Research Group

A center, program or initiative whose main activity is focused on research, improving our understanding of neuropsychiatric conditions and disseminating such knowledge to the wider community.

Jonathan Flint

Jonathan Flint

I am a psychiatrist and behavioral geneticist, currently holding the Billy and Audrey Wilder Endowed Chair in Psychiatry and Neuroscience, based in UCLA’s Department of Psychiatry and Biobehavioral Science where I arrived at the end of 2015. Previously I was the Michael Davys Professor of Neuroscience at the University of Oxford and a fellow of Merton college, Oxford.

I trained in medicine at St. Mary’s hospital London and Oxford University where I graduated with a BM Bch in 1988. However I obtained my first undergraduate degree, in history, from the University of Oxford in 1979. I trained in psychiatry at the Maudsley and Bethlem Royal Hospitals, in London, from 1989 to 1992, and then moved back to Oxford, first to the Institute of Molecular Medicine (now the Weatherall Institute of Molecular Medicine) and then to the Wellcome Trust Centre for Human Genetics where I stayed until 2016. Throughout my career in Oxford I received support from the Wellcome Trust, progressing through their fellowship scheme from a Clinical Training Fellowship in 1992 to a Principal Fellowship in 2007.

Jonathan Flint personal website

Division of Population Behavioral Health

Division of Population Behavioral Health

The UCLA Department of Psychiatry Division of Population Behavioral Health facilitates the integration of behavioral health services, research and education into healthcare, community and home settings. By working closely with behavioral health and healthcare providers, the division implements a variety of programs to provide integrated care and reduce the burden of mental health disorder for individuals and families. These programs and initiatives are based on effective strategies and treatment models that have been implemented and developed by the expert clinical faculty at UCLA.

This division responds to changing national and health system priorities and represents a partnership between the UCLA Department of Psychiatry and UCLA Behavioral Health Associates.

Director

Patricia Lester, MD

Associate Director

Jessica Jeffrey, MD, MPH, MBA

Affiliated Faculty
Armen Arevian, MD PhD Timothy Fong, MD Sheryl Kataoka, MD, MSHS  Gary Small, MD
Joan Asarnow, PhD Marcy Forgey Borlik, MD James McCracken, MD Thomas Strouse, MD
Robert Bilder, PhD Michael Gitlin, MD David Merrill, MD PhD Margaret Stuber, MD
Brenda Bursch, PhD Christine Grella, PhD Norweeta Milburn, PhD
Kenneth Wells, MD MPH
Roya Ijadi-Maghsoodi, MD Catherine Mogil, PsyD

Centers & Programs

  • UCLA Nathanson Family Resilience Center
    • An academic center combining research and services for the whole family. The center bridges the gap between research and practice to help families become more resilient in the face of challenges. 
  • UCLA Child Anxiety Resilience Education and Support (CARES) Center 
    •  An academic center providing training, research, and community resources to help clinicians, school staff, and parents recognize the early signs of childhood anxiety and enhance family and community resilience.
  • UCLA Behavioral Health Checkup
    • The Behavioral Health Checkup allows patients to complete behavioral health assessments with ease on a tablet computer or other web-enabled device. Contact us for more information about using the Behavioral Health Checkup in your clinic.
  • Training Institute
    • The Division offers training in evidence-based practices that are trauma informed, including FOCUS (Families OverComing Under Stress).


Contact the Division of Population Behavioral Health

Division of Population Behavioral Health

Aftercare Research Program

WELCOME to the Aftercare Research Program at the UCLA Semel Institute

The Aftercare Research Program is an outpatient research clinic that provides assessment and treatment and conducts research with people who have recently experienced psychotic symptoms.  The Program is designed to aid in the adjustment to life in the community.  Our Program psychiatrists provide medication management, and our case managers provide education, psychotherapy, and cognitive training. Our staff also helps our participants in accomplishing goals such as returning to school and/or work.

Our team is comprised of a diverse group of professionals who have had extensive training in helping young adults who have recently become ill with a psychotic disorder.   Our staff works as a team to provide the best possible care to our participants. We believe our Program’s strength lies in the comprehensive and individualized treatment we provide to our participants. 

Aftercare Research Program Website

Treatment for ADHD, Irritability, and Mood Dysregulation

Participate in
ADHD Research
for Children and Adolescents

Participate in
New Non-Medication Treatment
for ADHD

As members of the ADHD, Irritability, and Mood Dysregulation treatment studies group, we seek to develop a better understanding of childhood emotional and behavioral disorders, as well as to develop new treatment approaches.  By studying the interaction between physiological and psychological processes in children and adolescents, we hope to learn more about how specific brain functions can cause specific behaviors. This may ultimately lead us to design and evaluate more effective treatments, and to provide better diagnosis.

Currently 1 in 10 children have been diagnosed with ADHD (CDC, 2015).  There are many established treatments for ADHD, and all were developed through the process of clinical research.  Clinical research helps to advance our understanding of ADHD and novel treatment approaches that may best target symptoms of the disorder. 

As a research team, we have seen many children and adults in our clinical practices at UCLA struggle with ADHD.  Our new research interests involve novel non-medication treatments for ADHD in addition to further study of children and adolescents who have severe difficulties with chronic irritability, moodiness, restlessness, agitation, or distractibility.

We hope to better serve individuals and families through research opportunities that target a child’s emotional and behavioral needs. If you are interested in participating in research regarding ADHD and/or Mood Dysregulation, contact us! You can also learn more about our interdisciplinary team by checking out the "Our Team" tab.  

Treatment for ADHD, Irritability, and Mood Dysregulation

Bearden Lab

The Bearden lab’s research aims to understand genetic, cognitive and neurobiological risk factors for the development of adolescent-onset neuropsychiatric disorders. We are examining these questions through two complementary lines of research: 1) The investigation of intermediate neuroanatomic and cognitive   traits associated with the development of psychosis and  mood disorder; and 2) The study of neurobehavioral manifestations of syndromes with an identified genetic origin

One of these studies  focuses on the 22q11.2 Deletion Syndrome, a genetic disorder which results in a disruption of early neuronal migration and confers a particularly high risk for psychosis. Dr. Bearden’s research group has an ongoing, NIMH-funded longitudinal study of risk factors for psychiatric disorder  in children and adolescents  with this syndrome. This project involves comprehensive phenotyping (i.e., dimensional measures of  psychopathology, neurocognition, and structural and functional neuroanatomy) which will be examined in relation to genetic variation at the 22q11.2 locus.

We are also investigating risk factors for psychosis in  youth with subthreshold clinical symptoms indicating high risk for the development of psychotic illness, in the Center for Assessment and Prevention of Prodromal States (CAPPS). The CAPPS program, directed by Dr. Bearden, is part of the NIMH-funded North American Prodromal Longitudinal Study (NAPLS) Consortium.

In collaboration with Alcino Silva, Dr. Bearden’s lab is also conducting two translational studies of the neural basis of cognitive and social difficulties in children with another genetic disorder, Neurofibromatosis I, one of the most common single-gene disorders affecting neurologic function in humans. We have just completed  enrollment for an NIMH-funded exploratory intervention grant , which examines a potential pharmacologic treatment for cognitive disability in individuals with NF1, the HMG-CoA reductase inhibitor lovastatin, which acts as a potent inhibitor of Ras activity and is commonly used for the treatment of hypercholesterolemia. The rationale for this novel intervention is based on findings from the mouse model of the disorder, in which lovastatin treatment was able to reverse the biochemical, electrophysiological and cognitive deficits associated with NF1 (Li et al. Curr Biol. 2005). This study represents one of the first translational clinical trials for developmental learning disabilities.

The Bearden lab also has a  new study funded by the Department of Defense NF1 Research Program. This study  aims to investigate potential blood biochemical and brain biomarkers of  cognitive control and social deficits, both cross-sectionally and longitudinally over a two-year period,  in school-age children with NF1.


Director: 
Carrie Bearden, Ph.D.
Bearden Lab

Integrated Substance Abuse Programs

Integrated Substance Abuse Programs

The UCLA Integrated Substance Abuse Programs (ISAP) was established in 1999 to consolidate research efforts in many areas of drug abuse research at UCLA. Since then, ISAP has steadily established its presence as a major entity in the drug abuse research community, both domestically and internationally.

The group continues to advance the knowledge base on drug problems and to improve the delivery of drug abuse treatment services through an array of projects.

More information currently at www.uclaisap.org

Looking for treatment? Visit the Matrix Institute Web site for more information on treatment services or call 1-800-310-7700. Other questions? E-mail our External Communications Director at isap@ucla.edu.

Director: 
Walter Ling
Advance the knowledge base on drug problems and to improve the delivery of drug abuse treatment services through an array of projects

UCLA Integrative Center for Neurogenetics

The UCLA Integrative Center for Neurogenetics (ICNG) focuses on discovering the genetic basis of major psychiatric and neurological disorders, and genetically dissecting additional traits that will shed light on the development, function, or degeneration of the central nervous system. Lack of understanding of the causes of brain diseases limits our capacity to develop better treatments and for prevention. We now have the research tools necessary to identify and characterize the specific genetic variations that predispose to brain disorders or that are associated with important nervous system traits in a wide range of model organisms.

Investigators in the ICNG utilize – and in some cases helped to develop – state of the art genomic and genetic methodologies including high throughput genotyping and DNA sequencing, gene expression analysis, genetic manipulation of model organisms, as well as bioinformatics, statistics, and cell biology. The investigations within the ICNG depend on sophisticated approaches for assessing brain and behavioral phenotypes in humans and model organisms. The development and application of such assessments provide the basis for numerous collaborations with investigators outside of the ICNG. The ICNG also occupies an important niche in the educational mission of UCLA. It is the focal point on campus for training graduate students and postdoctoral fellows in the genetic investigation of complex traits.

UCLA Integrative Center for Neurogenetics

Fuster Laboratory of Cognitive Neuroscience

Fuster Laboratory of Cognitive Neuroscience

Knowing how the discharges of single neurons and groups of neurons give rise to our thoughts, feelings, decisions and choices of action, lies at the fore of cognitive neuroscience. We know very little about how the activity of populations of neurons relate to behavioral choices, yet answers to such questions stand to reveal the fundamental mechanisms underlying neurological and psychiatric diseases ranging from Parkinson’s disease to addiction and schizophrenia. In my research program at UCLA we focus on understanding the role of the basal ganglia and its inputs to the superior colliculus in cognitive processes related to decision-making. We incorporate a variety of experimental approaches. Our primary focus emphasizes behavioral, electrophysiological and computational techniques in the non-human primate. We work closely with neurologists, neurosurgeons and neuropsychologists to translate our work with monkeys in to humans with disease. Although powerful, work with monkeys and humans is limited in its ability to reveal insights into the cellular and molecular mechanisms underlying cognitive processes. Therefore, to uncover cellular mechanisms, we perform experiments using the in vitro rodent model and biophysical tools such as patch-clamp recording and voltage imaging. In the laboratory we explore fundamental questions in cognitive neuroscience: 1) how are decisions represented in the sensorimotor networks of the basal ganglia and superior colliculus? 2) what are the computational principles that underlie decision-making? 3) how might these mechanisms go awry in disease? and 4) what are the cellular and synaptic mechanisms and dynamic properties of sensorimotor networks in the superior colliculus underlying decision-making? Below I provide an overview of our ongoing experiments and those planned for the near future.

Decision-Making in the Superior Colliculus and Basal Ganglia

Many lines of evidence are converging on the idea that regions of the brain involved in the generation of movement are also involved in making decisions based on sensory information. Because decision-making is considered a cognitive process, much of the work in this area emphasizes the cerebral cortex. However, the superior colliculus is a midbrain structure with inputs from much of the cerebral cortex and with outputs to brainstem regions critical for the generation of movement. This confluence of processing makes the superior colliculus well-poised to participate in events that occur between seeing and acting, such as decision-making. Our work focuses on whether and how the superior colliculus might be involved in these processes. Additionally, a set of forebrain nuclei called the basal ganglia also receive input from virtually the entire cerebral cortex and in turn, have direct input to the superior colliculus. Therefore, we also focus on the role of the basal ganglia in decision-making. By comparing the behavior of neurons in the superior colliculus and the basal ganglia we can assess the similarities and differences in processing that occurs in these two pathways leading to action. Since the basal ganglia are also associated with many diseases such as Parkinson’s disease, Huntington’s disease, Tourette syndrome, obsessive compulsive disorder, addiction and schizophrenia, understanding the role of the basal ganglia in these processes has tremendous clinical relevance.

We are approaching the question of whether and how populations of superior colliculus neurons contribute to decision-making by simultaneously recording multiple neurons while monkeys perform simple and complex decision tasks. In one experiment we present monkeys with an array of four possible target choices. Each recorded neuron in the superior colliculus represents one of the locations of the four possible targets. By doing this, we are able to observe directly the dynamics of the processing leading up to a single choice from the populations of neurons involved in making the choice. We implemented a signal detection theory approach to analyze our data and discovered that the relative level of activity of neurons representing targets and distractors signals the movement choice. Specifically, when the level of neuronal activity representing the target and distractor locations is highly overlapping, monkeys are more likely to make errors. When the level of neuronal activity representing the target and distractor locations is highly discriminable, monkeys are more likely to choose accurately. This result suggests that many neurons across the entire population within the superior colliculus are involved in decision-making for action (Kim and Basso, 2008).

Based on our results, we asked how superior colliculus neurons were pooled and read-out to inform a choice of action. In this line of work we applied theoretical models of population decoding schemes.

For example, we implemented a population vector average, a winner-takes-all and a Bayesian estimator to our colliculus neuronal data. We found that when the neuronal activity was pooled, the Bayesian estimator predicted the choices more accurately than either the winner-takes-all or the population vector average (Kim and Basso, 2010). Our results reveal that variability in neuronal discharge is an important parameter to consider for a complete understanding of how the brain represents choices of action and importantly, the uncertainty monkeys may have regarding their choices. figure 1This result prompted us to begin asking the question of how decisions are made when sensory information is ambiguous. Indeed, making decisions in the face of uncertainty is a situation with which we are often confronted. An example of the task that our monkeys perform to assess decision-making under uncertainty is shown in the figure on the left. In the easy trials (a), the image appears clearly as an arrow and the monkeys’ task is to look at the circle to which the arrow points. On the difficult trials (b), the arrow is not seen clearly and the monkeys must still make a decision, right or left. By varying how difficult the arrow is to see we can vary parametrically the uncertainty that monkeys have in their decision. What cues are used when forced to make a decision under uncertainty? One possibility is that we use our memories, or past experience. Therefore, we also vary which target is correct on the trials. For example, we can set the probability structure of the task such that on 70% of the trials, a rightward choice is always correct and on 30% of the trials, a leftward choice is correct. Monkeys have to learn and remember this 70-30 split over time. Then we can assess to what extent monkeys rely on sensory information versus information stored in memory to make decisions when faced with uncertainty. This work is based in a strong theoretical framework of statistical decision theory called Bayesian inference. Our plan is to perform simultaneous multiple neuron recordings during performance of this task to look for neurophysiological signatures of decision-making with and without sensory uncertainty.

A number of clinical phenomena seen in movement disorders may result from underlying deficits in higher cognitive processes, such as decision-making. We have been translating our findings in monkey into the clinic by testing patients with Parkinson’s disease on the same decision-making task that we use in our monkeys. In medically-treated patients with Parkinson’s disease and in those patients who received surgical treatment of their disease, we are testing whether the disease or the treatment influences the ability to make decisions in collaboration with Dr. Nader Pouratian in the Department of Neurosurgery and Dr. Allan Wu in the Department of Neurology. Whereas others focus on decision-making under risk and the influence of reward, we are interested in understanding how the basal ganglia contribute to decision-making in the presence of sensory uncertainty and with memory information available (or not) to inform decisions. By comparing results in monkeys and humans directly we are well-poised to reveal mechanisms of decision-making in health and disease. We recently received an award from the Dana Foundation to perform this work. 

Since Parkinson’s disease is a basal ganglia disease, we also explore the role of the inhibitory input arising from the basal ganglia to the superior colliculus in decision-making in monkeys. One of two output nuclei of the basal ganglia is the substantia nigra pars reticulata. The nigra has direct, inhibitory input to the superior colliculus. Our first tack has been to perform stimulation and recording experiments to reveal the circuitry of the nigra - superior colliculus connection and its influence on movement behavior in monkeys. Our first series of experiments explored the influence of electrical stimulation of the nigra on behavior and on superior colliculus neuronal activity. In addition to providing useful information on which to base further experiments, the results of these experiments provide us with a model to test some hypotheses about the mechanisms of action of a therapy that is used to treat a number of psychiatric and neurological disorders called deep brain stimulation. This neurosurgical treatment is used to treat patients with movement disorders most commonly, but it is also used to treat patients with medically refractory depression, Tourrette syndrome and obsessive compulsive disorder. Although the nigra is not typically a target of deep brain stimulation in patients, we reasoned that the relatively well-known role of this pathway in eye movement behavior would make it an ideal model system to study. By performing systematic, parametric studies of electrical stimulation of the nigra and measuring eye movements, we determined how the stimulation affects behavioral output (Basso and Liu, 2007).Electrical stimulation of the nigra results in impairments in monkeys’ ability to make eye movements when guided by memory. When the eye movements are guided by vision, electrical stimulation of the nigra has little effect. Following up on this experimental result, we performed an experiment to determine whether the electrical stimulation results from effects on the movement per se, or whether the effects result from alterations in spatial memory abilities. Our results, soon to appear in the Journal of Neurophysiology, are consistent with a role for the nigra in spatial memory. These results have important implications for a clinical phenomenon seen in patients with Parkinson’s disease calledparadoxical movement. The results also provide the basis for our overarching hypothesis: the basal ganglia play a role in representing prior information (memory) for decision-making.

We also performed simultaneous recording of superior colliculus neurons and electrical stimulation of the nigra to determine the cause of the behavioral changes (Liu and Basso, 2008). The nigra has a short lasting, profound inhibition of superior colliculus neurons bilaterally. In addition to providing us with a tractable model system to explore how a popular clinical therapy works, the results of our experiments provide us with a solid foundation to expand our decision work into the basal ganglia. Moving forward, we plan to extend this work to explore the combined roles of the frontal eye field and the colliculus as well as the lateral intraparietal area and the colliculus in decision-making under conditions of sensory uncertainty and with manipulations of prior (memory) information.

Linking Cellular and Cognitive Neuroscience: An in vitro Model of Decision-Making

Because the results of our experiments are leading us more and more into questions related to problems of local circuitry, I realized that we needed to expand our range of techniques to includeinvitrowork. In particular, because our stimulation results in the monkey showed that the nigra can influence saccadic eye movements in all directions, we believe the entire superior colliculus map is affected by alterations in basal ganglia activity. We began collaborating with Dr. Meyer Jackson in the Department of Neuroscience at the University of Wisconsin Madison. We are performing voltage imaging and whole cell patch clamp experiments in rodent superior colliculus slices. Because much of the circuitry of the colliculus is conserved evolutionarily, the rodent is a superb model of the monkey colliculus. We also began patch clamp recording experiments to complement our population level studies with single neuron studies. These powerful biophysical tools will provide important insights into the underlying cellular basis for decision-making. figure 2Our in vitro experiments are driven by the results of our non-human primate work and provide an important complement to that work (Vokoun et al., 2010). An example of more recent findings using this approach is shown in the figure on the left.

In this experiment we identified for the first time, an excitatory pathway from the intermediate layers of the superior colliculus to the superficial layers. Seminal work in the superior colliculus showed that when monkeys made saccadic eye movements to visual targets, the visual response of neurons in the superficial layers was enhanced compared to when monkeys saw the same visual stimulus but remained fixating elsewhere (Goldberg and Wurtz, 1972). Enhancement is thought to underlie selective visual attention. As such, a pathway from deeper eye movement regions of the colliculus was proposed to target the upper layers of the colliculus and modulate the visual responsiveness of these neurons (Mohler and Wurtz, 1976). Traditional anatomical methods are insufficiently sensitive to reveal this pathway, and single neuron patch clamp experiments have been too specific to reveal the pathway. By using electrical current to release glutamate into the deep layers of the colliculus slice combined with voltage imaging of population responses, we found an activation of the neurons in the upper layers. The activation was blocked by bath application of a glutamate receptor blocker (Kyenuric acid), and it was absent when the electrode polarity was revered. This latter method resulted in the same intensity of current released from the electrode but no release of glutamate. By bridging the gap between cellular and systems neuroscience with experiments like these, we are hopeful that our work will shed light on the cellular basis of higher mental function. Ultimately we hope to provide critical information leading to rational approaches for extending molecular and genetic techniques from invertebrates and lower mammals into non-human primates.

In net, I am committed to maintaining a strong research program focused on basic science questions that have direct clinical importance and growing my research program in a strong, neuroscience community to achieve these goals.

Fuster Laboratory of Cognitive Neuroscience