Hemisphere-specific effects of prefrontal theta-burst stimulation on visual recognition memory accuracy and awareness.

BACKGROUND: The prefrontal cortex has been implicated in episodic memory and the awareness of memory. Few studies have probed the nature and necessity of its role via brain stimulation. There are uncertainties regarding whether the hemisphere of stimulation predicts effects on memory and whether effects of stimulation are format-specific, with most previous studies utilizing verbal/semantic stimuli. OBJECTIVE: Our primary objective was to determine if theta-burst transcranial magnetic stimulation (TBS) to prefrontal cortex modulates visual memory accuracy, visual memory awareness, or both, and whether these effects depend on brain hemisphere. METHODS: We administered TBS to 12 individuals in either left prefrontal, right prefrontal, or a sham location on three separate days. We then administered a visual associative-memory task incorporating global-level awareness judgments and feeling-of-knowing (FOK) judgments on test trials for which retrieval failed. RESULTS: Overall memory accuracy significantly improved after right hemisphere TBS compared to sham. Simultaneously, subjects were relatively underconfident after right TBS, suggesting minimal awareness of memory accuracy improvements. The correspondence between FOKs and later recognition accuracy suggested a pattern of disruption in prospective memory monitoring accuracy after left TBS. CONCLUSIONS: Our findings provide unique evidence for improved visual memory accuracy after right prefrontal TBS. These results also suggest right prefrontal lateralization for visual memory and left-hemisphere specialization for item-level prospective memory awareness judgments. Taken together, these results provided continued support for noninvasive stimulation to prefrontal cortex as a means of potentially improving memory and causally influencing prospective memory awareness.

Memory awareness disruptions in amnestic mild cognitive impairment: comparison of multiple awareness types for verbal and visuospatial material.

Successful memory is normally accompanied by explicit awareness of retrieval and confidence in the accuracy of the retrieval product. Prior findings suggest that these features of metamemory can be dissociated from retrieval accuracy in Amnestic Mild Cognitive Impairment (aMCI). However, the literature on this question contains variable and conflicting results, likely because of differences in experimental conditions. We sought to systematically evaluate memory awareness disruptions in aMCI using multiple measures and stimulus formats within the same individuals. Memory awareness was tested with global predictions and postdictions, judgments of learning, confidence level ratings, and modified feeling-of-knowing ratings in tasks of visuospatial and verbal memory. These tests were administered to 14 individuals with aMCI and 15 healthy, age-matched controls. Memory awareness accuracy was calculated as the correspondence between subjective judgments and memory performance.Individuals with aMCI demonstrated impaired global and trial-level retrospective task awareness for visuospatial and verbal stimuli. Additionally, modified feeling-of-knowing awareness was impaired selectively for verbal stimuli. Statistical effect sizes for global awareness impairments were comparable to impairments in several objective neuropsychological memory assessments.Memory awareness (metamemory) disruptions in aMCI were most evident for a subset of subjective judgment types and task input modalities. These findings advance understanding of the nature of memory impairments in aMCI and support the utility of incorporating memory awareness testing to better characterize memory integrity in older adults.

Early-life stress exposure associated with altered prefrontal resting-state fMRI connectivity in young children.

Early-life stress (ELS) exposure is associated with adverse outcomes across the lifespan. We examined the relation of ELS exposure to resting-state fMRI in children ages 4-7 years. ELS in the first years of life, but not concurrent, was associated with higher regional homogeneity of resting-state fMRI in the left lateral frontal cortex. Resting-state fMRI functional connectivity analyses showed that the region of left lateral frontal cortex demonstrating heightened regional homogeneity associated with ELS was negatively correlated with right temporal/parahippocampal areas. Moreover, higher regional homogeneity in the left lateral frontal cortex and its negative coupling with the right middle temporal/parahippocampal areas were associated with poorer performance on a reversal-learning task performed outside the scanner. Association of ELS exposure with regional homogeneity was independent of other early adversities. These findings suggest that ELS may influence the development of cognitive control in the lateral prefrontal cortex and its interactions with temporal cortex.

Adolescent development of context-dependent stimulus-reward association memory and its neural correlates.

Expression of learned stimulus-reward associations based on context is essential for regulation of behavior to meet situational demands. Contextual regulation improves during development, although the developmental progression of relevant neural and cognitive processes is not fully specified. We therefore measured neural correlates of flexible, contextual expression of stimulus-reward associations in pre/early-adolescent children (ages 9-13 years) and young adults (ages 19-22 years). After reinforcement learning using standard parameters, a contextual reversal manipulation was used whereby contextual cues indicated that stimulus-reward associations were the same as previously reinforced for some trials (consistent trials) or were reversed on other trials (inconsistent trials). Subjects were thus required to respond according to original stimulus-reward associations vs. reversed associations based on trial-specific contextual cues. Children and young adults did not differ in reinforcement learning or in relevant functional magnetic resonance imaging (fMRI) correlates. In contrast, adults outperformed children during contextual reversal, with better performance specifically for inconsistent trials. fMRI signals corresponding to this selective advantage included greater activity in lateral prefrontal cortex (LPFC), hippocampus, and dorsal striatum for young adults relative to children. Flexible expression of stimulus-reward associations based on context thus improves via adolescent development, as does recruitment of brain regions involved in reward learning and contextual expression of memory. HighlightsEarly-adolescent children and young adults were equivalent in reinforcement learning.Adults outperformed children in contextual expression of stimulus-reward associations.Adult advantages correlated with increased activity of relevant brain regions.Specific neurocognitive developmental changes support better contextual regulation.