Digital Health Technology Research Funded by the National Institutes of Health.

Importance: Digital health in biomedical research and its expanding list of potential clinical applications are rapidly evolving. A combination of new digital health technologies (DHTs), novel uses of existing DHTs through artificial intelligence- and machine learning-based algorithms, and improved integration and analysis of data from multiple sources has enabled broader use and delivery of these tools for research and health care purposes. The aim of this study was to assess the growth and overall trajectory of DHT funding through a National Institutes of Health (NIH)-wide grant portfolio analysis.

Mechanistic link between right prefrontal cortical activity and anxious arousal revealed using transcranial magnetic stimulation in healthy subjects.

Much of the mechanistic research on anxiety focuses on subcortical structures such as the amygdala; however, less is known about the distributed cortical circuit that also contributes to anxiety expression. One way to learn about this circuit is to probe candidate regions using transcranial magnetic stimulation (TMS). In this study, we tested the involvement of the dorsolateral prefrontal cortex (dlPFC), in anxiety expression using 10 Hz repetitive TMS (rTMS).

New directions in the rational design of electrical and magnetic seizure therapies: individualized Low Amplitude Seizure Therapy (iLAST) and Magnetic Seizure Therapy (MST).

Electroconvulsive therapy remains a key treatment option for severe cases of depression, but undesirable side-effects continue to limit its use. Innovations in the design of novel seizure therapies seek to improve its risk benefit ratio through enhanced control of the focality of stimulation. The design of seizure therapies with increased spatial precision is motivated by avoiding stimulation of deep brain structures implicated in memory retention, including the hippocampus.

Classification algorithms for the identification of structural injury in TBI using brain electrical activity.

Background: There is an urgent need for objective criteria adjunctive to standard clinical assessment of acute Traumatic Brain Injury (TBI). Details of the development of a quantitative index to identify structural brain injury based on brain electrical activity will be described.

Methods: Acute closed head injured and normal patients (n=1470) were recruited from 16 US Emergency Departments and evaluated using brain electrical activity (EEG) recorded from forehead electrodes.

Testosterone depletion in adult male rats increases mossy fiber transmission, LTP, and sprouting in area CA3 of hippocampus.

Androgens have dramatic effects on neuronal structure and function in hippocampus. However, androgen depletion does not always lead to hippocampal impairment. To address this apparent paradox, we evaluated the hippocampus of adult male rats after gonadectomy (Gdx) or sham surgery.

Dynamics of Active Sensing and perceptual selection.

Sensory processing is often regarded as a passive process in which biological receptors like photoreceptors and mechanoreceptors transduce physical energy into a neural code. Recent findings, however, suggest that: first, most sensory processing is active, and largely determined by motor/attentional sampling routines; second, owing to rhythmicity in the motor routine, as well as to its entrainment of ambient rhythms in sensory regions, sensory inflow tends to be rhythmic; third, attentional manipulation of rhythms in sensory pathways is instrumental to perceptual selection. These observations outline the essentials of an Active Sensing paradigm, and argue for increased emphasis on the study of sensory processes as specific to the dynamic motor/attentional context in which inputs are acquired.

Role of cortical cell type and morphology in subthreshold and suprathreshold uniform electric field stimulation in vitro.

Background: The neocortex is the most common target of subdural electrotherapy and noninvasive brain stimulation modalities, including transcranial magnetic stimulation (TMS) and transcranial current simulation (TCS). Specific neuronal elements targeted by cortical stimulation are considered to underlie therapeutic effects, but the exact cell type(s) affected by these methods remains poorly understood.

Objective: We determined whether neuronal morphology or cell type predicted responses to subthreshold and suprathreshold uniform electric fields.

One-dimensional representation of a neuron in a uniform electric field.

The neocortex is the most common target of sub-dural electrotherapy and non-invasive brain stimulation modalities including transcranial magnetic stimulation (TMS) and transcranial direct current simulation (tDCS). Specific neuronal elements targeted by cortical stimulation are considered to underlie therapeutic effects, but the exact cell-type(s) affected by these methods remains poorly understood. We determined if neuronal morphology predicted responses to subthreshold uniform electric fields.

Effects of glucose and glutamine concentration in the formulation of the artificial cerebrospinal fluid (ACSF).

The composition of the ACSF is fundamental in controlling the extracellular environment of the brain slice preparation. 'Typical' formulations lack amino acids and contain a higher concentration of glucose (10 mM) than in the cerebrospinal fluid (0.47-4.

Effects of high-frequency stimulation on epileptiform activity in vitro: ON/OFF control paradigm.

Purpose: To determine the effects of high-frequency electrical stimulation on electrographic seizure activity during and after stimulation (ON-effect and OFF-effect).

Methods: The modulation and suppression of epileptiform activity during (ON-effect) and after (OFF-effect) high-frequency electrical stimulation was investigated using the high-K(+) and picrotoxin hippocampal slice epilepsy models. Uniform sinusoidal fields (50 Hz) were applied with various intensity levels for 1 min across brain slices.

Amplification of small electric fields by neurons; implications for spike timing.

Small (down to 1 mV/mm) electric fields will polarize neurons by only a small amount; for this reason small electric fields have previously been considered to have no physiologically relevant effects. However, here we propose a novel mechanism by which the non-linear properties of single neurons 'amplify' very small electric fields. Specifically, an amplified change in timing of action potential firing (DeltaT) is inversely proportional to the slope of depolarizing ramp stimulation and proportional to the amount of polarization (DeltaV) caused by the electric fields: DeltaT=DeltaV/(ramp slope).

Rational modulation of neuronal processing with applied electric fields.

Traditional approaches to electrical stimulation, using trains of supra-threshold pulses to trigger action potentials, may be replaced or augmented by using 'rational' sub-threshold stimulation protocols that incorporate knowledge of single neuron geometry, inhomogeneous tissue properties, and nervous system information coding. Sub-threshold stimulation, at intensities (well) below those sufficient to trigger action potentials, may none-the-less exert a profound effect on brain function through modulation of concomitant neuronal activity. For example, small DC fields may coherently polarize a network of neurons and thus modulate the simultaneous processing of afferent synaptic input as well as resulting changes in synaptic plasticity.

Spike timing amplifies the effect of electric fields on neurons: implications for endogenous field effects.

Despite compelling phenomenological evidence that small electric fields (<5 mV/mm) can affect brain function, a quantitative and experimentally verified theory is currently lacking. Here we demonstrate a novel mechanism by which the nonlinear properties of single neurons "amplify" the effect of small electric fields: when concurrent to suprathreshold synaptic input, small electric fields can have significant effects on spike timing. For low-frequency fields, our theory predicts a linear dependency of spike timing changes on field strength.