Biology subjects

Horn, A.

Publications and source records attributed to Horn, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Ultrasensitive detection of neuronal DNA using genome-wide non-CG methylation patterns

Methylation-based liquid biopsies can identify the tissue origins of circulating cell-free DNA (cfDNA). A major constraint on the sensitivity of these assays is the limited number of cell-type-specific CpG markers. Here we exploit the high abundance of non-CpG (CpH) methylation in neurons to enable ultrasensitive detection of neuronal DNA. We show that neurons carry 100-fold higher CpH methylation than other tissues, in which apparent CpH methylation largely reflects experimental artifacts. Using a computational criterion to identify cfDNA molecules carrying clusters of methylated CpA sites, we detect neuronal DNA at proportions as low as 20 parts per million. Analysis of 231 samples from 163 individuals revealed minimal neuronal cfDNA in the plasma of healthy subjects; elevated levels in patients with measles or acute neurological conditions; strikingly high levels in brain-dead donors, indicating extensive ongoing neuronal death; and the highest levels in the cerebrospinal fluid of patients in a neurological intensive care unit. These findings establish genome-wide, fragment-level analysis of non-CpG methylation as an ultrasensitive approach for blood-based monitoring of brain injury and disease.

genomics↗

bioRxiv2026

The SWAN atlas: an open multimodal resource combining neuroimaging and high-resolution histology of the human brain in stereotactic space

Precise localization of human brain regions is critical in clinical practice and population neuroimaging, particularly in stereotactic functional neurosurgery, where small targeting errors may lead to treatment failure. Although MRI provides in vivo and postmortem brain parcellation, histology offers complementary mesoscopic and microscopic information. A major limitation of histological atlases for clinical use is accurate coregistration with in vivo imaging, since tissue processing introduces deformation. To reduce this problem, we sectioned an entire human brain using high-thickness slices, which are less prone to slice-level deformation. Histological sections were registered to the brain's own MRI and normalized to standard stereotactic space through a multistep transform chain. Users can apply MRI-to-MRI registration to transform the atlas into patient space and vice versa, with further nonlinear refinement using SwanWarp or WarpDrive tools. Segmentations and software are being prepared for open distribution. This resource may empower both clinical neurosurgical research and the broader neuroimaging field at large.

neuroscience↗

bioRxiv2026

Fibroblast response to burn injury in larval zebrafish mirrors developmental maturation and is inhibited by infiltrating neutrophils

Fibroblasts mediate tissue repair after damage, but aberrant fibroblast behavior in response to injury can result in impaired wound healing. Severe burn injury often results in tissue scarring, but the underlying mechanisms by which fibroblasts respond to burn injury and the role of inflammation in fibrosis are not well understood. Here we developed fluorescent reporters of collagen expressing mesenchymal cells enabling real time imaging of fibroblasts during homeostatic development and in response to burn injury using larval zebrafish. We find that fibroblasts derived from the mesenchyme respond to burn injury by engaging in a maturation process, characterized by the expression of vimentin, which is reminiscent of larval development. In burned tissue, fibroblast maturation is perturbed by prolonged neutrophil infiltration, resulting in disorganized extracellular matrix (ECM) and delayed ECM remodeling, which can be rescued by neutrophil depletion. This work adds to our understanding of fibroblast development in zebrafish and shows that collagen expressing mesenchymal cells regulate ECM remodeling in coordination with immune cells during burn wound healing. Summary StatementVimentin-positive fibroblasts are required for normal wound healing in larval zebrafish, but the presence of inflammatory neutrophils after burn injury impairs fibroblast maturation and collagen remodeling.

Developmental Biology↗

bioRxiv2026

Data sources shape species niches: integrating citizen science and state agency data expands habitat suitability models and improves biological invasion predictions

Species distribution models (SDMs) are widely used to support risk assessment for invasive non-native plant species (INNPS), but their performance is constrained by the coverage of occurrence data. Combining occurrences from citizen science (CS) platforms with data from structured state agency (StAg) monitoring provides unique advantages, yet they are rarely integrated. Here, we systematically compare how CS, StAg, and combined (COM) occurrence data influence the inferred environmental niches, predictive performance, and spatial applicability of SDMs for three widespread INNPS (A. altissima, H. mantegazzianum, I. glandulifera) in central Germany. We quantified niche overlap between datasets using PCA and Schoeners D and applied a hierarchical SDM utilizing boosted regression trees, while the Area of Applicability (AOA) was assessed to identify monitoring gaps. CS data were strongly biased toward lower-elevation, urbanized environments, whereas StAg data captured higher-elevation, remote habitats, particularly along watercourses. Niche overlap reflected both invasion stage and habitat preferences: A. altissima, a species that is spreading, showed the lowest overlap. H. mantegazzianum, associated with linear habitats like watercourses and infrastructure, exhibited intermediate overlap, while I. glandulifera, a widespread species, displayed the highest overlap. Overall, combined models achieved the highest predictive performance (AUC: 0.85, TSS: 0.58), reduced uncertainty along environmental gradients and produced more ecologically plausible suitability patterns. AOA analysis revealed high applicability ([≥]59%) across data sources and species, with COM models consistently reducing extrapolation uncertainty. Our findings highlight that integrating CS and StAg data reduces spatial biases and enhances SDM robustness, which is vital to improve INNPS risk assessments and management. HighlightsO_LICitizen science and state agency data capture distinct environmental spaces. C_LIO_LIOverlap between data sources is related to invasion stage and habitat preference. C_LIO_LICombined data improves invasive species niche representation and model accuracy. C_LIO_LIAOA analysis reveals monitoring gaps, especially in remote and high-elevation areas. C_LI

ecology↗

bioRxiv2026

The methodological foundations of lesion network mapping remain sound

Lesion network mapping (LNM) and related techniques have been used in over 200 studies, primarily to test whether anatomically distributed lesions that cause the same symptom fall within a common brain network. A recent article1 challenges the specificity and validity of this technique, suggesting that lesion network maps primarily reflect intrinsic properties of the normative connectome rather than lesion-symptom relationships. However, the data and procedures in van den Heuvel et al. do not reflect those used in most LNM studies. Further, the main conclusions were based on similarity between maps, but similarity does not imply the absence of meaningful differences. In contrast, LNM provides evidence for meaningful differences using specificity testing. Exemplary analyses of 1090 lesion locations from 34 prior LNM studies do not support van den Heuvels concerns and confirm the lesion-deficit specificity of LNM. While we encourage further methodological investigation, the analyses of van den Heuvel et al. do not invalidate prior LNM findings or future applications.

neuroscience↗

bioRxiv2026

A precise atlas of the human subcortex

Clinical interventions and neuroimaging in the subcortex require anatomical definitions that exceed the resolution and anatomical detail of currently available deformable brain atlases. Here, we introduce a high-resolution human brain atlas comprising 95 manually segmented grey and white matter structures as well as 82 white matter tracts compiled from a multitude of resources including ex-vivo MRI, histology, fibre dissections, and neuroanatomy textbooks. The atlas is defined at an isotropic resolution of 100 m and can be precisely deformed to individual subject brain anatomy. By providing precise definitions of both grey and white matter structures within and around the basal ganglia, thalamus, subthalamus, midbrain and cerebellum, the atlas provides a foundational resource for stereotactic surgery and subcortical brain imaging research, as well as for development of next-generation neuromodulation strategies.

neuroscience↗

bioRxiv2025

Functional fractionation of large-scale brain networks in the human subcortex

Brain network mapping plays a crucial role in advancing our understanding of human brain organization and the neuroanatomic foundations of cognition. Historically, the identification of large-scale brain networks has focused on the cerebral cortex. Some cortical networks have been fractionated into subnetworks, yielding valuable insights into their domain-specific cognitive functions. In contrast, functional mapping of large-scale brain networks within subcortical regions remains an emerging and challenging field, hindered by a low signal-to-noise ratio in subcortical functional MRI data and an inability to distinguish networks with substantial spatiotemporal overlap. In this study, we fractionated and identified fifteen spatially overlapped and temporally correlated subnetworks, which can be categorized into four large-scale brain networks. The subcortical functional connectivity patterns of these subnetworks exhibited distinct, yet overlapping, spatial configurations, with widely connected hub nodes identified in the caudate, putamen, hippocampus, and thalamus. These subnetworks are highly reproducible across healthy human brains and provide normative functional atlases, which we release here as a resource for the academic community. As a proof-of-principle demonstration of how the atlases can be used to elucidate the pathophysiology of neuropsychiatric disorders, we show that the spatial patterns of the subnetworks predict the level of consciousness in patients with severe traumatic brain injury. These observations indicate a highly conserved and spatially overlapped subcortical functional architecture in the human brain, providing opportunities to elucidate pathophysiologic mechanisms and develop new neuromodulatory therapies for a broad spectrum of neuropsychiatric diseases.

neuroscience↗

bioRxiv2025

An Interactive Brain Atlas of Knowledge

Biomedical knowledge about the brain increases every day, with a rapidly growing number of scientific publications, datasets, and software tools. While this informational plethora is not merely comprehensible by human beings, recent developments in information science and computational linguistics aim to make this knowledge programmatically accessible by literature mining. However, integrating these semantic methods into neuroimaging standards remains insufficient, hindering researchers from unraveling their full potential. Therefore, we developed the semantic meta-analysis platform The Virtual Brain adapter of semantics (TVBase) that projects biomedical knowledge preserved in over 36 million scientific articles onto a 3D standardized brain. The literature-mining platform SCAIView was used to extract ontologically defined biomedical entities and their associations with brain anatomy from the PubMed database. By querying a specific concept, the association strength with each anatomical term was calculated using entropy. To project the data onto a standardized brain, we created a unique transformation matrix that links over 800 anatomical terms to voxel coordinates of a parcellated standard brain. This novel method of knowledge projection extracts region-specific information about biomedical concepts from the literature to support translational multi-scale approaches to computational neuroscience. The multi-purpose software framework TVBase is openly available as a Python library. It aims for hypothesis-free neuroimaging pattern interpretation, hypothesis generation, and applications in personalized medicine.

neuroscience↗

bioRxiv2025

Deciphering the Survival Strategies of the Entomopathogenic Nematode Steinernema carpocapsae Using Rapid Desiccation Assisted by Nanoparticle-Based Emulsion

Water retention is essential for survival under desiccating conditions, especially for entomopathogenic nematodes (EPNs) used as biocontrol agents. Foliar application of EPNs causes rapid desiccation (RD), severely reducing their survival and efficacy. We investigated the physiological and molecular responses of Steinernema carpocapsae to RD, delivered in a novel nanoparticle-stabilized emulsion to improve tolerance under variable humidity. We hypothesized that the formulation would enhance EPNs survival, by promoting early stress-responsive pathways and water-retention mechanisms. Formulated nematodes exhibited delayed water loss and increased survival under low humidity compared with non-formulated controls. The emulsion mitigated RD by enhanced hydration retention and reduced water loss, effects that were strongly associated with differential trehalose accumulation. In addition, maintenance of basement membrane integrity and cytoskeletal organization, emerged as a critical component of desiccation. These findings advance understanding of RD tolerance in EPNs and demonstrate how tailored formulation strategies can protect biocontrol agents under desiccation stress.

developmental biology↗

bioRxiv2025

Differential modulation of movement speed with state-dependent deep brain stimulation in Parkinson's disease

Subthalamic deep brain stimulation (STN-DBS) provides unprecedented spatiotemporal precision for the treatment of Parkinsons disease (PD), allowing for direct real-time state-specific adjustments. Inspired by findings from optogenetic stimulation in mice, we hypothesized that STN-DBS effects on movement speed depend on ongoing movement kinematics that patients exhibit during stimulation. To investigate this hypothesis, we implemented a motor state-dependent closed-loop neurostimulation algorithm, adapting DBS burst delivery to ongoing movement speed in 24 PD patients. We found a stronger anti-bradykinetic effect, raising movement speed to the level of healthy controls, when STN-DBS was applied during fast but not slow movements, while only stimulating 5% of overall movement time. To study underlying brain circuits and neurophysiological mechanisms, we investigated the behavioral effects with MRI connectomics and motor cortex electrocorticography. Finally, we demonstrate that machine learning-based brain signal decoding can be used to predict continuous movement speed for fully embedded state-dependent closed-loop algorithms. Our findings provide novel insights into the state-dependency of invasive neuromodulation, which could inspire advanced state-dependent neurostimulation algorithms for brain disorders.

neuroscience↗

bioRxiv2024

Time is encoded by methylation changes at clustered CpG sites

Age-dependent changes in DNA methylation allow chronological and biological age inference, but the underlying mechanisms remain unclear. Using ultra-deep sequencing of >300 blood samples from healthy individuals, we show that age-dependent DNA methylation changes are regional and occur at multiple adjacent CpG sites, either stochastically or in a coordinated block-like manner. Deep learning analysis of single-molecule patterns in two genomic loci achieved accurate age prediction with a median error of 1.46-1.7 years on held-out human blood samples, dramatically improving current epigenetic clocks. Factors such as gender, BMI, smoking and other measures of biological aging do not affect chronological age inference. Longitudinal 10-year samples revealed that early deviations from epigenetic age are maintained throughout life and subsequent changes faithfully record time. Lastly, the model inferred chronological age from as few as 50 DNA molecules, suggesting that age is encoded by individual cells. Overall, DNA methylation changes in clustered CpG sites illuminate the principles of time measurement by cells and tissues, and facilitate medical and forensic applications. O_FIG O_LINKSMALLFIG WIDTH=174 HEIGHT=200 SRC="FIGDIR/small/626674v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@c4dd52org.highwire.dtl.DTLVardef@9e6e62org.highwire.dtl.DTLVardef@160f8c3org.highwire.dtl.DTLVardef@16be7a3_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗

bioRxiv2024

A conserved in vivo burn wound infection model for diverse pathogenic fungi.

Secondary fungal infections represent a major complication following thermal injuries. However, the mechanisms of fungal colonization of burn tissue and how the host subsequently responds to fungi within this niche remain unclear. We have previously reported a zebrafish model of thermal injury that recapitulates many of the features of human burn wounds. Here, we characterize host-fungal interaction dynamics within the burn wound niche using two of the most common fungal pathogens isolated from burn injuries, Aspergillus fumigatus and Candida albicans. Both A. fumigatus and C. albicans colonize burned tissue in zebrafish larvae and induce a largely conserved innate immune response following colonization. Using drug-induced cell depletion strategies and transgenic zebrafish lines with impaired innate immune function, we found that macrophages control fungal burden while neutrophils primarily control invasive hyphal growth at the early stages of infection. However, we also found that loss of either immune cell can be compensated by the other at the later stages of infection, and that fish with both macrophage and neutrophil deficiencies show more invasive hyphal growth that is sustained throughout the infection process, suggesting redundancy in their antifungal activities. Finally, we demonstrate that C. albicans strains with increased {beta}(1,3)-glucan exposure are cleared faster from the burn wound, demonstrating a need for shielding this immunogenic cell wall epitope for successful fungal colonization of burn tissue. Together, our findings support the use of zebrafish larvae as a model to study host-fungal interaction dynamics within burn wounds. ImportanceSecondary fungal infections within burn wound injuries are a significant problem that delay wound healing and increase the risk of patient mortality. Currently, little is known about how fungi colonize and infect burn tissue or how the host responds to pathogen presence. In this report, we expand upon an existing thermal injury model using zebrafish larvae to begin to elucidate both the host immune response to fungal burn colonization and fungal mechanisms for persistence within burn tissue. We found that both Aspergillus fumigatus and Candida albicans, common fungal burn wound isolates, successfully colonize burn tissue and are effectively cleared in immunocompetent zebrafish by both macrophages and neutrophils. We also find that C. albicans mutants harboring mutations that impact their ability to evade host immune system recognition are cleared more readily from burn tissue. Collectively, our work highlights the efficacy of using zebrafish to study host-fungal interaction dynamics within burn wounds.

microbiology↗

bioRxiv2024

Isotonic medium treatment limits burn wound microbial colonization and improves tissue repair

Burn injuries undergo a complex healing process in which progressive spreading of epithelial damage can lead to secondary complications such as wound infection, which is a major driver of mortality among burn patients. We recently reported that burning larval zebrafish triggers dysregulated keratinocyte dynamics compared to mechanical injury. Here, we investigate keratinocyte behavior following burn injury and the subsequent potential for microbial colonization of burn wounds over time. Real-time imaging, coupled with tracking of photoconverted cells, revealed that early keratinocyte motility contributes to the spread of epithelial damage beyond the initial site of burn injury and that increased epithelial damage was associated with wound colonization by the fungal pathogen Candida albicans. Modulating osmotic balance by treating larval zebrafish with isotonic medium limited the spread of epithelial damage and reduced microbial colonization of burn wounds. Using cultured human skin, we found that topical treatment with isotonic solution (saline) similarly prevented the spread of epithelial damage over time. These findings indicate that keratinocyte behavior contribute to burn wound progression in larval zebrafish and link keratinocyte dynamics to microbial colonization of burn wounded tissue.

cell biology↗

bioRxiv2024

Subcortical Hubs of Brain Networks Sustaining Human Consciousness

Neuromodulation of subcortical network hubs by pharmacologic, electrical, or ultrasonic stimulation is a promising therapeutic strategy for patients with disorders of consciousness (DoC). However, optimal subcortical targets for therapeutic stimulation are not well established. Here, we leveraged 7 Tesla resting-state functional MRI (rs-fMRI) data from 168 healthy subjects from the Human Connectome Project to map the subcortical connectivity of six canonical cortical networks that modulate higher-order cognition and function: the default mode, executive control, salience, dorsal attention, visual, and somatomotor networks. Based on spatiotemporally overlapped networks generated by the Nadam-Accelerated SCAlable and Robust (NASCAR) tensor decomposition method, our goal was to identify subcortical hubs that are functionally connected to multiple cortical networks. We found that the ventral tegmental area (VTA) in the midbrain and the central lateral (CL) and parafascicular (Pf) nuclei of the thalamus - regions that have historically been targeted by neuromodulatory therapies to restore consciousness - are subcortical hubs widely connected to multiple cortical networks. Further, we identified a subcortical hub in the pontomesencephalic tegmentum that overlapped with multiple reticular and extrareticular arousal nuclei and that encompassed a well-established "hot spot" for coma-causing brainstem lesions. Multiple hubs within the brainstem arousal nuclei and thalamic intralaminar nuclei were functionally connected to both the DMN and SN, emphasizing the importance of these cortical networks in integrative subcortico-cortical signaling. Additional subcortical connectivity hubs were observed within the caudate head, putamen, amygdala, hippocampus, and bed nucleus of the stria terminalis, regions classically associated with modulation of cognition, behavior, and sensorimotor function. Collectively, these results suggest that multiple subcortical hubs in the brainstem tegmentum, thalamus, basal ganglia, and medial temporal lobe modulate cortical function in the human brain. Our findings strengthen the evidence for targeting subcortical hubs in the ventral tegmental area, central lateral thalamus, and pontomesencephalic tegmentum to restore consciousness in patients with DoC. We release all subcortical connectivity maps to support ongoing efforts at therapeutic neuromodulation of consciousness.

neuroscience↗

bioRxiv2024

Shared subcortical arousal systems across sensory modalities during transient modulation of attention

Subcortical arousal systems are known to play a key role in controlling sustained changes in attention and conscious awareness. Recent studies indicate that these systems have a major influence on short-term dynamic modulation of visual attention, but their role across sensory modalities is not fully understood. In this study, we investigated shared subcortical arousal systems across sensory modalities during transient changes in attention using block and event-related fMRI paradigms. We analyzed massive publicly available fMRI datasets collected while 1,561 participants performed visual, auditory, tactile, and taste perception tasks. Our analyses revealed a shared circuit of subcortical arousal systems exhibiting early transient increases in activity in midbrain reticular formation and central thalamus across perceptual modalities, as well as less consistent increases in pons, hypothalamus, basal forebrain, and basal ganglia. Identifying these networks is critical for understanding mechanisms of normal attention and consciousness and may help facilitate subcortical targeting for therapeutic neuromodulation.

neuroscience↗

bioRxiv2024

Live imaging in zebrafish reveals tissue-specific strategies for amoeboid migration

Amoeboid cells like leukocytes can enter and migrate within virtually every tissue of the body, even though tissues vary widely in their chemical and mechanical composition. Here, we imaged motile T cells as they colonized peripheral tissues during zebrafish development to ask if cells tailor their migration strategy to their local tissue environment. We found that T cells in most sites migrated with f-actin-rich leading-edge pseudopods, matching how they migrate in vitro. T cells notably deviated from this strategy in the epidermis, where they instead migrated using a rearward concentration of f-actin and stable leading-edge blebs. This mode of migration occurs under planar confinement in vitro, and we correspondingly found the stratified keratinocyte layers of the epidermis impose planar-like confinement on leukocytes in vivo. By imaging the same cell type across the body, our data collectively indicates that cells adapt their migration strategy to navigate different tissue geometries in vivo.

cell biology↗

bioRxiv2024

Lesions that Cause Psychosis Map to a Common Brain Circuit in the Hippocampus

ImportanceIdentifying anatomy causally involved in psychosis could inform therapeutic neuromodulation targets for schizophrenia. ObjectiveTo assess whether lesions that cause secondary psychosis have functional connections to a common brain circuit. DesignThis case-control study mapped functional connections of published cases of lesions causing secondary psychosis compared with control lesions unassociated with psychosis. SettingThis study was conducted in a computational laboratory. ParticipantsPublished cases of lesion-induced psychosis were analyzed. Included subjects had documented brain lesions associated with new-onset psychotic symptoms without prior history of psychosis. Control cases included 1156 patients with lesions not associated with psychosis. Generalizability across lesional datasets was assessed using an independent cohort of 181 patients with brain lesions who subsequently underwent neurobehavioral testing. ExposuresLesions causing secondary psychosis. Main Outcomes and MeasuresPsychosis or no psychosis. Results153 lesions from published cases were determined to be causal of psychosis (65 [42%] male; mean [SD] age, 50.0 [20.8] years), 42 of which were described as "schizophrenia" or "schizophrenia-like". Lesions that caused secondary psychosis mapped to a common brain circuit defined by functional connectivity to the posterior subiculum of the hippocampus (84% functional overlap, pFWE<5 x 10-5). At a lower statistical threshold (75%> overlap, pFWE<5 x 10-4), this circuit included the ventral tegmental area, retrosplenial cortex, lobule IX and dentate nucleus of the cerebellum, and the mediodorsal and midline nuclei of the thalamus. This circuit was consistent when derived from "schizophrenia-like" cases (spatial r=0.98). We repeated these analyses after excluding lesions intersecting the hippocampus (n=47) and found a consistent functional connectivity profile (spatial r=0.98) with the posterior subiculum remaining the center of connectivity (>75% overlap, pFWE<5x10-5), demonstrating a circuit-level effect. In an independent observational cohort of patients with penetrating head trauma (n=181), lesions associated with symptoms of psychosis exhibited significantly similar connectivity profiles to the lesion-derived psychosis circuit (suspiciousness, p=0.025; unusual thought content, p=0.046). Voxels in the rostromedial prefrontal cortex (rmPFC) are highly correlated with this psychosis circuit (spatial r=0.82), suggesting the rmPFC as a promising TMS target for psychosis. Conclusions and RelevanceLesions that cause secondary psychosis affect a common brain circuit in the hippocampus. These results can help inform therapeutic neuromodulation targeting. Key PointsO_ST_ABSQuestionC_ST_ABSDo lesions that cause psychosis affect a common brain circuit? FindingsThis case-control study found that lesions causing psychosis specifically affected a common functional circuit aligning with the posterior subiculum of the hippocampus. This functional circuit was consistent across different psychotic symptoms, suggesting a shared neural substrate for psychosis. A similar circuit was derived when excluding lesions directly intersecting the hippocampus, indicating a circuit-level effect. MeaningIdentifying a common brain circuit causally involved in psychotic symptoms suggests that the hippocampus may be pivotal in the pathophysiology and treatment targeting of psychotic disorders.

neuroscience↗

bioRxiv2024

Shared pathway-specific network mechanisms of dopamine and deep brain stimulation for the treatment of Parkinson's disease

Deep brain stimulation is a brain circuit intervention that can modulate distinct neural pathways for the alleviation of neurological symptoms in patients with brain disorders. In Parkinsons disease, subthalamic deep brain stimulation clinically mimics the effect of dopaminergic drug treatment, but the shared pathway mechanisms on cortex - basal ganglia networks are unknown. To address this critical knowledge gap, we combined fully invasive neural multisite recordings in patients undergoing deep brain stimulation surgery with normative MRI-based whole-brain connectomics. Our findings demonstrate that dopamine and stimulation exert distinct mesoscale effects through modulation of local neural population activity. In contrast, at the macroscale, stimulation mimics dopamine in its suppression of excessive interregional network synchrony associated with indirect and hyperdirect cortex - basal ganglia pathways. Our results provide a better understanding of the circuit mechanisms of dopamine and deep brain stimulation, laying the foundation for advanced closed-loop neurostimulation therapies.

neuroscience↗