Biology subjects

Mayberg, H.

Publications and source records attributed to Mayberg, H..

7 recordsLinked to original sources

bioRxiv2025

Longitudinal Changes in Cortical Response Dynamics with Deep Brain Stimulation to the Subcallosal Cingulate for Treatment-Resistant Depression

Deep brain stimulation (DBS) of the subcallosal cingulate cortex (SCC) is a promising intervention for treatment-resistant depression, yet objective biomarkers that track recovery remain limited. This study examined longitudinal changes in stimulation-evoked potentials (SEPs) to characterize how SCC-driven cortical communication evolves during treatment. Ten patients across three SCC-DBS trials underwent high-density EEG recordings at 4 and 24 weeks. SEP features were extracted from source-localized SCC signals and related to clinical outcomes and fractional anisotropy (FA) of midcingulate cingulum. Cortical responses showed a consistent reduction in latency and an increase in magnitude over time, indicating faster and stronger electrocortical signaling with chronic stimulation. Higher baseline midcingulate FA predicted greater latency acceleration, linking SEP timing to white-matter integrity. These findings identify temporal SEP dynamics as candidate mechanistic biomarkers that reflect circuit engagement during SCC-DBS and offer a pathway toward physiology-guided optimization of neuromodulation for depression. HighlightsO_LIReduced latency of stimulation evoked potential after 6 months of DBS C_LIO_LILarger cortical evoked response to single pulse perturbation after 6 months of DBS C_LIO_LIBaseline myelin integrity in MCC predicts magnitude of change in EP latency C_LI

neuroscience↗

bioRxiv2025

Ephaptic coupling and power fluctuations in depression

The initial therapeutic exposure to DBS during implantation surgery has reproducible acute behavioral effects that carry over without further stimulation. We analyzed LFP data from the first month following brief therapeutic intraoperative DBS. Data were recorded from the subcallosal cingulate cortex (SCC). During this month no further stimulation was applied. Recent studies have identified beta power fluctuations in LFP data as an acute putative depression biomarker of this exposure. However, a detailed description of neural dynamics underlying brain power fluctuations is missing. Here, we consider how these fluctuations are related to brain itinerancy, that is neural activity changes between stable and unstable states. We also provide a proof of principle study that these dynamics can be described using two new dynamical systems measures: instability frequency and relative wandering time. These capture interactions between neural activity and the mesoscale oscillatory electric fields generated by it. The two measures seem to split low vs. high HDRS scores within a small patient cohort. They are motivated by the cytoelectric coupling hypothesis, that suggests that efficient information processing results from mesoscale electric fields; and that the re-emergence of depression symptoms might result from altered electric fields. Whether the new measures reflect general mechanisms of rapid antidepressant action remains to be tested.

neuroscience↗

bioRxiv2024

Intracranial substrates of meditation-induced neuromodulation in amygdala and hippocampus

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 ones attention on thoughts of well-being for oneself and others. Meditation has been proven to be beneficial in a variety of settings, including therapeutical applications, but the neural activity underlying meditative practices and their positive effects are not well understood. In particular, its been difficult to understand the contribution of deep limbic structures given the difficulty of studying neural activity directly in the human brain. Here, we leverage a unique patient population, epilepsy patients chronically implanted with responsive neurostimulation device that allow chronic, invasive electrophysiology recording to investigate the physiological correlates of loving-kindness meditation in the amygdala and hippocampus of novice meditators. We find that LKM-associated changes in physiological activity specific to periodic, but not aperiodic, features of neural activity. LKM was associated with an increase in {gamma} (30-55 Hz) power and an alternation in the duration of {beta} (13-30 Hz) and {gamma} oscillatory bursts in both the amygdala and hippocampus, two regions associated with mood disorders. These findings reveals the nature of LKM-induced modulation of limbic activity in first-time meditators. SIGNIFICANCE STATEMENTWe leverage rare chronic, invasive electrophysiology recordings while participants engage in loving-kindness meditation to demonstrate that meditation induces neural changes in beta and {gamma} activity in the amygdala and hippocampus of novice meditators. These results build on previous findings in experienced meditators and reveal meditations potential for noninvasive neuromodulation of neural mechanisms associated with emotional regulation and mood disorders.

neuroscience↗

bioRxiv2023

A computational account of joint SSRI and anti-inflammatory treatment

We present a computational model that elucidates the interplay between inflammation, serotonin levels, and brain activity. The model delineates how inflammation impacts extracellular serotonin, while cerebral activity reciprocally influences serotonin concentration. Understanding the reciprocal interplay between the immune system and brain dynamics is important, as unabated inflammation can lead to relapsing depression. The model predicts dynamics within the prefrontal cortex (PFC) and subcallosal cingulate cortex (SCC), mirroring patterns observed in depressive conditions. It also accommodates pharmaceutical interventions that encompass anti-inflammatory and antidepressant agents, concurrently evaluating their efficacy with regard to the severity of depressive symptoms.

neuroscience↗

bioRxiv2023

Differential patterns of automatic segmentation of 3T and 7T MRI: Implications in neuropsychiatric disease

Automatic segmentation was performed on T1-MPRAGE structural MRI data acquired at 3T and 7T from 37 and 69 distinct healthy controls, respectively. Additionally, segmentation was performed on imaging acquired from 215 major depressive disorder (MDD) patients at 3T and 40 MDD patients at 7T. Of 259 segmentation-derived imaging features evaluated, 120 showed significant 3T vs. 7T differences among controls, and 153 among patients. 7T imaging metrics showed consistently lower cortical thickness and cortical gray/white matter ratios. Subcortical and cortical volumes measured at 7T were more mixed, with 7T images showing greater frontal lobe volume, but lower cortical volumes elsewhere.

bioengineering↗

bioRxiv2022

CRF Neurons Establish Resilience via Stress-History-Dependent BNST Modulation

IntroductionCumulative stress is a major risk factor for developing major depressive disorder (MDD), yet not everyone experiencing chronic stress develops MDD. In those who do not, it is unclear at what point, or by what mechanism, a trajectory of stable resiliency emerges. MethodsUtilizing a 10-day repeated social defeat stress model (RSDS) for MDD, we observed that a critical period between 7 and 10 daily defeats marks the phenotypical divergence of resilient from susceptible mice. Using cell-type selective electrophysiology, chemogenetics, optogenetics, fiber photometry and RNA quantification was employed to investigate the nature of stress effects on neuroadaptation in the oval nucleus of the bed nucleus of the stria terminalis (BNSTov) required to determine resilience. ResultsIn response to ongoing stress, corticotropin-releasing factor (CRF+, but not CRF-) neurons of the (BNSTov) displayed a sustained increased firing rate in resilient, but not susceptible mice. This neurophysiological adaptation was self-sustaining, but only after 7 critical stress exposures, indicating that the process of developing resilience is dependent on stress history. ConclusionOur study reveals a novel process by which individuals might persist in the face of adversity by way of stress-provoked activation, not inhibition of a key CRF limbic region that establishes a pathway to resilience.

neuroscience↗

bioRxiv2022

Decoding Depression During Subcallosal Cingulate Deep Brain Stimulation

AO_SCPLOWBSTRACTC_SCPLOWDeep brain stimulation of subcallosal cingulate white matter (SCCwm-DBS) alleviates symptoms of treatment resistant depression (TRD) over months of therapy. Readouts of depression symptom severity derived from neural recordings are needed for more systematic study and improvement of the therapy. In this study, we measured local field potentials (LFP) multiple times a day alongside seven months of therapy using the Activa PC+S in six patients treated with SCCwm-DBS. We found significant changes in oscillatory power between early and late therapy after accounting for stimulation-related distortions, particularly within the {beta} band. We then used a decoder strategy to identify oscillatory activity that tracked with depression measurements over seven months, with asymmetric{delta} and {beta} oscillations contributing to a statistically significant prediction of 10% of the measured depression signal. Simulating its use in clinical decision-making, we demonstrated that the DR-SCC yield clinically meaningful information that can augment other measures of depression state. Ultimately, this DR-SCC provides a data-driven first-step towards objectively tracking chronic recovery after antidepressant DBS implantation and developing adaptive DBS strategies in the presence of active stimulation.

neuroscience↗