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Perception – Gain Control Task Name Description Cognitive Construct Neural Construct Validity Reliability Psychometric Animal Model Stage of Research Validity Characteristics Steady state Magnocellular and The magnocellular-biased The contrast response curves There has been The task does not Single cell recordings There is evidence visual evoked parvocellular visual pathway condition produces a steeply obtained in human studies in some work on test appear to have from magnocellular that this specific task potentials to function assessed using rising increase in response to healthy controls (Butler et al., retest reliability practice effects. It is a and parvocellular elicits deficits in magnocellular steady-state visual evoked low contrast stimuli which 2001; Butler et al., 2005; (Butler et al., passive viewing task neurons in monkey schizophrenia. vs. potentials. This task that reaches a saturation-level Zemon & Gordon, 2006) unpublished in which lateral geniculate parvocellular takes ~ 15 min. The once luminance contrast (Fox, Sato, & Daw, 1990) to observations). electrophysiological nucleus (LGN) show We need to assess biased magnocellular system reaches ~16% (Butler et al., magnocellular- and Twenty participants responses are characteristic psychometric stimuli. responds to low luminance 2001; Butler et al., 2005; parvocellular-biased stimuli (10 controls and 10 obtained. The electrophysiological characteristics such contrast and the parvocellular Zemon & Gordon, 2006). This are very similar to what is schizophrenia responses do not responses. as test-retest system does not begin to leads to a characteristic S- seen in single-cell recordings patients) have been habituate even Magnocellular neurons reliability, practice respond until contrast has shaped, non-linear contrast in monkeys supporting the tested twice. The following repeated show steep increases effects, and reached about 16%. In this gain control curve. The initial concept that magnocellular correlation between presentation of the in responding at low ceiling/floor effects task, isolated checks are steeply rising part of the and parvocellular responses signal-to-noise ratios stimulus conditions. It contrast and for this task. modulated at low contrasts to curve reflects substantial are being examined. In (the dependent is not a learned task, saturation at higher bias responding towards the amplification of low contrast addition, visual pathways measure which is a so that presentation contrast. Parvocellular We need to study magnocellular visual pathway stimuli, permitting M-pathway within the brain use glutamate measure of amplitude at multiple test dates neurons show a whether or not and are modulated around a neurons to respond robustly as their primary corrected for noise) is not affected by shallow slope at low performance on this high contrast "pedestal" to even at low contrasts. This neurotransmitter and NMDA obtained in first and prior testing. There contrast and a non- task changes in bias responding towards the magnocellular-pathway appears to have a central role second test sessions do not appear to be saturating response. response to parvocellular pathway. response is an example of in gain control. For instance, was significant (total floor effects because The curves found in psychological or Signal-to-noise ratio, which is gain control because NMDA receptors amplify group: r=0.81, most people, the proposed task are pharmacological the amplitude of the response response levels are optimized responses to isolated stimuli p<0.0001; patients including patients, very similar to those intervention. corrected for noise, is within a limited dynamic as well as amplifying the alone: r=0.72, n=14, give at least a small seen in monkey work. calculated for each contrast signaling range and the effects of lateral inhibition p=0.004; controls response at low Studies in cat LGN and is the dependent sensory signal is amplified. (e.g., increase surround alone: r=0.88, n=6, contrast and a slightly show decreased slope variable. antagonism of center p=0.02). higher response as and decreased (Butler et al., 2001) receptive field responses) contrast increases. plateau following (Butler et al., 2001) (Butler et al., 2005) (Daw, Stein, & Fox, 1993) There is not a ceiling infusion of NMDA (Butler et al., 2005) (Zemon & Gordon, 2006) (Kwon, Nelson, Toth, & Sur, effect because the antagonists (Daw et (Zemon & Gordon, 2006) 1992). Thus, an NMDA amplitude of the al., 1993) (Kwon et al., deficit would result in electrophysiological 1992) similar to what MANUSCRIPTS ON THE decreased amplification and response does not is seen in WEBSITE: less lateral inhibition. have a ceiling. schizophrenia patients Microinufsion of NMDA in this task (Butler et al Butler, P. D., Zemon, V., antagonists into cat lateral 2005). Schechter, I., Saperstein, A. geniculate nucleus or primary M., Hoptman, M. J., Lim, K. visual cortex produced O., et al. (2005). Early-stage shallower gain at low contrast visual processing and cortical and a much lower plateau amplification deficits in indicating decreased signal schizophrenia. Arch Gen amplification in Psychiatry, 62(5), 495-504. electrophysiological studies (Fox et al., 1990). Thus, the Zemon, V., & Gordon, J. magnocellular-biased task (2006). Luminance-contrast may be assessing NMDA- mechanisms in humans: mediated signal amplification. visual evoked potentials and Indeed, schizophrenia a nonlinear model. Vision patients show curves very Res, 46(24), 4163-4180. similar to those seen following infusion of NMDA antagonists in animal studies. (Daw et al., 1993) (Fox et al., 1990) (Kwon et al., 1992) Contrast- Gain control has been This task is ideal for Converging evidence from This has not been An important feature Not Known There is evidence Contrast successfully studied using the examining gain control in psychophysics and fMRI assessed. of this task is that full that this specific task Effect (CCE) Contrast-Contrast Effect schizophrenia because: 1) indicates that the contrast- psychometric elicits deficits in Task (CCE) task in which contrast reduced gain control, or contrast effect is linked to functions can be schizophrenia. sensitivity for a ringed target contextual modulation, would gain control within primary obtained for subjects. can be influenced by the be indicated by more visual cortex (V1) (Zenger- From these, separate We need to assess contrast of a circular surround accurate contrast judgments Landolt & Heeger, 2003). indicators of precision psychometric (Chubb, Sperling, & Solomon, regarding the inner circle Further evidence indicates (the minimum size of characteristics such 1989). In this task, compared to controls; and 2) that the effect within V1 is contrast differences as test-retest participants are asked to there is already evidence for likely due to both activity that are detectable, reliability, practice match a variable contrast reduced spatial context arising within V1 and to top- which is indicated by effects, and patch to a central patch. effects in vision in down feedback from higher, the slope of the ceiling/floor effects When the surround is high- schizophrenia (Must, Janka, object-processing areas to V1 function) and bias for this task. contrast, the inner target is Benedek, & Keri, 2004; (Lotto & Purves, 2001). (reflecting the amount perceived to be of lower Uhlhaas et al., 2006). An Because 90% of cells in V1 of offset that is We need to study contrast than when the same important feature of this task are subject to suppression needed between the whether or not target is perceived without a is that full psychometric from neighboring cells, tasks target and the performance on this surround (Chubb et al., 1989; functions can be obtained for such as this that are known to surround to produce task changes in Dakin, Carlin, & Hemsley, subjects. From these, act on V1 neurons are ideal a perceptual match) response to 2005). separate indicators of methods for the study of gain can be obtained, psychological or precision (the minimum size control. allowing us to pharmacological MANUSCRIPTS ON THE of contrast differences that examine intervention. WEBSITE: are detectable, which is (Zenger-Landolt & Heeger, discrimination indicated by the slope of the 2003) accuracy Dakin, S., Carlin, P., & function) and bias (reflecting (Lotto & Purves, 2001) independent of Hemsley, D. (2005). Weak the amount of offset that is response bias (as suppression of visual context needed between the target with other signal- in chronic schizophrenia. Curr and the surround to produce detection analyses). Biol, 15(20), R822-824. a perceptual match) can be This suggests the obtained, allowing us to absence of Zenger-Landolt, B., & examine discrimination floor/ceiling effects Heeger, D. J. (2003). accuracy independent of Response suppression in v1 response bias (as with other agrees with psychophysics of signal-detection analyses). surround masking. J Neurosci, 23(17), 6884-6893. (Uhlhaas et al., 2006) (Must et al., 2004) Mismatch Mismatch negativity (MMN) is MMN indexes perception of At the neural level, MMN Test-retest reliability MMN is generated Homologues exist in There is evidence Negativity an auditory event-related stimulus deviance at the level reflects current flow through of mismatch preattentively in the monkeys (Javitt et al., that this specific task potential (ERP) elicited in an of auditory cortex. open, unblocked NMDA negativity for absence of a 1996) (definitely) and elicits deficits in "oddball" task, in which a Generation of MMN depends receptors within auditory duration, frequency behavioral task. rodents schizophrenia. sequence of repetitive upon gain control (i.e. signal cortex. Similar mechanisms and intensity changes Floor effects depend (probably)(Ehrlichman, standard tones is interrupted amplification) of neurons mediate gain control within (Hall et al., 2006; upon quality of EEG Maxwell, Majumdar, & Data already exists by a physically different sensitive to stimulus visual cortex, suggesting a Tervaniemi et al., recording and can be Siegel, 2008; on psychometric "deviant" tone that violates deviance. Presentation of parallel phenomenon. MMN 1999). minimized through Umbricht, Vyssotki, characteristics of this expectancies created by the repetitive standards should, generation can be good Latanov, Nitsch, & task, such as test- standard. MMN can be under normal conditions, lead antagonized by administration Hall (average of 18 electrophysiological Lipp, 2005). retest reliability, recorded and quantified using to upward bias of the gain of NMDA agonists such as days): 0.34-0.66 technique. Test- practice effects, standard ERP recording process. In schizophrenia, PCP or ketamine in either ICCs retest studies show ceiling/floor effects. systems (e.g. Neuroscan, this bias mechanism appears human or animal models no significant Biosemi, ANT). (Umbricht & to be impaired. (Javitt, 2000; Javitt, Tervaniemi (average "learning" (i.e. There is evidence Krljes, 2005) Steinschneider, Schroeder, & of 8.3 days): repetition effects - that performance on Arezzo, 1996; Turetsky et al., Correlations between see references on this task can improve MANUSCRIPTS ON THE 2007; Umbricht et al., 2000). 0.41 and 0.78. test/retest reliability). in response to WEBSITE: As MMN amplitude psychological or MMN tracks auditory increases with dF pharmacological Javitt, D. C., Spencer, K. M., perceptual performance and interventions. Thaker, G. K., Winterer, G., & across a variety of standards/deviant Hajos, M. (2008). dimensions (Pakarinen, ratio, ceiling effect is Neurophysiological Takegata, Rinne, Huotilainen, not relevant (Javitt, biomarkers for drug & Naatanen, 2007). Spencer, Thaker, development in Winterer, & Hajos, schizophrenia. Nat Rev Drug 2008). Discov, 7(1), 68-83. Pakarinen, S., Takegata, R., Rinne, T., Huotilainen, M., & Naatanen, R. (2007). Measurement of extensive auditory discrimination profiles using the mismatch negativity (MMN) of the auditory event-related potential (ERP). Clin Neurophysiol, 118(1), 177- 185. Prepulse Individuals are presented with It is not clear whether this There is a large literature on YES There is evidence Inhibition of two auditory probes in correlates with other the neural substrates of that this specific task Startle sequences. The P50 measures of inhibition. Prepulse inhibition in animals, elicits deficits in response to the second probe and a large literature on schizophrenia is typically reduced in pharmacological effects. (Swerdlow et al., individuals with intact sensory There are now human 2006). gating. imaging studies (at least one) looking at prepulse inhibition We need to assess (Swerdlow, Braff, Taaid, & in the scanner. psychometric Geyer, 1994) characteristics such (Braff & Geyer, 1990) (Joober, Zarate, Rouleau, as test-retest (Cadenhead, Carasso, Skamene, & Boksa, 2002) reliability, practice Swerdlow, Geyer, & Braff, effects, and 1999) (Kumari, Antonova, & Geyer, ceiling/floor effects 2008) for this task. MANUSCRIPTS ON THE (Campbell et al., 2007) WEBSITE: (Kumari et al., 2007) This task has been (Kumari et al., 2003) studies with Swerdlow, N. R., Light, G. A., psychopharamcology Cadenhead, K. S., Sprock, J., methods Hsieh, M. H., & Braff, D. L. (2006). Startle gating deficits in a large cohort of patients with schizophrenia: relationship to medications, symptoms, neurocognition, and level of function. Arch Gen Psychiatry, 63(12), 1325-1335. Turetsky, B. I., Calkins, M. E., Light, G. A., Olincy, A., Radant, A. D., & Swerdlow, N. R. (2007). Neurophysiological endophenotypes of schizophrenia: the viability of selected candidate measures. Schizophr Bull, 33(1), 69-94. Contrast This is a classic Contrast is an example of Gain control in the visual I am not aware of any The task does not There have been There is evidence Sensitivity psychophysical task that has gain control, which takes into system refers to processes published data on have a ceiling effect, numerous studies that this specific task been used for over 50 years account spatial and temporal that generally occur at early test retest reliability. but, in theory, could done in a variety of elicits deficits in (Bodis-Wollner, 1972; context. Contrast sensitivity stages of processing such as In our laboratory, 29 have a floor effect. species including schizophrenia (Butler Movshon & Kiorpes, 1988; varies with spatial context (as at the level of the LGN or people have been Higher contrast goldfish, cat, and et al., 2005; Keri, Robson, 1966). There are well as with temporal context primary visual cortex and tested twice and sensitivity indicates falcon (Movshon & Antal, Szekeres, different variations on the (Robson, 1966). In addition, utilizes excitatory and there was a better performance. Kiorpes, 1988). Benedek, & Janka, method. One method is use gain control assists sensory inhibitory lateral interactions significant correlation Contrast sensitivity is Contrast sensitivity 2002; Slaghuis, of a two-alternative forced subsystems in increasing between neurons. Contrast between first and the inverse of can be obtained in 1998). choice design. In this design, contrast between adjacent sensitivity can be assessed second test time for threshold so that a macaques using contrast sensitivity functions and successive stimuli. and contrast sensitivity all spatial frequencies high contrast behavioral methods We need to assess can be obtained by curves obtained from (0.5 - 21c/degree) sensitivity of 100 (Movshon & Kiorpes, psychometric presenting sine-wave gratings recordings of LGN neurons examined (r=0.67- corresponds to a low 1988). characteristics such at several different spatial as well as from neurons in 0.4, p=0.0001-0.02 threshold of 1% as test-retest frequencies from low to high primary visual cortex for the different contrast. There is no reliability, practice (e.g., 0.5 to 21 (Kiorpes, Tang, Hawken, & spatial frequencies). theoretical limit on effects, and cycles/degree). Gratings are Movshon, 2003). Contrast how high contrast ceiling/floor effects presented on one half (either sensitivity curves produce an sensitivity can go. A for this task. the right or left side) of a inverted U shaped function contrast sensitivity of visual display, with the other with a peak in the mid-range 500, for instance, We need to study side having a uniform field. of spatial frequencies and fall- would correspond to whether or not Participants are asked to off at lower and higher spatial a threshold of 0.2% performance on this state which side of the display frequencies. The fall-off at contrast. On the task changes in contains the grating. Contrast lower spatial frequencies is other hand, poor response to is varied across trials using mainly a function of inhibitory performance leads to psychological or an up-and-down transformed lateral interactions between low contrast pharmacological response method to center and surround whereas sensitivity and intervention. determine contrast sensitivity fall-off at higher spatial corresponding high (e.g., the contrast at which frequencies is more a thresholds. For the side the grating is on is function of excitatory example, a contrast correctly detected 79% of the interactions (Burbeck & Kelly, sensitivity of 1 would time). 1980). correspond to a threshold of 100% MANUSCRIPTS ON THE contrast. It is not WEBSITE: possible to go higher than 100% contrast. Butler, P. D., Zemon, V., However, in practice, Schechter, I., Saperstein, A. unless there is a M., Hoptman, M. J., Lim, K. serious visual O., et al. (2005). Early-stage problem, people do visual processing and cortical not need 100% amplification deficits in contrast to do this schizophrenia. Arch Gen task. I am not aware Psychiatry, 62(5), 495-504. of data on practice effects, though this is Keri, S., Antal, A., Szekeres, not a learned task so G., Benedek, G., & Janka, Z. that practice effects (2002). Spatiotemporal visual should be minimal. processing in schizophrenia. J Neuropsychiatry Clin Neurosci, 14(2), 190-196. REFERENCES: Bodis-Wollner, I. (1972). Contrast sensitivity and increment threshold. Perception, 1(1), 73-83. Braff, D. L., & Geyer, M. A. (1990). Sensorimotor gating and schizophrenia. Human and animal model studies. Arch Gen Psychiatry, 47(2), 181-188. Burbeck, C. A., & Kelly, D. H. (1980). Spatiotemporal characteristics of visual mechanisms: excitatory-inhibitory model. J Opt Soc Am, 70(9), 1121-1126. Butler, P. D., Schechter, I., Zemon, V., Schwartz, S. G., Greenstein, V. C., Gordon, J., et al. (2001). 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