Intracerebral delivery of antiseizure medications by microinvasive neural implants.

Focal epilepsy is a difficult disease to treat as two-thirds of patients will not respond to oral anti-seizure medications (ASMs) or have severe off-target effects that lead to drug discontinuation. Current non-pharmaceutical treatment methods (resection or ablation) are underutilized due to the associated morbidities, invasive nature and inaccessibility of seizure foci. Less invasive non-ablative modalities may potentially offer an alternative.

Development of an MR-Guided Focused Ultrasound (MRgFUS) Lesioning Approach for the Fornix in the Rat Brain.

Objective: High-intensity magnetic resonance-guided focused ultrasound (MRgFUS) is a non-invasive therapy to lesion brain tissue, used clinically in patients and pre-clinically in several animal models. Challenges with focused ablation in rodent brains can include skull and near-field heating and accurately targeting small and deep brain structures. We overcame these challenges by creating a novel method consisting of a craniectomy skull preparation, a high-frequency transducer (3 MHz) with a small ultrasound focal spot, a transducer positioning system with an added manual adjustment of ∼0.

Ultrasonic therapies for seizures and drug-resistant epilepsy.

Ultrasonic therapy is an increasingly promising approach for the treatment of seizures and drug-resistant epilepsy (DRE). Therapeutic focused ultrasound (FUS) uses thermal or nonthermal energy to either ablate neural tissue or modulate neural activity through high- or low-intensity FUS (HIFU, LIFU), respectively. Both HIFU and LIFU approaches have been investigated for reducing seizure activity in DRE, and additional FUS applications include disrupting the blood-brain barrier in the presence of microbubbles for targeted-drug delivery to the seizure foci.

Development of an MR-guided focused ultrasound (MRgFUS) lesioning approach for small and deep structures in the rat brain.

Objective: High-intensity magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive therapy to lesion brain tissue, used clinically in patients and preclinically in several animal models. Challenges with focused ablation in rodent brains can include skull and near-field heating and accurately targeting small and deep brain structures. We overcame these challenges by creating a novel method consisting of a craniectomy skull preparation, a high-frequency transducer (3 MHz) with a small ultrasound focal spot, a transducer positioning system with an added manual adjustment of ∼0.

An electroencephalographic signature predicts antidepressant response in major depression.

Antidepressants are widely prescribed, but their efficacy relative to placebo is modest, in part because the clinical diagnosis of major depression encompasses biologically heterogeneous conditions. Here, we sought to identify a neurobiological signature of response to antidepressant treatment as compared to placebo. We designed a latent-space machine-learning algorithm tailored for resting-state electroencephalography (EEG) and applied it to data from the largest imaging-coupled, placebo-controlled antidepressant study (n = 309).

An Electroencephalography Connectomic Profile of Posttraumatic Stress Disorder.

Objective: The authors sought to identify brain regions whose frequency-specific, orthogonalized resting-state EEG power envelope connectivity differs between combat veterans with posttraumatic stress disorder (PTSD) and healthy combat-exposed veterans, and to determine the behavioral correlates of connectomic differences.

Methods: The authors first conducted a connectivity method validation study in healthy control subjects (N=36). They then conducted a two-site case-control study of veterans with and without PTSD who were deployed to Iraq and/or Afghanistan.