EVALUATING DEFAULT MODE NETWORK RESTING-STATE FUNCTIONAL CONNECTIVITY AS A BIOMARKER OF TREATMENT RESPONSE TO MINDFULNESS-BASED COGNITIVE THERAPY FOR ANHEDONIA

Anhedonia is a transdiagnostic symptom referring to impairments in motivation and pleasure. Depression and other anhedonic disorders are associated with aberrant function in the default mode network (DMN), the neural substrates of self-referential processing. Mindfulness practice has shown therapeutic value for mood impairments and alters DMN functioning. The current study examined whether DMN resting-state connectivity is a biomarker for treatment response to Mindfulness-Based Cognitive Therapy (MBCT, n=35), as compared to a novel psychosocial intervention (n=38), in a transdiagnostic sample of adults with clinically-significant anhedonia. Multiple regression and multilevel modeling were used to evaluate relations between connectivity and treatment effects. Anhedonia symptoms and DMN connectivity significantly decreased over time, equally across treatments. Contrary to predictions, baseline and changes in connectivity were unrelated to outcomes. Results showed DMN connectivity was neither a predictor nor mechanism of response to MBCT, but that attenuation of DMN connectivity may be a non-specific psychological treatment effect.Master of Art

The Effect of Testing Can Increase or Decrease Misinformation Susceptibility Depending on the Retention Interval

Research has consistently demonstrated that testing prior to the presentation of misleading post-event information, within the context of a standard eyewitness misinformation paradigm, results in an increase in the misinformation effect. The present study investigated whether changes in misinformation susceptibility in the context of interim testing are affected by retention interval differences between misinformation presentation and final testing. Further, this study tested possible divergences in original and post-event learning between conditions where elaboration in processing of critical details was encouraged either indirectly, via interim testing, or directly, by visually emphasizing critical details. In two experiments, we compared three groups of participants. All participants were exposed to an event, presented with misleading post-event misinformation, and then given a final test on the original event. One group was given an interim test between the original event and the post-event synopsis. A second was presented with a post-event synopsis in which critical details were visually emphasized. A third group served as a baseline comparison group for which synopsis processing was not manipulated. All experimental phases occurred in a single session in Experiment 1. A 48-hour retention interval was inserted between the post-event synopsis and final test in Experiment 2. In Experiment 1, we found that interim testing and emphasizing critical details increased misinformation susceptibility as compared to that found in the standard misinformation group. In Experiment 2, misinformation susceptibility was reduced in the interim testing group. These results suggest that interim testing and emphasizing critical details influence the rate of original detail forgetting. At a longer retention interval, the benefits of testing in learning emerged

The effect of testing can increase or decrease misinformation susceptibility depending on the retention interval

Abstract Research has consistently demonstrated that testing prior to the presentation of misleading post-event information, within the context of a standard eyewitness misinformation paradigm, results in an increase in the misinformation effect. The present study investigated whether changes in misinformation susceptibility in the context of interim testing are affected by retention interval differences between misinformation presentation and final testing. Further, this study tested possible divergences in original and post-event learning between conditions where elaboration in processing of critical details was encouraged either indirectly, via interim testing, or directly, by visually emphasizing critical details. In two experiments, we compared three groups of participants. All participants were exposed to an event, presented with misleading post-event misinformation, and then given a final test on the original event. One group was given an interim test between the original event and the post-event synopsis. A second was presented with a post-event synopsis in which critical details were visually emphasized. A third group served as a baseline comparison group for which synopsis processing was not manipulated. All experimental phases occurred in a single session in Experiment 1. A 48-hour retention interval was inserted between the post-event synopsis and final test in Experiment 2. In Experiment 1, we found that interim testing and emphasizing critical details increased misinformation susceptibility as compared to that found in the standard misinformation group. In Experiment 2, misinformation susceptibility was reduced in the interim testing group. These results suggest that interim testing and emphasizing critical details influence the rate of original detail forgetting. At a longer retention interval, the benefits of testing in learning emerged

Neural Mechanisms of Reward Prediction Error in Autism Spectrum Disorder.

Few studies have explored neural mechanisms of reward learning in ASD despite evidence of behavioral impairments of predictive abilities in ASD. To investigate the neural correlates of reward prediction errors in ASD, 16 adults with ASD and 14 typically developing controls performed a prediction error task during fMRI scanning. Results revealed greater activation in the ASD group in the left paracingulate gyrus during signed prediction errors and the left insula and right frontal pole during thresholded unsigned prediction errors. Findings support atypical neural processing of reward prediction errors in ASD in frontostriatal regions critical for prediction coding and reward learning. Results provide a neural basis for impairments in reward learning that may contribute to traits common in ASD (e.g., intolerance of unpredictability).</p

The effect of testing can increase or decrease misinformation susceptibility depending on the retention interval

Abstract Research has consistently demonstrated that testing prior to the presentation of misleading post-event information, within the context of a standard eyewitness misinformation paradigm, results in an increase in the misinformation effect. The present study investigated whether changes in misinformation susceptibility in the context of interim testing are affected by retention interval differences between misinformation presentation and final testing. Further, this study tested possible divergences in original and post-event learning between conditions where elaboration in processing of critical details was encouraged either indirectly, via interim testing, or directly, by visually emphasizing critical details. In two experiments, we compared three groups of participants. All participants were exposed to an event, presented with misleading post-event misinformation, and then given a final test on the original event. One group was given an interim test between the original event and the post-event synopsis. A second was presented with a post-event synopsis in which critical details were visually emphasized. A third group served as a baseline comparison group for which synopsis processing was not manipulated. All experimental phases occurred in a single session in Experiment 1. A 48-hour retention interval was inserted between the post-event synopsis and final test in Experiment 2. In Experiment 1, we found that interim testing and emphasizing critical details increased misinformation susceptibility as compared to that found in the standard misinformation group. In Experiment 2, misinformation susceptibility was reduced in the interim testing group. These results suggest that interim testing and emphasizing critical details influence the rate of original detail forgetting. At a longer retention interval, the benefits of testing in learning emerged

Ultra high-field (7tesla) magnetic resonance spectroscopy in Amyotrophic Lateral Sclerosis

The main objective of this study was to utilize high field (7T) in vivo proton magnetic resonance imaging to increase the ability to detect metabolite changes in people with ALS, specifically, to quantify levels of glutamine and glutamine separately. The second objective of this study was to correlate metabolic markers with clinical outcomes of disease progression. 13 ALS participants and 12 age-matched healthy controls (HC) underwent 7 Tesla MRI and MRS. Single voxel MR spectra were acquired from the left precentral gyrus using a very short echo time (TE = 5 ms) STEAM sequence. MRS data was quantified using LCModel and correlated to clinical outcome markers. N-acetylaspartate (NAA) and total NAA (tNA, NAA + NAAG) were decreased by 17% in people with ALS compared to HC (P = 0.004 and P = 0.005, respectively) indicating neuronal injury and/or loss in the precentral gyrus. tNA correlated with disease progression as measured by forced vital capacity (FVC) (P = 0.014; Rρ = 0.66) and tNA/tCr correlated with overall functional decline as measured by worsening of the ALS Functional Rating Scale-Revised (ALSFRS-R) (P = 0.004; Rρ = -0.74). These findings underscore the importance of NAA as a reliable biomarker for neuronal injury and disease progression in ALS. Glutamate (Glu) was 15% decreased in people with ALS compared to HC (P = 0.02) while glutamine (Gln) concentrations were similar between the two groups. Furthermore, the decrease in Glu correlated with the decrease in FVC (P = 0.013; Rρ = 0.66), a clinical marker of disease progression. The decrease in Glu is most likely driven by intracellular Glu loss due to neuronal loss and degeneration. Neither choline containing components (Cho), a marker for cell membrane turnover, nor myo-Inositol (mI), a suspected marker for neuroinflammation, showed significant differences between the two groups. However, mI/tNA was correlated with upper motor neuron burden (P = 0.004, Rρ = 0.74), which may reflect a relative increase of activated microglia around motor neurons. In summary, 7T 1H MRS is a powerful non-invasive imaging technique to study molecular changes related to neuronal injury and/or loss in people with ALS

Glial activation colocalizes with structural abnormalities in amyotrophic lateral sclerosis

Objective: In this cross-sectional study, we aimed to evaluate brain structural abnormalities in relation to glial activation in the same cohort of participants. Methods: Ten individuals with amyotrophic lateral sclerosis (ALS) and 10 matched healthy controls underwent brain imaging using integrated MR/PET and the radioligand [11C]-PBR28. Diagnosis history and clinical assessments including Upper Motor Neuron Burden Scale (UMNB) were obtained from patients with ALS. Diffusion tensor imaging (DTI) analyses including tract-based spatial statistics and tractography were applied. DTI metrics including fractional anisotropy (FA) and diffusivities (mean, axial, and radial) were measured in regions of interest. Cortical thickness was assessed using surface-based analysis. The locations of structural changes, measured by DTI and the areas of cortical thinning, were compared to regional glial activation measured by relative [11C]-PBR28 uptake. Results: In this cohort of individuals with ALS, reduced FA and cortical thinning colocalized with regions demonstrating higher radioligand binding. [11C]-PBR28 binding in the left motor cortex was correlated with FA (r = −0.68, p < 0.05) and cortical thickness (r = −0.75, p < 0.05). UMNB was correlated with glial activation (r = +0.75, p < 0.05), FA (r = −0.77, p < 0.05), and cortical thickness (r = −0.75, p < 0.05) in the motor cortex. Conclusions: Increased uptake of the glial marker [11C]-PBR28 colocalizes with changes in FA and cortical thinning. This suggests a link between disease mechanisms (gliosis and inflammation) and structural changes (cortical thinning and white and gray matter changes). In this multimodal neuroimaging work, we provide an in vivo model to investigate the pathogenesis of ALS

Imaging of glia activation in people with primary lateral sclerosis

Background: Glia activation is thought to contribute to neuronal damage in several neurodegenerative diseases based on preclinical and human post-mortem studies, but its role in primary lateral sclerosis (PLS) is unknown. Objectives: To localize and measure glia activation in people with PLS compared to healthy controls (HC). Methods: Ten participants with PLS and ten age-matched HCs underwent simultaneous magnetic resonance (MR) and proton emission tomography (PET). The radiotracer [11C]-PBR28 was used to obtain PET-based measures of 18 kDa translocator protein (TSPO) expression, a marker of activated glial cells. MR techniques included a structural sequence to measure cortical thickness and diffusion tensor imaging (DTI) to assess white matter integrity. Results: PET data showed increased [11C]-PBR28 uptake in anatomically-relevant motor regions which co-localized with areas of regional gray matter atrophy and decreased subcortical fractional anisotropy. Conclusions: This study supports a link between glia activation and neuronal degeneration in PLS, and suggests that these disease mechanisms can be measured in vivo in PLS. Future studies are needed to determine the longitudinal changes of these imaging measures and to clarify if MR-PET with [11C]-PBR28 can be used as a biomarker for drug development in the context of clinical trials for PLS

Absolute metabolic concentrations (mM in institutional units) and relative metabolic concentrations of the left motor cortex in ALS patients vs. age-matched healthy controls.

<p>Absolute metabolic concentrations (mM in institutional units) and relative metabolic concentrations of the left motor cortex in ALS patients vs. age-matched healthy controls.</p