Rescuing the Ruminating Brain: Identifying Biomarkers of Rumination and Mindfulness Through Concurrent EEG and fMRI Studies of Schizophrenia and Depression
Principal Investigator: Judith M. Ford
Rumination involves recursive negative thinking focused on causes and consequences rather than solutions. It is common in major depressive disorder (MDD) and is also related to hallucinations and delusions in schizophrenia (SZ). Mindfulness involves attending to present moment experiences and allowing emotions and thoughts to pass without judgment, thereby avoiding a downward spiral into rumination. We assess basic sensory, cognitive, and emotional responses in people who tend to be ruminators and compare them to people who adopt a more mindful approach to life. We will simultaneously acquire EEG/ERP and fMRI to assess these basic processes and the current state of the brain, respectively. Understanding how rumination affects engagement with environmental events is the first step towards assessing its far-reaching cognitive and emotional costs. Conversely, we will ask how mindfulness restores information processing.
Neural and Cognitive Consequences of COVID-19 Survival
Principal Investigator: Judith M. Ford and Lynn Pulliam
Since the start of the pandemic in 2020, people have been experiencing symptoms of LongCOVID. We are asking about the underlying causes of LongCOVID, loosely defined as symptoms persisting more than 3 months since testing positive for COVID. We will collect EEG, Neuropsychological, MRI and fasting blood from people with LongCOVID. People will be compensated for their time. The entire study can be done in one day.
Can Neural Network Instability in Schizophrenia be Improved with a Very Low Carbohydrate Ketogenic Diet?
Principal Investigator: Judith M. Ford
While glucose is normally considered to be the brain’s default fuel, ketones provide 27% more free energy than glucose. In addition, ketones have been shown to reduce inflammation and increase brain metabolism. Finally, psychosis is associated with network dysconnection/instability, which in turn is associated with cognitive deficits. One possible antidote to these problems is a ketogenic diet, which has been used for 102 years to treat childhood epilepsy.
We are looking for people with a diagnosis of schizophrenia, schizoaffective disorder, and bipolar disorder with psychotic features to participate in a clinical trial of ketogenic diets. We supply the food for 4 weeks and up to 4 months. MRI, Neuropsychological, and blood data would be collected before and after the diet. People are compensated for their time.
Reward Processing and Depressive Subtypes: Identifying Neural Biotypes Related to Suicide Risk, Resilience, and Treatment Response
Principal Investigator: Susanna Fryer
This VA Merit Review project uses neurobiological measures of reward processing to understand how reward system neurobiology contributes to the expression of anhedonia and amotivation in Veterans with major depressive disorder (MDD). One goal of this work is to identify clinically relevant subtypes across depressed individuals on the basis of reward system brain functioning.
Multimodal Neural Investigation of Reward Processing in Mental Illness
Principal Investigator: Susanna Fryer
This study is motivated by interrelated questions about i) the nature of reward processing dysfunctions in schizophrenia (SZ), major depressive disorder (MDD), post-traumatic stress disorder (PTSD), and gambling disorder ii) the extent to which reward incentives modulate higher-order cognitive performance and brain functioning in SZ, MDD, PTSD and iii) how reward-related brain activations relate to negative symptoms in SZ, MDD, and PTSD. Neuroimaging techniques that capture aspects of in vivo brain functioning, such as EEG and fMRI, can inform these questions by noninvasively identifying brain responses to sub-component processes of interest.
Deficient Neural Plasticity and its Functional Consequences in Schizophrenia
Principal Investigator: Holly Hamilton
The VA cares for over 250,000 Veterans with psychotic disorders, primarily schizophrenia, which is a chronic illness associated with impaired cognition, lifelong disability, and high healthcare costs. While antipsychotic medications alleviate psychotic symptoms for many patients, treatments do not adequately target cognitive impairments and the poor functional outcomes to which these impairments contribute. Recent research suggests that basic mechanisms of neuroplasticity, which are the fundamental building blocks of learning and memory, may be altered in schizophrenia, thus contributing to cognitive deficits and limiting the potential benefit of interventions targeting poor cognition. This study seeks to advance our knowledge about mechanisms of neuroplasticity in schizophrenia in order to set the stage for the development of new treatments aiming to ameliorate deficient neuroplasticity, thereby restoring the capacity of Veterans with schizophrenia to benefit from treatments involving new learning. Specifically, this study combines EEG and fMRI to 1) identify when and where plasticity effects, and their deficiencies in schizophrenia, occur in the brain; 2) test the hypothesis that variation in plasticity is associated with variation in learning; 3) examine whether the integrity of plasticity predicts learning and cognition changes following computerized visual training exercises, and 4) explore whether greater deficits in plasticity are correlated with more severe symptoms and poorer functional outcomes in schizophrenia.
Understanding Prodromes and Lessening Illness in Family Therapy (UPLIFT)
Principal Investigator: Daniel H. Mathalon
UCSF Path Program joins UPLIFT, a family treatment study for teens and young adults (ages 13-25 years) showing early symptoms indicating risk for psychosis. The Path Program is collaborating with seven university-based early psychosis clinics in North America to make advances in family-focused treatments for young people at clinical high risk for psychosis.
This study tests the idea that effective prevention and treatment involves working with the whole family, not just the person affected. Through mental health education, communication enhancement training, and problem-solving skills training, the treatment program aims to prevent young people from developing more severe forms of psychosis and to improve their functioning.
Psychosis Risk Outcomes Network (ProNET)
Principal Investigator: Daniel H. Mathalon
UCSF Path Program joins the National Institutes of Mental Health’s (NIMH) Accelerating Medicines Partnership® (AMP®)* focused on the development of promising therapies for those at risk of developing psychosis, including schizophrenia (SCZ).
The AMP-SCZ public-private partnership brings together NIMH, US Food and Drug Administration, pharmaceutical companies, non-profit organizations, and two networks of university-based clinical research programs across the world, to discover better ways to identify and treat young people at clinical high risk for psychosis. UCSF is one of 26 participating U.S.-based ProNET sites.