Self-appraisal decisions evoke dissociated dorsal-ventral aMPFC networks

The anterior medial prefrontal cortex (aMPFC) is consistently active during personally salient decisions, yet the differential contributory processes of this region along the dorsal-ventral axis are less understood. Using a self-appraisal decision-making task and functional magnetic resonance imaging, we demonstrated task-dependent connectivity of ventral aMPFC with amygdala, insula, and nucleus accumbens, and dorsal aMPFC connectivity with dorsolateral PFC and bilateral hippocampus. These aMPFC networks appear to subserve distinct contributory processes inherent to self-appraisal decisions, specifically a dorsally mediated cognitive and a ventrally mediated affective/self-relevance network. © 2005 Elsevier Inc. All rights reserved

Relevance to self: A brief review and framework of neural systems underlying appraisal

We argue that many similar findings observed in cognitive, affective, and social neuroimaging research may compose larger processes central to generating self-relevance. In support of this, recent findings from these research domains were reviewed to identify common systemic activation patterns. Superimposition of these patterns revealed evidence for large-scale supramodal processes, which are argued to mediate appraisal of self-relevant content irrespective of specific stimulus types (e.g. words, pictures) and task domains (e.g. induction of reward, fear, pain, etc.). Furthermore, we distinguish between two top-down sub-systems involved in appraisal of self-relevance, one that orients pre-attentive biasing information (e.g. anticipatory or mnemonic) to salient or explicitly self-relevant phenomena, and another that engages introspective processes (e.g. self-reflection, evaluation, recollection) either in conjunction with or independent of the former system. Based on aggregate patterns of activation derived from the reviewed studies, processes in a ventral medial prefrontal cortex (MPFC)-subcortical network appear to track with the former pathway, and processes in a dorsal MPFC-cortical-subcortical network with the latter. As a whole, the purpose of this framework is to re-conceive the functionality of these systems in terms of supramodal processes that more directly reflect the influences of relevance to the self. © 2007 Elsevier Ltd. All rights reserved

Failing to ignore: Paradoxical neural effects of perceptual load on early attentional selection in normal aging

We examined visual selective attention under perceptual load - simultaneous presentation of task-relevant and -irrelevant information - in healthy young and older adult human participants to determine whether age differences are observable at early stages of selection in the visual cortices. Participants viewed 50/50 superimposed face/place images and judged whether the faces were male or female, rendering places perceptible but task-irrelevant. Each stimulus was repeated, allowing us to index dynamic stimulus-driven competition from places. Consistent with intact early selection in young adults, we observed no adaptation to unattended places in parahippocampal place area (PPA) and significant adaptation to attended faces in fusiform face area (FFA). Older adults, however, exhibited both PPA adaptation to places and weak FFA adaptation to faces. We also probed participants\u27 associative recognition for face-place pairs post-task. Older adults with better place recognition memory scores were found to exhibit both the largest magnitudes of PPA adaptation and the smallest magnitudes of FFA adaptation on the attention task. In a control study, we removed the competing perceptual information to decrease perceptual load. These data revealed that the initial age-related impairments in selective attention were not due to a general decline in visual cortical selectivity; both young and older adults exhibited robust FFA adaptation and neither group exhibited PPA adaptation to repeated faces. Accordingly, distracting information does not merely interfere with attended input in older adults, but is co-encoded along with the contents of attended input, to the extent that this information can subsequently be recovered from recognition memory. Copyright © 2010 the authors

Shared neural substrates of emotionally enhanced perceptual and mnemonic vividness

It is well known that emotionally salient events are remembered more vividly than mundane ones. Our recent research has demonstrated that such memory vividness is due in part to the subjective experience of emotional events as more perceptually vivid, an effect we call emotion-enhanced vividness, or EEV. The present study built on previously reported research in which fMRI data were collected while participants rated relative levels of visual noise overlaid on emotionally salient and neutral images. Ratings of greater EEV were associated with greater activation in the amygdala, visual cortex, and posterior insula. In the present study, we measured BOLD activation that predicted recognition memory vividness for these same images one week later. Results showed that, after controlling for differences between scenes in low-level objective features, hippocampus activation uniquely predicted subsequent memory vividness. In contrast, amygdala and visual cortex regions that were sensitive to EEV were also modulated by subsequent ratings of memory vividness. These findings suggest shared neural substrates for the influence of emotional salience on perceptual and mnemonic vividness, with amygdala and visual cortex activation at encoding contributing to the experience of both perception and subsequent memory. © 2013 Todd, Schmitz, Susskind and Anderson

Longitudinal basal forebrain degeneration interacts with TREM2/C3 biomarkers of inflammation in presymptomatic Alzheimer’s disease

Copyright © 2020 the authors Cholinergic inputs originating from the peripheral nervous system regulate the inflammatory immune responses of macrophages during clearance of blood-based pathogens. Because microglia are involved in clearing amyloid and tau pathology from the central nervous system, we hypothesized that cholinergic input originating from the basal forebrain might similarly regulate inflammatory immune responses to these pathologies in the aging brain. To explore this hypothesis, we leveraged the Alzheimer’s Disease Neuroimaging Initiative dataset. Cognitively normal older male and female human adults were differentiated according to the relative concentration of phosphorylated tau and amyloid in their cerebrospinal fluid, yielding neurotypical and preclinical, cognitively healthy, subgroups. We then tracked these two groups longitudinally with structural MRI and biomarkers of inflammation, including soluble sTREM2 levels in the CSF and complement C3 expression in the blood transcriptome. Longitudinal loss of basal forebrain volume was larger in the preclinical compared with the neurotypical subgroup. Across preclinical adults, loss of basal forebrain volume was associated with greater longitudinal accumulation of sTREM2 and higher peripheral blood C3 expression. None of these relationships were attributable to degeneration in the whole-brain gray matter volume. Preclinical APOE e4 carriers exhibited the largest loss of basal forebrain volume and highest C3 expression. Consistent with the known anti-inflammatory influence of the peripheral cholinergic pathways on macrophages, our findings indicate that a loss of central cholinergic input originating from the basal forebrain might remove a key check on microglial inflammation induced by amyloid and tau accumulation

Longitudinal Alzheimer\u27s Degeneration Reflects the Spatial Topography of Cholinergic Basal Forebrain Projections

© 2018 The Author(s) The cholinergic neurons of the basal forebrain (BF) provide virtually all of the brain\u27s cortical and amygdalar cholinergic input. They are particularly vulnerable to neuropathology in early Alzheimer\u27s disease (AD) and may trigger the emergence of neuropathology in their cortico-amygdalar projection system through cholinergic denervation and trans-synaptic spreading of misfolded proteins. We examined whether longitudinal degeneration within the BF can explain longitudinal cortico-amygdalar degeneration in older human adults with abnormal cerebrospinal fluid biomarkers of AD neuropathology. We focused on two BF subregions, which are known to innervate cortico-amygdalar regions via two distinct macroscopic cholinergic projections. To further assess whether structural degeneration of these regions in AD reflects cholinergic denervation, we used the [ 18 F] FEOBV radiotracer, which binds to cortico-amygdalar cholinergic terminals. We found that the two BF subregions explain spatially distinct patterns of cortico-amygdalar degeneration, which closely reflect their cholinergic projections, and overlap with [ 18 F] FEOBV indices of cholinergic denervation

Psychophysical and neural evidence for emotion-enhanced perceptual vividness

Highly emotional events are associated with vivid flashbulb memories. Here we examine whether the flashbulb metaphor characterizes a previously unknown emotion-enhanced vividness (EEV) during initial perceptual experience. Using a magnitude estimation procedure, human observers estimated the relative magnitude of visual noise overlaid on scenes. After controlling for computational metrics of objective visual salience, emotional salience was associated with decreased noise, or heightened perceptual vividness, demonstrating EEV, which predicted later memory vividness. Event-related potentials revealed a posterior P2 component at ~200 ms that was associated with both increased emotional salience and decreased objective noise levels, consistent with EEV. Blood oxygenation level-dependent response in the lateral occipital complex (LOC), insula, and amygdala predicted online EEV. The LOC and insula represented complimentary influences on EEV, with the amygdala statistically mediating both. These findings indicate that the metaphorical vivid light surrounding emotional memories is embodied directly in perceptual cortices during initial experience, supported by cortico-limbic interactions. © 2012 the authors

A supramodal role of the basal ganglia in memory and motor inhibition: Meta-analytic evidence

© 2017 The Authors The ability to stop actions and thoughts is essential for goal-directed behaviour. Neuroimaging research has revealed that stopping actions and thoughts engage similar cortical mechanisms, including the ventro- and dorso-lateral prefrontal cortex. However, whether and how these abilities require similar subcortical mechanisms remains unexplored. Specifically of interest are the basal ganglia, subcortical structures long-known for their motor functions, but less so for their role in cognition. To investigate the potential common mechanisms in the basal ganglia underlying action and thought stopping, we conducted meta-analyses using fMRI data from the Go/No-Go, Stop-signal, and Think/No-Think tasks. All three tasks require active stopping of prepotent actions or thoughts. To localise basal ganglia activations, we performed high-resolution manual segmentations of striatal subregions. We found that all three tasks recovered clusters in the basal ganglia, although the specific localisation of these clusters differed. Although the Go/No-Go and Stop-signal tasks are often interchangeably used for measuring action stopping, their cluster locations in the basal ganglia did not significantly overlap. These different localised clusters suggest that the Go/No-Go and Stop-signal tasks may recruit distinct basal ganglia stopping processes, and therefore should not be treated equivalently. More importantly, the basal ganglia cluster recovered from the Think/No-Think task largely co-localised with that from the Stop-signal task, but not the Go/No-Go task, possibly indicating that the Think/No-Think and Stop-signal tasks share a common striatal circuitry involved in the cancellation of unwanted thoughts and actions. The greater similarity of the Think/No-Think task to the Stop-Signal rather than Go/No-Go task also was echoed at the cortical level, which revealed highly overlapping and largely right lateralized set of regions including the anterior DLPFC, VLPFC, Pre-SMA and ACC. Overall, we provide novel evidence suggesting not only that the basal ganglia are critical for thought stopping, but also that they are involved in specific stopping subprocesses that can be engaged by tasks in different domains. These findings raise the possibility that the basal ganglia may be part of a supramodal network responsible for stopping unwanted processes more broadly

Dynamic targeting enables domain-general inhibitory control over action and thought by the prefrontal cortex.

Over the last two decades, inhibitory control has featured prominently in accounts of how humans and other organisms regulate their behaviour and thought. Previous work on how the brain stops actions and thoughts, however, has emphasised distinct prefrontal regions supporting these functions, suggesting domain-specific mechanisms. Here we show that stopping actions and thoughts recruits common regions in the right dorsolateral and ventrolateral prefrontal cortex to suppress diverse content, via dynamic targeting. Within each region, classifiers trained to distinguish action-stopping from action-execution also identify when people are suppressing their thoughts (and vice versa). Effective connectivity analysis reveals that both prefrontal regions contribute to action and thought stopping by targeting the motor cortex or the hippocampus, depending on the goal, to suppress their task-specific activity. These findings support the existence of a domain-general system that underlies inhibitory control and establish Dynamic Targeting as a mechanism enabling this ability

Hippocampal GABA enables inhibitory control over unwanted thoughts.

Intrusive memories, images, and hallucinations are hallmark symptoms of psychiatric disorders. Although often attributed to deficient inhibitory control by the prefrontal cortex, difficulty in controlling intrusive thoughts is also associated with hippocampal hyperactivity, arising from dysfunctional GABAergic interneurons. How hippocampal GABA contributes to stopping unwanted thoughts is unknown. Here we show that GABAergic inhibition of hippocampal retrieval activity forms a key link in a fronto-hippocampal inhibitory control pathway underlying thought suppression. Subjects viewed reminders of unwanted thoughts and tried to suppress retrieval while being scanned with functional magnetic resonance imaging. Suppression reduced hippocampal activity and memory for suppressed content. 1H magnetic resonance spectroscopy revealed that greater resting concentrations of hippocampal GABA predicted better mnemonic control. Higher hippocampal, but not prefrontal GABA, predicted stronger fronto-hippocampal coupling during suppression, suggesting that interneurons local to the hippocampus implement control over intrusive thoughts. Stopping actions did not engage this pathway. These findings specify a multi-level mechanistic model of how the content of awareness is voluntarily controlled