Biology subjects

Herrington, T. M.

Publications and source records attributed to Herrington, T. M..

3 recordsLinked to original sources

bioRxiv2026

Acute stress reorganizes pregenual cingulate and subthalamic coupling to approach-avoidance decisions in remitted depression

Major depressive disorder (MDD) is highly recurrent, and psychosocial stress is a central precipitant of relapses. Daily choices require weighing potential rewards against costs, a process disrupted in MDD that may contribute to relapse. Here, we tested whether a psychosocial stressor affects neural and computational mechanisms underlying approach-avoidance decision making in individuals with remitted MDD (rMDD, N=50) and healthy controls (N=74), prioritizing pregenual anterior cingulate cortex (pgACC) and subthalamic nucleus (STN) due to their roles in value integration and decision caution, respectively. Participants performed a dynamic approach-avoidance conflict task with fMRI before and after psychosocial stress. Hierarchical Bayesian drift-diffusion modeling evaluated whether stress modulated computational and neural mechanisms, with trial-wise pgACC and STN activity entered as neural regressors on evidence accumulation and decision threshold, respectively. Before stress, groups did not differ in any decision parameter, but pgACC activity contributed to evidence accumulation toward avoidance in controls only. After stress, rMDD showed larger increases than controls in the impact of both reward and aversiveness on accumulation toward approach and avoidance, respectively, predominantly for net-aversive offers. Furthermore, in rMDD, stress rendered both approach and avoidance decisions more sensitive to pgACC activity, and STN activity was more strongly coupled to the decision threshold than in controls. Finally, stress-induced increases in reward sensitivity in rMDD predicted one-year course of depressive symptoms. Thus, MDD remission is not characterized by a generalized blunting of decision-making, but by a latent circuit difference that acute stress reorganizes and predicts future symptoms.

neuroscience↗

bioRxiv2025

Independent Basal Ganglia Neural Populations Encode Speech Production and Ambient-Noise Levels

The function of the basal ganglia (BG), a set of nuclei deep in the brain, is still under debate despite their clinical relevance. Lines of evidence from non-human primate and human experiments suggest that one key causal contribution of the adult primate BG is invigoration of movement according to environmental and energetic constraints. Previous studies have come to this conclusion using primarily limb motor control tasks. We hypothesized BG are also important for invigorating the respiratory, vocal, and articulatory motor systems during speech production. To test this, we used a rare clinical opportunity to record local field potentials-broadband gamma activity (LFP-BGA) and single unit (SU) activity from human basal ganglia during deep brain stimulation implant surgeries. Participants repeated sentences aloud in the operating room. We modulated environmental and energetic constraints of speech production by inducing the Lombard Effect, wherein people reliably increase the intensity of their voice in the presence of background noise. Participants increased voice intensity, pitch, vowel space size, and respiratory depth in the presence of ambient noise. [~]40% of LFP and SU sites were modulated by speech production. Comparing globus pallidus (GP) LFP-BGA, herein reported for the first time during speech, to subthalamic nucleus (STN) LFP-BGA revealed GP activated after STN. STN was more coincident with the speech preparatory period and GP more coincident with speech onset, suggesting differential roles in speech production. We found only weak evidence that STN or GP activity encodes the level of produced speech intensity. Instead, we found that LFP-BGA and SU-FR robustly track the ambient background noise levels. Linear decoding from SU-firing rate revealed we could infer the background noise levels with >75% accuracy in any given time point in the trial, including baseline. Importantly, the ambient-noise-modulated sites were an independent population from speech-modulated sites. We conclude that human BG encode the energetic constraints of communication. We theorize that the code is leveraged in downstream BG-cortical loop nodes to invigorate speech oro-motor gestures and co-speech manual limb gestures, both of which respond to ambient noise levels to maintain high-fidelity communication.

neuroscience↗

bioRxiv2018

Lead-DBS v2: Toward a comprehensive pipeline for deep brain stimulation imaging

Deep brain stimulation (DBS) is a highly efficacious treatment option for movement disorders and a growing number of other indications are investigated in clinical trials. To ensure optimal treatment outcome, exact electrode placement is required. Moreover, to analyze the relationship between electrode location and clinical results, a precise reconstruction of electrode placement is required, posing specific challenges to the field of neuroimaging. Since 2014 the open source toolbox Lead-DBS is available, which aims at facilitating this process. The tool has since become a popular platform for DBS imaging. With support of a broad community of researchers worldwide, methods have been continuously updated and complemented by new tools for tasks such as multispectral nonlinear registration, structural / functional connectivity analyses, brain shift correction, reconstruction of microelectrode recordings and orientation detection of segmented DBS leads. The rapid development and emergence of these methods in DBS data analysis require us to revisit and revise the pipelines introduced in the original methods publication. Here we demonstrate the updated DBS and connectome pipelines of Lead-DBS using a single patient example with state-of-the-art high-field imaging as well as a retrospective cohort of patients scanned in a typical clinical setting at 1.5T. Imaging data of the 3T example patient is co-registered using five algorithms and nonlinearly warped into template space using ten approaches for comparative purposes. After reconstruction of DBS electrodes (which is possible using three methods and a specific refinement tool), the volume of tissue activated is calculated for two DBS settings using four distinct models and various parameters. Finally, four whole-brain tractography algorithms are applied to the patients preoperative diffusion MRI data and structural as well as functional connectivity between the stimulation volume and other brain areas are estimated using a total of eight approaches and datasets. In addition, we demonstrate impact of selected preprocessing strategies on the retrospective sample of 51 PD patients. We compare the amount of variance in clinical improvement that can be explained by the computer model depending on the method of choice.\n\nThis work represents a multi-institutional collaborative effort to develop a comprehensive, open source pipeline for DBS imaging and connectomics, which has already empowered several studies, and may facilitate a variety of future studies in the field.

neuroscience↗