Biology subjects

Mattfeld, A. T.

Publications and source records attributed to Mattfeld, A. T..

10 recordsLinked to original sources

bioRxiv2025

Error-Related Memory Biases Are Specific to Social Stimuli for Socially Anxious Individuals

Social anxiety (SA) is associated with enhanced error monitoring, yet underlying mechanisms remain unclear. Consistent with cognitive models of SA, we propose that stronger error monitoring contributes to SA by strengthening memory encoding of errors (including relevant social cues), negatively biasing what is remembered. Supporting this hypothesis, our prior work demonstrated that high SA individuals exhibit better memory for faces presented during error (vs. correct) trials. To test whether this Memory Bias for Error Events is specific to social stimuli, 140 participants completed a Flanker task with trial-unique faces (social) or objects (non-social) as background images, followed by a surprise memory test. Results revealed that higher SA symptoms were associated with enhanced memory for faces on error (vs. correct) trials, but not for objects. These findings replicate and extend our prior work, demonstrating that SA-related memory biases for errors are specific to social stimuli, rather than reflecting general encoding biases.

neuroscience↗

bioRxiv2023

Nucleus Reuniens: Modulating Negative Overgeneralization in Preadolescent Anxiety

BackgroundAnxiety affects 4.4-million children in the United States with an onset between childhood and adolescence, a period marked by neural changes that impact emotions and memory. Negative overgeneralization - or responding similarly to innocuous events that share features with past aversive experiences - is common in anxiety but remains mechanistically underspecified. The nucleus reuniens (RE) has been considered a crucial candidate in the modulation of memory specificity. Our study investigated its activation and functional connectivity with the medial prefrontal cortex (mPFC) and hippocampus (HPC) as neurobiological mechanisms of negative overgeneralization in anxious youth. MethodsAs part of a secondary data analysis, we examined data from 34 participants between 9-14 years (mean age {+/-} SD, 11.4 {+/-} 2.0 years, 16 females) with varying degrees of anxiety severity. During the Study session participants rated images as negative, neutral, and positive. After 12-hours, participants returned for a Test session, where they performed a memory recognition test with repeated (targets) and similar (lures) images. Labeling negative relative to neutral lures as "old" (false alarms) was our operational definition of negative overgeneralization. ResultsNegative relative to neutral false alarmed stimuli displayed elevated RE activation (at Study and Test) and increased functional connectivity with the CA1 (at Test only). Elevated anxiety severity was associated with reductions in the RE-mPFC functional coupling for neutral relative to negative stimuli. Exploratory analyses revealed similar patterns in activation and functional connectivity with positive stimuli. ConclusionsOur findings demonstrate the importance of the RE in the overgeneralization of memories in anxious youth.

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bioRxiv2023

Towards a mechanistic understanding of the role of error monitoring and memory in social anxiety

Cognitive models state social anxiety (SA) involves biased cognitive processing that impacts what is learned and remembered within social situations, leading to the maintenance of SA. Neuroscience work links SA to enhanced error monitoring, reflected in error-related neural responses arising from mediofrontal cortex (MFC). Yet, the role of error monitoring in SA remains unclear, as it is unknown whether error monitoring can drive changes in memory, biasing what is learned or remembered about social situations. Thus, we developed a novel paradigm to investigate the role of error-related MFC theta oscillations (associated with error monitoring) and memory biases in SA. EEG was collected while participants completed a novel Face-Flanker task, involving presentation of task-unrelated, trial-unique faces behind target/flanker arrows on each trial. A subsequent incidental memory assessment evaluated memory biases for error events. Severity of SA symptoms were associated with greater error-related theta synchrony over MFC, as well as between MFC and sensory cortex. SA was positively associated with memory biases for error events. Consistent with a mechanistic role in biased cognitive processing, greater error-related MFC-sensory theta synchrony during the Face-Flanker predicted subsequent memory biases for error events. Our findings suggest high SA individuals exhibit memory biases for error events, and that this behavioral phenomenon may be driven by error-related MFC-sensory theta synchrony associated with error monitoring. Moreover, results demonstrate the potential of a novel paradigm to elucidate mechanisms underlying relations between error monitoring and SA.

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bioRxiv2022

Identifying the midline thalamus in humans in vivo

The midline thalamus is essential to flexible cognition, memory, and stress regulation and its dysfunction is associated with several neurological and mental health disorders including Alzheimers disease, schizophrenia, and depression. Despite the pervasive role of the midline thalamus in cognition and disease, almost nothing is known about it in humans due to the lack of a rigorous methodology for finding this brain region using noninvasive imaging technologies. Here, we introduce a new method for identifying the midline thalamus in vivo using probabilistic tractography and k-means clustering with diffusion weighted imaging data. This method clusters thalamic voxels based on data-driven cortical and subcortical connectivity profiles, and then segments midline thalamic nuclei based on connectivity profiles established in rodent and macaque tracer studies. Results from two different diffusion weighted imaging sets, including adult data (22-35yrs) from the Human Connectome Project (n=127) and adolescent data (9-14yrs) collected at Florida International University (n=34) showed that this approach reliably classifies midline thalamic clusters. As expected, these clusters were most evident along the dorsal/ventral extent of the third ventricle and primarily connected to the agranular medial prefrontal cortex (e.g., anterior cingulate cortex), nucleus accumbens, and medial temporal lobe regions. The midline thalamic clusters were then bisected based on a human brain atlas (Ding et al., 2016) into a dorsal midline thalamic cluster (paraventricular and paratenial nuclei) and a ventral midline thalamic cluster (rhomboid and reuniens nuclei). This anatomical connectivity-based identification procedure for the midline thalamus offers new opportunities to study this region in vivo in healthy populations and in those with psychiatric and neurological disorders. Significance StatementThe midline thalamus is essential for flexible cognition, decision making, and stress regulation. Abnormal development, dysfunction, and neurodegeneration of the midline thalamus is thought to be a critical pathology in several psychiatric and neurological disorders. Yet, little is known about the role of the human midline thalamus. Here we solve the problem of localization in vivo by using probabilistic tractography and data driven clustering (k-means), a method capable of capitalizing on known connectivity in non-human animal tracer studies. Localizing the midline thalamus based on its connectivity patterns provides a useful tool for future functional and structural human MRI studies to investigate clinical implications of the midline thalamus in diseases such as Alzheimers and schizophrenia.

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bioRxiv2022

Hippocampal Volume, Neurite Density and Trace Eye-Blink Conditioning in Young Children

The current study examined the relations between hippocampal structure (e.g., volume and neurite density) and performance on a trace eye blink conditioning (EBC) task in young children. Our first aim assessed whether individual differences in hippocampal volume were associated with trace EBC performance, using both percent Conditioned Responses (% CR) and CR onset latency or the average latency (ms) at which the child started their blink, as measures of hippocampal-dependent associative learning. Our second aim evaluated whether individual differences in hippocampal neurite density were associated with EBC performance using the same outcome measures. Typically developing 4- to 6-year-olds (N = 31; 14 girls; Mage = 5.67; SDage = 0.89) completed T1 and diffusion-weighted MRI scans and a 15-minute trace eyeblink conditioning task outside of the scanner. % CR and CR onset latency were computed across all tone-puff and tone-alone trials. While hippocampal volume was not associated with any of our EBC measures, greater hippocampal neurite density bilaterally, was associated with later CR onset. In other words, children with greater left and right hippocampal neurite density blinked closer to the US (i.e., air puff) than children with less hippocampal neurite density, indicating that structural changes in the hippocampus assisted in the accurate timing of conditioned responses.

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bioRxiv2020

Differential effects of emotional valence on mnemonic performance with greater hippocampal maturity

The hippocampal formation (HF) facilitates the creation of declarative memories, with subfields providing unique contributions to the discriminability and generalizability of events. The HF itself and its connections with other structures exhibit a protracted development. Maturational differences across subfields facilitate a shift towards memory specificity, with peri-puberty sitting at the inflection point. Peri-puberty also happens to be a sensitive period in the development of anxiety disorders. Taken together, we believe HF development is critical to negative overgeneralization, a common feature of anxiety disorders. To investigate the role of the HF in behavioral discrimination and generalization we examined the relation between behavior and cross-sectional indices of HF maturity derived from subfield volume. Participants aged 9-14 years, recruited from clinical and community sources, performed a recognition task with emotionally valent (positive, negative) and neutral images. T1-weighted and diffusion-weighted structural scans were collected. Partial least squares correlations were used to derive a singular metric of maturity for both HF volume and structural connectivity. We found our volumetric HF maturity index was positively associated with discrimination for neutral images and generalization for negative images. Hippocampal-medial prefrontal cortex structural connectivity maturity metric evidenced a similar trend with behavior as the HF volumetric approach. These findings are important because they reflect a novel developmentally related balance between discrimination and generalization behavior supported by the hippocampus and its connections with other regions. Maturational shifts in this balance may contribute to negative overgeneralization, a common feature of anxiety disorders that escalates during the same developmental window. Significance StatementThe hippocampal formation (HF) facilitates declarative memory specificity and is composed of subfields whose development during adolescence overlaps with the onset of anxiety disorders. Aberrations in mechanisms governing memory specificity may contribute to negative overgeneralization in anxious youth. Participants completed an emotional memory discrimination task while in the scanner. Using a multivariate maturity metric based on subfield volume we found individuals with more "mature" HF were better at differentiating similar neutral images and more likely to generalize similar negative images. These findings are important because they capture a novel developmental mechanism related to the balance between discrimination and generalization. Shifts in this balance, may contribute to negative overgeneralization, a common feature of anxiety disorders.

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bioRxiv2020

Common default mode network dysfunction across psychopathologies: A neuroimaging meta-analysis of the n-back working memory paradigm

The National Institute of Mental Healths (NIMH) Research Domain Criteria (RDoC) classifies disorders based on shared aspects of behavioral and neurobiological dysfunction. One common behavioral deficit observed in various psychopathologies, namely ADHD, addiction, bipolar disorder, depression, and schizophrenia, is a deficit in working memory performance. However, it is not known to what extent, if any, these disorders share common neurobiological abnormalities that contribute to decrements in performance. The goal of the present study was to examine convergence and divergence of working memory networks across psychopathologies. We used the Activation Likelihood Estimate (ALE) meta-analytic technique to collapse prior data obtained from published studies using the n-back working memory paradigm in individuals with a DSM-criteria diagnosis of the aforementioned disorders. These studies examined areas in the brain that showed increases in activity as a function of working memory-related load compared to a baseline condition, both within subjects and between healthy individuals and those with psychiatric disorder. A meta-analysis of 281 foci covering 81 experiments and 2,629 participants found significant convergence of hyperactivity in medial prefrontal cortex (mPFC) for DSM-diagnosed individuals compared to healthy controls. Foci from ADHD, addiction, bipolar disorder, schizophrenia, and major depression studies contributed to the formation of this cluster. These results provide evidence that default-mode intrusion may constitute a shared seed of dysregulation across multiple psychopathologies, ultimately resulting in poorer working memory performance.

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bioRxiv2020

Negative Overgeneralization is Associated with Pattern Completion in Peripubertal Youth

BACKGROUNDThis study examines neural mechanisms of negative overgeneralization in peri-puberty to identify potential contributors to escalating anxiety during this sensitive period. Theories suggest that weak pattern separation (a neurocomputational process by which overlapping representations are made distinct, indexed by DG/CA3 hippocampal subfields) is a major contributor to negative overgeneralization. We alternatively propose that neuromaturation related to generalization and anxiety-related pathology in peri-puberty predicts contributions from strong pattern completion (a partial match of cues reinstates stored representations, indexed by CA1) and related modulatory mechanisms (amygdala, medial prefrontal cortices [mPFC]). METHODSYouth (N=34, 9-14 years) recruited from community and clinic settings participated in an emotional mnemonic similarity task while undergoing MRI. At Study, participants indicated the valence of images; at Test, participants made an old/new recognition memory judgment. Critical lure stimuli, that were similar but not the same as images from Study, were presented at Test, and errors ("false alarms") to negative relative to neutral stimuli reflected negative overgeneralization. Univariate, multivariate, and functional connectivity analyses were performed to evaluate mechanisms of negative overgeneralization. RESULTSNegative overgeneralization was related to greater and more similar patterns of activation in CA1 and both dorsal and ventral mPFC for negative relative to neutral stimuli. At Study, amygdala increased functional coupling with CA1 and dorsal mPFC during negative items that were later generalized. CONCLUSIONSNegative overgeneralization is rooted in amygdala and mPFC modulation at encoding and pattern completion at retrieval. These mechanisms could prove to reflect etiological roots of anxiety that precede symptom escalation across adolescence.

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bioRxiv2019

Prospective hippocampus and putamen activations support conditional memory-guided behavior

Memory of past events, in addition to contextual cues, influence conditional behavior. The hippocampus (HPC), medial prefrontal cortex (mPFC), and striatum are important contributors to this process. The mechanisms by which these regions facilitate conditional memory-guided behavior remains unclear. We developed a conditional-associative task in which the correct conditional choice was dependent on the preceding stimulus. We examined activations related to successful conditional behavior and the timing of their contributions. Two distinct networks emerged: (1) a prospective system consisting of the HPC, putamen, mPFC, and other cortical regions, which exhibited increased activation preceding successful conditional decisions; and (2) a concurrent system supported by the caudate, dlPFC, and additional cortical structures that engaged during execution of correct conditional choices. Our findings demonstrate two distinct neurobiological circuits through which memory prospectively biases conditional memory-guided decisions, as well as influence the execution of current choices.

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bioRxiv2018

Hippocampus activations reflect temporal contexts while medial prefrontal cortex activations reflect ordinal positions during sequence memory in humans

Remembering sequences of events defines episodic memory, but retrieval can be driven by both ordinality and temporal contexts. Whether these modes of retrieval operate at the same time or not remains unclear. Theoretically, medial prefrontal cortex (mPFC) confers ordinality, while the hippocampus (HC) associates events in gradually changing temporal contexts. Here, we looked for evidence of each with BOLD fMRI in a sequence task that taxes both retrieval modes. To test ordinal modes, items were transferred between sequences but retained their position (e.g., AB3). Ordinal modes activated mPFC, but not HC. To test temporal contexts, we examined items that skipped ahead across lag distances (e.g., ABD). HC, but not mPFC, tracked temporal contexts. There was a mPFC and HC by retrieval mode interaction. These current results suggest that the mPFC and HC are concurrently engaged in different retrieval modes in support of remembering when an event occurred. Significance StatementMemory for sequences of events is a defining aspect of everyday episodic memory allowing our brain to separate unique experiences that otherwise have overlapping sensory and spatial content. Sequence memory is impaired in typical aging and in disorders such as Alzheimers disease. The results of the current study provide new evidence that two retrieval modes concurrently arise during sequence memory, and they have distinct neural correlates. The medial prefrontal cortex contributes to an ordinal retrieval mode, while at the same time, the hippocampus contributes a gradually-changing temporal context mode of retrieval. These data shed new light on why typical episodic memory requires both the medial prefrontal cortex and the hippocampus, and suggests a functional dissociation between the medial prefrontal cortex and hippocampus across these modes of retrieval.

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