Park Clinical Neuroscience Lab

Schizophrenia

Neurocognitive deficits are core features of schizophrenia that may determine functional outcome. Working memory (WM) deficit has been identified as one of the most important components of the neurocognitive deficits in schizophrenia. WM is a limited-capacity, active short-term memory system that guides and controls behavior. A majority of patients with schizophrenia and about half of their healthy first-degree relatives have WM deficits and these deficits are linked to poor social and adaptive functioning yet the origins and consequences of WM deficit are unclear. Thus it has not been possible to develop targeted interventions that might ameliorate WM deficits and improve adaptive functioning.

We are interested in to identifying mechanisms that are central to WM deficit and their neural correlates. We also want to examine the effects of WM deficit on social functioning. Cognitive and neuroanatomical data suggest that selective attention and affect modulate encoding and maintenance in WM but schizophrenic patients are unable to effectively integrate attention and affect to guide goal-directed behavior.

1. We investigate the roles of perceptual, attentional and affective factors in encoding to specify both optimal and detrimental encoding conditions. Encoding affects all forms of memory and thus has far-reaching consequences. In addition to impaired encoding there is good evidence for abnormal maintenance in schizophrenia.
2. The effects of attentional control and affect on maintenance are examined to identify where vulnerabilities lie. We are particularly interested in studying the role mental imagery in the manipulation of memory representations. A series of experiments on manipulation and maintenance interactions are currently being conducted.
3. The roles of prefrontal and parietal cortices in normal and abnormal WM are being investigated with event-related fMRI and near infrared optical imaging experiments. The neural correlates of correct and incorrect performance are observed to elucidate the difference between remembering and forgetting in the brain.

To summarize, we aim to identify the key components of WM deficits in schizophrenia. We recruit unaffected siblings of schizophrenic patients to observe potential deficits as well as spared abilities. We also study bipolar individuals to compare the two psychotic disorders. Identification and elucidation of core neurocognitive deficits of schizophrenia will contribute towards the understanding of the complex interplay between cortical functions and cognitive deficits in schizophrenia. Moreover, specifying abnormal mechanisms within WM in relation to attention, affect and brain activation patterns could lead to targeted strategies that might ameliorate WM deficits and improve adaptive functioning in schizophrenia.

Parkinson's Disease

Parkinson's Disease results in a wide range of motor, cognitive and affective deficits. With Dr. Joseph Neimat in Neurosurgery, we are investigating working memory deficits in Parkinson's disease patients who have deep brain stimulation (DBS) device implanted to stimulate the subthalamic nucleus. DBS is a relatively new treatment option when drugs no longer work. When DBS is switched on, there is a remarkable improvement in motor behavior. Although the efficacy of DBS for movement initiation and control is excellent, there is some evidence to suggest that cognitive functioning may get worse. We are examining working memory on and off DBS in Parkinsonian patients. In addition, we collect near infrared optical imaging data during a spatial working memory task in Parkinson's disease patients to examine frontal cortical activity in relation to DBS stimulation in the subthalamic nucleus.

Dr. Neimat discusses and demonstrates DBS

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Successful interaction with the world depends on how well we are able to adjust our ongoing behavior to meet the contextual and situational demands. On-line adjustments of behavior require a certain degree of self and response monitoring. Individuals with psychosis are thought to be impaired in their ability to monitor, inhibit and control ongoing behavior.

To study control of action, we examine response monitoring in schizophrenia and bipolar disorder with the countermanding paradigm (stop signal reaction time task). To learn more about this project, please go to Katy Thakkar's website.

To study control of mental representations, a series of experiments involving mental rotation, perspective-taking and simulation are currently in progress. The ability to mentally transform visuospatial perspectives and internally simulate external events may be very important for understanding the social world.

Control of action and mental representation also depend on internally stored regularities and predictions. We appear to have an implicit understanding of probabilities of events in the world, which we use to guide our behavior. But it is unclear how we come to acquire these probabilities. One possibility is that working memory and long-term memory interactively glue sequential events over time. We are examining how healthy individuals and psychosis patients deduce probabilities of simple events over time. Some people need to accumulate a lot of data whereas others jump to conclusion with very little evidence. Again, individual differences interact with cognitive machinery in complex ways.

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Cognitive deficits, such as impairments of working memory and attention are associated with reduced social functioning and poor outcome in schizophrenia but it is unknown how they cascade into abnormal social behavior. Schizophrenic patients have a wide range of socio-affective deficits including abnormal emotion recognition, social cue perception, "theory-of-mind" (TOM) and attribution styles but the origins of these deficits and their neural underpinnings are not yet clearly understood. We are studying the relationship between socio-affective and cognitive functions in schizophrenia using behavioral and functional neuroimaging methods.

Successful social interactions depend on fast and accurate interpretation of actions, intentions and emotions of others. We hypothesize that deficits in attentional orienting and working memory may be responsible for abnormal perception and interpretation of social stimuli in schizophrenia. The neural network that supports attention and working memory largely overlap with regions that are heavily implicated in the pathophysiology of schizophrenia, including the prefrontal, the posterior parietal, the anterior cingulate cortices and basal ganglia. Abnormalities of this network also result in social/affective deficits.

Cognitive roots of social deficits in schizophrenia may be characterized by:

1. Inability to attend to socially or emotionally relevant features
2. Inability to generate internal representation to guide behavior
3. Inability to maintain social/emotional context in working memory

We study perceptual and cognitive abnormalities that may lead to inaccurate interpretation of external events. To better understand possible perceptual origins of ToM problems, we have examined eye gaze perception and biological motion processing in schizophrenic patients. Accurate decoding of social attention in real time is important for grasping the significance of social behavior. In the case of biological motion processing, we find that schizophrenic patients are impaired in the detection and discrimiation of biological motion (i.e., movements generated by living things. See also Point Light Display Movies) and that these deficits arise from high 'false alarm' rate in the patients; they tend to see scrambled, nonsense motion as 'living'. In healthy people, biological motion stimuli are clearly associated with increased activation of the superior temporal sulcus whereas in schizophrenic subjects, this association is not observed. An inability to detect and discern socially relevant stimuli (e.g. people) could lead to subtle deficits in social behavior and indeed we observe a correlation between biological motion deficit and social functioning scores in schizophrenic subjects.

We are also interested in understanding the relationship between spatial and affective functions. We and other labs have observed the role of affect in attentional orienting, spatial localization and other tasks. It is not surprising that spatial attention and affective arousal should be closely linked. The affective nature of the stimulus determines whether the organism moves towards or away from the stimulus. In addition, neurological data indicate that right hemisphere deficits are associated with emotional and social problems. However, the role of the right parietal cortex in spatial and affective processes is not well understood. We are currently investigating individual differences in empathy in relation to spatial information processing (perspective taking, mental rotation, pseudoneglect).

To elucidate generation of internal representation of the social world, we are examining a wide range of imitation abilities in relation to social functioning. Schizophrenic patients seem unable to imitate very simple manual gestures, mouth movements or facial expressions even thought they can correctly identify these acts. Imitation ability is related to simulation of external events is linked to the "mirror neuron" mechanism supported by the left inferior frontal region that includes Broca's area. We are currently conducting a fMRI study of language and imitation in healthy and schizophrenic subjects to relate behavior, structural findings and functional activation patterns.

To summarize, we aim to better understand how cognitive deficits may lead to social deficits and to elucidate functional neuroanatomy of social cognition.

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Thoughts, Delusions, and Beliefs

Theories of delusion formation can be roughly divided into more perceptual vs cognitive accounts. The perceptual account proposed by Brendan Maher and others posit that delusions are natural product of rational explanation of abnormal sensory experiences. Cognitive accounts take a more top-down approach and point to the roles of cognitive biases, abnormal hypothesis testing, and "jumping to conclusions" in delusion formation (e.g., Helmsley, Bentall, Garety, David). Interacting with cognitive and perceptual theories, are the motivational and emotional factors (e.g. Freud, Bentall). Delusions are rarely non-emotional and may often reflect projections of unconscious unresolved conflicts to external targets or attempts to protect self. There are also hybrid models such as the two process theory (Langdon, Davis) and similarly, the jump-to- perception-and-conclusion theory (Fleminger). While delusions held by individuals with psychosis do not necessarily have specific neuroanatomical correlates, there are neurological lesion cases that offer fascinating insight into specific delusions. Delusional misidentification syndromes, autoscopic phenomena, paranormal beliefs have been studied extensively in lesion patients (Brugger). Last but not least, there are sociocultural and ecological influences on delusion formation (see Van Os).

We study the possible interactions between in pattern recognition and personality traits as major factors in delusion formation. Our studies of biological motion perception, eye gaze direction perception and other perceptual tasks suggest that increased false alarm rates (seeing something where there is none) may be related to the presence of delusions. This may be due to too much top-down control, poor quality sensory data and an interaction between the two. Noisy input from abnormal sensory systems necessitate increased top-down, cognitive processing, which may then lead to faulty conclusions. Over time, these experiences may result in an accumulation of inaccurate information and probabilities about the world. We are currently investigating visual and auditory detection of living and nonliving stimuli in relation to delusion formation in healthy individuals and psychosis patients.

Read the summary of a workshop on delusions held at the International Congress on Schizophrenia Research in San Diego, March 2009 here.

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