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A sample of 85 seniors was given experience (10 trials) playing two computer tasks using four input devices (touch screen, enlarged mouse [EZ Ball], mouse, and touch pad). Performance measures assessed both accuracy and time to complete components of the game for these devices. As well, participants completed a survey where they evaluated each of the devices. Seniors also completed a series of measures assessing visual memory, visual perception, motor coordination, and motor dexterity. Overall, previous experience with computers had a significant impact on the type of device that yielded the highest accuracy and speed performance, with different devices yielding better performance for novices versus experienced computer users. Regression analyses indicated that the mouse was the most demanding device in terms of the cognitive and motor-demand measures. Discussion centers on the relative benefits and perceptions regarding these devices among senior populations.

Over the last two decades, the discovery of ketamine's antidepressant properties has galvanized research into the neurobiology of treatment-resistant depression. Nevertheless, the mechanism of action underlying antidepressant response to ketamine remains unclear. This study reviews electrophysiological studies of ketamine's effects in individuals with depression as well as healthy controls, with a focus on two putative markers of synaptic potentiation: gamma oscillations and long-term potentiation. The review focuses on: 1) measures of gamma oscillations and power and their relationship to both acute, psychotomimetic drug effects as well as delayed antidepressant response in mood disorders; 2) changes in long-term potentiation as a promising measure of synaptic potentiation following ketamine administration; and 3) recent efforts to model antidepressant response to ketamine using novel computational modeling techniques, in particular the application of dynamic causal modeling to electrophysiological data. The latter promises to better characterize the mechanisms underlying ketamine's antidepressant effects.

Background The glutamatergic modulator ketamine has created a blueprint for studying novel pharmaceuticals in the field. Recent studies suggest that “classic” serotonergic psychedelics (SPs) may also have antidepressant efficacy. Both ketamine and SPs appear to produce rapid, sustained antidepressant effects after a transient psychoactive period. Methods This review summarizes areas of overlap between SP and ketamine research and considers the possibility of a common, downstream mechanism of action. The therapeutic relevance of the psychoactive state, overlapping cellular and molecular effects, and overlapping electrophysiological and neuroimaging observations are all reviewed. Results Taken together, the evidence suggests a potentially shared mechanism wherein both ketamine and SPs may engender rapid neuroplastic effects in a glutamatergic activity-dependent manner. It is postulated that, though distinct, both ketamine and SPs appear to produce acute alterations in cortical network activity that may initially produce psychoactive effects and later produce milder, sustained changes in network efficiency associated with therapeutic response. However, despite some commonalities between the psychoactive component of these pharmacologically distinct therapies—such as engagement of the downstream glutamatergic pathway—the connection between psychoactive impact and antidepressant efficacy remains unclear and requires more rigorous research. Conclusions Rapid-acting antidepressants currently under investigation may share some downstream pharmacological effects, suggesting that their antidepressant effects may come about via related mechanisms. Given the prototypic nature of ketamine research and recent progress in this area, this platform could be used to investigate entirely new classes of antidepressants with rapid and robust actions.

Clinical assessments of brain function rely upon visual inspection of electroencephalographic waveform abnormalities in tandem with functional magnetic resonance imaging. However, no current technology proffers in vivo assessments of activity at synapses, receptors and ion-channels, the basis of neuronal communication. Using dynamic causal modeling we compared electrophysiological responses from two patients with distinct monogenic ion channelopathies and a large cohort of healthy controls to demonstrate the feasibility of assaying synaptic-level channel communication non-invasively. Synaptic channel abnormality was identified in both patients (100% sensitivity) with assay specificity above 89%, furnishing estimates of neurotransmitter and voltage-gated ion throughput of sodium, calcium, chloride and potassium. This performance indicates a potential novel application as an adjunct for clinical assessments in neurological and psychiatric settings. More broadly, these findings indicate that biophysical models of synaptic channels can be estimated non-invasively, having important implications for advancing human neuroimaging to the level of non-invasive ion channel assays.

NCT#00088699.

Rapid-acting interventions for the suicide crisis have the potential to transform treatment. In addition, recent innovations in suicide research methods may similarly expand our understanding of the psychological and neurobiological correlates of suicidal thoughts and behaviors. This review discusses the limitations and challenges associated with current methods of suicide risk assessment and presents new techniques currently being developed to measure rapid changes in suicidal thoughts and behavior. These novel assessment strategies include ecological momentary assessment, digital phenotyping, cognitive and implicit bias metrics, and neuroimaging paradigms and analysis methodologies to identify neural circuits associated with suicide risk. This review is intended to both describe the current state of our ability to assess rapid changes in suicide risk as well as to explore future directions for clinical, neurobiological, and computational markers research in suicide-focused clinical trials.

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