Michael D Fox

• MD, PhD
• Managing Director at Brigham and Women's Hospital

Significance Brain stimulation is a powerful treatment for an increasing number of psychiatric and neurological diseases, but it is unclear why certain stimulation sites work or where in the brain is the best place to stimulate to treat a given patient or disease. We found that although different types of brain stimulation are applied in different...

Recently, multifocal transcranial current stimulation (tCS) devices using several relatively small electrodes have been used to achieve more focal stimulation of specific cortical targets. However, it is becoming increasingly recognized that many behavioral manifestations of neurological and psychiatric disease are not solely the result of abnormal...

Transcranial magnetic stimulation (TMS) to the left dorsolateral prefrontal cortex (DLPFC) is used clinically for the treatment of depression however outcomes vary greatly between patients. We have shown that average clinical efficacy of different left DLPFC TMS sites is related to intrinsic functional connectivity with remote regions including the...

Transcranial magnetic stimulation (TMS) to the left dorsolateral prefrontal cortex (DLPFC) is used clinically for the treatment of depression. However, the antidepressant mechanism remains unknown and its therapeutic efficacy remains limited. Recent data suggest that some left DLPFC targets are more effective than others; however, the reasons for t...

Magnetic resonance–guided focused ultrasound (MRgFUS) thalamotomy is an effective treatment for medically refractory essential tremor. We investigate ablation sites and potential tracts associated with optimal tremor control and side effects based on the analysis of 351 cases from three international hospitals. Lesions were segmented on day 1 thin-...

Background Clinical neuroradiologists routinely look for expansion of CSF spaces to help identify atrophy on patient MRI scans. In contrast, automated methods for identifying atrophy rely on changes in grey matter volume or cortical thickness. It is unclear if evaluating CSF spaces could improve detection of brain atrophy, which may be relevant to...

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms in patients with Parkinsons disease. Using functional MRI, optimal DBS response networks have been characterized. However, neural activity associated with Parkinsonian symptoms is magnitudes faster than what can be resolved by this method. While both spatial and t...

Objectives: The relevant neuroanatomy for gait dysfunction remains unclear. We sought 1) to identify a brain circuit for gait impairment post stroke, 2) to identify a brain circuit for gait changes after subthalamic DBS for Parkinson′s disease, 3) to test for convergence between these two circuits. Methods: This cross-sectional retrospective study...

Idiopathic generalized epilepsy (IGE) is a brain network disease, but the location of this network and its relevance for treatment remain unclear. We combine the locations of brain abnormalities in IGE (131 coordinates from 21 studies) with the human connectome to identify an IGE network. We validate this network by showing alignment with structura...

Background The orbitofrontal cortex (OFC) and its role in the regulation of urges/compulsion has been identified as a critical component of circuit-based addiction models. Building on such models, it was recently shown that brain lesions disrupting addictive behavior can be mapped to a common brain circuit. Methods We present a case of a 42-year-o...

Once taken into consideration, sex differences in neurological diseases emerge in abundance: (i) Stroke severity is significantly higher in females than in males, (ii) Alzheimer’s disease (AD) pathology is more pronounced in females, and (iii) conspicuous links with hormonal cycles led to female-specific diagnoses, such as catamenial migraines and...

The Deep Brain Stimulation (DBS) Think Tank XII was held on August 21st to 23rd. This year we showcased groundbreaking advancements in neuromodulation technology, focusing heavily on the novel uses of existing technology as well as next-generation technology. Our keynote speaker shared the vision of using neuro artificial intelligence to predict de...

Importance Identifying anatomy causally involved in psychosis could inform therapeutic neuromodulation targets for schizophrenia. Objective To assess whether lesions that cause secondary psychosis have functional connections to a common brain circuit. Design, Setting, and Participants This case-control study mapped functional connections of publi...

Brain atrophy may precede symptoms in Alzheimer's disease (AD), but it remains unclear whether atrophy in this preclinical stage falls within a distinct brain network or is associated with transitional cognitive changes. We investigated cortical thickness in cognitively unimpaired older adults with varying amyloid-β accumulation and estimated the c...

Importance Creativity is important for problem solving, adaptation to a changing environment, and innovation. Neuroimaging studies seeking to map creativity have yielded conflicting results, and studies of patients with brain disease have reported both decreases and paradoxical increases in creativity, leaving the neural basis of creativity unclear...

Background: Obsessive-compulsive disorder (OCD) may develop following brain lesions, but lesion distribution and connectivity patterns are unknown. Methods: OCD-associated lesions, identified from systematic literature search, were traced on common brain space and compared to control lesions (N=608). Topography was analyzed using brain atlases, and...

Background Anxiety is prevalent among cognitively unimpaired older adults and is associated with accelerated amyloid‐ß‐related cognitive decline and incident cognitive impairment. Investigating these mechanisms is challenging due to low pathologic burden, high individual variability, and subsyndromal level of symptoms. Recently, brain networks invo...

Deep brain stimulation is an efficacious treatment for dystonia. While the internal pallidum serves as the primary target, recently, stimulation of the subthalamic nucleus (STN) has been investigated. However, optimal targeting within this structure and its surroundings have not been studied in depth. Indeed, historical targets that have been used...

Background Anxiety is prevalent among cognitively unimpaired older adults and is associated with accelerated amyloid‐β‐related cognitive decline and incident cognitive impairment. Investigating these mechanisms is challenging due to low pathologic burden, high individual variability, and subsyndromal level of symptoms. Recently, brain networks invo...

Gilles de la Tourette Syndrome (GTS) is a chronic tic disorder, characterized by unwanted motor actions and vocalizations. While brain stimulation techniques show promise in reducing tic severity, optimal target networks are not well-defined. Here, we leverage datasets from two independent deep brain stimulation (DBS) cohorts and a cohort of tic-in...

Disorders of consciousness (DoC) are states of impaired arousal or awareness. Deep brain stimulation (DBS) is a potential treatment, but outcomes vary, possibly due to differences in patient characteristics, electrode placement, or stimulation of specific brain networks. We studied 40 patients with DoC who underwent DBS targeting the thalamic centr...

Objective To systematically evaluate which lesion‐based imaging features and methods allow for the best statistical prediction of poststroke deficits across independent datasets. Methods We utilized imaging and clinical data from three independent datasets of patients experiencing acute stroke (N1 = 109, N2 = 638, N3 = 794) to statistically predic...

Deep brain stimulation (DBS) is an established treatment for Parkinson's disease. Still, DBS parameter programming currently follows a tedious trial-and-error process. DBS-evoked cortical potentials (EP) might guide parameter selection but this concept has not yet been tested. Further, mounting wet EEG systems is too time-consuming to scale in outp...

Task functional magnetic resonance imaging research has generally shielded away from studying individuals due to the low reproducibility. Here, we propose that heterogeneous brain activations across individuals localize to a common network. To test this hypothesis, we use working memory (WM) as our example. First, we showed that discrete-brain-base...

Importance Drug-resistant temporal lobe epilepsy (TLE) has been associated with hippocampal pathology. Most surgical treatment strategies, including resection and responsive neurostimulation (RNS), focus on this disease epicenter; however, imaging alterations distant from the hippocampus, as well as emerging data from responsive neurostimulation tr...

Neuromodulation trials for the treatment of posttraumatic stress disorder (PTSD) have yielded mixed results, and the optimal neuroanatomical target remains unclear. Here we analyzed three datasets to study brain circuitry causally linked to PTSD in military veterans. In veterans with penetrating traumatic brain injury, lesion locations that reduced...

Importance Because withdrawal of life-sustaining therapy based on perceived poor prognosis is the most common cause of death after moderate or severe traumatic brain injury (TBI), the accuracy of clinical prognoses is directly associated with mortality. Although the location of brain injury is known to be important for determining recovery potentia...

Religious fundamentalism, characterized by rigid adherence to a set of beliefs putatively revealing inerrant truths, is ubiquitous across cultures and has a global impact on society. Understanding the psychological and neurobiological processes producing religious fundamentalism may inform a variety of scientific, sociological, and cultural questio...

Frontal-eyed species use a combination of conjugate and vergence eye movements, termed 3-D gaze, to scan their environment 1–3 . The neural circuits mediating conjugate gaze have been extensively characterized, but those governing vergence remain disproportionately obscure ⁴ . Here, we combine lesion and deep brain stimulation data from 67 humans a...

Background Recent imaging studies identified a brain network associated with clinical improvement following deep brain stimulation (DBS) in Parkinson's disease (PD), the PD response network. Objectives This study aimed to assess the impact of neuromodulation on PD motor symptoms by targeting this network noninvasively using multifocal transcranial...

Transcranial magnetic stimulation (TMS) is effective for major depressive disorder (MDD) despite imprecise scalp-based targeting. Retrospective analyses suggest that targeting one brain circuit improves “dysphoric” symptoms, while targeting a different brain circuit improves “anxiosomatic” symptoms. Here, we tested this hypothesis prospectively. In...

Objective Alice in Wonderland syndrome (AIWS) profoundly affects human perception of size and scale, particularly regarding one's own body and the environment. Its neuroanatomical basis has remained elusive, partly because brain lesions causing AIWS can occur in different brain regions. Here, we aimed to determine if brain lesions causing AIWS map...

Recent epidemiological studies propose an association between parkinsonism and seizures, but the direction of this association is unclear. Focal brain lesions causing new-onset parkinsonism versus seizures may provide a unique perspective on the causal relationship between the two symptoms and involved brain networks. We studied lesions causing par...

Deep Brain Stimulation can improve tremor, bradykinesia, rigidity, and axial symptoms in patients with Parkinson’s disease. Potentially, improving each symptom may require stimulation of different white matter tracts. Here, we study a large cohort of patients (N = 237 from five centers) to identify tracts associated with improvements in each of the...

Stuttering affects approximately 1 in 100 adults and can result in significant communication problems and social anxiety. It most often occurs as a developmental disorder but can also be caused by focal brain damage. These latter cases may lend unique insight into the brain regions causing stuttering. Here, we investigated the neuroanatomical subst...

Recent epidemiological studies propose an association between parkinsonism and seizures, but the direction of this association is unclear. Focal brain lesions causing new-onset parkinsonism versus seizures may provide a unique perspective on the causal relationship between the two symptoms and involved brain networks. We studied lesions causing par...

Transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS) can treat some neuropsychiatric disorders, but there is no consensus approach for identifying new targets. We localized causal circuit-based targets for anxiety that converged across multiple natural experiments. Lesions (n=451) and TMS sites (n=111) that modify anxiety mapped...

Gilles de la Tourette Syndrome (GTS) is the most severe form of chronic tic disorders, characterized by uncontrollable motor actions and vocalizations. While brain stimulation techniques show promise in reducing tic severity, optimal target networks are not well-defined. Here, we leveraged datasets from two independent deep brain stimulation (DBS)...

Oculogyric crises are acute episodes of sustained, typically upward, conjugate deviation of the eyes. Oculogyric crises usually occur as the result of acute D2-dopamine receptor blockade, but the brain areas causally involved in generating this symptom remain elusive. Here, we used data from 14 previously reported cases of lesion-induced oculogyric...

Objective Patients with Alzheimer's disease (AD) have diffuse brain atrophy, but some regions, such as the anterior cingulate cortex (ACC), are spared and may even show increase in size compared to controls. The extent, clinical significance, and mechanisms associated with increased cortical thickness in AD remain unknown. Recent work suggested neu...

Background: In Lewis Carroll s 1865 novel "Alice s Adventures in Wonderland", the protagonist experiences distortions in the size of her body and those of others. This fiction becomes reality in neurological patients with Alice in Wonderland Syndrome (AIWS). Brain lesions causing AIWS may offer unique insights into the syndrome s elusive neuroanato...

Religious fundamentalism, characterized by rigid adherence to a set of beliefs putatively revealing inerrant truths, is ubiquitous across cultures and has a global impact on society. Understanding the psychological and neurobiological processes producing religious fundamentalism may inform a variety of scientific, sociological, and cultural questio...

There is disagreement regarding the major components of the brain network supporting spatial cognition. To address this issue, we applied a lesion mapping approach to the clinical phenomenon of topographical disorientation. Topographical disorientation is the inability to maintain accurate knowledge about the physical environment and use it for nav...

Background: Deep brain stimulation (DBS) is a promising treatment option for treatment- refractory obsessive-compulsive disorder (OCD). Several stimulation targets have been used, mostly in and around the anterior limb of the internal capsule and ventral striatum (VC/VS). However, the precise target within this region remains a matter of debate. Me...

Noninvasive brain stimulation technologies such as transcranial electrical and magnetic stimulation (tES and TMS) are emerging neuromodulation therapies that are being used to target the neural substrates of substance use disorders. By the end of 2022, 205 trials of tES or TMS in the treatment of substance use disorders had been published, with het...

Understanding the neuroanatomy of schizophrenia remains elusive due to heterogenous findings across neuroimaging studies. Here, we investigated whether patterns of brain atrophy associated with schizophrenia would localize to a common brain network. Using the human connectome as a wiring diagram, we identified a connectivity pattern, a schizophreni...

Background: Disconjugate eye movements play a crucial role in depth perception for frontal-eyed species. Midbrain lesions cause disconjugate eye movement deficits, such as skew deviation and hemi-seesaw nystagmus in the vertical plane or esodeviation and convergence-retraction nystagmus in the horizontal plane. While the former have been linked to...

Background Nearly 1 million Americans are living with multiple sclerosis (MS) and 30–50% will experience memory dysfunction. It remains unclear whether this memory dysfunction is due to overall white matter lesion burden or damage to specific neuroanatomical structures. Here we test if MS memory dysfunction is associated with white matter lesions t...

The principle of targeting brain circuits has drawn increasing attention with the growth of brain stimulation treatments such as transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), and focused ultrasound (FUS). Each of these techniques can effectively treat different neuropsychiatric disorders, but treating any given disorder dep...

Objective: Spontaneous confabulation is a symptom in which false memories are conveyed by the patient as true. The purpose of the study was to identify the neuroanatomical substrate of this complex symptom and evaluate the relationship to related symptoms, such as delusions and amnesia. Methods: Twenty-five lesion locations associated with spont...

Importance: It remains unclear why lesions in some locations cause epilepsy while others do not. Identifying the brain regions or networks associated with epilepsy by mapping these lesions could inform prognosis and guide interventions. Objective: To assess whether lesion locations associated with epilepsy map to specific brain regions and netwo...

Neuromodulation trials for PTSD have yielded mixed results, and the optimal neuroanatomical target remains unclear. We analyzed three datasets to study brain circuitry causally linked to PTSD in military Veterans. After penetrating traumatic brain injury (n=193), lesions that reduced probability of PTSD were preferentially connected to a circuit in...

Importance: Multiple sclerosis (MS) is an immune-mediated neurological disorder that affects nearly one million people in the United States. Up to 50% of patients with MS experience depression. Objective: To investigate how white matter network disruption is related to depression in MS. Design: Retrospective case-control study of participants who r...

Objective: Unawareness of a deficit, anosognosia, can occur for visual or motor deficits and lends insight into awareness itself; however, lesions associated with anosognosia occur in many different brain locations. Methods: We analyzed 267 lesion locations associated with either vision loss (with and without awareness) or weakness (with and withou...

Characterizing human thalamocortical network is fundamental for understanding a vast array of human behaviors since the thalamus plays a central role in cortico-subcortical communication. Over the past few decades, advances in functional magnetic resonance imaging have allowed for spatial mapping of intrinsic resting-state functional connectivity (...

Historically, pathological brain lesions provided the foundation for localization of symptoms and therapeutic lesions were used as a treatment for brain diseases. New medications, functional neuroimaging and deep brain stimulation led to a decline in lesions in the past few decades. However, recent advances have improved our ability to localize les...

Vertigo is a common neurological complaint, which can result in significant morbidity and decreased quality of life. While pathology to peripheral and subtentorial brain structures is a well-established cause of vertigo, cortical lesions have also been linked to vertigo and may lend insight into relevant neuroanatomy. Here, we investigate the supra...

Introduction: Predicting individual outcomes post-stroke with the highest possible accuracy is a crucial steppingstone in the realization of precision medicine. We here evaluated various types of lesion information in their capacity to predict stroke severity in a large cohort of patients with acute ischemic stroke. Methods: A total of 1,075 patien...

Background: Emotion regulation has been linked to specific brain networks based on functional neuroimaging, but networks causally involved in emotion regulation remain unknown. Methods: We studied patients with focal brain damage (n=167) who completed the "managing emotion" subscale of the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT...

The deep brain stimulation (DBS) Think Tank X was held on August 17–19, 2022 in Orlando FL. The session organizers and moderators were all women with the theme women in neuromodulation . Dr. Helen Mayberg from Mt. Sinai, NY was the keynote speaker. She discussed milestones and her experiences in developing depression DBS. The DBS Think Tank was fou...

Multiple sclerosis (MS), a demyelinating disease that causes focal white matter lesions, is commonly associated with depression. However, it remains unclear whether depression risk is selectively increased by specific white matter lesion locations. Recent work shows that stroke lesions and therapeutic neuromodulation sites that modify depression se...

A confluence of evidence indicates that brain functional connectivity is not static but rather dynamic. Capturing transient network interactions in the individual brain requires a technology that offers sufficient within-subject reliability. Here, we introduce an individualized network-based dynamic analysis technique and demonstrate that it is rel...

Psychiatric disorders share neurobiology and frequently co-occur. This neurobiological and clinical overlap highlights opportunities for transdiagnostic treatments. In this study, we used coordinate and lesion network mapping to test for a shared brain network across psychiatric disorders. In our meta-analysis of 193 studies, atrophy coordinates ac...

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...