Electroconvulsive therapy (ECT) remains the gold-standard treatment for patients with depressive episodes, but the underlying mechanisms for antidepressant response and procedure-induced cognitive side effects have yet to be elucidated. Such mechanisms may be complex and involve certain ECT parameters and brain regions. Regarding parameters, the electrode placement (right unilateral or bitemporal) determines the geometric shape of the electric field (E-field), and amplitude determines the E-field magnitude in select brain regions (e.g., hippocampus). Here, we aim to determine the relationships between hippocampal E-field strength, hippocampal neuroplasticity, and antidepressant and cognitive outcomes. We used hippocampal E-fields and volumes generated from a randomized clinical trial that compared right unilateral electrode placement with different pulse amplitudes (600, 700, and 800 mA). Hippocampal E-field strength was variable but increased with each amplitude arm. We demonstrated a linear relationship between right hippocampal E-field and right hippocampal neuroplasticity. Right hippocampal neuroplasticity mediated right hippocampal E-field and antidepressant outcomes. In contrast, right hippocampal E-field was directly related to cognitive outcomes as measured by phonemic fluency. We used receiver operating characteristic curves to determine that the maximal right hippocampal E-field associated with cognitive safety was 112.5 V/m. Right hippocampal E-field strength was related to the whole-brain ratio of E-field strength per unit of stimulation current, but this whole-brain ratio was unrelated to antidepressant or cognitive outcomes. We discuss the implications of optimal hippocampal E-field dosing to maximize antidepressant outcomes and cognitive safety with individualized amplitudes.

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Forty patients with intractable seizures were studied in an epilepsy unit for an average of 8 weeks with video-electroencephalographic telemetry and continuous observation by trained personnel. Drugs were administered on the basis of antiepileptic drug measurements and seizure classification determined by clinical observation and telemetry. Seizure frequency was reduced in 24 patients (60%). Unrecognized seizure types were identified in 8 patients (20%), and diagnostic classification was changed in 19 patients (47.5). At least one antiepileptic drug was eliminated in 25 patients (60%), and the average drug reduction per patient--0.60--was highly significant (p less than 0.01). In patients with seizures refractory to conventional out-patient and hospital management, improvement in diagnostic accuracy and refinement in observation techniques result in significant reduction of seizure frequency, elimination of drugs, and limitation of toxicity.

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A 67-year-old organist and minister with diabetes mellitus had stereotyped focal seizures of the left lower face, jaw, and neck. Attacks occurred spontaneously or were induced when he played a specific hymn on the organ. The seizures were not induced by reading, singing, hearing, or playing the hymn silently. The patient had interictal weakness of the left lower face and left side of the tongue. Focal seizures were recorded on an electroencephalogram (EEG) at the right temporofrontal area. This patient illustrates partial seizures induced by playing music.

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Background Electroconvulsive therapy (ECT) is an effective treatment for all bipolar states. However, ECT remains underutilized, likely stemming from stigma and the risk of neurocognitive impairment. Neuroimaging research has identified state-specific areas of aberrant brain activity that may serve as targets for therapeutic brain stimulation. Electrode placement determines the geometry of the electric field and can be either non-focal (bitemporal) or more focal (right unilateral or bifrontal). Previous research has shown that electrode placement can impact clinical and cognitive outcomes independent of seizure activity. This review critically examines the evidence that focal (unilateral or bifrontal) electrode placements target specific aberrant circuitry in specific bipolar states to optimize clinical outcomes. We hypothesize that optimal target engagement for a bipolar state will be associated with equivalent efficacy relative to bitemporal non-focal stimulation with less neurocognitive impairment. Methods We performed a literature search in the PubMed database. Inclusion criteria included prospective, longitudinal investigations during the ECT series with specific electrode placements within a bipolar state from 2000 to 2018. Results We identified investigations that met our inclusion criteria with bipolar mania (n = 6), depression (n = 6), mixed (n = 3) and catatonia (n = 1) states. These studies included clinical outcomes and several included cognitive outcomes, which were discussed separately. Conclusions While the heterogeneity of the studies makes comparisons difficult, important patterns included the reduced cognitive side effects, faster rate of response, and equivalent efficacy rates of the focal electrode placements (right unilateral and bifrontal) when compared to non-focal (bitemporal) placement. Further avenues for research include more robust cognitive assessments to separate procedure-related and state-related impairment. In addition, future studies could investigate novel electrode configurations with more specific target engagement for different bipolar states.

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