Michael D Fox

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

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...

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...

Objective: Tuberous Sclerosis Complex (TSC) is associated with focal brain "tubers" and a high incidence of autism spectrum disorder (ASD). The location of brain tubers associated with autism may provide insight into the neuroanatomical substrate of ASD symptoms. Methods: We delineated tuber locations for 115 TSC participants with ASD (n = 31) a...

Background and Objectives Brain lesions are a well-recognized etiology of dystonia. These cases are especially valuable as they offer causal insight into the neuroanatomical substrates of dystonia. To date, knowledge of lesion-induced dystonia comes mainly from isolated case reports or small case series, restricting broader description and analysis...

Objective: This study was undertaken to test whether lesions causing central poststroke pain (CPSP) are associated with a specific connectivity profile, whether these connections are associated with metabolic changes, and whether this network aligns with neuromodulation targets for pain. Methods: Two independent lesion datasets were utilized: (1...

Purpose of review: Focal lesions causing specific neurological or psychiatric symptoms can occur in multiple different brain locations, complicating symptom localization. Here, we review lesion network mapping, a technique used to aid localization by mapping lesion-induced symptoms to brain circuits rather than individual brain regions. We highlig...

Brain lesions can allow for causal links between symptoms and human neuroanatomy. However, lesions causing the same symptom often fail to overlap a single brain region, leaving the localization unclear. Resting-state functional connectivity MRI is a powerful tool for mapping human brain networks. Using resting-state functional connectivity, one can...

Objective Chronic tinnitus is a clinical symptom that affects 10% to 15% of the adult population. Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment, but significant heterogeneity exists in the treatment outcomes and stimulation parameters. In this study, we perform a qualitative systematic review to determine if there is...

Drug addiction is a public health crisis for which new treatments are urgently needed. In rare cases, regional brain damage can lead to addiction remission. These cases may be used to identify therapeutic targets for neuromodulation. We analyzed two cohorts of patients addicted to smoking at the time of focal brain damage (cohort 1 n = 67; cohort 2...

Despite the prevalence of anhedonia across multiple psychiatric disorders, its relevance to treatment selection and prognostication can be unclear (Davey et al., Psychol Med 42(10):2071-81, 2012). Given the challenges in pharmacological and psychosocial treatment, there has been increasing attention devoted to neuroanatomically-targeted treatments....

Lesion network mapping is a neuroimaging technique that explores the network of regions functionally connected to lesions causing a common syndrome. The technique uses resting state functional connectivity from large databases of healthy individuals, i.e., connectomes, and has allowed for important insight into the potential network mechanisms unde...

Mapping human brain function is a long-standing goal of neuroscience that promises to inform the development of new treatments for brain disorders. Early maps of human brain function were based on locations of brain damage or brain stimulation that caused a functional change. Over time, this approach was largely replaced by technologies such as fun...

This report presents an overview of how machine learning is rapidly advancing clinical translational imaging in ways that will aid in the early detection, prediction, and treatment of diseases that threaten brain health. Towards this goal, we aresharing the information presented at a symposium, “Neuroimaging Indicators of Brain Structure and Functi...

There is growing evidence that placebo effects can meaningfully modulate the brain. However, there has been little consideration of whether these changes may overlap with regions/circuits targeted by depression treatments and what the implications of this overlap would be on measuring efficacy in placebo-controlled clinical trials. In this systemat...

Objectives Delirium is common among patients with acute stroke and associated with worse outcomes. However, it is unclear which stroke locations or types are most associated with delirium. Materials and Methods We systematically reviewed studies of patients with acute stroke that reported stroke locations and types by delirium status. We included...

Emotion regulation has been linked to specific brain networks based on functional neuroimaging. We found that damage to these networks was associated with emotion regulation impairment in patients following focal brain injury (n = 167). Next, we used this lesion dataset to derive a de novo brain network for emotion regulation, which was defined by...

Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity...

Introduction: Understanding the relations between lesions and outcomes is a particularly promising avenue to support tailored stroke care. We here employed a novel Bayesian framework integrating lesion location and functional lesion connectivity, i.e., lesion network mapping data, aiming to augment the prediction of stroke severity and the interpre...

Background Repetitive transcranial magnetic stimulation (rTMS) is entering wider use as a therapeutic intervention for many psychiatric illnesses. The efficacy of this therapeutic intervention may depend on accurately localizing target brain regions. Recent work investigating whole-brain maps of circuits associated with depression and its successfu...

Deep brain stimulation (DBS) is an effective treatment for Parkinson’s disease but can be complicated by side-effects such as cognitive decline. There is often a delay before this side-effect is apparent and the mechanism is unknown, making it difficult to identify patients at risk or select appropriate DBS settings. Here, we test whether connectiv...

Deep brain stimulation is an effective treatment for Parkinson’s disease but can be complicated by side-effects such as cognitive decline. There is often a delay before this side-effect is apparent and the mechanism is unknown, making it difficult to identify patients at risk or select appropriate deep brain stimulation settings. Here, we test whet...

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...

Background and Objectives Disorders of consciousness, EEG background suppression and epileptic seizures are associated with poor outcome after cardiac arrest. Our objective was to identify the distribution of diffusion MRI-measured anoxic brain injury after cardiac arrest and to define the regional correlates of disorders of consciousness, EEG back...

Brain lesions, such as the ones caused by stroke or tumors, disrupt normal brain function and cause a wide spectrum of neurological and psychiatric symptoms. Studying brain lesions has formed the foundation for localization of symptoms throughout the history of neurology, providing unique causal evidence. In exceedingly rare cases, spontaneous brai...

Deep brain stimulation (DBS) is just one of many ways to modulate brain circuits. Noninvasive brain stimulation tools, such as transcranial magnetic stimulation and transcranial direct current stimulation may provide insights that are relevant for understanding and improving DBS outcomes. These different brain stimulation modalities target differen...

Objective Blindsight is a disorder where brain injury causes loss of conscious but not unconscious visual perception. Prior studies have produced conflicting results regarding the neuroanatomical pathways involved in this unconscious perception. Methods We performed a systematic literature search to identify lesion locations causing visual field l...

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...

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...

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

Background Over 80% of the global population consider themselves religious with even more identifying as spiritual, but the neural substrates of spirituality and religiosity remain unresolved. Methods In two independent brain lesion datasets (N1=88; N2=105), we apply lesion network mapping to test whether lesion locations associated with spiritual...

Introduction Disorders of consciousness, EEG background suppression and epileptic seizures are associated with poor outcome after cardiac arrest. The underlying patterns of anoxic brain injury associated with each remain unknown. Our objective was to identify the distribution of anoxic brain injury after cardiac arrest, as measured with diffusion M...

The brain regions responsible for hallucinations remain unclear. We studied 89 brain lesions causing hallucinations using a recently validated technique termed lesion network mapping. We found that hallucinations occurred following lesions to a variety of different brain regions, but these lesion locations fell within a single functionally connecte...

Whether antagonistic brain states constitute a fundamental principle of human brain organization has been debated over the past decade. Some argue that intrinsically anti-correlated brain networks in resting-state functional connectivity are an artifact of preprocessing. Others argue that anti-correlations are biologically meaningful predictors of...

Objective Approximately 50% of patients with Tuberous Sclerosis Complex develop infantile spasms, a sudden‐onset epilepsy syndrome associated with poor neurological outcomes. While an increased burden of tubers confers an elevated risk of infantile spasms, it remains unknown whether some tuber locations confer higher risk than others. Here, we test...

Interhemispheric inhibition (IHI) is a dual-site TMS protocol measuring inhibitory interactions between the primary motor cortices (M1). IHI is performed by applying an initial conditioning stimulus followed by a test stimulus to the contralateral M1. Conventionally, the response in the contralateral hand to the conditioning TMS pulse is either not...

Four deep brain stimulation electrodes implanted for treatment of obsessive compulsive disorder within the anterior limb of the thalamus and nucleus accumbens (blue) and anteromedial subthalamic nucleus (orange). Stimulation of fibertracts associated with positive clinical outcome are colored in red (anterior limb of the internal capsule, „associat...

This article is based on a consensus conference, promoted and supported by the International Federation of Clinical Neurophysiology (IFCN), which took place in Siena (Italy) in October 2018. The meeting intended to update the ten-year-old safety guidelines for the application of transcranial magnetic stimulation (TMS) in research and clinical setti...

BACKGROUND Although mania is characteristic of bipolar disorder, it can also occur following focal brain damage. Such cases may provide unique insight into brain regions responsible for mania symptoms and identify therapeutic targets. METHODS Lesion locations associated with mania were identified using a systematic literature search (n = 41) and ma...

The process of altering neural activity – neuromodulation – has long been used to treat patients with brain disorders and answer scientific questions. Deep brain stimulation in particular has provided clinical benefit to over 150,000 patients. However, our understanding of how neuromodulation impacts the brain is evolving. Instead of focusing on th...

Transcranial magnetic stimulation (TMS) is an effective treatment for depression but is limited in that the optimal therapeutic target remains unknown. Early TMS trials lacked a focal target, and thus positioned the TMS coil over the prefrontal cortex using scalp measurements. Over time, it became clear that this method leads to variation in the st...