David W. McMillan

To meet the energetic needs of life, metabolic fuels—or macronutrients—are introduced to our system through a single entry point whereby they must be transported widely to their cellular end fate of utilization or storage. The coordination of this complex system—a milieu of nested and ever-specializing organs👉tissues👉cell types—is achieved via a distributed control system. In vertebrates, it follows that the brain is a player in this control system. But the role of the brain in certain metabolic process is no self-evidence... not least from a phenomenological perspective (you cannot, in fact, cause your blood sugar levels to decrease by consciously willing your blood sugar to drop).

• Transport of new (e.g., dietary) and existing (e.g., stored) fuels occurs via complex trafficking of molecular cargo via blood and lymph vessels between different organ systems.

• Use, or expenditure, of energy occurs due to different processes (e.g., aerobic vs anaerobic) and acting on different kinds of energetic molecules (e.g., carbohydrates or fats). The aerobic combustion of hydrocarbons—such as "carbs" and fats—requires oxygen. Energy can also be expended at a higher rate, although less sustainably, by anaerobic processes that do not directly require oxygen.

• Storage of carbohydrates is limited in humans but importantly occurs in the liver and muscles. Fat storage has a higher capacity and occurs mainly in the liver, muscles, and adipocytes (fat cells).

How does our brain, consciously or subconsciously, contribute to these processes?

Experiments

• Effect of SCI on dietary fat metabolism with and without pre-meal exercise (Registered Clinical Trial NCT03691532) (Conference Presentation, Conference Presentation; Original Research Paper)

• Impact of exercise mode and intensity on dietary metabolism in persons with paraplegia (Registered Clinical Trial NCT03545867) (Conference Presentation, Conference Presentation; Original Research Paper, Original Research Paper, Original Research Paper)

• Metabolism during recovery from circuit resistance exercise in persons with SCI (Conference Presentation, Conference Presentation, Conference Presentation; Original Research Paper)

• Metabolic economy of functional electrical stimulation (FES) cycling in persons with SCI (Conference Presentation, Conference Presentation)

• Cardiopulmonary physiology during self-paced maximal exercise in college men (Conference Presentation; Original Research Paper)

• Metabolic adaptations to periodized high intensity interval training (HIIT) in sedentary women (Original Research Paper, Original Research Paper, Original Research Paper)

Thoughts

• Stay tuned 😉

My dissertation co-mentor, Dr. Mark S. Nash, was the committee chair for the inaugural efforts to construct the Consortium for Spinal Cord Medicine (CSCM) clinical practice guidelines (CPG) for cardiometabolic disease (CMD) in people with spinal cord injury and disorder (SCI). Furthermore, my postdoctoral fellowship was conducted with Dr. David R. Gater, a physician-scientist expert on the management and study of metabolic complications of SCI such as (but not limited to) obesity.

Experiments

• Spinal Cord Injury Exercise and Nutrition Conceptual Engagement (SCIENCE) (Registered Clinical Trial NCT03495986)

Thoughts

• Using the internet to broadly deliver high intensity exercise to people with SCI: Narrative Review Paper

• Limits of treating obesity with exercise in people with SCI: Narrative Review Paper

• Energy expenditure and nutrient intake after SCI: Narrative Review and Guideline Synthesis

Spinal cord injury (SCI) disrupts the transmission of signals between the brain and the final target tissues, such as skeletal muscle cells in the case of volitional motor control. Certain approaches to restoring function aim to either protect or restore the neuronal connections between the brain and the body via the spine. Maybe signals coming from the brain can inspire the nerve to regrow and/or make new connections. Well for restoration these descending signals are likely necessary, but certainly not sufficient (least people could will their way out of paralysis).

We must also remember that the spinal cord is not merely a conduit. The primary computational unit of the nervous system is the synapse, a junction between (not within) neurons. Since direct connection between the brain and muscles is rare, synapses in the spine allow for computation. As the now-old adage goes: the spinal cord is smart. Thus strategies for augmenting spinal output, with or without varying levels of input from the brain, are merited.

Experiments

• The Up-LIFT Study of Non-Invasive ARC Therapy for Spinal Cord Injury (Registered Clinical Trial NCT04697472)

• Interappendicular neuromuscular coupling during body weight supported treadmill training (BWSTT) in persons with SCI (Conference Presentation; Original Research Paper)

• Synchronization of gait during side-by-side treadmill walking in college men and women (Original Research Paper)

Thoughts

• Pending

Surely we all appreciate our brains, but phenomenology alone does not lend itself to an appreciation of everything this amazing organ is doing. Along with the self-evident volitional—or somatic—processes that allow us to move and feel, our brains are conducting a silent orchestra to coordinate the many other bodily functions that don't feel to be under our control. Some of these functions occur via the autonomous action of organs: for example the pancreas has its own internal mechanisms for detecting sugar in the blood that it samples from the hepatic vein. But many of these bodily processes are, to some degree, augmented via signals from the autonomic nervous system that may or may not travel through the spinal cord. Autonomic neurological signals that do travel through the cord, such as the sudomotor cholinergic sympathetic efferents controlling dilation of blood vessels in skin capillary beds, are disrupted by spinal cord injury.

Maybe a clever measure of something external, like the surface of the skin, could allow us to understand the changes to the autonomic nervous system that are complex and otherwise subconscious.

Experiments

• Using galvanic skin conductance to determine the sympathetic level of injury in persons with SCI (Conference Presentation)

• Ishial skin blood flow during and after a bout of functional electrical stimulation (FES) cycling in persons with SCI (Conference Presentation)

Thoughts

• Pending

Both the rate and total magnitude of bone loss following spinal cord injury (SCI) exceeds that of unabated space flight. Clinically, this speaks to the importance of skeletal pathology in this population. SCI greatly increases risk of fracture in a manner that is unique to this population. Interestingly, lumbar spine bone density is largely preserved, and the most common fracture site—which is similar across all levels of injury—is the "knee region" (distal femur/proximal tibia). But physiologically, that bone loss in SCI exceeds what is observed in mechanical unloading alone is a hint. Bone are not just scaffolding.

Experiments

• Bone mineral density (BMD) and trabecular bone score (TBS) for bone health in persons with SCI (Conference Presentation)

• Cardiovascular Health Study (CHS) bone working group (Conference Presentation; Original Research Paper)

Thoughts

• Obesity and skeletal pathology in people with SCI: Narrative Review Paper

Florida’s sociogeographic, economic, and medical affordances have enticed a migration of persons with spinal cord injury (SCI) to this region. Specifically, Southeastern Florida is flat, snowless, has no State income taxes, and contains specialized medical centers. These conditions are advantageous given the mobility, medical, and monetary needs of individuals living with SCI, resulting in a robust community of those who have the means to relocate. Ironically, here in Southeastern Florida the conditions beneficial to living with SCI exist in one of North American’s prominent loci for coastal climate disasters. Yes, modern affordances in this region permit a long and well lived life with SCI; but external stressors resulting in deviations from standards of care quickly result in superimposed and intersecting risks to health and survival. Climatic hazards can impose deviations—such as disruptions of supply chains, alternations in access to energy and materials, and shifts in the type and availability of human resources required for care. In sub-tropical and tropical coastal areas, hurricanes have a disproportionate and often devastating effect on persons living with disabilities such as SCI.

Experiments

• Pending

Thoughts

• Pending

I am leading an international team, self-titled the Neurotherapeutic Psychedelic Research Group, of academic medical professionals who are interested in this topic. We are considering the potential neuromotor and psychological effects of psychedelic substances in the specific use-case of spinal cord injury (SCI). There is existing evidence in basic and pre-clinical models for modulation and even regeneration of spinal neurons. In people, we are working on generating the first evidence for neuromodulatory effects in this population. Low volume (i.e., "microdose") or local (i.e., intrathecal) delivery could allow for neuromotor benefits without perceptual "side effects." But we are also considering how to optimize "macrodose" approaches targeting psychological effects. Will substances interact with standard SCI pharmacopia? Will sitters need to be prepared for physical responses not seen in other populations? Ought at least one sitter be a person with SCI ("peer-sitting")? In the field of SCI, the topic of psychedelics has yet to be addressed. But the time is now.

Experiments

• Reported use of hallucinogenic substances in Spinal Cord Injury Model Systems registrants (ongoing study)

• Reported spasticity after self-administered psychedelics in people with SCI (ongoing study)

Thoughts

• On the Potential Therapeutic Application of Psychedelic Substances in Spinal Cord Injury (flagship review in preparation)