Biology subjects

Coenen, V. A.

Publications and source records attributed to Coenen, V. A..

5 recordsLinked to original sources

bioRxiv2026

Spatiotemporal characterization of corticolimbic dopamine and noradrenaline signaling and affective state modulation by mfb stimulation

Background: Deep brain stimulation of the medial forebrain bundle (mfb DBS) is a promising intervention for psychiatric disorders, but the neurochemical mechanisms underlying its effects remain incompletely understood. Methods: In adult Sprague Dawley rats, fiber photometry was used to monitor mfb-DBS evoked dopamine (DA) and noradrenaline (NA)-signaling in the nucleus accumbens (NAc) and prefrontal cortex (PFC), following different stimulation patterns, laterality conditions, and prolonged stimulation paradigms. Ultrasonic vocalizations (USVs) were recorded in parallel as a behavioral measure. Results: Bilateral stimulation robustly increased catecholaminergic signals relative to sham in both NAc and PFC. The magnitude and temporal profile of these responses depended more on stimulation pattern rather than on laterality, with long pulse-width generally evoking the largest responses and laterality producing no significant differences across the four recording groups. During 10 min bilateral stimulation, catecholaminergic signals increased rapidly and remained elevated throughout stimulation, with the clearest sustained effect observed in NAc DA. mfb DBS also increased USV calls and peak frequencies, whereas these behavioral changes showed no consistent region-specific correlation with catecholaminergic signal magnitude. Conclusions: mfb DBS recruits catecholaminergic signaling in a parameter-dependent and region specific manner and increases positive-affective USV output. These findings identify temporal patterning as an important determinant of downstream circuit engagement, whereas the relationship between acute USV responses and regional catecholamine signaling appears more complex.

neuroscience↗

bioRxiv2026

An electronically steerable epidural ultrasound interface for deep brain neuromodulation in freely moving rats

Low-intensity focused ultrasound (LI-FUS) clinical trials exploit either the neural activity modulating, or the blood-brain barrier opening, capacity of this stimulation modality. However, LI-FUS currently is applied only transcranially which means that it is conducive only for episodic and intermittent stimulation, although, clinical data shows that in numerous neurological and psychiatric applications, chronic and continuous stimulation is required for long-term, stable therapeutic effect. The paper presents experimental data on a novel and innovative approach describing an implantable, epidural focus ultrasound (eFUS) device, designed for continuous, chronic and multi-site steerable neuromodulation. The miniaturized eFUS device consists of a two-dimensional piezoelectric transducer array directly integrated onto a custom ASIC, specifically engineered for proof-of-principle neuromodulation studies in the rat brain. The system generates electronically steerable focused ultrasound with software-defined focal coordinates, sufficient to stimulate neuronal activity in deep brain structures. In vitro acoustic characterization confirmed accurate beam steering and focusing, while in vivo validation demonstrated reliable stimulation of a deep subcortical target with measurable physiological effects. eFUS-mediated targeting of the ventral tegmental area in awake and freely moving rats produced increase in dopamine release in the nucleus accumbens as confirmed using fiber photometry recordings. Post-mortem histological analysis of the target regions showed the absence of inflammatory markers, although the epidural placement of the eFUS device was associated with mild tissue damage. Overall, the study provides in vitro data demonstrating the energy efficiency, and steerability of the technology, and in vivo physiological evidence of neuromodulatory ability of a deep, subcortical brain structure.

neuroscience↗

bioRxiv2026

In Search for Biomarkers Reflecting Neural Implant-Induced Tissue Response Dynamics

Extracellular matrix (ECM) remodeling is a fundamental determinant of neural tissue repair and implant integration, yet its conserved regulatory architecture remains undefined. While transcriptomic alterations following neural injury and implantation have been described, the ECM-centered programs that unify traumatic injury and neural implant responses remain unclear. Here, integrative systems-level transcriptomic analysis identifies a dominant and conserved ECM regulatory axis linking traumatic brain injury (BI), spinal cord injury (SCI), and neural implant-induced injury. By integrating transcriptomic datasets from brain and spinal cord injury models using weighted gene co-expression network analysis (WGCNA), six conserved ECM-associated gene modules are identified, with hyaluronan (HA)-centered networks emerging as the dominant and conserved regulatory axis across both injury types. Modules enriched for low-molecular-weight HA (LMW-HA) are linked to Toll-like receptor signaling and pro-inflammatory cytokine expression, whereas high-molecular-weight HA (HMW-HA)-associated modules correlate with Cd44 signaling, tissue stabilization and repair. Furthermore, independent validation in thin-film intracortical microelectrode datasets confirms robust activation of HA damage-associated molecular pattern (HA-DAMP) signaling following implantation, with 9/10 injury-derived modules preserved and 88% of transcripts exhibiting resolving temporal dynamics. These findings indicate that neural implants engage conserved trauma-associated ECM programs rather than a conventional foreign-body response, highlighting HA-related metabolisms. Given that HA fragments and HA-modifying enzymes are detectable in cerebrospinal fluid and peripheral circulation, HA-associated signatures may serve as minimally invasive biomarkers of neural injury and implant biocompatibility, enabling longitudinal monitoring and informing next-generation neural interface design.

bioengineering↗

bioRxiv2026

Episodic memory consolidation by reactivation of human concept neurons during sleep reflects contents, not sequence of events

How do our brains manage to store our everyday experiences into memory? Neurons in the human temporal lobe that respond to the concept of an individual person or object have been shown to provide the semantic building blocks for episodic memory. Recording from 1433 neurons in neurosurgical patients who learned a story involving specific concepts, we found reactivation of neurons representing these concepts during slow-wave sleep after learning. Concept neurons were conjointly reactivated, particularly during sharp-wave ripples, with time lags suitable for synaptic modification. However, the temporal sequence of reactivation did not reflect the sequence of concepts in the learned story. Unlike rodent place cells, which can acquire preferred firing locations during exploration of new environments according to their pre-existing preferred sequence of activation, human concept neurons are tuned to specific semantic contents before learning starts. Consequently, pre-existing firing sequences correlate with consecutive place fields in rodents, but not with sequences of events in human experience. Thus, in contrast to reactivation of rodent place cells, reactivation of human concept cells does not reflect sequences of events in human experience.

neuroscience↗

bioRxiv2017

Global and Local Dynamics of High-Gamma Activity Underlying Error Processing in the Human Brain Revealed by Noninvasive and Intracranial EEG

Error detection in motor behavior is a fundamental cognitive function heavily relying on cortical information processing. Neural activity in the high-gamma frequency band (HGB) closely reflects such local cortical processing, but little is known about its role in error processing, particularly in the healthy human brain. Here we characterize the error-related response of the human brain based on data obtained with noninvasive EEG optimized for HGB mapping in 31 healthy subjects (15 females, 16 males), and additional intracranial EEG data from 9 epilepsy patients (4 females, 5 males). Our findings reveal a comprehensive picture of the global and local dynamics of error-related HGB activity in the human brain. On the global level as reflected in the noninvasive EEG, the error-related response started with an early component dominated by anterior brain regions, followed by a shift to parietal regions, and a subsequent phase characterized by sustained parietal HGB activity. This phase lasted for more than 1 s after the error onset. On the local level reflected in the intracranial EEG, a cascade of both transient and sustained error-related responses involved an even more extended network, spanning beyond frontal and parietal regions to the insula and the hippocampus. HGB mapping appeared especially well suited to investigate late, sustained components of the error response, possibly linked to downstream functional stages such as error-related learning and behavioral adaptation. Our findings establish the basic spatio-temporal properties of HGB activity as a neural correlate of error processing, complementing traditional error-related potential studies.\n\nSignificance StatementThere is great interest to understand how the human brain reacts to errors in goal-directed behavior. An important index of cortical and subcortical information processing is fast oscillatory brain activity, particularly in the high-gamma band (above 50 Hz). Here we show that it is possible to detect signatures of errors in event-related high-gamma responses with noninvasive techniques, characterize these responses comprehensively, and validate the EEG procedure for the detection of such signals. In addition, we demonstrate the added value of intracranial recordings pinpointing the fine-grained spatio-temporal patterns in error-related brain networks. We anticipate that the optimized noninvasive EEG techniques as described here will be helpful in many areas of cognitive neuroscience where fast oscillatory brain activity is of interest.

neuroscience↗