Abstract
This symposium application highlights the development of novel, cutting-edge biomarkers using neurophysiological and neuroimaging approaches that are relevant for geriatric populations. The presenters will show how these novel biomarkers have been developed in older populations. The practical utility of these biomarkers to track symptom or disease progression, understand treatment effects, and predict treatment response will also be highlighted.
First, Dr. Daniel Blumberger will introduce transcranial magnetic stimulation (TMS), which is a non-invasive form of brain stimulation that capitalizes on the ability of time-varying magnetic fields to induce electrical currents in biological tissue via the principle of electromagnetic induction. TMS can measure dysfunctional cortical inhibition (CI) and neuroplasticity, which have been postulated as a neuro-physiological mechanisms involved in treatment resistant depression (TRD). These paradigms also have potential to predict response to existing psychopharmacological treatments. Neurophysiological data from three groups will be presented (i.e., from non-depressed older adults, depressed older adults without treatment resistance and depressed older adults with treatment resistance.) Neurophysiological predictors of response to treatment will also be shown, highlighting the utility of TMS neurophysiology paradigms as biological predictors of treatment response and illness severity.
Second, Dr. Tarek Rajji will discuss deficits in neuroplasticity in patients with schizophrenia across the adult lifespan. Deficits in working memory performance are a core feature of people with schizophrenia across adult life. Modulation of gamma oscillations amplitude by theta oscillations phase (“theta–gamma coupling”) is thought to mediate working memory in the dorsolateral prefrontal cortex (DLPFC). Dr. Rajji will describe the results of a study which assessed deficits in coupling in response to a brain stimulation intervention delivered to the DLPFC in healthy people and people with schizophrenia, using a paired associative stimulation (PAS) paradigm. He will show that people with schizophrenia are impaired compared to the healthy subjects who also received PAS on PAS-induced potentiation of cortical evoked activity or coupling, compared with a PAS control intervention. Dr. Rajji will then describe how PAS paradigms can be used to improve brain plasticity and working memory.
Third, Dr. Aristotle Voineskos will describe a novel diffusion tensor imaging (DTI)-based approach that can index biomarkers of normal and pathological aging. While DTI studies have shed light on white matter microstructural abnormalities associated with aging, the focus has been on deep white matter (DWM) tracts, the long-range connections between brain regions. We now have a method to measure superficial white matter (SWM), which can index local brain connectivity, and may be important for cognitive function. Dr. Voineskos will describe results from a large study of normal aging individuals across the adult lifespan who underwent DTI and a full cognitive battery. Areas of SWM susceptible to aging and areas predicting cognitive performance will be described. The results of this study show that SWM declines in integrity with age, and could be a key neural substrate for age-related cognitive decline. SWM should be considered as an early outcome biomarker in clinical intervention studies aimed at improving or preserving cognitive performance in late-life.
Finally, Dr. Benoit Mulsant, the symposium discussant, will provide perspective regarding biomarker utilization in clinical trials and interventions, particularly in light of new position statements from major funding agencies expecting the use of biomarkers in such studies.