Helen Mayberg

• Emory University

Introduction Deep brain stimulation (DBS) is a promising treatment for refractory depression, utilizing surgically implanted electrodes to stimulate specific anatomical targets within the brain. However, limitations of patient-reported and clinician-administered mood assessments pose obstacles in evaluating DBS treatment efficacy. In this study, we...

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...

Treatments for major depressive disorder (MDD) include antidepressant medications and evidence-based psychotherapies, which are approximately equally efficacious. Individual response to treatment, however, is variable, implying individual differences that could allow for prospective differential prediction of treatment response and personalized tre...

Meditation is an accessible mental practice associated with emotional regulation and well-being. Loving-kindness meditation (LKM), a specific subtype of meditative practice, involves focusing one’s attention on thoughts of well-being for oneself and others. Meditation has been proven to be beneficial in a variety of settings, including therapeutic...

These are exciting times for psychiatry and clinical neuroscience. Our knowledge of basic brain function continues to increase at an accelerating pace as the experimental tools available to basic and clinical scientists become ever more powerful and penetrating. After decades of frustration and relatively slow progress, this explosion of knowledge...

Objective Bile acids may contribute to pathophysiologic markers of Alzheimer’s disease, including disruptions of the executive control network (ECN) and the default mode network (DMN). Cognitive dysfunction is common in major depressive disorder (MDD), but whether bile acids impact these networks in MDD patients is unknown. Methods Resting state f...

Introduction: Subthalamic nucleus deep brain stimulation (STN DBS) improves motor symptoms of Parkinson’s disease (PD), but its effect on motivation is controversial. Apathy, the lack of motivation, commonly occurs in PD and is often exacerbated after surgery and its concomitant levodopa reduction. Apathy and reward processing are associated with t...

Brain connectivity analysis is crucial for understanding brain structure and neurological function, shedding light on the mechanisms of mental illness. To study the association between individual brain connectivity networks and the clinical characteristics, we develop BSNMani: a Bayesian scalar-on-network regression model with manifold learning. BS...

This study sought to further evaluate an observational measure of rumination that occurs during psychotherapy (i.e., in-session rumination). Specifically, the study aimed to replicate the reliability of an observational rating procedure in new therapy sessions and a new sample, clarify the relationship between in-session rumination and depressive s...

Deep brain stimulation (DBS) is an emerging therapeutic option for treatment resistant neurological and psychiatric disorders, most notably depression. Despite this, little is known about the anatomical and functional mechanisms that underlie this therapy. Here we targeted stimulation to the white matter adjacent to the subcallosal anterior cingula...

Meditation is an accessible mental practice associated with emotional regulation and well-being. Loving-kindness meditation (LKM), a specific sub-type of meditative practice, involves focusing one’s attention on thoughts of well-being for oneself and others. Meditation has been proven to be beneficial in a variety of settings, including therapeutic...

What happens at the end of a clinical trial for an investigational neural implant? It may be surprising to learn how difficult it is to answer this question. While new trials are initiated with increasing regularity, relatively little consensus exists on how best to conduct them, and even less on how to ethically end them. The landscape of recent n...

Metabolomics provides powerful tools that can inform about heterogeneity in disease and response to treatments. In this study, we employed an electrochemistry-based targeted metabolomics platform to assess the metabolic effects of three randomly-assigned treatments: escitalopram, duloxetine, and Cognitive Behavior Therapy (CBT) in 163 treatment-nai...

Subcallosal cingulate (SCC) deep brain stimulation (DBS) is an emerging therapy for refractory depression. Good clinical outcomes are associated with the activation of white matter adjacent to the SCC. This activation produces a signature cortical evoked potential (EP), but it is unclear which of the many pathways in the vicinity of SCC is responsi...

Dopamine and serotonin are hypothesized to guide social behaviours. In humans, however, we have not yet been able to study neuromodulator dynamics as social interaction unfolds. Here, we obtained subsecond estimates of dopamine and serotonin from human substantia nigra pars reticulata during the ultimatum game. Participants, who were patients with...

The Deep Brain Stimulation (DBS) Think Tank XI was held on August 9–11, 2023 in Gainesville, Florida with the theme of “Pushing the Forefront of Neuromodulation”. The keynote speaker was Dr. Nico Dosenbach from Washington University in St. Louis, Missouri. He presented his research recently published in Nature inn a collaboration with Dr. Evan Gord...

Deep brain stimulation (DBS) of the subcallosal cingulate cortex (SCC) is an experimental therapy for treatment-resistant depression (TRD). Chronic SCC DBS leads to long-term changes in the electrophysiological dynamics measured from local field potential (LFP) during wakefulness, but it is unclear how it impacts sleep-related brain activity. This...

Deep brain stimulation (DBS) has emerged as a promising treatment for select patients with refractory major depressive disorder (MDD). The clinical effectiveness of DBS for MDD has been demonstrated in meta-analyses, open-label studies, and a few controlled studies. However, randomized controlled trials have yielded mixed outcomes, highlighting cha...

Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw M...

Background A critical advance in depression research is to clarify the hypothesized role of interoceptive processing in neural mechanisms of treatment efficacy. This study tests whether cortical interoceptive processing, as indexed by the heartbeat-evoked potential (HEP), is modulated by deep brain stimulation (DBS) to the subcallosal cingulate (SC...

Deep brain stimulation (DBS) of the subcallosal cingulate cortex (SCC) is an experimental therapy for treatment-resistant depression (TRD). Chronic SCC DBS leads to long-term changes in the electrophysiological dynamics measured from local field potential (LFP) during wakefulness, but it is unclear how it impacts sleep-related brain activity. This...

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...

Ongoing experimental studies of subcallosal cingulate deep brain stimulation (SCC DBS) for treatment-resistant depression (TRD) show a differential timeline of behavioral effects with rapid changes after initial stimulation, and both early and delayed changes over the course of ongoing chronic stimulation. This study examined the longitudinal resti...

Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) can provide long-term symptom relief for treatment-resistant depression (TRD)¹. However, achieving stable recovery is unpredictable², typically requiring trial-and-error stimulation adjustments due to individual recovery trajectories and subjective symptom reporting³. We currently lack...

Background: Deep brain stimulation of the subcallosal cingulate area (SCC-DBS) is a promising neuromodulatory therapy for treatment-resistant depression (TRD). Biomarkers of optimal target engagement are needed to guide surgical targeting and stimulation parameter selection and to reduce variance in clinical outcome. Objective/Hypothesis: We aimed...

Recurrent episodes in major depressive disorder (MDD) are common but the neuroimaging features predictive of recurrence are not established. Participants in the Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) study who achieved remission after 12 weeks of treatment withcognitive behavior therapy, duloxetine, or...

Biological assay and imaging techniques have made visible a great deal of the machinery of mental illness. Over fifty years of investigation of mood disorders using these technologies has identified several biological regularities in these disorders. Here we present a narrative connecting genetic, cytokine, neurotransmitter, and neural-systems-leve...

It remains elusive what language markers derived from psychotherapy sessions are indicative of therapeutic alliance, limiting our capacity to assess and provide feedback on the trusting quality of the patient-clinician relationship. To address this critical knowledge gap, we leveraged feature extraction methods from natural language processing (NLP...

Objective: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus interna (GPi) have differential therapeutic effects for Parkinson's disease (PD) that drive patient selection. For example, GPi DBS is preferred for dystonic features and dyskinesia, whereas STN DBS has shown faster tremor control and medication reduction....

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...

Objective: The authors sought to determine the shared and unique changes in brain resting-state functional connectivity (rsFC) between patients with major depressive disorder who achieved remission with cognitive-behavioral therapy (CBT) or with antidepressant medication. Methods: The Predictors of Remission in Depression to Individual and Combi...

Major depressive disorder (MDD) exhibits diverse symptomology and neuroimaging studies report widespread disruption of key brain areas. Numerous theories underpinning the network degeneration hypothesis (NDH) posit that neuropsychiatric diseases selectively target brain areas via meaningful network mechanisms rather than as indistinct disease effec...

Deep brain stimulation (DBS) devices capable of measuring differential local field potentials (∂LFP) enable neural recordings alongside clinical therapy. Efforts to identify oscillatory correlates of various brain disorders, or disease readouts , are growing but must proceed carefully to ensure readouts are not distorted by brain environment. In...

Depression is an ancient illness. Rich descriptions of the clinical phenomenology of depression are found in the writings of the Greek physician, Hippocrates (460–377 B.C.), and the Roman physician, Galen (129–199 A.D.), as well as those of the Arabic physician, Ishaq Ibn Imran (tenth century A.D.), who anticipated the precipitating role of stress...

The study evaluated if rumination of patients during therapy (i.e., in-session rumination) relates to whether or not they do less well in CBT treatment. We developed a reliably assessed in-session rumination observational measure and evaluated its relationship to depression over the course of CBT. Rated sessions came from 63 treatment-naïve patient...

Precision targeting of specific white matter bundles that traverse the subcallosal cingulate (SCC) has been linked to efficacy of deep brain stimulation (DBS) for treatment resistant depression (TRD). Methods to confirm optimal target engagement in this heterogenous region are now critical to establish an objective treatment protocol. As yet unexam...

A bstract Deep brain stimulation (DBS) within the subcallosal cingulate cortex (SCC) alleviates symptoms of depression through an unclear therapeutic mechanism. Precise stimulation of SCC white matter (SCCwm) is thought to be necessary to achieve therapeutic response, and clinical recordings can now be used to test this hypothesis. In this paper we...

Deep brain stimulation has been extensively studied as a therapeutic option for treatment-resistant depression (TRD). DBS across different targets is associated with on average 60% response rates in previously refractory chronically depressed patients. However, response rates vary greatly between patients and between studies and often require exten...

Deep brain stimulation is an effective treatment for obsessive–compulsive disorder but is rarely used. Action is needed by psychologists, psychiatrists and insurers so that patients with otherwise intractable cases can receive this therapy to improve their mental health.

Background: Efforts to develop neuroimaging-based biomarkers in major depressive disorder (MDD), at the individual level, have been limited to date. As diagnostic criteria are currently symptom-based, MDD is conceptualized as a disorder rather than a disease with a known etiology; further, neural measures are often confounded by medication status a...

Bidirectional deep brain stimulation (bdDBS) devices capable of recording differential local field potentials (dLFP) enable neural recordings alongside clinical therapy. Efforts to identify objective signals of various brain disorders, or disease readouts, are challenging in dLFP, especially during active DBS. In this report we identified, characte...

INTRODUCTION Deep brain stimulation of the anterior limb of the internal capsule (ALIC-DBS) is an effective treatment for refractory obsessive-compulsive disorder (OCD). Animal tracing studies and human tractography suggest that the putative ALIC target for OCD impacts brain circuits for reward, affect and inhibitory control, including projections...

DBS Think Tank IX was held on August 25–27, 2021 in Orlando FL with US based participants largely in person and overseas participants joining by video conferencing technology. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers and researchers (from industry and academia) can freely discuss current and e...

Background Individuals experiencing socioeconomic deprivation consistently demonstrate poorer physical and mental health. Income alone is inadequate as a measure of socioeconomic status (SES); a better measure for assessing the deprivation status of individuals is needed. Methods The New Zealand Index of Socioeconomic Deprivation for Individuals,...

Background Major depressive disorder (MDD) is a highly heterogenous disease, both in terms of clinical profiles and pathobiological alterations. Recently, immunometabolic dysregulations were shown to be correlated with atypical, energy-related symptoms but less so with the Melancholic or Anxious distress symptom dimensions of depression in The Neth...

In this perspective article, we consider the critical issue of data and other research object standardisation and, specifically, how international collaboration, and organizations such as the International Neuroinformatics Coordinating Facility (INCF) can encourage that emerging neuroscience data be Findable, Accessible, Interoperable, and Reusable...

Background: Hippocampal atrophy has been consistently reported in major depressive disorder with more recent focus on subfields. However, literature on hippocampal volume changes after antidepressant treatment has been limited. The first-line treatments for depression include antidepressant medication (ADM) or cognitive-behavior therapy (CBT). To u...

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...

Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) is a promising intervention for treatment-resistant depression (TRD). Despite the failure of a clinical trial, multiple case series have described encouraging results, especially with the introduction of improved surgical protocols. Recent evidence further suggests that tractography ta...

It is unknown whether indoles, metabolites of tryptophan that are derived entirely from bacterial metabolism in the gut, are associated with symptoms of depression and anxiety. Serum samples (baseline, 12 weeks) were drawn from participants (n = 196) randomized to treatment with cognitive behavioral therapy (CBT), escitalopram, or duloxetine for ma...

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

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: Major depressive disorder (MDD) is a highly heterogenous disease, both in terms of clinical profiles and pathobiological alterations. Recently, immunometabolic dysregulations were shown to be correlated with atypical, energy-related symptoms but less so with the Melancholic or Anxious distress symptom dimensions of depression in The Net...

Objective Deep brain stimulation (DBS) has been used as a treatment of last resort for treatment-resistant depression (TRD) for more than a decade. Many DBS targets have been proposed and tested clinically, but the underlying circuit mechanisms remain unclear. Uncovering white matter tracts (WMT) activated by DBS targets may provide crucial informa...

Background: Electroconvulsive therapy (ECT) is one of the most effective treatments for major depressive disorder. Recently, there has been increasing attention to evaluate the effect of ECT on resting-state functional magnetic resonance imaging (rs-fMRI). This study aims to compare rs-fMRI of depressive disorder (DEP) patients with healthy partici...

Selective serotonin reuptake inhibitors (SSRIs) are standard of care for major depressive disorder (MDD) pharmacotherapy, but only approximately half of these patients remit on SSRI therapy. Our previous genome-wide association study identified a single-nucleotide polymorphism (SNP) signal across the glutamate-rich 3 (ERICH3) gene that was nearly g...

We estimate that 208,000 deep brain stimulation (DBS) devices have been implanted to address neurological and neuropsychiatric disorders worldwide. DBS Think Tank presenters pooled data and determined that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. The DBS Think Tank was fou...

A Correction to this paper has been published: https://doi.org/10.1007/s12021-021-09522-x

Background Electroconvulsive Therapy (ECT) is one of the most effective treatments for major depressive disorder (DEP). There is recently increasing attention to evaluate ECT’s effect on resting-state functional magnetic resonance imaging (rs-fMRI). This study aims to compare rs-fMRI of DEP patients with healthy participants, investigate whether dy...

Deep brain stimulation (DBS) of the subcallosal cingulate has emerged as a promising therapy for treatment-resistant depression (TRD). To date, all studies have employed bilateral stimulation; however, the physiology of affect and pathophysiology of depression are known to be asymmetric across hemispheres. Unilateral stimulation may provide efficac...

Lasting effects of adversity, such as exposure to childhood adversity (CA) on disease risk, may be embedded via epigenetic mechanisms but findings from human studies investigating the main effects of such exposure on epigenetic measures, including DNA methylation (DNAm), are inconsistent. Studies in perinatal tissues indicate that variability of DN...

Background Although a number of neuroimaging biomarkers for response have been proposed, none have been tested prospectively for direct effects on treament outcomes. This is the first prospective test of the clinical utility of the use of an imaging biomarker to select treatment for patients with major depressive disorder (MDD). Methods Eligible p...

There is great need for coordination around standards and best practices in neuroscience to support efforts to make neuroscience a data-centric discipline. Major brain initiatives launched around the world are poised to generate huge stores of neuroscience data. At the same time, neuroscience, like many domains in biomedicine, is confronting the is...

Chronic activation and dysregulation of the neuroendocrine stress response have severe physiological and psychological consequences, including the development of metabolic and stress-related psychiatric disorders. We provide the first unbiased, cell type–specific, molecular characterization of all three components of the hypothalamic-pituitary-adre...

Neurosurgery for psychiatric disorders (NPD), also sometimes referred to as psychosurgery, is rapidly evolving, with new techniques and indications being investigated actively. Many within the field have suggested that some form of guidelines or regulations are needed to help ensure that a promising field develops safely. Multiple countries have en...

Background It is unknown whether indoles, metabolites of tryptophan that are derived entirely from bacterial metabolism in the gut, are associated with symptoms of depression and anxiety. Methods Serum samples (baseline, 12 weeks) were drawn from participants (n=196) randomized to treatment with cognitive behavioral therapy (CBT), escitalopram, or...

Background: Antidepressant medication (ADM) and psychotherapy are effective treatments for major depressive disorder (MDD). It is unclear, however, if treatments differ in their effectiveness at the symptom level and whether symptom information can be utilised to inform treatment allocation. The present study synthesises comparative effectiveness...

Background Traditional rating scales for depression rely heavily on patient self-report, and lack detailed measurement of non-verbal behavior. However, there is evidence that depression is associated with distinct non-verbal behaviors, assessment of which may provide useful information about recovery. This study examines non-verbal behavior in a sa...