Perception � Gain Control by 29z84v


									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 This task that        reaches a saturation-level        Zemon & Gordon, 2006)              unpublished              in which                    lateral geniculate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-
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),

                Turetsky, B. I., Calkins, M. E.,
                Light, G. A., Olincy, A.,
                Radant, A. D., & Swerdlow,
                N. R. (2007).
                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.


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