CSRD Research Career Scientist Award Application

Dr. Ford is an established investigator in neuroscience and psychiatry, with a PhD in neuroscience and life-long appointments in mental health/psychiatry. She uses electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), to investigate the neurobiology of schizophrenia (SZ) and major depressive disorder

(MDD). And now, she is adding COVID19 “long haulers” to the conditions she studies with brain imaging methods. SZ. Dr. Ford’s work in SZ was focused on an elemental neural system that dampens neural responses to self- generated stimuli compared to stimuli arising from the environment. It is thought to reflect the operation of an

efference copy/corollary discharge mechanism involving signaling from motor to sensory regions, preparing sensory regions for self-generated sensory events. This mechanism is ubiquitous across all animal species, and her work in translating this mechanism to a human paradigm has uncovered a fundamental deficit in sensory

information processing in people on the psychosis spectrum. With NIH R01 funding, she has shown deficiencies in these mechanisms are linked to auditory hallucinations and delusions. With current NIH R03 funding, she is now asking about the role of the thalamo-pontine-cerebellar circuit in the successful operation of this system.

Two of Dr. Ford’s VA trainees are now extending this work to a new sample of people with psychosis, their 1st degree relatives, youth at clinical risk for developing psychosis, and non-affected control participants. They are finding connectivity between cerebellum and pons is related to the action of the efference copy/corollary

discharge mechanism. With a more recently funded NIH R03 grant, she is asking whether EEG-assessed slowed perception has upstream effects on cognition and contributes to clinical features of psychosis in the schizophrenia spectrum. With a to-be-funded mechanistic clinical trial (NIH R21) involving a VA psychiatrist, a

VA radiologist, and a UCSF cardiologist, she is asking whether a ketogenic diet can restore neural network stability in SZ, thereby addressing both cognitive deficits and metabolic syndrome, associated with poor function and a shortened life span, respectively. MDD/SZ. About 4-years ago, she added MDD to the clinical populations she studies and is asking about the

negative consequences of rumination and whether they can be rescued by a mindfulness approach to life. Rumination is an internal cognitive state characterized by recursive thinking of self-distress and negative events focusing on the causes and consequences of distress rather than solutions. It cuts across diagnostic boundaries:

It is associated with symptom severity and chronicity in both MDD and SZ. Mindfulness is associated with less distress from auditory hallucinations in SZ and fewer residual symptoms in MDD. It involves attending to present moment experiences and sensations and allowing emotions and thoughts to enter and leave consciousness

without judgment, thereby avoiding a downward spiral into rumination. Compared to simple mind wandering, mindfulness recruits an attention network including parietal and prefrontal structures while mind wandering only recruits the default mode network. Long-COVID19. The newest population she is studying is the so-called ‘long-haulers’ following COVID19

infection. While the lungs are ground zero, COVID19 tears through organ systems from brain to blood vessels. Some who recover complain of ongoing problems, including lingering cognitive problems, depression, and anxiety. Dr. Ford has joined forces with both Lab Medicine and Radiology at SFVAMC to use psychological

testing, neuroimaging methods, and markers in the blood signaling damage in the brain. A close look at these problems is timely and imperative if we are to understand the pathophysiology of “COVID brain” and prepare for down-stream problems.