Biology subjects

Fineberg, S. K.

Publications and source records attributed to Fineberg, S. K..

4 recordsLinked to original sources

bioRxiv2025

Ketamine Alters Tuning of Neural and Behavioral Spatial Working Memory Precision

Deficits in working memory (WM) are a hallmark of neuropsy-chiatric disorders such as schizophrenia, yet their neurobiological basis remains poorly understood. Glutamate N-methyl-D-aspartate receptors (NMDARs) are critical for spatial WM (sWM), with NMDAR antagonist ketamine known to attenuate task-evoked activation and reduce sWM accuracy. Cortical microcircuit models hypothesize that NMDAR antagonism impairs sWM by broadening neural spatial tuning, but this mechanism has not been directly tested in humans. Using a pharmacological fMRI approach, we showed how ketamine broadened neural spatial tuning, attenuated activation across visual, parietal, and frontal areas, and worsened sWM performance in healthy humans. Ketamine-induced changes in tuning were more consistent across individuals and brain regions than changes in overall activation and correlated with individual differences in sWM performance. These findings provide empirical evidence linking NMDAR antagonism to disruptions in cortical microcircuit dynamics, the resulting neural tuning alterations, and sWM impairments, advancing frameworks for therapeutic development.

neuroscience↗

bioRxiv2023

Ketamine Effects on Energy Metabolism, Functional Connectivity and Working Memory in Healthy Humans

Working memory (WM) is a crucial resource for temporary memory storage and the guiding of ongoing behavior. N-methyl-D-aspartate glutamate receptors (NMDARs) are thought to support the neural underpinnings of WM. Ketamine is an NMDAR antagonist that has cognitive and behavioral effects at subanesthetic doses. To shed light on subanesthetic ketamine effects on brain function, we employed a multimodal imaging design, combining gas-free calibrated functional magnetic resonance imaging (fMRI) measurement of oxidative metabolism (CMRO2), resting-state cortical functional connectivity assessed with fMRI, and WM-related fMRI. Healthy subjects participated in two scan sessions in a randomized, double-blind, placebo-controlled design. Ketamine increased CMRO2 and cerebral blood flow (CBF) in prefrontal cortex (PFC) and other cortical regions. However, resting-state cortical functional connectivity was not affected. Ketamine did not alter CBF-CMRO2 coupling brain-wide. Higher levels of basal CMRO2 were associated with lower task-related PFC activation and WM accuracy impairment under both saline and ketamine conditions. These observations suggest that CMRO2 and resting-state functional connectivity index distinct dimensions of neural activity. Ketamines impairment of WM-related neural activity and performance appears to be related to its ability to produce cortical metabolic activation. This work illustrates the utility of direct measurement of CMRO2 via calibrated fMRI in studies of drugs that potentially affect neurovascular and neurometabolic coupling.

neuroscience↗

bioRxiv2019

Induced illusory body ownership in Borderline Personality Disorder

BackgroundOne aspect of selfhood that may have relevance for Borderline Personality Disorder (BPD) is variation in sense of body ownership. We employed the rubber hand illusion (RHI) to manipulate sense of body ownership in BPD. We extended previous research on illusory body ownership in BPD by testing: 1) two illusion conditions: asynchronous & synchronous stimulation, 2) relationship between Illusion experience and BPD symptoms, and 3) relationship between illusion experience and maladaptive personality traits.\n\nMethodsWe measured illusion strength (questionnaire responses), proprioceptive drift (perceived shift in physical hand position), BPD symptoms (DIB-R score), and maladaptive personality traits (PID-5) in 24 BPD and 21 control participants.\n\nResultsFor subjective illusion strength, we found a main effect of group (BPD > HC, F = 11.94 p = 0.001), and condition (synchronous > asynchronous, F(1,43) = 22.80, p < 0.001). There was a group x condition interaction for proprioceptive drift (F(1,43) = 6.48, p = 0.015) such that people with BPD maintained illusion susceptibility in the asynchronous condition. Borderline symptom severity correlated with illusion strength within the BPD group, and this effect was specific to affective symptoms (r = 0.48, p < 0.01). Across all participants, trait psychoticism correlated with illusion strength (r = 0.44, p < 0.01).\n\nConclusionPeople with BPD are more susceptible to illusory body ownership than controls. This is consistent with the clinical literature describing aberrant physical and emotional experience of self in BPD. A predictive-coding framework holds promise to develop testable mechanistic hypotheses for disrupted bodily self in BPD.\n\nHighlightsO_LIThe rubber hand illusion (RHI) allows measurement of self-disturbance.\nC_LIO_LIPeople with BPD had greater illusion susceptibility and this correlated with affective symptoms.\nC_LIO_LIInteroception stabilizes representations of body ownership, and is impaired in BPD.\nC_LIO_LIIllusion strength correlates with psychotic traits across levels of psychopathology.\nC_LIO_LIPredictive coding frameworks can probe mechanisms of impaired body ownership in psychopathology.\nC_LI

neuroscience↗

bioRxiv2018

Differential valuation and learning from social and non-social cues in Borderline Personality Disorder

BackgroundVolatile interpersonal relationships are a core feature of Borderline Personality Disorder (BPD), and lead to devastating disruption of patients personal and professional lives. Quantitative models of social decision making and learning hold promise for defining the underlying mechanisms of this problem. In this study, we tested BPD and control subject weighting of social versus non-social information, and their learning about choices under stable and volatile conditions. We compared behavior using quantitative models.\n\nMethodsSubjects (n=20 BPD, n=23 control) played an extended reward learning task with a partner (confederate) that requires learning about non-social and social cue reward probability (The Social Valuation Task). Task experience was measured using language metrics: explicit emotions/beliefs, talk about the confederate, and implicit distress (using the previously established marker self-referentiality). Subjects weighting of social and non-social cues was tested in mixed-effects regression models. Subjects learning rates under stable and volatile conditions were modelled (Rescorla-Wagner approach) and group x condition interactions tested.\n\nResultsCompared to controls, BPD subject debriefings included more mentions of the confederate and less distress language. BPD subjects also weighted social cues more heavily, but had blunted learning responses to (non-social and social) volatility.\n\nConclusionsThis is the first report of patient behavior in the Social Valuation Task. The results suggest that BPD subjects expect higher volatility than do controls. These findings lay the groundwork for a neuro-computational dissection of social and non-social belief updating in BPD, which holds promise for the development of novel clinical interventions that more directly target pathophysiology.

neuroscience↗