Current Research Projects
Stress, Emotion, and Motivated Attention in Schizophrenia
Among the core features of schizophrenia, memory deficits, attentional impairment, and disrupted emotional processing are prominent. Research investigations into these domains have typically approached each area separately rather than to probe their interrelationships. We believe it is equally important to consider neurocognitive and emotional processes jointly. Work activities, for instance, may occur within a stressful context while social situations are often emotionally engaging or carry emotional significance. Emanating from our previous findings that irrespective of phase of illness, motivational systems associated with emotional responding are intact across psychophysiological systems whereas stress reactivity is heightened, this research project seeks to determine the malleability of memory deficits and to examine the influence of stress on memory in individuals vulnerable for schizophrenia. By focusing on patients in the prodromal, first episode and chronic phases of schizophrenia, there is the unique opportunity to examine how stress and emotional reactivity contribute to the onset and progression of the illness and to daily functioning. This research is one of four projects within the NIMH-funded Center for Neurocognition and Emotion in Schizophrenia at UCLA that fosters collaborative efforts between researchers from the fields of psychology, psychiatry, and other disciplines.
Attentional and Affective Modulation of Sensory Gating in Schizophrenia
This research involves a series of studies that examine the influence of attention, emotion, and stress on sensory gating or filtering in patients with a recent-onset or chronic course of schizophrenia. Investigators hypothesize that the sensory overload, cognitive fragmentation, and conceptual disorganization frequently observed in schizophrenia patients may reflect a failure of normal filtering or gating mechanisms, and they have applied various measures to study this phenomenon. One measure that has been found to be well suited for examining impairments associated with sensory gating is the P50 component of the event-related brain potential (ERP), with P50 suppression serving as an operational definition of gating. P50 suppression is of considerable interest among clinical researchers because it appears to index neurophysiological substrates underlying the sensory overload observed in schizophrenia patients and because it appears to be a promising indicator of genetic vulnerability for schizophrenia. Our research has extended early P50 findings by examining factors that influence or exacerbate the dysfunction, identifying approaches that might be taken to normalize the deficit in schizophrenia patients, and investigating the mechanisms that underlie the P50 deficit.
We have also conducted numerous studies of event-related and oscillatory responses in schizophrenia that use magnetoencephalography (MEG) with collaborators at other sites. Some of this work has led to developing and testing sensory and cognitive training protocols that we have shown can normalize MEG activity in patients with schizophrenia.
Reduced Efficiency of Neurocognitive Processes in Schizophrenia
The capacity to maintain and control attention or top-down processing, along with the inhibition of responses to distracters, typically achieved with bottom-up processes, is central to effective neurocognitive functioning. This capacity is widely seen as impaired in schizophrenia. In addition to clarifying the nature of the P50 component and the processes that drive its abnormality, we have begun to explore other forms of inhibitory processing that can be inferred from the EEG signal. For instance, increases in event-related synchronization (ERS) in the upper (i.e., fast) alpha frequency band appear to reflect large-scale inhibition (i.e., decreased excitability) of cortical activity during cognitive processing. Work in this area includes collaborative research between UCLA and Finnish investigators.
Conflict Monitoring in Schizophrenia and Healthy Individuals
Expanding upon our interest in attention and inhibitory processes in schizophrenia, we have conducted several studies on the error monitoring system. For instance, we have used the error-related negativity (ERN) of the ERP and behavioral indices to provide a detailed characterization of conflict monitoring abnormalities in schizophrenia. In contrast to results from our work showing that schizophrenia patients can benefit from instructions that alter the functional significance of a stimulus to improve or even normalize neurocognitive performance, we determined that ERN deficits in schizophrenia persist even under conditions that have been demonstrated to maximize the response in healthy individuals. At the same time, the functional characteristics of the ERN appear to remain intact in patients with schizophrenia who were able to modulate their performance, suggesting greater inefficiency rather than pervasive disruption of the conflict monitoring system. In research with healthy individuals, we have utilized a conflict-monitoring paradigm and the associated ERPs and EEG to understand individual differences in motivation, personality, and political attitudes.
Functional Brain Connectivity Disruptions Associated with Depression/Anxiety Comorbidity
Using a combination of sMRI, fMRI, and dense-array EEG source localization, we have found distinct functional connectivity problems in depression and anxiety. There appears to be a functional disconnect between dorsal-lateral prefrontal cortex (DLPFC) and dorsal anterior cingulate cortex (dACC) associated with the dimensional construct of anhedonic depression but not with anxiety. In contrast, the dimensional construct of anxious apprehension, but not depression, is associated with a disruption of the relationship between dACC and reaction-time performance. These relationships were manifest when we experimentally and statistically avoided the interpretative challenges that comorbidity often brings. We are following up these findings with graph-theory approaches to connectivity using both fMRI and EEG data.