3dISC


             ================== Welcome to 3dISC ==================
       Program for Voxelwise Inter-Subject Correlation (ISC) Analysis
#+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
Version 1.0.7, Sept 24, 2023
Author: Gang Chen (gangchen@mail.nih.gov)
SSCC/NIMH, National Institutes of Health, Bethesda MD 20892, USA
#+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

Introduction
------

 Intersubject correlation (ISC) measures the extent of BOLD response similarity
 or synchronization between two subjects who are scanned under the same
 experience such as movie watching, music learning, etc. The program performs
 voxelwise analysis with linear mixed-effects modeling that is laid out in the
 following paper:

 Chen, G., Taylor, P.A., Shin, Y.W., Reynolds, R.C., Cox, R.W., 2017. Untangling
 the Relatedness among Correlations, Part II: Inter-Subject Correlation Group
 Analysis through Linear Mixed-Effects Modeling. Neuroimage 147:825-840.

 Input files for 3dISC are voxelwise correlation values from all subject pairs.
 If they are not Fisher-transformed, use option -r2z in 3dISC to transform the
 data. If there are two or more groups of subjects, ISCs across groups are also
 required as input unless the data are analyzed for each group separately.
 Input files can be in AFNI, NIfTI or surface (niml.dset) format. In other words,
 with totally n subjects, you should provide n(n-1)/2 input files (no duplicates
 allowed). Currently 3dISC provides in the output the effect estimate (e.g., ISC
 value) and the corresponding t-statistic at each voxel.

 For data preprocessing, you may consider the steps discussed in Appendix B of
 the above paper. 3dTcorrelate in AFNI can be utilized to compute the voxelwise
 ISC of time series between any two subjects.

 The LME platform allows for the incorporation of various types of explanatory
 variables including categorical (between- and within-subject factors) and
 quantitative variables (e.g., age, behavioral data). The burden of properly
 specifying the weights for each effect (e.g., contrast) is unfortunately
 placed on the user's shoulder, and sorting out the number and order of
 predictors (regressors) can be overwhelming especially when there are more
 than two factor levels or when an interaction effect is involved. So,
 familiarize yourself with the details of the two popular factor coding
 strategies (dummy and deviation coding):
 https://stats.idre.ucla.edu/r/library/r-library-contrast-coding-systems-for-categorical-variables/

 The four exemplifying scripts below are good demonstrations.More examples will
 be added in the future if I could crowdsource more scenarios from the users
 (including you the reader). In case you find one or two of them that
 are similar to your data structure, use the example(s) as a template and then
 build up your own script.

 In addition to R installation, the following R packages need to be installed
 first before running 3dISC: "lme4" and "snow". To install these packages,
 run the following command at the terminal:

 rPkgsInstall -pkgs "lme4,snow"

 Alternatively you may install them in R:

 install.packages("lme4")
 install.packages("snow")

 Once the 3dISC command script is constructed, it can be run by copying and
 pasting to the terminal. Alternatively (and probably better) you save the
 script as a text file, for example, called ISC.txt, and execute it with the
 following (assuming on tc shell),

 nohup tcsh -x ISC.txt &

 or,

 nohup tcsh -x ISC.txt > diary.txt &
 nohup tcsh -x ISC.txt |& tee diary.txt &

 The advantage of the latter commands is that the progression is saved into
 the text file diary.txt and, if anything goes awry, can be examined later.

Example 1 --- Simplest case: ISC analysis for one group of subjects without
  any explanatory variables. In other words, the effect of interest is the ISC
  at the populaton level. The output is the group ISC plus its t-statistic.
  The components within parentheses in the -model specifications are R
  notations for random effects.

-------------------------------------------------------------------------
    3dISC -prefix ISC -jobs 12                    \
          -mask myMask+tlrc                       \
          -model  '1+(1|Subj1)+(1|Subj2)          \
          -dataTable                              \
          Subj1   Subj2  InputFile                \
          s1       s2    s1_s2+tlrc               \
          s1       s3    s1_s3+tlrc               \
          s1       s4    s1_s4+tlrc               \
          s1       s5    s1_s5+tlrc               \
          s1       s6    s1_s6+tlrc               \
          s1       s7    s1_s7+tlrc               \
          ...
          s2       s3    s2_s3+tlrc               \
          s2       s4    s2_s4+tlrc               \
          s2       s5    s2_s5+tlrc               \
          ...


Example 2 --- ISC analysis with two groups (G1 and G2). Three ISCs can be
  inferred at the population level, G11 (ISC among subjects within the first
  group G1), G22 (ISC among subjects within the second group G2), and G12 (ISC
  between subjects in the first group G1 and those in the second group G2). The
  research interest can be various comparisons among G11, G22 and G12, and this
  is the reason the group column 'grp' is coded with three types of population
  ISC: G11, G22 and G12. By default each factor (categorical variable) is
  internally quantified in the model using deviation coding with alphabetically
  the last level as the reference. Notice the semi-esoteric weights for those
  comparisons with -gltCode: the first weight corresponds to the intercept in
  the model, which is the average effect across all the factor levels (and
  corresponds to the zero value of a quantitative variable if present). If dummy
  coding is preferred, check out the next script below. The components within
  parentheses in the -model specifications are R notations for random effects.
  Here is a good reference about factor coding strategies:
  https://stats.idre.ucla.edu/r/library/r-library-contrast-coding-systems-for-categorical-variables/

-------------------------------------------------------------------------
    3dISC -prefix ISC2a -jobs 12                \
          -mask myMask+tlrc                     \
          -model  'grp+(1|Subj1)+(1|Subj2)'     \
          -gltCode ave     '1 0 -0.5'           \
          -gltCode G11     '1 1 0'              \
          -gltCode G12     '1 0 1'              \
          -gltCode G22     '1 -1 -1'            \
          -gltCode G11vG22 '0 2 1'              \
          -gltCode G11vG12 '0 1 -2'             \
          -gltCode G12vG22 '0 1 2'              \
          -gltCode ave-G12 '0 0 -1.5'           \
          -dataTable                            \
          Subj1 Subj2    grp      InputFile       \
          s1     s2      G11      s1_2+tlrc     \
          s1     s3      G11      s1_3+tlrc     \
          s1     s4      G11      s1_4+tlrc     \
          ...
          s1     s25     G12      s1_25+tlr     \
          s1     s26     G12      s1_26+tlr     \
          s1     s27     G12      s1_26+tlr     \
          ...
          s25    s26     G22     s25_26+tlr     \
          s25    s27     G22     s25_27+tlr     \
          s25    s48     G22     s51_28+tlr     \
         ...

  The above script is equivalent to the one below. The only difference is that
  we force 3dISC to adopt dummy coding by adding a zero in the -model
  specification, which makes the weight coding much more intuitive. In this
  particular case, the three weights are associated with the three
  categories, G11, G12 and G22 (no intercept is assumed in the model as
  requested with the zero (0) in the model specifications).
  ** Alert ** This coding strategy, using no intercept, only works when
  there is a single explanatory variable (e.g., 'group' in this example).
  For cases with more than one explanatory variable, consider adopting
  other coding methods.

-------------------------------------------------------------------------
    3dISC -prefix ISC2b -jobs 12                  \
          -model  '0+grp+(1|Subj1)+(1|Subj2)'     \
          -gltCode ave     '0.5 0 0.5'            \
          -gltCode G11     '1 0  0'               \
          -gltCode G12     '0 1 0'                \
          -gltCode G22     '0 0 1'                \
          -gltCode G11vG22 '1 0 -1'               \
          -gltCode G11vG12 '1 -1 0'               \
          -gltCode G12vG22 '0 1 -1'               \
          -gltCode ave-G12 '0.5 -1 0.5'           \
          -dataTable                              \
          Subj1 Subj2    grp      InputFile       \
          s1     s2      G11      s1_2+tlrc       \
          s1     s3      G11      s1_3+tlrc       \
          s1     s4      G11      s1_4+tlrc       \
          ...
          s1     s25     G12      s1_25+tlr       \
          s1     s26     G12      s1_26+tlr       \
          s1     s27     G12      s1_26+tlr       \
          ...
          s25    s26     G22     s25_26+tlr       \
          s25    s27     G22     s25_27+tlr       \
          s25    s48     G22     s51_28+tlr       \
         ...

  There is a third way to analyze this same dataset if we are NOT
  interested in the between-group ISC, G12. First, we adopt deviation
  coding for the two groups by replacing two groups G1 and G2 with 0.5 and
  -0.5. Then add up the two values for each row (each subject pair),
  resulting in three possible values of 1, -1 and 0. Put those three values
  in the group column in the data table.

-------------------------------------------------------------------------
    3dISC -prefix ISC2c -jobs 12                       \
          -model  'grp+(1|Subj1)+(1|Subj2)'            \
          -qVars   grp                                 \
          -gltCode ave     '1 0'                       \
          -gltCode G11vG22 '0 1'                       \
          -gltCode G11     '1 0.5'                     \
          -gltCode G22     '1 -0.5'                    \
          -dataTable                                   \
          Subj1 Subj2    grp      InputFile            \
          s1     s2       1      s1_2+tlrc             \
          s1     s3       1      s1_3+tlrc             \
          s1     s4       1      s1_4+tlrc             \
          ...
          s1     s25      0      s1_25+tlr             \
          s1     s26      0      s1_26+tlr             \
          s1     s27      0      s1_26+tlr             \
          ...
          s25    s26     -1     s25_26+tlr             \
          s25    s27     -1     s25_27+tlr             \
          s25    s48     -1     s51_28+tlr             \
          ...


Example 3 --- ISC analysis for one group of subjects. The only difference
  from Example 1 is that we want to add an explanatory variable 'Age'.
  Before the age values are incorporated in the data table, do two things:
  1) center the age by subtracting the cener (e.g., overall mean) from each
  subject's age, and 2) for each subject pair (each row in the data table)
  add up the two ages (after centering). The components within parentheses
  in the -model specifications are R notations for random effects.

-------------------------------------------------------------------------
    3dISC -prefix ISC3 -jobs 12                       \
          -mask myMask+tlrc                           \
          -model  'Age+(1|Subj1)+(1|Subj2)'           \
          -qVars   Age                                \
          -gltCode ave     '1 0'                      \
          -gltCode Age     '0 1'                      \
          -dataTable                                  \
          Subj1   Subj2  Age  InputFile               \
          s1       s2    2   s1_s2+tlrc               \
          s1       s3    5   s1_s3+tlrc               \
          s1       s4    -4  s1_s4+tlrc               \
          s1       s5    3   s1_s5+tlrc               \
          s1       s6    -2  s1_s6+tlrc               \
          s1       s7    -1  s1_s7+tlrc               \
          ...
          s2       s3    2   s2_s3+tlrc               \
          s2       s4    4   s2_s4+tlrc               \
          s2       s5    -5  s2_s5+tlrc               \
         ...


Example 4 --- ISC analysis with two groups of subject (Sex: females and males)
  plus a quantitative explanatory variable (Age). We are going to combine the
  modeling strategy in the third analysis of Example 2 with Example 3. In
  addition, we consider the interaction between Sex and Age by adding their
  product as another column (called 'SA' in the data table). The components
  within parentheses in the -model specifications are R notations for random
  effects.

-------------------------------------------------------------------------
    3dISC -prefix ISC2c -jobs 12                          \
          -mask myMask+tlrc                               \
          -model  'Sex+Age+SA+(1|Subj1)+(1|Subj2)'        \
          -qVars  'Sex,Age,SA'                            \
          -gltCode ave       '1   0  0  0'                \
          -gltCode G11vG22   '0   1  0  0'                \
          -gltCode G11       '1  0.5 0  0'                \
          -gltCode G22       '1 -0.5 0  0'                \
          -gltCode Age       '0   0  1  0'                \
          -gltCode Age1vAge2 '0   0  0  1'                \
          -gltCode Age1      '0   0  1  0.5'              \
          -gltCode Age2      '0   0  1 -0.5'              \
          -dataTable                                      \
          Subj1 Subj2    Sex Age SA     InputFile         \
          s1     s2       1  2   2    s1_2+tlrc           \
          s1     s3       1  5   5    s1_3+tlrc           \
          s1     s4       1  -4 -4    s1_4+tlrc           \
          ...
          s1     s25      0  -2  0    s1_25+tlr           \
          s1     s26      0  -1  0    s1_26+tlr           \
          s1     s27      0   3  0    s1_26+tlr           \
          ...
          s25    s26     -1  4  -4    s25_26+tlr          \
          s25    s27     -1  -5  5    s25_27+tlr          \
          s25    s48     -1  2  -2    s51_28+tlr          \
         ...


Example 5 --- ISC analysis with two conditions (C1 and C2). The research interest
  is regarding the contrast of ISC between the two conditions. The basic strategy
  is to convert the data to the contrast between the conditions. In other words,
  obtain the contrast of ISC after the Fisher-transformation between the two
  conditions for each subject pair with a command like the following:

  3dcalc -a subj1_subj2_cond1 -b subj1_subj2_cond2 -expr 'atanh(a)-atanh(b)'
     -prefix subj1_subj2

  The function of inverse hyperbolic tangent 'atanh' is the same as the Fisher
  z-transform. Then follow Example 1 with the contrasts from the above 3dcalc output
  as input.


Options in alphabetical order:
------------------------------

   -cio: Use AFNI's C io functions, which is default. Alternatively -Rio
         can be used.

   -dataTable TABLE: List the data structure with a header as the first line.

         NOTE:

         1) This option has to occur last in the script; that is, no other
         options are allowed thereafter. Each line should end with a backslash
         except for the last line.

         2) The table should contain at least three columns, two of which are
         for the two subjects in each pair, 'Subj1' and 'Subj2'. These two columns
         code the labels of the two subjects involved
         for each ISC file that is listed in the column 'InputFile'. The order of
         the columns does not matter. Any subject-level explanatory variables
         (e.g., age, sex, etc.) can be
         specified as columns in the table. Each row should contain only one
         ISC file in the table of long format (cf. wide format) as defined in R.
         The level labels of a factor should contain at least
         one character. Input files can be in AFNI, NIfTI or surface format.
         AFNI files can be specified with sub-brick selector (square brackets
         [] within quotes) specified with a number or label.

         3) It is fine to have variables (or columns) in the table that are
         not modeled in the analysis.

         4) The context of the table can be saved as a separate file, e.g.,
         called table.txt. Do not forget to include a backslash at the end of
         each row. In the script specify the data with '-dataTable @table.txt'.
         This option is useful: (a) when there are many input files so that
         the program complains with an 'Arg list too long' error; (b) when
         you want to try different models with the same dataset.

   -dbgArgs: This option will enable R to save the parameters in a
         file called .3dISC.dbg.AFNI.args in the current directory
          so that debugging can be performed.

   -gltCode label weights: Specify the label and weights of interest. The
       weights should be surrounded with quotes.

   -help: this help message

   -IF var_name: var_name is used to specify the column name that is designated for
        input files of effect estimate. The default (when this option is not invoked
        is 'InputFile', in which case the column header has to be exactly as 'InputFile'
        This input file for effect estimates has to be the last column.

   -jobs NJOBS: On a multi-processor machine, parallel computing will speed
         up the program significantly.
         Choose 1 for a single-processor computer.

   -mask MASK: Process voxels inside this mask only.
          Default is no masking.

   -model FORMULA: Specify the model structure for all the variables. The
         expression FORMULA with more than one variable has to be surrounded
         within (single or double) quotes. Variable names in the formula
         should be consistent with the ones used in the header of -dataTable.
         In the ISC context the simplest model is "1+(1|Subj1)+(1|Subj2)"in
         while the random effect from each of the two subjects in a pair is
         symmetrically incorporated in the model. Each random-effects factor is
         specified within parentheses per formula convention in R. Any
         effects of intereste and confounding variables (quantitative or
         categorical variables) can be added as fixed effects without parentheses.

   -prefix PREFIX: Output file name. For AFNI format, provide prefix only,
         with no view+suffix needed. Filename for NIfTI format should have
         .nii attached (otherwise the output would be saved in AFNI format).

   -qVarCenters VALUES: Specify centering values for quantitative variables
         identified under -qVars. Multiple centers are separated by
         commas (,) without any other characters such as spaces and should
         be surrounded within (single or double) quotes. The order of the
         values should match that of the quantitative variables in -qVars.
         Default (absence of option -qVarsCetners) means centering on the
         average of the variable across ALL subjects regardless their
         grouping. If within-group centering is desirable, center the
         variable YOURSELF first before the values are fed into -dataTable.

   -qVars variable_list: Identify quantitative variables (or covariates) with
         this option. The list with more than one variable has to be
         separated with comma (,) without any other characters such as
         spaces and should be surrounded within (single or double) quotes.
          For example, -qVars "Age,IQ"
         WARNINGS:
         1) Centering a quantitative variable through -qVarsCenters is
         very critical when other fixed effects are of interest.
         2) Between-subjects covariates are generally acceptable.
         However EXTREME caution should be taken when the groups
         differ substantially in the average value of the covariate.


   -r2z: This option performs Fisher transformation on the response variable
         (input files) if it is correlation value. Do not invoke the option
         if the transformation has already been applied.

   -Rio: Use R's io functions. The alternative is -cio.

   -show_allowed_options: list of allowed options

   -Subj1 var_name: var_name is used to specify the column name that is designated as
        as the first measuring entity variable (usually subject). This option,
        combined with the another option '-Subj2', forms a pair of two subjects;
        the order between the two subjects does not matter. The default (when
        the option is not invoked) is 'Subj1', in which case the column header has
        to be exactly as 'Subj1'.

   -Subj2 var_name: var_name is used to specify the column name that is designated as
        as the first measuring entity variable (usually subject). This option,
        combined with the another option '-Subj1', forms a pair of two subjects;
        the order between the two subjects does not matter. The default (when
        the option is not invoked) is 'Subj2', in which case the column header has
        to be exactly as 'Subj1'.