Perception – Gain Control



Perception – Gain Control

|Task Name |Description |Cognitive Construct Validity |Neural Construct Validity |Sensitivity to Manipulation |Relationships to Behavior and |Psychometrics |Stage of Research |

| | | | | |Schizophrenia | | |

|Steady state visual |Steady-state visual evoked potentials to |The initial gain of the |The contrast response curves obtained in|Studies in cat LGN show |Several studies have shown impaired |Practice effects are being |There is evidence that this |

|evoked potentials to |magnocellular- and parvocellular-biased |magnocellular-biased contrast response |human studies in healthy controls |decreased slope and decreased |initial gain and saturation of |assessed, but there do not |specific task elicits deficits|

|magnocellular vs. |stimuli. In this paradigm checks are |function exemplifies adaptive signal |(Butler et al., 2001; Butler et al., |plateau following infusion of |magnocellular-biased responses in |appear to be practice effects, |in schizophrenia at the |

|parvocellular biased |presented rapidly (12 Hz) with the |amplification so that steep gain |2005; Zemon & Gordon, 2006) (Fox, Sato, |NMDA antagonists (Daw et al., |schizophrenia using this paradigm (Butler|floor or ceiling effects. The |behavioral and neural level. |

|stimuli |contrast of the checks increasing every |indicates intact function of signal |& Daw, 1990) to magnocellular- and |1993) (Kwon et al., 1992) |et al., 2007; Butler et al., 2001; Butler|paradigm does not require the |Unknown at the |

| |second for 7 seconds, so that an entire |amplification. A plateau at higher |parvocellular-biased stimuli are very |similar to what is seen in |et al., 2005; Kim, Wylie, Pasternak, |participant to do anything | |

|ERP |contrast response function is generated |contrasts exemplifies divisive gain |similar to what is seen in single-cell |schizophrenia patients in this|Butler, & Javitt, 2006) |beyond looking at checks on a |We need to assess psychometric|

| |in this time and several runs are |control and thus lack of saturation at |recordings in monkeys supporting the |task (Butler et al 2005). | |computer screen for a brief |characteristics such as |

| |averaged together. The magnocellular |high contrast in this paradigm |concept that magnocellular and | | |time, so that learning of a |test-retest reliability, |

| |visual pathway is activated by utilizing |indicates lack of adaptive gain |parvocellular responses are being | | |response is not involved. |practice effects, and |

| |lower contrasts and the parvocellular |control. |examined. In addition, visual pathways | | |Amplitude of the visual evoked |ceiling/floor effects for the |

| |visual pathway is activated by higher | |within the brain use glutamate as their | | |potential response can go as |imaging and behavioral data, |

| |contrasts. Only one active electrode |(Butler et al., 2001) |primary neurotransmitter and NMDA | | |high as each individual’s |though there is reason to |

| |over Oz is necessary. The |(Butler et al., 2005) |appears to have a central role in gain | | |response, so that there are not|believe these will be good. |

| |magnocellular-biased stimuli produce a |(Zemon & Gordon, 2006) |control. For instance, NMDA receptors | | |ceiling effects. A small | |

| |contrast response function with a steep | |amplify responses to isolated stimuli as| | |proportion of people do not |We need to study whether or |

| |increase in amplitude to low-contrast | |well as amplifying the effects of | | | |not performance on this task |

| |stimuli and plateau at higher contrast. | |lateral inhibition (e.g., increase | | | |changes in response to |

| |Gain control refers to processes that | |surround antagonism of center receptive | | | |psychological or |

| |allow sensory systems to adapt and | |field responses) (Daw, Stein, & Fox, | | | |pharmacological intervention. |

| |optimize their responses to stimuli | |1993) (Kwon, Nelson, Toth, & Sur, 1992).| | | | |

| |within a particular context. The steep | |Thus, an NMDA deficit would result in | | | | |

| |increase in slope at low contrast | |decreased amplification and less lateral| | | | |

| |reflects substantial amplification of | |inhibition. Microinufsion of NMDA | | | | |

| |low-contrast stimuli, permitting | |antagonists into cat lateral geniculate | | | | |

| |magnocellular-pathway neurons to respond | |nucleus or primary visual cortex | | | | |

| |robustly even at low contrast. The | |produced shallower gain at low contrast | | | | |

| |plateau at higher contrast shows divisive| |and a much lower plateau indicating | | | | |

| |gain control in which the signal is | |decreased signal amplification in | | | | |

| |decreased. | |electrophysiological studies (Fox et | | | | |

| |(Butler et al., 2001) | |al., 1990). Thus, the | | | | |

| |(Butler et al., 2005) | |magnocellular-biased task may be | | | | |

| |(Zemon & Gordon, 2006) | |assessing NMDA-mediated signal | | | | |

| | | |amplification. Indeed, schizophrenia | | | | |

| |MANUSCRIPTS ON THE WEBSITE: | |patients show curves very similar to | | | | |

| | | |those seen following infusion of NMDA | | | | |

| |Butler, P. D., Martinez, A., Foxe, J. J.,| |antagonists in animal studies. | | | | |

| |Kim, D., Zemon, V., Silipo, G., et al. | | | | | | |

| |(2007). Subcortical visual dysfunction in| | | | | | |

| |schizophrenia drives secondary cortical | |(Daw et al., 1993) | | | | |

| |impairments. Brain, 130(Pt 2), 417-430. | |(Fox et al., 1990) | | | | |

| |Zemon, V., & Gordon, J. (2006). | |(Kwon et al., 1992) | | | | |

| |Luminance-contrast mechanisms in humans: | | | | | | |

| |visual evoked potentials and a nonlinear | | | | | | |

| |model. Vision Res, 46(24), 4163-4180. | | | | | | |

|Contrast-Contrast |Gain control has been successfully |This task is ideal for examining gain |Converging evidence from psychophysics |This has not been assessed. |in a behavioral study, Dakin et al. |An important feature of this |There is evidence that this |

|Effect (CCE) Task |studied using the Contrast-Contrast |control in schizophrenia because: 1) |and fMRI indicates that the | |(2005) found significantly reduced |task is that full psychometric |specific task elicits deficits|

| |Effect (CCE) task in which contrast |reduced gain control, or contextual |contrast-contrast effect is linked to | |suppression in schizophrenia. This was |functions can be obtained for |in schizophrenia at the |

|fMRI |sensitivity for a ringed target can be |modulation, would be indicated by more |gain control within primary visual | |replicated, although in a much weaker |subjects. From these, separate|behavioral level. Neural level|

| |influenced by the contrast of a circular |accurate contrast judgments regarding |cortex (V1) (Zenger-Landolt & Heeger, | |form, by the CNTRaCS consortium. It |indicators of precision (the |is unknown. |

| |surround (Chubb, Sperling, & Solomon, |the inner circle compared to controls; |2003). Further evidence indicates that | |appears likely that there is a strong |minimum size of contrast | |

| |1989). In this task, participants are |and 2) there is already evidence for |the effect within V1 is likely due to | |state effect to the finding and that in |differences that are |We need to assess psychometric|

| |asked to match a variable contrast patch |reduced spatial context effects in |both activity arising within V1 and to | |more psychotic or disorganized patients, |detectable, which is indicated |characteristics such as |

| |to a central patch. When the surround is |vision in schizophrenia (Must, Janka, |top-down feedback from higher, | |suppressive effects are weakest (i.e., |by the slope of the function) |test-retest reliability, |

| |high-contrast, the inner target is |Benedek, & Keri, 2004; Uhlhaas et al., |object-processing areas to V1 (Lotto & | |there is less gain control), whereas in |and bias (reflecting the amount|practice effects, and |

| |perceived to be of lower contrast than |2006). An important feature of this |Purves, 2001). Because 90% of cells in | |recovered patients, suppression |of offset that is needed |ceiling/floor effects for this|

| |when the same target is perceived without|task is that full psychometric |V1 are subject to suppression from | |approaches normal levels (similar to with|between the target and the |task. |

| |a surround (Chubb et al., 1989; Dakin, |functions can be obtained for subjects.|neighboring cells, tasks such as this | |other indices of inhibition such as |surround to produce a | |

| |Carlin, & Hemsley, 2005). |From these, separate indicators of |that are known to act on V1 neurons are | |latent inhibition). |perceptual match) can be |We need to study whether or |

| | |precision (the minimum size of contrast|ideal methods for the study of gain | | |obtained, allowing us to |not performance on this task |

| |MANUSCRIPTS ON THE WEBSITE: |differences that are detectable, which |control. | | |examine discrimination accuracy|changes in response to |

| | |is indicated by the slope of the | | | |independent of response bias |psychological or |

| |Dakin, S., Carlin, P., & Hemsley, D. |function) and bias (reflecting the |(Zenger-Landolt & Heeger, 2003) | | |(as with other signal-detection|pharmacological intervention. |

| |(2005). Weak suppression of visual |amount of offset that is needed between|(Lotto & Purves, 2001) | | |analyses). This suggests the | |

| |context in chronic schizophrenia. Curr |the target and the surround to produce | | | |absence of floor/ceiling | |

| |Biol, 15(20), R822-824. |a perceptual match) can be obtained, | | | |effects. | |

| | |allowing us to examine discrimination | | | | | |

| |Zenger-Landolt, B., & Heeger, D. J. |accuracy independent of response bias | | | |These characteristics are | |

| |(2003). Response suppression in v1 agrees|(as with other signal-detection | | | |currently being studied for | |

| |with psychophysics of surround masking. J|analyses). | | | |behavioral version of the task.| |

| |Neurosci, 23(17), 6884-6893. | | | | | | |

| | |(Uhlhaas et al., 2006) | | | | | |

| | |(Must et al., 2004) | | | | | |

|Mismatch Negativity |Mismatch negativity (MMN) is an auditory |MMN indexes perception of stimulus |At the neural level, MMN reflects |NMDA dysfunction is thought to|MMN amplitude is reduced in schizophrenia|MMN reliability is very high, |There is evidence that this |

| |event-related potential (ERP) elicited in|deviance at the level of auditory |current flow through open, unblocked |underlie deficits in MMN in |across many studies with an effect of |with intra-class correlations |specific task elicits deficits|

| |an "oddball" task, in which a sequence of|cortex. Generation of MMN depends upon|NMDA receptors within auditory cortex. |schizophrenia. NMDA |about 1, with larger effect sizes |of greater than 0.9, although |in schizophrenia at both the |

| |repetitive standard tones is interrupted |gain control (i.e. signal |Similar mechanisms mediate gain control |antagonists decrease MMN |observes for duration deviant tones. MMN|reliability may vary with |behavioral and neural level. |

| |by a physically different "deviant" tone |amplification) of neurons sensitive to |within visual cortex, suggesting a |amplitude in primate models |reductions may worsen with illness |stimulus characteristics in the| |

| |that violates expectancies created by the|stimulus deviance. Presentation of |parallel phenomenon. MMN generation can |and in healthy controls |progression, and is correlated with |paradigm. It can be |Data already exists on |

| |standard. MMN can be recorded and |repetitive standards should, under |be antagonized by administration of NMDA|(Turetsky et al., 2007). |measures of psychosocial function. MMN |administered with distractor |psychometric characteristics |

| |quantified using standard ERP recording |normal conditions, lead to upward bias |agonists such as PCP or ketamine in | |deficits converge with anatomic finding |tasks to minimize learning |of this task, such as |

| |systems (e.g. Neuroscan, Biosemi, ANT). |of the gain process. In schizophrenia,|either human or animal models (Javitt, | |of reduced grey matter volume of the |effects. Ceiling-Floor effects|test-retest reliability, |

| |(Umbricht & Krljes, 2005) and can be |this bias mechanism appears to be |2000; Javitt, Steinschneider, Schroeder,| |auditory cortex to suggest early stage, |associated with behavioral |practice effects, |

| |measured in animals. |impaired. |& Arezzo, 1996; Turetsky et al., 2007; | |preattentive disturbances in auditory |performance are not relevant to|ceiling/floor effects. |

| | | |Umbricht et al., 2000). | |processing in schizophrenia. MMN has |MMN. The MMN is heritable, | |

| |MANUSCRIPTS ON THE WEBSITE: | | | |been shown in human and animal studies to|with estimates of > .6. |There is evidence that |

| | | |MMN tracks auditory perceptual | |be sensitive to pharmacological | |performance on this task can |

| |Javitt, D. C., Spencer, K. M., Thaker, G.| |performance across a variety of | |manipulations that affect neural systems |Test-retest reliability of |improve in response to |

| |K., Winterer, G., & Hajos, M. (2008). | |dimensions (Pakarinen, Takegata, Rinne, | |implicated in schizophrenia (NMDA |mismatch negativity for |psychological or |

| |Neurophysiological biomarkers for drug | |Huotilainen, & Naatanen, 2007). | |receptors, GABA neurotransmission, |duration, frequency and |pharmacological interventions.|

| |development in schizophrenia. Nat Rev | | | |serotonin neurotransmission).(Turetsky et|intensity changes | |

| |Drug Discov, 7(1), 68-83. | | | |al., 2007) |(Hall et al., 2006; Tervaniemi | |

| | | | | | |et al., 1999). | |

| |Turetsky, B. I., Calkins, M. E., Light, | | | | | | |

| |G. A., Olincy, A., Radant, A. D., & | | | | |Hall (average of 18 days): | |

| |Swerdlow, N. R. (2007). | | | | |0.34-0.66 ICCs | |

| |Neurophysiological endophenotypes of | | | | | | |

| |schizophrenia: the viability of selected | | | | |Tervaniemi (average of 8.3 | |

| |candidate measures. Schizophr Bull, | | | | |days): Correlations between | |

| |33(1), 69-94. | | | | |0.41 and 0.78. | |

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|Prepulse Inhibition of|Individuals are presented with two |In rodents, the essential brainstem |There is a large literature on the |Much evidence for various |Evidence for startle gating deficits in a|For results from multisite |There is evidence that this |

|Startle |auditory probes in sequences. The P50 |circuitry is established and complex |neural substrates of Prepulse inhibition|pharmacological manipulations |large cohort of patients with |trials, see (Swerdlow et al., |specific task elicits deficits|

| |response to the second probe is typically|forebrain circuits that regulate the |in animals, and a large literature on |of startle. For reviews, see |schizophrenia: relationship to |2007) |in schizophrenia at the neural|

|ERP |reduced in individuals with intact |response are known. |pharmacological effects. There are now |(Javitt, Spencer, Thaker, |medications, symptoms, neurocognition, | |level. |

| |sensory gating. | |human imaging studies (at least one) |Winterer, & Hajos, 2008; |and level of function. (Swerdlow et al.,| | |

| | | |looking at prepulse inhibition in the |Turetsky et al., 2007) |2006) | |We have some information on |

| |(Swerdlow, Braff, Taaid, & Geyer, 1994) | |scanner. | | | |the psychometric |

| |(Braff & Geyer, 1990) | | | | | |characteristics such as |

| |(Cadenhead, Carasso, Swerdlow, Geyer, & | |(Joober, Zarate, Rouleau, Skamene, & | | | |test-retest reliability, |

| |Braff, 1999) | |Boksa, 2002) | | | |practice effects, and |

| | | | | | | |ceiling/floor effects for this|

| |MANUSCRIPTS ON THE WEBSITE: | |(Kumari, Antonova, & Geyer, 2008) | | | |task. |

| | | |(Campbell et al., 2007) | | | | |

| |Javitt, D. C., Spencer, K. M., Thaker, G.| |(Kumari et al., 2007) | | | |This task has been studied |

| |K., Winterer, G., & Hajos, M. (2008). | |(Kumari et al., 2003) | | | |with psychopharamcology |

| |Neurophysiological biomarkers for drug | | | | | |methods |

| |development in schizophrenia. Nat Rev | | | | | | |

| |Drug Discov, 7(1), 68-83. | | | | | | |

| |Swerdlow, N. R., Sprock, J., Light, G. | | | | | | |

| |A., Cadenhead, K., Calkins, M. E., Dobie,| | | | | | |

| |D. J., et al. (2007). Multi-site studies | | | | | | |

| |of acoustic startle and prepulse | | | | | | |

| |inhibition in humans: initial experience | | | | | | |

| |and methodological considerations based | | | | | | |

| |on studies by the Consortium on the | | | | | | |

| |Genetics of Schizophrenia. Schizophr Res,| | | | | | |

| |92(1-3), 237-251. | | | | | | |

| | | | | | | | |

| |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. | | | | | | |

| | | | | | | | |

|Paired Click Paradigm |Paired-click sensory gating paradigm - no|-- |Highly consistent source localization to|Evidence that sensory gating |Strong evidence from multiple studies |Good test-retest in MEG |There is evidence that this |

| |overt task, pairs of clicks 500 ms apart,| |superior temporal gyrus. Emerging |can change in response to |(Edgar et al., 2008; Edgar et al., 2003; |measurements |specific task elicits deficits|

|ERP or MEG |~8 sec between pairs - after Adler et al.| |evidence of additional frontal-lobe |cognitive training (Popov et |Hanlon et al., 2005; Smith et al., 2010; |(Lu et al., 2007) |in schizophrenia |

| |(1982)(Adler et al., 1982) | |source(s). |al., in press). |Thoma et al., 2004) | | |

| | | | | | | |We have some information on |

| |MANUSCRIPTS ON THE WEBSITE: | | | | | |psychometric characteristics |

| | | | | | | |such as test-retest |

| |Lu, B. Y., Edgar, J. C., Jones, A. P., | | | | | |reliability, practice effects,|

| |Smith, A. K., Huang, M. X., Miller, G. | | | | | |and ceiling/floor effects for |

| |A., et al. (2007). Improved test-retest | | | | | |this task. |

| |reliability of 50-ms paired-click | | | | | | |

| |auditory gating using | | | | | |We have evidence that |

| |magnetoencephalography source modeling. | | | | | |performance on this task |

| |Psychophysiology, 44(1), 86-90. | | | | | |changes in response to |

| | | | | | | |psychological or |

| |Smith, A. K., Edgar, J. C., Huang, M., | | | | | |pharmacological intervention. |

| |Lu, B. Y., Thoma, R. J., Hanlon, F. M., | | | | | | |

| |et al. (2010). Cognitive abilities and | | | | | | |

| |50- and 100-msec paired-click processes | | | | | | |

| |in schizophrenia. Am J Psychiatry, | | | | | | |

| |167(10), 1264-1275. | | | | | | |

|N1 during passive |N1 during Passive auditory |-- |Generators of this component have been |Evidence for pharmacological |N1 deficits are well replicated in |Psychometric characteristics |There is evidence that this |

|auditory distraction |stimulation/visual distraction/ | |mapped using intracranial recordings in |manipulation in humans and |schizophrenia (Ford, Mathalon, Kalba, |described in (Javitt et al., |specific task elicits deficits|

| | | |humans, monkeys and rodents. Reviewed in|animals. Reviewed in (Javitt |Marsh, & Pfefferbaum, 2001; Rosburg, |2008). Little evidence of |in schizophrenia |

|ERP |MANUSCRIPTS ON THE WEBSITE: | |(Javitt et al., 2008) |et al., 2008). |Boutros, & Ford, 2008; Shelley, Silipo, &|practice effects or floor or | |

| | | | | |Javitt, 1999; Turetsky, Bilker, Siegel, |ceiling effects. |We have some information on |

| | | | | |Kohler, & Gur, 2009). | |psychometric characteristics |

| |Javitt, D. C., Spencer, K. M., Thaker, G.| | | | | |such as test-retest |

| |K., Winterer, G., & Hajos, M. (2008). | | | | | |reliability, practice effects,|

| |Neurophysiological biomarkers for drug | | | | | |and ceiling/floor effects for |

| |development in schizophrenia. Nat Rev | | | | | |this task. |

| |Drug Discov, 7(1), 68-83. | | | | | | |

| | | | | | | |We have evidence that |

| |Turetsky, B. I., Bilker, W. B., Siegel, | | | | | |performance on this task |

| |S. J., Kohler, C. G., & Gur, R. E. | | | | | |changes in response to |

| |(2009). Profile of auditory | | | | | |psychological or |

| |information-processing deficits in | | | | | |pharmacological intervention. |

| |schizophrenia. Psychiatry Res, 165(1-2), | | | | | | |

| |27-37. | | | | | | |

| | | | | | | | |

|Motion Perception |The paradigm measures cortical |When the visual motion system is | When the visual motion system is |Psilocybin impairs high-level |Application of this paradigm has |Not known |There is evidence that this |

| |activations during visual motion |damaged, both perceptual and neural |damaged, both perceptual and neural |but not low-level motion |indicated deficient as well excessive | |specific task elicits deficits|

|fMRI |perception, using fMRI. It provides |response to motion signals in primates |response to motion signals in primates |perception (Carter et al., |cortical responses to visual signals in | |in schizophrenia |

| |assessments of both sensory and cognitive|will be deficient (Tootell et al., |will be deficient (Tootell et al., |2004). |schizophrenia patients (Chen et al., | | |

| |systems. |1995). |1995). | |2008; Chen, Nakayama, Levy, Matthysse, & | |We need to assess psychometric|

| | | | |Contrast detection is |Holzman, 1999). | |characteristics such as |

| |(Chen et al., 2008) | | |influenced by antipsychotic | | |test-retest reliability, |

| | | | |medications (Chen et al., | | |practice effects, and |

| |MANUSCRIPTS ON THE WEBSITE: | | |2003). | | |ceiling/floor effects for this|

| | | | | | | |task. |

| | | | | | | | |

| |Chen, Y., Grossman, E. D., Bidwell, L. | | | | | | |

| |C., Yurgelun-Todd, D., Gruber, S. A., | | | | | |We have evidence that |

| |Levy, D. L., et al. (2008). Differential | | | | | |performance on this task |

| |activation patterns of occipital and | | | | | |changes in response to |

| |prefrontal cortices during motion | | | | | |psychological or |

| |processing: evidence from normal and | | | | | |pharmacological intervention. |

| |schizophrenic brains. Cogn Affect Behav | | | | | | |

| |Neurosci, 8(3), 293-303. | | | | | | |

| | | | | | | | |

| |Chen, Y., Palafox, G. P., Nakayama, K., | | | | | | |

| |Levy, D. L., Matthysse, S., & Holzman, P.| | | | | | |

| |S. (1999). Motion perception in | | | | | | |

| |schizophrenia. Arch Gen Psychiatry, | | | | | | |

| |56(2), 149-154. | | | | | | |

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