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ICOSR 2011—Visual Processing Deficits of Schizophrenia Probed

As part of our ongoing coverage of the 2011 International Congress on Schizophrenia Research (ICOSR), 2-6 April, in Colorado Springs, Colorado, we bring you session summaries from some of the Young Investigator travel award winners. For this report, we thank Mitsouko van Assche of INSERM in Strasbourg, France.


11 April 2011. The Tuesday, April 6, morning session entitled “Early visual processing in schizophrenia: more than meets the eye” was introduced by chair Michael Green of the University of California, Los Angeles. The main goal of the session was to let speakers present current methods exploring perceptual process deficits and their relationships with more downstream consequences.

Pamela Butler, New York School of Medicine, inaugurated the session with her talk entitled “Contributions of early-stage visual processing to emotion recognition deficits in schizophrenia.” She outlined two possible hypotheses to account for deficits in emotion processing: 1) a specific deficit in processing emotion information, versus 2) a generalized deficit in processing visual stimuli. Earlier work conducted in her lab was interpreted as showing a deficit in the magnocellular stream, which responds quickly to low-contrast stimuli and low-spatial frequencies. In a contrast sensitivity task and an emotion recognition task, patients needed higher contrasts than controls to equalize performance, suggesting magnocellular stream deficits. The authors hypothesized that patients need more input from the parvocellular stream—which responds more slowly, specifically to high-contrast stimuli and high-spatial frequencies—to achieve the same performance level.

In an event-related potential study that Butler presented, patients showed a diminished P1 (indexing early-stage visual processing, presumed to be magnocellular) at low contrast. Controls showed a higher gain than did patients at low contrast, with performance matching that of patients at high contrast. Correlation data showed a relationship between contrast sensitivity to faces and P1 only. No deficit was observed for the N170 (indexing encoding of objects, presumed to be parvocellular) in patients, but a deficit in the P250 (later-stage visual processing) was observed. Her main conclusion was that the results indicate a dysfunction of the magnocellular pathway, and future studies should focus on the precise neural circuitry involved.

The second talk was presented by Steven Silverstein, University of Medicine and Dentistry of New Jersey, who talked about perceptual organization deficits in schizophrenia and their relationships with other cognitive domains. In the first study he presented (Silverstein et al., 2010), patients categorized the gender of faces as well as control subjects did. However, they performed worse when shown faces with low spatial frequency (LSF) information only, but better in the most difficult condition for control subjects—faces with high spatial frequency information only. Whereas controls showed supplementary activations in the visual cortex for the LSF task, patients recruited areas beyond visual cortex more strongly (middle temporal and fusiform gyrii). Silverstein hypothesized that a poorer quality of form information leads patients to compensate with areas involved in identification processes. He then presented the Ebbinghaus illusion, requiring intact perceptual organization abilities. Disorganized patients were less susceptible than non-disorganized ones to experience the visual illusion, indicating that the former are less sensitive to the visual context. Furthermore, the more sensitive to visual context patients were, the better they performed on Theory of Mind, emotion identification, and discrimination tasks.

Silverstein then focused on the effects of perceptual organization on visual memory. In the study he discussed (Silverstein et al., 1996), subjects were first presented with stimuli that were more or less well organized. A subsequent test phase showed that patients were only able to memorize well-organized stimuli. Silverstein concluded that perceptual organization impairments belong to a more widespread deficit in binding components of mental representations, with downstream consequences in face and emotion identification, visual memory, and many more.

The third speaker, Peter Uhlhaas, Max Planck Institute, Frankfurt, Germany, talked about “High γ band oscillations and visual closure processing during face perception in schizophrenia.” In his magnetoencephalography study, subjects were briefly presented degraded pictures of upright, inverted, or scrambled faces. Chronic patients were impaired at recognizing upright faces only. Analyses in the parietal sensors for high γ frequencies indicated impairments of early and late activity, and at the stimuli offset. The more disorganized patients were, the more reduced activity was in the high γ range. A comparison between patients and controls for the face condition in the 60-120 Hz range revealed supplementary activity in controls (inferior frontal and temporal cortices, lingual gyrus and fusiform face area) but also in patients (posterior cingulum). For the face-versus-no-face contrast, controls showed more activity than did patients in the inferior parietal lobule and inferior frontal cortex, and vice versa in the medial frontal gyrus and precuneus. There was also a difference in the phase of synchrony around 60-90 Hz, with controls showing enhanced responses to the face stimuli in the fusiform face and frontal areas.

Uhlhaas also presented data from first-episode, never-medicated patients, who more frequently perceived a face in the no-face condition, along with having longer response times and less deficit in γ-band activity than did chronic patients. They also recruited a different network, with reduced contribution of inferior/medial frontal gyrus, superior parietal lobule, cuneus and inferior temporal gyrus in the face condition. He concluded that there may be a progressive pathophysiological process in the course of the disorder.

The last presentation was given by Michael Green, University of California, Los Angeles, and dealt with the translation of protocols from cognitive neuroscience into clinical applications. He presented a “cascade model from visual perception to social aspects of the disorder,” obtained by structural equation modelling (SEM). In this model, social cognition is connected with social perception, theory of mind, emotion processing, and beliefs. Beliefs are connected to negative symptoms, the latter being related to functional outcome.The model further relates masking tasks with social cognition. Green then presented data from three protocols and related the results to some clinical features of schizophrenia.

Patients were impaired at four-dot masking, a task assessing re-entrant processes (feedback mechanisms enabling one to refine the processing of visual information before objects reach awareness), and SEM analyses indicated a good model fit when it was connected to social cognition and functional outcome. He then presented an EEG study measuring steady-state adaptation to test the hypothesis that patients lack sufficient neural selectivity during visual processing. Unlike controls, patients did not show differential activity when suddenly presented with different objects. There was also an inverse association between steady-state adaptation and certain dimensions of the SANS. A third protocol, the Bubbles task, investigated which information is used during facial emotion categorization. Controls relied on high spatial frequency information around the eyes of the faces, whereas patients used information around the mouth. There were further positive correlations between some emotion perception tests and their social cognition measures. Green concluded that whether patients can learn to use more efficient information to improve their social skills should now be explored.—Mitsouko van Assche.

References:
Silverstein SM, Knight RA, Schwarzkopf SB, West LL, Osborn LM, Kamin D. Stimulus configuration and context effects in perceptual organization in schizophrenia. J Abnorm Psychol . 1996 Aug 1 ; 105(3):410-20. Abstract

Silverstein SM, All SD, Kasi R, Berten S, Essex B, Lathrop KL, Little DM. Increased fusiform area activation in schizophrenia during processing of spatial frequency-degraded faces, as revealed by fMRI. Psychol Med . 2010 Jul 1 ; 40(7):1159-69. Abstract

Comments on Related News


Related News: ICOSR 2011—Some Hope for Alleviating Negative Symptoms

Comment by:  Kimberly E. Vanover
Submitted 20 June 2011
Posted 20 June 2011

Thank you for your summary of the presentations from the New Drug Session at ICOSR 2011 on the Schizophrenia Research Forum. The Forum is a helpful and important resource.

I just wanted to clarify your description of ITI-007’s properties at the D2 site. As a dopamine phosphorylation modulator, ITI-007 acts as a pre-synaptic partial agonist and a post-synaptic antagonist with mesolimbic/mesocortical selectivity (Wennogle et al., 2008). In addition to its antagonism of 5-HT2A receptors and unique interaction with D2 receptors, it has affinity for D1 receptors, consistent with partial agonism linked to downstream increases in NMDA NR2B receptor phosphorylation (Zhu et al., 2008), and it is a serotonin reuptake inhibitor (Wennogle et al., 2008). Unfortunately, the short, 10-minute talk during the ICOSR session wasn’t sufficient time to go into the details of the mechanism and supporting preclinical data.

I did notice that a brief description for the mode of action for ITI-007 is listed as “5-HT2A antagonist + dopamine phosphoprotein modulator” with a role in schizophrenia listed as “DA stabilizer + 5hT-T inhibitor” in the Forum’s Drugs in Clinical Trials section. This is a nice, brief way to describe a rather complex mechanism.

References:

Wennogle LP, Snyder GL, Hendrick JP, Vanover KE, Tomesch JT, Li P, O’Callaghan JP, Miller DB, Fienberg AA, Davis RE, Mates S (2008) Unique antipsychotic profile of a novel 5-HT2A receptor antagonist and dopamine receptor protein phosphorylation modulator. Schizophrenia Research 98:Suppl1:15.

Zhu H, Snyder GL, Vanover KE, Rana M, Tsui T, Hendrick JP, Li P, Tomesch J, O’Brien JJ, Guo H, Davis RE, Fienberg AA, Wennogle LP, Mates S (2008) ITI-007: A novel 5-HT2A antagonist and dopamine protein phosphorylation modulator (DPPM) induces a distinct NR2B expression pattern in mouse brain. Program No. 155.14 2008 Neuroscience Meeting Planner. Washington, DC Society for Neuroscience, 2008. Online.

View all comments by Kimberly E. Vanover