Andreas Horn

Brigham and Women's Hospital | BWH · Department of Neurology

Objective: The benefit of deep brain stimulation (DBS) for Parkinson's disease (PD) may depend on connectivity between the stimulation site and other brain regions, but which regions and whether connectivity can predict outcome in patients remains unknown. Here, we identify the structural and functional connectivity profile of effective DBS to the...

Multiple surgical targets for treating obsessive-compulsive disorder with deep brain stimulation (DBS) have been proposed. However, different targets may modulate the same neural network responsible for clinical improvement. We analyzed data from four cohorts of patients (N = 50) that underwent DBS to the anterior limb of the internal capsule (ALIC...

Brain lesions are a rare cause of tic disorders. However, they can provide uniquely causal insights into tic pathophysiology and can also inform on possible neuromodulatory therapeutic targets. Based on a systematic literature review, we identified 22 cases of tics causally attributed to brain lesions and employed ‘lesion network mapping’ to interr...

The subthalamic nucleus and internal pallidum are main target sites for deep brain stimulation in Parkinson’s disease. Multiple trials that investigated subthalamic versus pallidal stimulation were unable to settle on a definitive optimal target between the two. One reason could be that the effect is mediated via a common functional network. To tes...

The frontal cortex is involved in motor, cognitive, and affective brain functions. In humans, however, neuroanatomy-function mappings are predominantly derived from correlative neuroimaging studies. Hence, exactly which frontal domains causally mediate which function remains largely elusive. Herein, we leverage a strategy that allows for causal inf...

Background: Deep brain stimulation has become an established technology for the treatment of patients with a wide variety of conditions, including movement disorders, psychiatric disorders, epilepsy, and pain. Surgery for implantation of DBS devices has enhanced our understanding of human physiology, which in turn has led to advances in DBS techno...

Background: Subthalamic nucleus (STN) beta (13 - 35 Hz) activity is a biomarker reflecting motor state in Parkinson's disease (PD). Adaptive deep brain stimulation (DBS) aims to use beta activity for therapeutic adjustments, but many aspects of beta activity in real-life situations are unknown. Objective: The aim was to investigate Christmas-rel...

Following its introduction in 2014 and with support of a broad international community, the open-source toolbox Lead-DBS has evolved into a comprehensive neuroimaging platform dedicated to localizing, reconstructing, and visualizing electrodes implanted in the human brain, in the context of deep brain stimulation (DBS) and epilepsy monitoring. Expa...

Understanding the structural connectivity of key brainstem nuclei with limbic cortical regions is essential to the development of therapeutic neuromodulation for depression, chronic pain, addiction, anxiety and movement disorders. Several brainstem nuclei have been identified as the primary central nervous system (CNS) source of important monoamine...

Background: Deep brain stimulation (DBS) is an established and expanding therapy for treatment-refractory obsessive-compulsive disorder. Previous work has suggested that a white matter circuit providing hyperdirect input from the dorsal cingulate and ventrolateral prefrontal regions to the subthalamic nucleus could be an effective neuromodulatory...

Deep brain stimulation (DBS) to the fornix is an investigational treatment for patients with mild Alzheimer’s Disease. Outcomes from randomized clinical trials have shown that cognitive function improved in some patients but deteriorated in others. This could be explained by variance in electrode placement leading to differential engagement of neur...

Background Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is highly effective in controlling motor symptoms in patients with Parkinson's disease. However, correct selection of stimulation parameters is pivotal to treatment success and currently follows a time-consuming and demanding trial-and-error process. We aimed to assess treatme...

Segmenting deep brain structures from magnetic resonance images is important for patient diagnosis, surgical planning, and research. Most current state-of-the-art solutions follow a segmentation-by-registration approach, where subject magnetic resonance imaging (MRIs) are mapped to a template with well-defined segmentations. However, registration-b...

Deep brain stimulation (DBS) to the fornix is an investigational treatment option for patients with mild Alzheimer's disease. Outcomes from randomised clinical trials have shown that cognitive function improved in some patients but deteriorated in others. One reason could be variance in electrode placement leading to differential engagement of neur...

Background: Deep brain stimulation (DBS) is an established therapy for patients with Parkinson’s disease. In silico computer models for DBS hold the potential to inform a selection of stimulation parameters. In recent years, the focus has shifted towards DBS-induced firing in myelinated axons, deemed particularly relevant for the external modulatio...

In the last decades, clinical neuroscience found a novel ally in neurotechnologies, devices able to record and stimulate electrical activity in the nervous system. These technologies improved the ability to diagnose and treat neural disorders. Neurotechnologies are concurrently enabling a deeper understanding of healthy and pathological dynamics of...

Background Understanding the structural connectivity of key brainstem nuclei with limbic cortical regions is essential to the development of therapeutic neuromodulation for depression, chronic pain, addiction, anxiety and movement disorders. Several brainstem nuclei have been identified as the primary central nervous system (CNS) source of importan...

OBJECTIVE Deep brain stimulation (DBS) for Parkinson disease (PD) is traditionally performed with awake intraoperative testing and/or microelectrode recording. Recently, however, the procedure has been increasingly performed under general anesthesia with image-based verification. The authors sought to compare structural and functional networks enga...

Lead-DBS is an open-source, semi-automatized and widely applied software tool facilitating precise localization of deep brain stimulation electrodes both in native as well as in standardized stereotactic space. While automatized preprocessing steps within the toolbox have been tested and validated in previous studies, the interrater reliability in...

Background Deep brain stimulation (DBS) is a promising novel approach for managing refractory Gilles de la Tourette’s syndrome (GTS). The subthalamic nucleus (STN) is the most common DBS target for treating movement disorders, and smaller case studies have reported the efficacy of bilateral STN-DBS treatment for relieving tic symptoms. However, man...

Background Gait disturbances are frequent side effects related to chronic thalamic deep brain stimulation (DBS) that may persist beyond cessation of stimulation. Objective We investigate the temporal dynamics and clinical effects of an overnight unilateral withdrawal of DBS on gait disturbances. Methods 10 essential tremor (ET) patients with gait...

Brain signal decoding promises significant advances in the development of clinical brain computer interfaces (BCI). In Parkinson's disease (PD), first bidirectional BCI implants for adaptive deep brain stimulation (DBS) are now available. Brain signal decoding can extend the clinical utility of adaptive DBS but the impact of neural source, computat...

Background: Deep Brain Stimulation (DBS) electrode implant trajectories are stereotactically defined using preoperative neuroimaging. To validate the correct trajectory, microelectrode recordings (MER) or local field potential recordings (LFP) can be used to extend neuroanatomical information (defined by magnetic resonance imaging) with neurophysio...

Introduction: Neurocircuits are involved in the motor, cognitive, and affective dysfunctions of multiple brain disorders. Functional segregation into these domains has been widely defined on a fronto-cortical basis. However, despite considerable interaction, these functional domains remain partitioned to some extent at (sub)thalamic levels (1). To...

Introduction Using cognitive control, humans can flexibly influence behavior based on set goals, which includes overriding impulses by inhibiting automatic responses in a conflicting environment. The basal ganglia have been hypothesized as an integral part in a cortico-subcortical network that modulates inhibitory control in both motor and non-moto...

Introduction: Tremor is defined as an involuntary, rhythmic oscillatory movement of a body part and represents one of the most common symptoms in movement disorders, existing across several diseases. Particularly, in advanced states of tremor-related diseases such as Parkinson’s disease (PD) and Essential tremor syndrome (ET), response to pharmacot...

Question: Finding the optimal deep brain stimulation (DBS) parameters out of a multitude of possible combinations by trial-and-error is time-consuming and requires highly trained medical personnel. We developed an automated algorithm to identify optimal stimulation settings in Parkinson’s disease (PD) patients treated with subthalamic nucleus (STN)...

The subthalamic nucleus (STN) is a primary target for deep brain stimulation in Parkinson's disease (PD). Although small in size, the STN is commonly partitioned into sensorimotor, cognitive/associative, and limbic subregions based on its structural connectivity profile to cortical areas. We investigated whether such a regional specialization is al...

Deep brain stimulation (DBS) for Tourette syndrome (TS) is an evolving therapy for severely affected patients. However, there is still ambiguity about the ideal target and networks that need to be modulated for optimal results. Recently, Johnson et al. demonstrated that tic reductions depend on normative structural connectivity seeding from stimula...

Background Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is highly effective in controlling motor symptoms in patients with Parkinson’s Disease (PD). However, correct selection of stimulation parameters is pivotal to treatment success and currently follows a time-consuming and demanding trial-and-error process. We conducted a double...

Dystonia is a debilitating disease with few treatment options. One effective option is deep brain stimulation (DBS) to the internal pallidum. While cervical and generalized forms of isolated dystonia have been targeted with a common approach to the posterior third of the nucleus, large-scale investigations regarding optimal stimulation sites and po...

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) effectively treats motor symptoms and quality of life (QoL) of advanced and fluctuating early Parkinson's disease. Little is known about the relation between electrode position and changes in symptom control and ultimately QoL. Objectives: The relation between the stimulated part o...

Objective: To obtain individual clinical and neuroimaging data of patients undergoing Deep Brain Stimulation for essential tremor from five different European centers to identify predictors of outcome and to identify an optimal stimulation site. Methods: We analysed retrospectively baseline covariates, pre- and postoperative clinical tremor scor...

Objective: With a growing appreciation for interindividual anatomical variability and patient-specific brain connectivity, advanced imaging sequences offer the opportunity to directly visualize anatomical targets for deep brain stimulation (DBS). The lack of quantitative evidence demonstrating their clinical utility, however, has hindered their br...

Microelectrode recordings (MERs) are often used during deep brain stimulation (DBS) surgeries to confirm the position of electrodes in patients with advanced Parkinson’s disease. The present study focused on 32 patients who had undergone DBS surgery for advanced Parkinson’s disease. The first objective was to confront the anatomical locations of in...

Deep Brain Stimulation (DBS) is an efficacious treatment option for an increasing range of brain disorders. To enhance our knowledge about the mechanisms of action of DBS and to probe novel targets, basic research in animal models with DBS is an essential research base. Beyond nonhuman primate, pig, and mouse models, the rat is a widely used animal...

Deep Brain Stimulation (DBS) has become an efficient clinical treatment for a variety of diseases and beyond that, it offers the possibility to systematically explore causal relationships between the stimulated brain areas and clinical as well as behavioral effects. For this purpose, it is necessary to investigate the observed DBS effects on a grou...

In this chapter, we will give an overview of important imaging concepts in the field of DBS before going into details in the subsequent chapters. We begin by motivating why imaging in the context of DBS is crucial and which additional scientific questions we can ask if we are able to create meaningful models of DBS. We then discuss several strategi...

Damage to specific brain circuits can cause specific neuropsychiatric symptoms. Therapeutic stimulation to these same circuits may modulate these symptoms. To determine whether these circuits converge, we studied depression severity after brain lesions (n = 461, five datasets), transcranial magnetic stimulation (n = 151, four datasets) and deep bra...

At the group-level, deep brain stimulation leads to significant therapeutic benefit in a multitude of neurological and neuropsychiatric disorders. At the single-patient level, however, symptoms may sometimes persist despite “optimal” electrode placement at established treatment coordinates. This may be partly explained by limitations of disease-cen...

Background: Finding the optimal deep brain stimulation (DBS) parameters from a multitude of possible combinations by trial and error is time consuming and requires highly trained medical personnel. Objective: We developed an automated algorithm to identify optimal stimulation settings in Parkinson's disease (PD) patients treated with subthalamic...

The default mode network (DMN) mediates self-awareness and introspection, core components of human consciousness. Therapies to restore consciousness in patients with severe brain injuries have historically targeted subcortical sites in the brainstem, thalamus, hypothalamus, basal forebrain, and basal ganglia, with the goal of reactivating cortical...

Segmenting deep brain structures from magnetic resonance images is important for patient diagnosis, surgical planning, and research. Most current state-of-the-art solutions follow a segmentation-by-registration approach, where subject MRIs are mapped to a template with well-defined segmentations. However, registration-based pipelines are time-consu...

Deep brain stimulation (DBS) is an established therapy for patients with Parkinson’s disease. In silico computer models for DBS allow to pre-select a set of potentially optimal stimulation parameters. If efficacious, they could further carry insight into the mechanism of action of DBS and foster the development of more efficient stimulation approac...

Why study the basal ganglia? This question starts off the journey that Bergman puts ahead of us in The Hidden Life of the Basal Ganglia: At the Base of Brain and Mind. In jest, he answers with an analogy quoting George Mallory1: “Because they are there.” – This beginning sets the tone of the book: A combination of deep insight with some of the fine...

Advances in computational neuroimaging techniques have expanded the armamentarium of imaging tools available for clinical applications in clinical neuroscience. Non-invasive, in vivo brain MRI structural and functional network mapping has been used to identify therapeutic targets, define eloquent brain regions to preserve, and gain insight into pat...

Objective: With a growing appreciation for interindividual anatomical variability and patient-specific brain connectivity, advanced imaging sequences offer the opportunity to directly visualize anatomical targets for deep brain stimulation (DBS). The lack of quantitative evidence demonstrating their clinical utility, however, has hindered their bro...

Tourette syndrome (TS) constitutes a childhood-onset brain disorder with the defining presence of tic behaviors. Tics are repetitive movements or sounds that resemble voluntary actions but appear without embedment to discernable context (1). Effective therapy is complicated by phenotypical hetero-geneity, which arises not only from a wide variabili...

[This corrects the article DOI: 10.3389/fnhum.2021.644593.].

Background and Purpose Deep brain stimulation (DBS) is the most common surgical treatment for essential tremor (ET), yet there is variation in outcome and stimulation targets. This study seeks to consolidate proposed stimulation “sweet spots,” as well as assess the value of structural connectivity in predicting treatment outcomes. Materials and Me...

At the group-level, deep brain stimulation leads to significant therapeutic benefit in a multitude of neurological and neuropsychiatric disorders. At the single-patient level, however, symptoms may sometimes persist despite "optimal" electrode placement at established treatment coordinates. This may be partly explained by limitations of disease-cen...

The book is available here: https://www.elsevier.com/books/connectomic-deep-brain-stimulation/horn/978-0-12-821861-7