Salience Network Segregation Mediates the Effect of Tau Pathology on Mild Behavioral Impairment.

INTRODUCTION: A recently developed mild behavioral impairment (MBI) diagnostic framework standardizes the early characterization of neuropsychiatric symptoms in older adults. However, the links between MBI, brain function, and Alzheimer's disease (AD) biomarkers are unclear. METHODS: Using data from 128 participants with diagnosis of amnestic mild cognitive impairment and mild dementia - Alzheimer's type, we test a novel model assessing direct relationships between AD biomarker status and MBI symptoms, as well as mediated effects through segregation of the salience and default-mode networks. RESULTS: We identified a mediated effect of tau positivity on MBI through functional segregation of the salience network from the other high-level, association networks. There were no direct effects of AD biomarkers status on MBI. DISCUSSION: Our findings suggest an indirect role of tau pathology in MBI through brain network dysfunction and emphasize the role of the salience network in mediating relationships between neuropathological changes and behavioral manifestations.

Comparing high definition transcranial direct current stimulation to left temporoparietal junction and left inferior frontal gyrus for logopenic primary progressive aphasia: A single-case study.

Logopenic variant primary progressive aphasia (lvPPA) is characterized by word-finding deficits and phonologic errors in fluent speech. Transcranial direct current stimulation (tDCS) targeting either left temporoparietal junction (TPJ) or left inferior frontal gyrus (IFG) show evidence of improving language function in lvPPA. The present case study evaluated the effects of two separate rounds of high definition tDCS (HD-tDCS) (4 mA; 30 sessions) on language and functional neuroimaging in a 57-year-old woman with lvPPA. Stimulation was centred on two different regions across rounds: (1) left TPJ, and (2) left (IFG). Results showed an improved proportion of content to floorholder words during a naturalistic speech task through both rounds as well as change in confrontation naming after TPJ (improvement) and IFG (worsened) stimulation. fMRI connectivity during task showed left lateralized positive correlations following round 1 and anti-correlations with components of the default mode network following round 2. Resting state segregation of a language-associated functional network increased following both rounds, and task-based segregation of the same network increased following IFG stimulation. These results suggest that stimulation to both regions using HD-tDCS may improve language function in lvPPA, while simultaneously eliciting widespread changes beyond the targeted area in neuronal activity and functional connectivity.

Biden or Trump? Working memory for emotion predicts the ability to forecast future feelings.

Affective forecasting-the ability to predict how different outcomes will make us feel-is a crucial aspect of making optimal decisions. Recent laboratory evidence suggests that working memory for emotion is a basic psychological mechanism underlying forecasting ability: Individual differences in affective working memory predict how accurately people can forecast their future feelings whereas measures of "cognitive" working memory do not. Here, we demonstrate that this selective relationship between affective forecasting and affective working memory generalizes to forecasted feelings about a major real-world event. We report results from a preregistered (online) study (N = 76) demonstrating that affective working memory performance predicted how accurately people anticipate their feelings about the outcome of the 2020 U.S. presidential election. This relationship was specific to affective working memory and was also demonstrated in a description-based forecasting measure with emotionally evocative photographs, replicating previous results. However, neither affective nor cognitive working memory was related to a novel event-based forecasting questionnaire, adapted to compare predicted and experienced feelings to everyday events. Together, these findings advance a mechanistic understanding of affective forecasting and underscore the potential importance of affective working memory in some forms of higher order emotional thought. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Tolerability and blinding of high-definition transcranial direct current stimulation among older adults at intensities of up to 4 mA per electrode.

BACKGROUND: Few studies have investigated tolerability, blinding, and double-blinding of High-Definition transcranial Direct Current Stimulation (HD-tDCS) at amplitudes above 2 milliamps (mA). OBJECTIVE: We examined a) tolerability of HD-tDCS during stimulation sessions and b) blinding and double blinding of participants and study team members. METHODS: Data from a mixed neurologic sample of 292 older adults were pooled from 3046 HD-tDCS sessions (2329 active; 717 sham). Per electrode amplitudes ranged from 1 mA to 4 mA with total currents up to 10 mA. Participants completed a standardized sensation (tolerability) questionnaire after each session. Participants and study team members stated whether the participant received active or sham stimulation at the end of various sessions. Data were collapsed into the presence/absence of a symptom due to low rates of positive responding and were analyzed for both differences and bioequivalency. RESULTS: There were no safety-related adverse events. HD-tDCS was well tolerated with mostly no ("none") or "mild" sensations reported across sessions, regardless of active or sham condition and in both stimulation naïve and experienced participants. There were no significant differences in side effects between active and sham, with some achieving bioequivalence. Tingling and itching were significantly more common after lower (<2 mA) than higher (≥3 mA) amplitude active sessions, while skin redness was significantly more common after higher amplitudes. Blinding was effective at the participant and study team levels. CONCLUSIONS: HD-tDCS was well tolerated with center electrode amplitudes up to 4 mA. The bimodal ramp-up/down format of the sham was effective for blinding. These results support higher scalp-based amplitudes that enable greater brain-based current intensities in older adults.

ConnSearch: A framework for functional connectivity analysis designed for interpretability and effectiveness at limited sample sizes.

Functional connectivity studies increasingly turn to machine learning methods, which typically involve fitting a connectome-wide classifier, then conducting post hoc interpretation analyses to identify the neural correlates that best predict a dependent variable. However, this traditional analytic paradigm suffers from two main limitations. First, even if classifiers are perfectly accurate, interpretation analyses may not identify all the patterns expressed by a dependent variable. Second, even if classifiers are generalizable, the patterns implicated via interpretation analyses may not replicate. In other words, this traditional approach can yield effective classifiers while falling short of most neuroscientists' goals: pinpointing the neural correlates of dependent variables. We propose a new framework for multivariate analysis, ConnSearch, which involves dividing the connectome into components (e.g., groups of highly connected regions) and fitting an independent model for each component (e.g., a support vector machine or a correlation-based model). Conclusions about the link between a dependent variable and the brain are based on which components yield predictive models rather than on interpretation analysis. We used working memory data from the Human Connectome Project (N = 50-250) to compare ConnSearch with four existing connectome-wide classification/interpretation methods. For each approach, the models attempted to classify examples as being from the high-load or low-load conditions (binary labels). Relative to traditional methods, ConnSearch identified neural correlates that were more comprehensive, had greater consistency with the WM literature, and better replicated across datasets. Hence, ConnSearch is well-positioned to be an effective tool for functional connectivity research.

Toward rational use of cognitive training in those with mild cognitive impairment.

The term cognitive training includes a range of techniques that hold potential for treating cognitive impairment caused by neurologic injury and disease. Our central premise is that these techniques differ in their mechanisms of action and therefore engage distinct brain regions (or neural networks). We support this premise using data from a single-blind randomized-controlled trial in which patients with mild cognitive impairment were randomized to either mnemonic strategy training (MST) or spaced retrieval training (SRT) as they learned ecologically relevant object-location associations. Both training approaches were highly effective in the short term, but MST demonstrated a clear advantage after days to weeks. MST also increased activation in and functional connectivity between frontal, temporal, and parietal regions as well as the hippocampus. In contrast, patterns of reduced activation and functional connectivity were evident following SRT. These findings support the rational development of cognitive training techniques.

High-definition transcranial direct current stimulation enhances network segregation during spatial navigation in mild cognitive impairment.

Spatial navigation is essential for everyday life and relies on complex network-level interactions. Recent evidence suggests that transcranial direct current stimulation (tDCS) can influence the activity of large-scale functional brain networks. We characterized brain-wide changes in functional network segregation (i.e. the balance of within vs. between-network connectivity strength) induced by high-definition (HD) tDCS in older adults with mild cognitive impairment (MCI) during virtual spatial navigation. Twenty patients with MCI and 22 cognitively intact older adults (healthy controls-HC) underwent functional magnetic resonance imaging following two counterbalanced HD-tDCS sessions (one active, one sham) that targeted the right parietal cortex (center anode at P2) and delivered 2 mA for 20 min. Compared to HC, MCI patients showed lower brain-wide network segregation following sham HD-tDCS. However, following active HD-tDCS, MCI patients' network segregation increased to levels similar to those in HC, suggesting functional normalization. Follow-up analyses indicated that the increase in network segregation for MCI patients was driven by HD-tDCS effects on the "high-level"/association brain networks, in particular the dorsal-attention and default-mode networks. HD-tDCS over the right parietal cortex may normalize the segregation/integration balance of association networks during spatial navigation in MCI patients, highlighting its potential to restore brain activity in Alzheimer's disease.

The impact of focused attention on emotional evaluation: An eye-tracking investigation.

Emotional well-being depends on the ability to successfully engage a variety of coping strategies to regulate affective responses. Most studies have investigated the effectiveness of emotion regulation (ER) strategies that are deployed relatively later in the timing of processing that leads to full emotional experiences (i.e. reappraisal and suppression). Strategies engaged in earlier stages of emotion processing, such as those involved in attentional deployment, have also been investigated, but relatively less is known about their mechanisms. Here, we investigate the effectiveness of self-guided focused attention (FA) in reducing the impact of unpleasant pictures on the experienced negative affect. Participants viewed a series of composite images with distinguishable foreground (FG, either negative or neutral) and background (BG, always neutral) areas and were asked to focus on the FG or BG content. Eye-tracking data were recorded while performing the FA task, along with participants' ratings of their experienced emotional response following the presentation of each image. First, proving the effectiveness of self-guided FA in down-regulating negative affect, focusing away from the emotional content of pictures (BG focus) was associated with lower emotional ratings. Second, trial-based eye-tracking data corroborated these results, showing that spending less time gazing within the negative FG predicted reductions in emotional ratings. Third, this reduction was largest among subjects who habitually use suppression to regulate their emotions. Overall, the present findings expand the evidence regarding the FA's effectiveness in controlling the impact of emotional stimuli and inform the development of training interventions emphasizing attentional control to improve emotional well-being. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Proof-of-concept evidence for trimodal simultaneous investigation of human brain function.

The link between spatial (where) and temporal (when) aspects of the neural correlates of most psychological phenomena is not clear. Elucidation of this relation, which is crucial to fully understand human brain function, requires integration across multiple brain imaging modalities and cognitive tasks that reliably modulate the engagement of the brain systems of interest. By overcoming the methodological challenges posed by simultaneous recordings, the present report provides proof-of-concept evidence for a novel approach using three complementary imaging modalities: functional magnetic resonance imaging (fMRI), event-related potentials (ERPs), and event-related optical signals (EROS). Using the emotional oddball task, a paradigm that taps into both cognitive and affective aspects of processing, we show the feasibility of capturing converging and complementary measures of brain function that are not currently attainable using traditional unimodal or other multimodal approaches. This opens up unprecedented possibilities to clarify spatiotemporal integration of brain function.

Age differences in functional network reconfiguration with working memory training.

Demanding cognitive functions like working memory (WM) depend on functional brain networks being able to communicate efficiently while also maintaining some degree of modularity. Evidence suggests that aging can disrupt this balance between integration and modularity. In this study, we examined how cognitive training affects the integration and modularity of functional networks in older and younger adults. Twenty three younger and 23 older adults participated in 10 days of verbal WM training, leading to performance gains in both age groups. Older adults exhibited lower modularity overall and a greater decrement when switching from rest to task, compared to younger adults. Interestingly, younger but not older adults showed increased task-related modularity with training. Furthermore, whereas training increased efficiency within, and decreased participation of, the default-mode network for younger adults, it enhanced efficiency within a task-specific salience/sensorimotor network for older adults. Finally, training increased segregation of the default-mode from frontoparietal/salience and visual networks in younger adults, while it diffusely increased between-network connectivity in older adults. Thus, while younger adults increase network segregation with training, suggesting more automated processing, older adults persist in, and potentially amplify, a more integrated and costly global workspace, suggesting different age-related trajectories in functional network reorganization with WM training.

Affective forecasting: A selective relationship with working memory for emotion.

Affective forecasting (AF), the ability to predict one's future feelings, is important for decision making. We posit that AF entails the ability to maintain and evaluate an emotional feeling state, and thus requires affective working memory (AWM; Mikels & Reuter-Lorenz, 2019). To test this hypothesis, a series of studies investigated whether individual differences in AWM are related to AF ability. In the first study, we document that measures of AWM and AF are positively related, whereas an analogous measure of visual working memory is unrelated to AF in separate groups of participants. Two further within-group studies (1 preregistered) demonstrate that maintenance of affective information predicts AF performance, whereas maintenance of brightness information does not. Further, 2 additional measures of visual working memory (Corsi block-tapping and change detection) did not independently predict AF ability. Taken together the results demonstrate a reliable and selective relationship between AWM and AF, suggesting that AWM is a separable working memory subsystem and an elemental capacity that contributes to the type of higher-order emotional processes involved in AF. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Neural correlates of working memory training: Evidence for plasticity in older adults.

Brain activity typically increases with increasing working memory (WM) load, regardless of age, before reaching an apparent ceiling. However, older adults exhibit greater brain activity and reach ceiling at lower loads than younger adults, possibly reflecting compensation at lower loads and dysfunction at higher loads. We hypothesized that WM training would bolster neural efficiency, such that the activation peak would shift towards higher memory loads after training. Pre-training, older adults showed greater recruitment of the WM network than younger adults across all loads, with decline at the highest load. Ten days of adaptive training on a verbal WM task improved performance and led to greater brain responsiveness at higher loads for both groups. For older adults the activation peak shifted rightward towards higher loads. Finally, training increased task-related functional connectivity in older adults, both within the WM network and between this task-positive network and the task-negative/default-mode network. These results provide new evidence for functional plasticity with training in older adults and identify a potential signature of improvement at the neural level.

Aging and Network Properties: Stability Over Time and Links with Learning during Working Memory Training.

Growing evidence suggests that healthy aging affects the configuration of large-scale functional brain networks. This includes reducing network modularity and local efficiency. However, the stability of these effects over time and their potential role in learning remain poorly understood. The goal of the present study was to further clarify previously reported age effects on "resting-state" networks, to test their reliability over time, and to assess their relation to subsequent learning during training. Resting-state fMRI data from 23 young (YA) and 20 older adults (OA) were acquired in 2 sessions 2 weeks apart. Graph-theoretic analyses identified both consistencies in network structure and differences in module composition between YA and OA, suggesting topological changes and less stability of functional network configuration with aging. Brain-wide, OA showed lower modularity and local efficiency compared to YA, consistent with the idea of age-related functional dedifferentiation, and these effects were replicable over time. At the level of individual networks, OA consistently showed greater participation and lower local efficiency and within-network connectivity in the cingulo-opercular network, as well as lower intra-network connectivity in the default-mode network and greater participation of the somato-sensorimotor network, suggesting age-related differential effects at the level of specialized brain modules. Finally, brain-wide network properties showed associations, albeit limited, with learning rates, as assessed with 10 days of computerized working memory training administered after the resting-state sessions, suggesting that baseline network configuration may influence subsequent learning outcomes. Identification of neural mechanisms associated with learning-induced plasticity is important for further clarifying whether and how such changes predict the magnitude and maintenance of training gains, as well as the extent and limits of cognitive transfer in both younger and older adults.

Age-related Change and the Predictive Value of the 'Resting State': A Commentary on Campbell and Schacter (2016).

This is a commentary on Campbell and Schacter (2016), 'Aging and the Resting State: Is Cognition Obsolete?'

Emotional influences on perception and working memory.

Although there has been steady progress elucidating the influence of emotion on cognition, it remains unclear precisely when and why emotion impairs or facilitates cognition. The present study investigated the mechanisms involved in the influence of emotion on perception and working memory (WM), using modified 0-back and 2-back tasks, respectively. First, results showed that attentional focus modulated the impact of emotion on perception. Specifically, emotion facilitated perceptual task performance when it was relevant to the task, but it impaired performance when it was irrelevant to the task. The differential behavioural effect of emotion on perception as a function of attentional focus diminished under high WM load. Second, attentional focus did not directly modulate the impact of emotion on WM, but rather its influence depended on the dynamic relationship between internal representations. Specifically, WM performance was worse when the material already being held online and the new input were of matching emotions (e.g. both were negative), compared to when they were not. We propose that the competition between "bottom-up" and "top-down" processing for limited cognitive resources explains the nature of the influence of emotion on both perception and WM.

Optimism and the brain: trait optimism mediates the protective role of the orbitofrontal cortex gray matter volume against anxiety.

Converging evidence identifies trait optimism and the orbitofrontal cortex (OFC) as personality and brain factors influencing anxiety, but the nature of their relationships remains unclear. Here, the mechanisms underlying the protective role of trait optimism and of increased OFC volume against symptoms of anxiety were investigated in 61 healthy subjects, who completed measures of trait optimism and anxiety, and underwent structural scanning using magnetic resonance imaging. First, the OFC gray matter volume (GMV) was associated with increased optimism, which in turn was associated with reduced anxiety. Second, trait optimism mediated the relation between the left OFC volume and anxiety, thus demonstrating that increased GMV in this brain region protects against symptoms of anxiety through increased optimism. These results provide novel evidence about the brain-personality mechanisms protecting against anxiety symptoms in healthy functioning, and identify potential targets for preventive and therapeutic interventions aimed at reducing susceptibility and increasing resilience against emotional disturbances.

Emotion-attention interactions in fear conditioning: Moderation by executive load, neuroticism, and awareness.

Despite increasing evidence suggesting interactive effects of emotion and attention on perceptual processing, it still remains unclear how their interplay influences affective learning, such as fear conditioning. In the present study, a conditioning procedure using threat-related conditioned stimuli (CSs) was implemented while executive load and attentional focus were manipulated. The modulation effects of neuroticism and contingency awareness were also examined. Results showed that fear conditioning depended on the available executive resources even with threat-related CSs. In addition, although individuals with high neuroticism showed an enhanced conditioning effect overall, this facilitation effect still depended on the availability of executive resources. Finally, the impact of attentional focus was most evident among individuals with high neuroticism who were aware of the contingency. Overall, the present study demonstrates interactive effects of emotion and attention in fear conditioning, while illuminating mechanisms of individual differences and clarifying the controversial role of contingency awareness in fear conditioning.

A comprehensive protocol for manual segmentation of the medial temporal lobe structures.

The present paper describes a comprehensive protocol for manual tracing of the set of brain regions comprising the medial temporal lobe (MTL): amygdala, hippocampus, and the associated parahippocampal regions (perirhinal, entorhinal, and parahippocampal proper). Unlike most other tracing protocols available, typically focusing on certain MTL areas (e.g., amygdala and/or hippocampus), the integrative perspective adopted by the present tracing guidelines allows for clear localization of all MTL subregions. By integrating information from a variety of sources, including extant tracing protocols separately targeting various MTL structures, histological reports, and brain atlases, and with the complement of illustrative visual materials, the present protocol provides an accurate, intuitive, and convenient guide for understanding the MTL anatomy. The need for such tracing guidelines is also emphasized by illustrating possible differences between automatic and manual segmentation protocols. This knowledge can be applied toward research involving not only structural MRI investigations but also structural-functional colocalization and fMRI signal extraction from anatomically defined ROIs, in healthy and clinical groups alike.

Neural correlates of opposing effects of emotional distraction on working memory and episodic memory: an event-related FMRI investigation.

A fundamental question in the emotional memory literature is why emotion enhances memory in some conditions but disrupts memory in other conditions. For example, separate studies have shown that emotional stimuli tend to be better remembered in long-term episodic memory (EM), whereas emotional distracters tend to impair working memory (WM) maintenance. The first goal of this study was to directly compare the neural correlates of EM enhancement (EME) and WM impairing (WMI) effects, and the second goal was to explore individual differences in these mechanisms. During event-related functional magnetic resonance imaging (fMRI), participants maintained faces in WM while being distracted by emotional or neutral pictures presented during the delay period. EM for the distracting pictures was tested after scanning and was used to identify successful encoding activity for the picture distracters. The first goal yielded two findings: (1) emotional pictures that disrupted face WM but enhanced subsequent EM were associated with increased amygdala (AMY) and hippocampal activity (ventral system) coupled with reduced dorsolateral PFC (dlPFC) activity (dorsal system); (2) trials in which emotion enhanced EM without disrupting WM were associated with increased ventrolateral PFC activity. The ventral-dorsal switch can explain EME and WMI, while the ventrolateral PFC effect suggests a coping mechanism. The second goal yielded two additional findings: (3) participants who were more susceptible to WMI showed greater amygdala increases and PFC reductions; (4) AMY activity increased and dlPFC activity decreased with measures of attentional impulsivity. Taken together, these results clarify the mechanisms linking the enhancing and impairing effects of emotion on memory, and provide insights into the role of individual differences in the impact of emotional distraction.

Reappraisal and suppression mediate the contribution of regulatory focus to anxiety in healthy adults.

Theory and research link regulatory focus (RF) in the form of promotion and prevention goal orientation with internalizing symptoms (e.g., anxiety), but the relevant mechanisms are not well understood. This study investigated the role of two emotion regulation (ER) strategies (cognitive reappraisal and expressive suppression) as possible mediators. Path analysis using data from 179 healthy young participants (110 women, 69 men) revealed that stronger promotion orientation was significantly associated with less anxiety, and that the use of reappraisal and suppression partially mediated this association. Prevention was associated with more suppression but was not directly associated with anxiety. There were no gender differences in these effects. Collectively, these findings suggest that effective ER, through heightened use of reappraisal and dampened use of suppression, serves as a mechanism through which promotion confers protection against anxiety. This research provides empirical support to initiatives aimed at promoting healthy psychological adjustment and preventing anxiety, by optimizing ER strategies with respect to RF goal orientations.