Joshua Cain, PhD

Glossary

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ASL (Arterial Spin Labeling):

An MRI technique that measures blood flow in the brain by magnetically 'labeling' water molecules in blood vessels — no injected contrast agent needed. ASL provides an indirect measure of brain activity and is especially useful for studying cerebral perfusion (blood delivery to brain tissue).

MRI (Magnetic Resonance Imaging):

A medical imaging technique that uses strong magnetic fields and radio waves to produce detailed images of the body's organs and tissues — without radiation. In neuroscience, MRI is the workhorse imaging tool: structural MRI maps brain anatomy, while functional variants (fMRI, ASL) capture brain activity. High spatial resolution makes it the gold standard for studying brain structure and function.

Neuronavigation:

A real-time tracking and guidance system used in neuroscience and neurosurgery to precisely locate instruments, electrodes, or stimulation devices relative to an individual's brain anatomy (from MRI or CT scans). In focused ultrasound and TMS research, neuronavigation ensures the stimulation beam is aimed at the intended brain target with millimeter accuracy.

PET (Positron Emission Tomography):

A nuclear medicine imaging technique that uses radioactive tracers injected into the bloodstream to visualize metabolic processes in the body in real time. In neuroscience, PET measures brain activity, cerebral blood flow, glucose metabolism, and receptor density — providing functional information complementary to the structural detail of MRI.

Pre-processing (Neuroimaging / EEG):

The initial pipeline of steps applied to raw neuroimaging or electrophysiological data to remove noise, artifacts, and unwanted signals before scientific analysis begins. For EEG, this typically includes filtering, artifact rejection (e.g., eye blinks, muscle noise), re-referencing, and epoch extraction. For fMRI, it includes slice-timing correction, motion correction, spatial normalization, and smoothing. The quality of pre-processing directly determines data quality.

Attenuation:

The loss of energy as waves (such as sound or light) travel through a medium. In focused ultrasound, attenuation refers to how much energy the beam loses as it passes through the scalp, skull, and brain tissue. Accurately modeling attenuation is essential for predicting where ultrasound energy will be deposited.

Basic Research:

Scientific inquiry conducted to expand fundamental knowledge and understanding of the natural world, without a specific immediate practical application in mind. Basic research forms the foundation upon which applied research and real-world technologies are built. It is sometimes called 'pure research' or 'fundamental research.'

Biophysical Simulations:

Computer models that simulate physical and biological processes — such as how sound waves travel through the skull and brain, or how heat spreads through tissue. These simulations allow researchers to predict and optimize treatment parameters before testing on humans.

BOLD Signal:

Blood Oxygen Level Dependent signal — the measure recorded during fMRI. When a brain region becomes active, blood flow increases to it, changing local oxygen levels. fMRI detects these changes as an indirect measure of neural activity.

Brain-Computer Interface (BCI):

Technology that creates a direct communication channel between the brain and an external device, allowing people to control computers, prosthetics, or other systems using only brain signals — without physical movement.

CEO (Chief Executive Officer):

The highest-ranking executive in a company, responsible for overall strategic direction, major organizational decisions, and serving as the primary point of accountability to the board of directors and investors. In early-stage companies, the CEO often also plays a hands-on role in day-to-day operations.

Clinical Trial:

A rigorously controlled study conducted in human volunteers to evaluate the safety, efficacy, or effects of a medical intervention — such as a drug, device, or procedure. Clinical trials must be pre-registered in public databases (e.g., ClinicalTrials.gov), follow strict ethical and regulatory guidelines (e.g., FDA, ICH-GCP), and require independent review and approval from an Institutional Review Board (IRB) — requirements that go well beyond those for standard academic research studies involving human subjects.

Cognitive Neuroscience:

The scientific study of how the brain gives rise to mental functions such as memory, attention, language, perception, and decision-making. It bridges biology (the structure and chemistry of the brain) and psychology (the study of behavior and the mind).

CSO (Chief Scientific Officer):

A senior executive responsible for overseeing an organization's scientific strategy, research programs, and technical direction. In early-stage companies and research institutions, the CSO often also leads hands-on research and ensures scientific rigor across all programs.

CT (Computed Tomography):

A medical imaging technique that uses X-rays taken from multiple angles to produce detailed cross-sectional images of the body's interior. In brain research, CT scans are commonly used to assess anatomy, detect injury, or inform treatment planning for focused ultrasound procedures.

Disorders of Consciousness (DOC) — Acute & Chronic:

Conditions in which a person's level of awareness is severely reduced, typically following brain injury. Acute DOC refers to an early, actively evolving state (such as coma immediately following injury) where rapid changes are still possible. Chronic DOC refers to a prolonged condition that has persisted for weeks, months, or years — including vegetative state (wakefulness without awareness) and minimally conscious state (partial, inconsistent awareness).

EEG (Electroencephalography):

A brain imaging technique that measures the brain's electrical activity using sensors placed on the scalp. EEG captures signals at very high time resolution (milliseconds), making it ideal for studying brain rhythms and real-time responses to stimuli.

fMRI (Functional Magnetic Resonance Imaging):

A brain scanning technique that detects changes in blood flow to identify which regions of the brain are active during specific tasks or mental states. It produces detailed 3D images and is one of the most widely used tools for studying brain function.

fNIRS (Functional Near-Infrared Spectroscopy):

A non-invasive brain imaging technique that uses harmless near-infrared light to measure changes in blood oxygenation near the brain's surface, providing an indirect measure of brain activity. More portable than fMRI and usable during natural movement.

Focused Ultrasound (FUS):

A non-invasive technique that uses precisely targeted beams of sound waves to stimulate or suppress specific brain regions — without surgery or implants. Focused ultrasound can reach deep brain structures with high spatial precision, making it a powerful tool for neuromodulation research and therapy.

Graph Theory:

A branch of mathematics used to study networks of connected nodes and edges. In neuroscience, graph theory is applied to brain connectivity data to understand how different brain regions communicate with one another and to identify disruptions in those networks associated with disease.

IP (Intellectual Property):

Legal protections for creations of the mind — including inventions (patents), written works (copyright), brand identifiers (trademarks), and trade secrets. In research and startup contexts, 'IP' typically refers to patents or proprietary knowledge that provides a competitive or scientific advantage.

IRB (Institutional Review Board):

An independent ethics committee that reviews and approves research studies involving human participants. The IRB ensures studies are conducted ethically, that risks are minimized, and that participants provide informed consent before enrolling.

LIFU (Low-Intensity Focused Ultrasound):

A form of focused ultrasound that uses sound waves at intensity levels low enough to modulate neural activity without causing tissue damage or heating. LIFU is especially valuable for safely stimulating or suppressing deep brain regions in both research and early clinical applications.

LIFUP (Low-Intensity Focused Ultrasound Pulsation):

A pulsed variant of LIFU in which ultrasound energy is delivered in brief, repeated bursts rather than continuously. The pulsed approach enables targeted neuromodulation while limiting heat buildup in surrounding tissue.

MD (Medical Device):

In this context, MD stands for Medical Device — any instrument, apparatus, or system used to diagnose, prevent, monitor, or treat a medical condition. Medical devices range from simple tools to complex electronic systems and are regulated by government agencies (such as the FDA in the USA) to ensure safety and effectiveness.

Neural Correlate:

A measurable brain activity pattern — such as an fMRI signal or electrical rhythm — that reliably co-occurs with a specific mental state, behavior, or experience. Identifying neural correlates helps researchers understand which brain processes underlie consciousness, emotion, cognition, and more.

Neural Network:

In neuroscience, a neural network is an interconnected system of neurons (brain cells) that communicate to perform functions like memory, perception, and learning. In computing and AI, 'neural network' refers to algorithms modeled after the brain's architecture, used to recognize patterns in data.

Neuromodulation:

The use of targeted energy — such as electrical pulses, magnetic fields, or sound waves — to alter the activity of the nervous system. Neuromodulation techniques can enhance or suppress specific brain circuits and are used in both research and treatment of neurological and psychiatric conditions.

Neuroimaging:

A broad term for techniques that produce images of brain structure or activity. Structural imaging (like MRI or CT) reveals anatomy; functional imaging (like fMRI or EEG) reveals which parts of the brain are active and when. Neuroimaging is central to both basic neuroscience research and clinical diagnosis.

Parcellation:

In structural MRI analysis, parcellation is the process of dividing the brain into distinct anatomical regions ('parcels') based on structural features, connectivity patterns, or functional boundaries. This allows researchers to study, compare, and quantify specific brain areas across individuals or conditions.

Preprint:

A version of a scientific paper posted publicly — often on platforms like bioRxiv, medRxiv, or PsyArXiv — before completing formal peer review by a journal. Preprints allow findings to be shared quickly with the community but have not yet been independently validated by external reviewers.

Pulvinar:

The largest sub-region of the thalamus, located at its posterior (rear) end. The pulvinar plays important roles in visual attention, awareness, and the coordination of information flow across the brain. It is a key target in research on consciousness and sensory processing.

Refraction:

The bending of waves (sound or light) as they pass from one medium into another with different physical properties. In focused ultrasound, refraction occurs as the beam travels through layers of tissue with varying density (particularly the skull), deflecting it away from its intended target. Correcting for refraction is critical for accurate brain stimulation.

Sonication:

The act of applying focused ultrasound energy to a specific target. In brain stimulation research, a 'sonication' refers to a single delivery of focused ultrasound to a brain region. Multiple sonications may be administered across a session to achieve the desired neuromodulatory effect.

Subcortical:

Referring to brain structures located beneath the cerebral cortex (the brain's outer folded layer). Subcortical regions — such as the thalamus, basal ganglia, and brainstem — are involved in essential functions like sensory relay, motor control, arousal, and emotion.

Surrogate Model:

A simplified computational model used to approximate the behavior of a more complex, expensive-to-run simulation. In focused ultrasound research, surrogate models can predict how sound waves will travel through the skull and brain quickly enough to be used in real-time treatment planning.

TBI (Traumatic Brain Injury):

Physical damage to the brain caused by an external force — such as a blow to the head, a fall, or a blast wave. TBIs range from mild concussions to severe injuries causing long-term disability or disorders of consciousness, and are a leading cause of death and disability worldwide.

tFUS (Transcranial Focused Ultrasound):

Focused ultrasound delivered non-invasively through the skull. tFUS allows researchers and clinicians to target specific brain regions with acoustic energy without surgery, making it a key technique in neuromodulation research and the basis of several clinical trials in consciousness and neurological disorders.

Thalamus:

A small but vital brain structure near the center of the brain that acts as a relay hub. It routes sensory and motor signals between the body and the cerebral cortex, and plays a central role in regulating consciousness, sleep, and alertness. It is a primary target in research on disorders of consciousness and neuromodulation.

TMS (Transcranial Magnetic Stimulation):

A non-invasive brain stimulation technique that uses brief magnetic pulses to induce small electrical currents in targeted brain regions. TMS is used in research (to temporarily disrupt or enhance specific brain functions) and in clinical treatment, notably for depression.

Transcranial:

Literally meaning 'across the skull.' Describes non-invasive techniques applied to the outside of the head that influence brain activity without surgery, implants, or penetration of the skull. Examples include Transcranial Magnetic Stimulation (TMS) and Transcranial Focused Ultrasound (tFUS).

Working Memory:

A short-term cognitive system that temporarily holds and manipulates information needed for immediate tasks — such as holding a phone number in mind while dialing it, or following multi-step instructions. Working memory is considered a core component of intelligence and is closely tied to attention and executive function.

Real-World Data / Real-World Evidence (RWD/RWE):

Health data collected outside of traditional randomized controlled trials — from electronic health records, insurance claims, registries, wearables, and patient surveys (RWD) — and the clinical evidence derived from analyzing it (RWE). Regulators increasingly accept RWE to understand how treatments perform in everyday practice, where patients are more diverse and less closely monitored than in trials.

Patient-Reported Outcomes (PROs):

Measurements of a patient's health status reported directly by the patient, without interpretation by a clinician — such as symptom severity, pain, fatigue, mood, or quality of life. PROs capture the lived experience of treatment and are increasingly required endpoints in clinical trials and health outcomes research.

CDISC:

Clinical Data Interchange Standards Consortium — the set of global standards (SDTM, ADaM, CDASH, and others) that define how clinical trial data should be structured, named, and submitted. Regulators such as the FDA require CDISC-conformant datasets for most drug and device submissions, making it the common language of clinical data management.

Statistical Analysis Plan (SAP):

A pre-specified document that defines exactly how a clinical study's data will be analyzed — endpoints, statistical models, handling of missing data, interim analyses, and multiplicity corrections — written and locked before the data are unblinded. The SAP protects a study from analytic 'cherry-picking' and is a core regulatory expectation.

Propensity Score:

A statistical method for making observational (non-randomized) comparisons fairer. Each subject's probability of receiving a treatment is estimated from their baseline characteristics, then subjects are matched or weighted on that score so treated and untreated groups look comparable — approximating, though never fully replacing, randomization.

Mixed Models:

Regression models that include both 'fixed' effects (population-level relationships of interest) and 'random' effects (subject-, site-, or cluster-level variation). They are the standard tool for longitudinal and repeated-measures data — such as tracking the same patients over multiple visits — because they handle correlated observations and unbalanced follow-up gracefully.

Survival Analysis:

A family of statistical methods for analyzing time-to-event data — how long until death, relapse, recovery, or device failure. Its defining feature is handling 'censored' subjects whose event has not occurred by the end of follow-up. Common tools include Kaplan-Meier curves and Cox proportional-hazards regression.

GCP (Good Clinical Practice):

An international ethical and scientific quality standard governing the design, conduct, recording, and reporting of clinical trials involving human subjects. GCP compliance protects participant rights and safety and ensures trial data are credible to regulators; researchers typically document it through CITI or equivalent certification.