Enhancing Cognitive Restructuring with Concurrent Repetitive Transcranial Magnetic Stimulation: A Transdiagnostic Randomized Controlled Trial.

INTRODUCTION: Emotional dysregulation constitutes a serious public health problem in need of novel transdiagnostic treatments. OBJECTIVE: To this aim, we developed and tested a one-time intervention that integrates behavioral skills training with concurrent repetitive transcranial magnetic stimulation (rTMS). METHODS: Forty-six adults who met criteria for at least one DSM-5 disorder and self-reported low use of cognitive restructuring (CR) were enrolled in a randomized, double-blind, sham-controlled trial that used a between-subjects design. Participants were taught CR and underwent active rTMS applied at 10 Hz over the right (n = 17) or left (n = 14) dorsolateral prefrontal cortex (dlPFC) or sham rTMS (n = 15) while practicing reframing and emotional distancing in response to autobiographical stressors. RESULTS: Those who received active left or active right as opposed to sham rTMS exhibited enhanced regulation (ds = 0.21-0.62) as measured by psychophysiological indices during the intervention (higher high-frequency heart rate variability, lower regulation duration). Those who received active rTMS over the left dlPFC also self-reported reduced distress throughout the intervention (d = 0.30), higher likelihood to use CR, and lower daily distress during the week following the intervention. The procedures were acceptable and feasible with few side effects. CONCLUSIONS: These findings show that engaging frontal circuits simultaneously with cognitive skills training and rTMS may be clinically feasible, well-tolerated and may show promise for the treatment of transdiagnostic emotional dysregulation. Larger follow-up studies are needed to confirm the efficacy of this novel therapeutic approach.

Hemisphere-specific Parietal Contributions to the Interplay between Working Memory and Attention.

To achieve our moment-to-moment goals, we must often keep information temporarily in mind. Yet, this working memory (WM) may compete with demands for our attention in the environment. Attentional and WM functions are thought to operate by similar underlying principles, and they often engage overlapping fronto-parietal brain regions. In a recent fMRI study, bilateral parietal cortex BOLD activity displayed an interaction between WM and visual attention dual-task demands. However, prior studies also suggest that left and right parietal cortices make unique contributions to WM and attentional functions. Moreover, behavioral performance often shows no interaction between concurrent WM and attentional demands. Thus, the scope of reciprocity between WM and attentional functions, as well as the specific contribution that parietal cortex makes to these functions, remain unresolved. Here, we took a causal approach, targeting brain regions that are implicated in shared processing between WM and visual attention, to better characterize how those regions contribute to behavior. We first examined whether behavioral indices of WM and visual search differentially correlate with left and right parietal dual-task BOLD responses. Then, we delivered TMS over fMRI-guided left and right parietal sites during dual-task WM-visual search performance. Only right-parietal TMS influenced visual search behavior, but the stimulation either helped or harmed search depending on the current WM load. Therefore, whereas the left and right parietal contributions were distinct here, attentional and WM functions were codependent. Right parietal cortex seems to hold a privileged role in visual search behavior, consistent with prior findings, but the current results reveal that behavior may be sensitive to the interaction between visual search and WM load only when normal parietal activity is perturbed. The parietal response to heightened WM and attentional demands may therefore serve to protect against dual-task interference.

Multivariate Patterns of Posterior Cortical Activity Differentiate Forms of Emotional Distancing.

Distancing is an effective tactic for emotion regulation, which can take several forms depending on the type(s) of psychological distance being manipulated to modify affect. We recently proposed a neurocognitive model of emotional distancing, but it is unknown how its specific forms are instantiated in the brain. Here, we presented healthy young adults (N = 34) with aversive pictures during functional magnetic resonance imaging to directly compare behavioral performance and brain activity across spatial, temporal, and objective forms of distancing. We found emotion regulation performance to be largely comparable across these forms. A conjunction analysis of activity associated with these forms yielded a high degree of overlap, encompassing regions of the default mode and frontoparietal networks as predicted by our model. A multivariate pattern classification further revealed distributed patches of posterior cortical activation that discriminated each form from one another. These findings not only confirm aspects of our overarching model but also elucidate a novel role for cortical regions in and around the parietal lobe in selectively supporting spatial, temporal, and social cognitive processes to distance oneself from an emotional encounter. These regions may provide new targets for brain-based interventions for emotion dysregulation.

Examining the Role of Lateral Parietal Cortex in Emotional Distancing Using TMS.

We recently proposed a neurocognitive model of distancing-an emotion regulation tactic-with a focus on the lateral parietal cortex. Although this brain area has been implicated in both cognitive control and self-projection processes during distancing, fMRI work suggests that these processes may be dissociable here. This preregistered (NCT03698591) study tested the contribution of left temporoparietal junction (TPJ) to distancing using repetitive transcranial magnetic stimulation. We hypothesized that inhibiting left TPJ would decrease the efficiency of distancing but not distraction, another regulation tactic with similar cognitive control requirements, thus implicating this region in the self-projection processes unique to distancing. Active and sham continuous theta burst stimulation (cTBS) were applied to 30 healthy adults in a single-session crossover design. Tactic efficiency was measured using online reports of valence and effort. The stimulation target was established from the group TPJ fMRI activation peak in an independent sample using the same distancing task, and anatomical MRI scans were used for individual targeting. Analyses employed both repeated-measures ANOVA and analytic procedures tailored to crossover designs. Irrespective of cTBS, distancing led to greater decreases in negative valence over time relative to distraction, and distancing effort decreased over time while distraction effort remained stable. Exploratory analyses also revealed that active cTBS made distancing more effortful, but not distraction. Thus, left TPJ seems to support self-projection processes in distancing, and these processes may be facilitated by repeated use. These findings help to clarify the role of lateral parietal cortex in distancing and inform applications of distancing and distraction.

White matter disease contributes to apathy and disinhibition in behavioral variant frontotemporal dementia.

OBJECTIVE: To relate changes in fractional anisotropy associated with behavioral variant frontotemporal dementia to measures of apathy and disinhibition. BACKGROUND: Apathy and disinhibition are the 2 most common behavioral features of behavioral variant frontotemporal dementia, and these symptoms are associated with accelerated patient decline and caregiver stress. However, little is known about how white matter disease contributes to these symptoms. METHODS: We collected neuropsychiatric data, volumetric magnetic resonance imaging, and diffusion-weighted imaging in 11 patients who met published criteria for behavioral variant frontotemporal dementia and had an autopsy-validated cerebrospinal fluid profile consistent with frontotemporal lobar degeneration. We also collected imaging data on 34 healthy seniors for analyses defining regions of disease in the patients. We calculated and analyzed fractional anisotropy with a white matter tract-specific method. This approach uses anatomically guided data reduction to increase sensitivity, and localizes results within canonically defined tracts. We used nonparametric, cluster-based statistical analysis to relate fractional anisotropy to neuropsychiatric measures of apathy and disinhibition. RESULTS: The patients with behavioral variant frontotemporal dementia had widespread reductions in fractional anisotropy in anterior portions of frontal and temporal white matter, compared to the controls. Fractional anisotropy correlated with apathy in the left uncinate fasciculus and with disinhibition in the right corona radiata. CONCLUSIONS: In patients with behavioral variant frontotemporal dementia, apathy and disinhibition are associated with distinct regions of white matter disease. The implicated fiber tracts likely support frontotemporal networks that are involved in goal-directed behavior.

Reappraisal and mentalizing: Perceived difficulty and effects on negative emotion.

Previous work suggests that, in some circumstances, cognitive processes can be facilitated by engaging related processes. In this study, we investigated whether engaging in mentalizing during reappraisal, an emotion regulation strategy, would lead to greater changes in affect and reduce the perceived difficulty of reappraisal. We trained participants to reappraise negative pictures through reinterpretation. For some trials, participants generated reappraisals as they would for themselves, while for others, they mentalized, generating reappraisals while taking the perspective of a specific, close friend viewing the pictures. Participants rated their own negative affect and the perceived difficulty of reappraisal both online (i.e., during the task) and immediately posttask. We observed different results for the impact of mentalizing through online and retrospective (posttask) reports. As predicted, participants retrospectively reported that reappraisal while mentalizing was less difficult and decreased their negative affect. Online, however, some evidence suggested that reappraisal while mentalizing was perceived as more difficult and resulted in greater negative affect. Overall, we did not observe a facilitative effect of mentalizing on reappraisal, but in retrospect, individuals may have believed that mentalizing was helpful for reappraisal. More broadly, these findings emphasize the importance of the cognitive context of reappraisal and different types of self-report. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Competitive interactions between cognitive reappraisal and mentalizing.

To better understand how cognitive context can impact emotion regulation through cognitive reappraisal, we evaluated the effects of an additional mentalizing instruction on reappraisal. This manipulation models an existing therapeutic technique in which a client is instructed to imagine advising a friend in a similar situation. We examined the effects of this manipulation on self-reported affect and difficulty as well as fMRI measures of neural function. We hypothesized that the mentalizing context would facilitate the cognitive processing and performance of reappraisal due to the engagement of common neurocognitive resources across these processes. We trained participants to reappraise negative pictures using reinterpretation, and crossed mentalizing with reappraisal in a within-subjects factorial design. Self-report results indicated that the mentalizing instruction did not impact reappraisal performance. We did, however, identify neural interactions between mentalizing and reappraisal. The particular patterns of interaction suggested that reappraisal processing may have been dominant and mentalizing processing diminished when both were instructed. Overall, our findings suggested that mentalizing and reappraisal did engage shared neurocognitive resources, but this overlap resulted in competition between these processes rather than facilitation. We discuss potential mechanisms and identify directions for future research. This study was preregistered at https://osf.io/ym28u/.

Regulating emotion through distancing: A taxonomy, neurocognitive model, and supporting meta-analysis.

Distancing is a type of emotion regulation that involves simulating a new perspective to alter the psychological distance and emotional impact of a stimulus. The effectiveness and versatility of distancing relative to other types of emotion regulation make it a promising tool for clinical applications. However, the neurocognitive mechanisms of this tactic are unclear, and inconsistencies in terminology and methods across studies make it difficult to synthesize the literature. To promote more effective research, we propose a taxonomy of distancing within the broader context of emotion regulation strategies; review the effects of this tactic; and offer a preliminary neurocognitive model describing key cognitive processes and their neural bases. Our model emphasizes three components-self-projection, affective self-reflection, and cognitive control. Additionally, we present results from a supporting meta-analysis of neuroimaging studies of distancing. These efforts are presented within the overarching goals of supporting effective applications of distancing in laboratory, clinical, and other real-world contexts, and advancing understanding of the relevant high-level cognitive functions in the brain.

Apathy in Frontotemporal Degeneration: Neuroanatomical Evidence of Impaired Goal-directed Behavior.

BACKGROUND: Apathy, the major manifestation of impaired goal-directed behavior (GDB), is the most common neuropsychiatric syndrome associated with behavioral variant frontotemporal degeneration (bvFTD). The behavioral and biological mechanisms of apathy, however, are not well understood. We hypothesized that GDB has multiple components-including at least initiation, planning and motivation-and that GDB is supported by a network of multiple frontal brain regions. In this study, we examined this hypothesis by evaluating the selective breakdown of GDB in bvFTD, and relating these deficits to gray matter (GM) atrophy and white matter (WM) integrity. METHODS: Eighteen apathetic bvFTD participants and 17 healthy controls completed the Philadelphia Apathy Computerized Test (PACT). This test quantifies each of three components of GDB hypothesized to contribute to apathy. We then used regression analyses to relate PACT scores to GM atrophy and reduced white matter (WM) fractional anisotropy (FA) in bvFTD. RESULTS: Compared to controls, bvFTD participants demonstrated significant impairments in each of the three hypothesized components of GDB that contribute to apathy. Regression analyses related each component to disease in specific GM structures and associated WM tracts. Poor initiation thus was related to GM atrophy in anterior cingulate and reduced FA in the cingulum. Planning impairment was related to GM atrophy in dorsolateral prefrontal cortex and reduced FA in superior longitudinal fasciculus. Poor motivation was related to GM atrophy in orbitofrontal cortex (OFC) and reduced FA in uncinate fasciculus (UNC). CONCLUSIONS: bvFTD patients have difficulty with initiation, planning and motivation components of GDB. These findings are consistent with the hypotheses that GDB encompasses at least three processes, that these are supported by a large-scale neural network within specific portions of the frontal lobe, and that degradation of any one of these prefrontal regions in bvFTD may contribute to apathy.

Counting or chunking? Mathematical and heuristic abilities in patients with corticobasal syndrome and posterior cortical atrophy.

A growing amount of empirical data is showing that the ability to manipulate quantities in a precise and efficient fashion is rooted in cognitive mechanisms devoted to specific aspects of numbers processing. The analog number system (ANS) has a reasonable representation of quantities up to about 4, and represents larger quantities on the basis of a numerical ratio between quantities. In order to represent the precise cardinality of a number, the ANS may be supported by external algorithms such as language, leading to a "precise number system". In the setting of limited language, other number-related systems can appear. For example the parallel individuation system (PIS) supports a "chunking mechanism" that clusters units of larger numerosities into smaller subsets. In the present study we investigated number processing in non-aphasic patients with corticobasal syndrome (CBS) and posterior cortical atrophy (PCA), two neurodegenerative conditions that are associated with progressive parietal atrophy. The present study investigated these number systems in CBS and PCA by assessing the property of the ANS associated with smaller and larger numerosities, and the chunking property of the PIS. The results revealed that CBS/PCA patients are impaired in simple calculations (e.g., addition and subtraction) and that their performance strongly correlates with the size of the numbers involved in these calculations, revealing a clear magnitude effect. This magnitude effect was correlated with gray matter atrophy in parietal regions. Moreover, a numeral-dots transcoding task showed that CBS/PCA patients were able to take advantage of clustering in the spatial distribution of the dots of the array. The relative advantage associated with chunking compared to a random spatial distribution correlated with both parietal and prefrontal regions. These results shed light on the properties of systems for representing number knowledge in non-aphasic patients with CBS and PCA.

White matter disease correlates with lexical retrieval deficits in primary progressive aphasia.

OBJECTIVE: To relate fractional anisotropy (FA) changes associated with the semantic and logopenic variants of primary progressive aphasia (PPA) to measures of lexical retrieval. METHODS: We collected neuropsychological testing, volumetric magnetic resonance imaging, and diffusion-weighted imaging on semantic variant PPA (svPPA) (n = 11) and logopenic variant PPA (lvPPA) (n = 13) patients diagnosed using published criteria. We also acquired neuroimaging data on a group of demographically comparable healthy seniors (n = 34). FA was calculated and analyzed using a white matter (WM) tract-specific analysis approach. This approach utilizes anatomically guided data reduction to increase sensitivity and localizes results within canonically defined tracts. We used non-parametric, cluster-based statistical analysis to relate language performance to FA and determine regions of reduced FA in patients. RESULTS: We found widespread FA reductions in WM for both variants of PPA. FA was related to both confrontation naming and category naming fluency performance in left uncinate fasciculus and corpus callosum in svPPA and left superior and inferior longitudinal fasciculi in lvPPA. CONCLUSION: SvPPA and lvPPA are associated with distinct disruptions of a large-scale network implicated in lexical retrieval, and the WM disease in each phenotype may contribute to language impairments including lexical retrieval.

White matter microstructure is associated with cognitive control in children.

Cognitive control, which involves the ability to pay attention and suppress interference, is important for learning and achievement during childhood. The white matter tracts related to control during childhood are not well known. We examined the relationship between white matter microstructure and cognitive control in 61 children aged 7-9 years using diffusion tensor imaging (DTI). This technique enables an in vivo characterization of microstructural properties of white matter based on properties of diffusion. Such properties include fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity, measures thought to reflect specific biological properties of white matter integrity. Our results suggest that children with higher estimates of white matter integrity in the corona radiata, superior longitudinal fasciculus, posterior thalamic radiation, and cerebral peduncle were more accurate during incongruent (> > < > >, < < > < <) and neutral (-->-, --<--) trials of a task of cognitive control. Importantly, less interference during the task (i.e., incongruent and neutral difference scores) was associated with greater white matter microstructure in the posterior thalamic radiation and cerebral peduncle. Fiber tracts in a frontal-parietal-striatal-motor circuit seem to play a role in cognitive control in children.

Blockade of D1 dopamine receptors in the medial prefrontal cortex attenuates amphetamine- and methamphetamine-induced locomotor activity in the rat.

The medial prefrontal cortex (mPFC) is a component of the mesolimbic dopamine (DA) system involved in psychostimulant-induced hyperactivity and previous studies have shown that altering DA transmission or D2 receptors within the mPFC can decrease this stimulant effect. The goal of this study was to investigate a potential modulatory role for D1 receptors in the mPFC in amphetamine (AMPH)- and methamphetamine (METH)-induced hyperactivity. Locomotor activity in an open-field arena was measured in male, Sprague-Dawley rats given an intra-mPFC infusion of vehicle or the D1 receptor antagonist SCH 23390 (0.25 or 1.0 microg) prior to systemic (i.p.) injection of saline, AMPH (1 mg/kg), or METH (1 mg/kg). We found that SCH 23390 produced a dose-dependent decrease in AMPH- and METH-induced locomotion and rearing but had no significant effect on spontaneous behavior that occurred following systemic saline injections. Because SCH 23390 has been shown to have agonist-like properties at 5-HT(2C) receptors, a follow-up experiment was performed to determine if this contributed to the attenuation of METH-induced activity that we observed. Rats were given intra-mPFC infusions of both SCH 23390 (1.0 microg) and the 5-HT(2C) antagonist RS 102221 (0.25 microg) prior to METH (1 mg/kg, i.p.). The addition of the 5-HT(2C) antagonist failed to alter SCH 23390-induced decreases in METH-induced locomotion and rearing; infusion of RS 102221 alone had no significant effects on locomotion and produced a non-significant decrease in rearing. The results of these studies suggest that D1 activation in the mPFC plays a significant role in AMPH- and METH-induced hyperactivity.