterior cingulate, orbitofrontal cortex, and ventral striatum covaried together and tracked behavior most strongly. These findings implicate a broader set of reward regions in reward modulation of memory than considered previously and provide new evidence that stable connectivity patterns between memory and reward centers relate to individual differences in how reward impacts memory.