References

Participants

TBIPFM01

Variables Over Time

Depression

MODEL

model1 <- lm(Dep_BDI ~ Time.since.injury, data=tbi1) model2 <- lm(Dep_BDI ~ Time.since.injury + I(Time.since.injury^2), data=tbi1)


SUMMARY

  Dep_LinearModel Dep_QuadraticModel
Predictors Estimates CI p Estimates CI p
(Intercept) 25.99 24.57 – 27.41 <0.001 35.84 34.19 – 37.48 <0.001
Time since injury -0.02 -0.03 – -0.01 0.004 -0.35 -0.40 – -0.31 <0.001
Time since injury^2 0.00 0.00 – 0.00 <0.001
Observations 486 486
R2 / R2 adjusted 0.017 / 0.015 0.368 / 0.365

ANOVA COMPARISON

Analysis of Variance Table
Res.Df RSS Df Sum of Sq F Pr(>F)
484 32623
483 20992 1 11631 267.6 3.497e-48

AIC

  • AIC for model 1 (i.e., linear model) 3430

  • AIC for model 2 (i.e.,quadratic model) 3217


INTERPRETATION

  • An ANOVA comparison suggests that there is a significant difference in the linear versus quadratic fit (p< 10^-29)
  • The R-squared value of the linear model is 0.12. The adjusted R-squared value of the quadratic model is 0.32, suggesting more variance is explained by the second model.
  • To ensure that that quadratic model is not better due to over-fitting, we also determined the AIC for each model. For the linear model, the AIC is 3152. For the quadratic model, the AIC is 3028. The ΔAIC is > 10, providing strong evidence that the model with lower AIC (i.e., the quadratic model) is a better fit.

Anxiety

MODEL

model1 <- lm(Anx_BAI ~ Time.since.injury, data=tbi1) model2 <- lm(Anx_BAI ~ Time.since.injury + I(Time.since.injury^2), data=tbi1)


SUMMARY

  Anx_LinearModel Anx_QuadraticModel
Predictors Estimates CI p Estimates CI p
(Intercept) 17.06 16.11 – 18.00 <0.001 24.11 23.07 – 25.14 <0.001
Time since injury -0.07 -0.08 – -0.06 <0.001 -0.31 -0.33 – -0.28 <0.001
Time since injury^2 0.00 0.00 – 0.00 <0.001
Observations 486 486
R2 / R2 adjusted 0.312 / 0.311 0.598 / 0.597

ANOVA COMPARISON

Analysis of Variance Table
Res.Df RSS Df Sum of Sq F Pr(>F)
484 14325
483 8364 1 5961 344.2 2.063e-58

AIC

  • AIC for model 1 (i.e., linear model) 3030

  • AIC for model 2 (i.e.,quadratic model) 2770


INTERPRETATION

  • An ANOVA comparison suggests that there is a significant difference in the linear versus quadratic fit (p< 10^-52)
  • The R-squared value of the linear model is 0.35. The adjusted R-squared value of the quadratic model is 0.60, suggesting more variance is explained by the second model.
  • To ensure that that quadratic model is not better due to over-fitting, we also determined the AIC for each model. For the linear model, the AIC is 2911. For the quadratic model, the AIC is 2678. The ΔAIC is >10, providing strong evidence that the model with lower AIC (i.e., the quadratic model) is a better fit.

FA (without tract info)

MODEL

model1 <- lm(FA ~ Time.since.injury, data=tbi1) model2 <- lm(FA ~ Time.since.injury + I(Time.since.injury^2), data=tbi1)


SUMMARY

  FA_LinearModel FA_QuadraticModel
Predictors Estimates CI p Estimates CI p
(Intercept) 0.54 0.53 – 0.55 <0.001 0.54 0.53 – 0.56 <0.001
Time since injury -0.00 -0.00 – 0.00 0.396 -0.00 -0.00 – 0.00 0.397
Time since injury^2 0.00 -0.00 – 0.00 0.516
Observations 486 486
R2 / R2 adjusted 0.001 / -0.001 0.002 / -0.002

ANOVA COMPARISON

Analysis of Variance Table
Res.Df RSS Df Sum of Sq F Pr(>F)
484 2.254
483 2.252 1 0.001968 0.4222 0.5161

AIC

  • AIC for model 1 (i.e., linear model) -1226

  • AIC for model 2 (i.e.,quadratic model) -1225


INTERPRETATION

  • FA over Time since injury (without tract info) is not significantly different over time.

FA by Tract and Time

MODEL BY TRACT AND TIME

model1 <- lm(FA ~ Tract.ID + Time.since.injury + Tract.ID*Time.since.injury, data=tbi1) model2 <- lm(FA ~ Tract.ID + Time.since.injury + I(Time.since.injury^2) + Tract.ID:Time.since.injury + Tract.ID:I(Time.since.injury^2), data=tbi1)


SUMMARY FOR MODEL BY TRACT AND TIME

  FA_LinearModel FA_QuadraticModel
Predictors Estimates CI p Estimates CI p
(Intercept) 0.68 0.68 – 0.68 <0.001 0.69 0.68 – 0.69 <0.001
Tract ID [forceps minor] -0.09 -0.10 – -0.08 <0.001 -0.09 -0.10 – -0.08 <0.001
Tract ID [left atr] -0.18 -0.19 – -0.18 <0.001 -0.19 -0.19 – -0.18 <0.001
Tract ID [left cab] -0.26 -0.26 – -0.25 <0.001 -0.26 -0.27 – -0.26 <0.001
Tract ID [left cing] -0.03 -0.03 – -0.02 <0.001 -0.03 -0.04 – -0.02 <0.001
Tract ID [left cst] -0.12 -0.13 – -0.11 <0.001 -0.12 -0.13 – -0.11 <0.001
Tract ID [left ilf] -0.14 -0.14 – -0.13 <0.001 -0.14 -0.15 – -0.13 <0.001
Tract ID [left slfp] -0.16 -0.17 – -0.16 <0.001 -0.16 -0.17 – -0.16 <0.001
Tract ID [left slft] -0.13 -0.13 – -0.12 <0.001 -0.13 -0.14 – -0.12 <0.001
Tract ID [left unc] -0.18 -0.18 – -0.17 <0.001 -0.18 -0.19 – -0.17 <0.001
Tract ID [right atr] -0.19 -0.19 – -0.18 <0.001 -0.19 -0.20 – -0.18 <0.001
Tract ID [right cab] -0.25 -0.26 – -0.24 <0.001 -0.26 -0.27 – -0.25 <0.001
Tract ID [right cing] -0.01 -0.02 – -0.01 <0.001 -0.01 -0.02 – -0.01 0.001
Tract ID [right cst] -0.12 -0.12 – -0.11 <0.001 -0.12 -0.13 – -0.11 <0.001
Tract ID [right ilf] -0.14 -0.14 – -0.13 <0.001 -0.14 -0.15 – -0.13 <0.001
Tract ID [right slfp] -0.18 -0.19 – -0.17 <0.001 -0.18 -0.19 – -0.17 <0.001
Tract ID [right slft] -0.16 -0.16 – -0.15 <0.001 -0.16 -0.17 – -0.15 <0.001
Tract ID [right unc] -0.18 -0.19 – -0.17 <0.001 -0.19 -0.19 – -0.18 <0.001
Time since injury -0.00 -0.00 – -0.00 0.001 -0.00 -0.00 – -0.00 <0.001
Tract ID [forceps minor]
× Time since injury
-0.00 -0.00 – 0.00 0.950 0.00 -0.00 – 0.00 0.500
Tract ID [left atr] ×
Time since injury
0.00 -0.00 – 0.00 0.081 0.00 -0.00 – 0.00 0.083
Tract ID [left cab] ×
Time since injury
0.00 0.00 – 0.00 0.011 0.00 0.00 – 0.00 0.001
Tract ID [left cing] ×
Time since injury
0.00 -0.00 – 0.00 0.518 0.00 -0.00 – 0.00 0.401
Tract ID [left cst] ×
Time since injury
0.00 -0.00 – 0.00 0.200 0.00 -0.00 – 0.00 0.236
Tract ID [left ilf] ×
Time since injury
0.00 -0.00 – 0.00 0.051 0.00 -0.00 – 0.00 0.356
Tract ID [left slfp] ×
Time since injury
0.00 -0.00 – 0.00 0.054 0.00 -0.00 – 0.00 0.135
Tract ID [left slft] ×
Time since injury
0.00 -0.00 – 0.00 0.122 0.00 -0.00 – 0.00 0.136
Tract ID [left unc] ×
Time since injury
0.00 0.00 – 0.00 0.032 0.00 -0.00 – 0.00 0.148
Tract ID [right atr] ×
Time since injury
-0.00 -0.00 – 0.00 0.472 0.00 -0.00 – 0.00 0.871
Tract ID [right cab] ×
Time since injury
0.00 -0.00 – 0.00 0.096 0.00 0.00 – 0.00 <0.001
Tract ID [right cing] ×
Time since injury
-0.00 -0.00 – -0.00 0.001 -0.00 -0.00 – 0.00 0.469
Tract ID [right cst] ×
Time since injury
0.00 -0.00 – 0.00 0.150 0.00 -0.00 – 0.00 0.121
Tract ID [right ilf] ×
Time since injury
-0.00 -0.00 – 0.00 0.708 0.00 -0.00 – 0.00 0.269
Tract ID [right slfp] ×
Time since injury
0.00 -0.00 – 0.00 0.302 0.00 -0.00 – 0.00 0.450
Tract ID [right slft] ×
Time since injury
-0.00 -0.00 – 0.00 0.493 0.00 -0.00 – 0.00 0.923
Tract ID [right unc] ×
Time since injury
-0.00 -0.00 – 0.00 0.307 0.00 0.00 – 0.00 0.043
Time since injury^2 0.00 0.00 – 0.00 0.001
Tract ID [forceps minor]
× Time since injury^2
-0.00 -0.00 – 0.00 0.474
Tract ID [left atr] ×
Time since injury^2
-0.00 -0.00 – 0.00 0.197
Tract ID [left cab] ×
Time since injury^2
-0.00 -0.00 – -0.00 0.005
Tract ID [left cing] ×
Time since injury^2
-0.00 -0.00 – 0.00 0.496
Tract ID [left cst] ×
Time since injury^2
-0.00 -0.00 – 0.00 0.393
Tract ID [left ilf] ×
Time since injury^2
-0.00 -0.00 – 0.00 0.699
Tract ID [left slfp] ×
Time since injury^2
-0.00 -0.00 – 0.00 0.323
Tract ID [left slft] ×
Time since injury^2
-0.00 -0.00 – 0.00 0.274
Tract ID [left unc] ×
Time since injury^2
-0.00 -0.00 – 0.00 0.381
Tract ID [right atr] ×
Time since injury^2
-0.00 -0.00 – 0.00 0.706
Tract ID [right cab] ×
Time since injury^2
-0.00 -0.00 – -0.00 0.001
Tract ID [right cing] ×
Time since injury^2
-0.00 -0.00 – 0.00 0.848
Tract ID [right cst] ×
Time since injury^2
-0.00 -0.00 – 0.00 0.234
Tract ID [right ilf] ×
Time since injury^2
-0.00 -0.00 – 0.00 0.211
Tract ID [right slfp] ×
Time since injury^2
-0.00 -0.00 – 0.00 0.630
Tract ID [right slft] ×
Time since injury^2
-0.00 -0.00 – 0.00 0.765
Tract ID [right unc] ×
Time since injury^2
-0.00 -0.00 – -0.00 0.017
Observations 486 486
R2 / R2 adjusted 0.993 / 0.993 0.995 / 0.994

ANOVA COMPARISON FOR MODELS BY TRACT AND TIME

Analysis of Variance Table
Res.Df RSS Df Sum of Sq F Pr(>F)
450 0.01487
432 0.01212 18 0.002743 5.431 1.614e-11

AIC FOR MODELS BY TRACT AND TIME

  • AIC for model 1 (i.e., linear model) -3599

  • AIC for model 2 (i.e.,quadratic model) -3662


INTERPRETATION

  • For models by tract and time, quadratic models are preferred (see ANOVA results, AIC scores)

Mixed Models

Statistical Framework

Should Tract.ID be considered a control variable or a moderating variable?

Time-Dep-FA

Research Q: How does depression moderate the relationship between time since injury and FA trajectory/recovery?

Hypotheses:

  • Time since injury has a positive effect on FA.
  • The positive effect of FA on time since injury is stronger for individuals with lower depressive symptoms.
Proposed Linear Mixed Effects Model

time.Dep.FA.lme.model <- nlme::lme(zFA ~ zTime.since.injury*zDep_BDI,random=list(ParticipantID=~1, Tract.ID=~1), data=tbi)

Checking Model Assumptions

ASSUMPTION 1: Linearity

ASSUMPTION 2: Normal Distribution of Residuals

ASSUMPTION 3: Homoscedasticity of model and random effects

## OK: Error variance appears to be homoscedastic (p = 0.879).

ASSUMPTION 4: No Auto-Correlation of Residuals

ASSUMPTION 5: NO MULTI-COLLINEARITY

## # Check for Multicollinearity
## 
## Low Correlation
## 
##                         Term  VIF    VIF 95% CI Increased SE Tolerance
##           zTime.since.injury 1.03 [1.00,  1.40]         1.01      0.97
##                     zDep_BDI 1.03 [1.00,  1.37]         1.02      0.97
##  zTime.since.injury:zDep_BDI 1.01 [1.00, 13.12]         1.01      0.99
##  Tolerance 95% CI
##      [0.71, 1.00]
##      [0.73, 1.00]
##      [0.08, 1.00]
Final Model Output
## Linear mixed-effects model fit by REML
##   Data: tbi 
##         AIC       BIC   logLik
##   -968.3397 -936.1501 491.1698
## 
## Random effects:
##  Formula: ~1 | ParticipantID
##          (Intercept)
## StdDev: 0.0001090306
## 
##  Formula: ~1 | Tract.ID %in% ParticipantID
##         (Intercept)  Residual
## StdDev:   0.9638819 0.1019467
## 
## Fixed effects:  zFA ~ zTime.since.injury * zDep_BDI 
##                                   Value  Std.Error  DF   t-value p-value
## (Intercept)                 -0.01741002 0.16070895 699 -0.108333  0.9138
## zTime.since.injury          -0.03147903 0.00381327 699 -8.255130  0.0000
## zDep_BDI                     0.03496452 0.00724110 699  4.828620  0.0000
## zTime.since.injury:zDep_BDI -0.00721407 0.00313233 699 -2.303096  0.0216
##  Correlation: 
##                             (Intr) zTm.s. zD_BDI
## zTime.since.injury           0.002              
## zDep_BDI                     0.013  0.156       
## zTime.since.injury:zDep_BDI -0.001 -0.071 -0.083
## 
## Standardized Within-Group Residuals:
##         Min          Q1         Med          Q3         Max 
## -4.20172246 -0.55503697 -0.01485419  0.55910632  4.49691635 
## 
## Number of Observations: 738
## Number of Groups: 
##               ParticipantID Tract.ID %in% ParticipantID 
##                           2                          36
##                             numDF denDF  F-value p-value
## (Intercept)                     1   699  0.02743  0.8685
## zTime.since.injury              1   699 85.56834  <.0001
## zDep_BDI                        1   699 21.66266  <.0001
## zTime.since.injury:zDep_BDI     1   699  5.30425  0.0216

Time-Anx-FA

Research Q: How does anxiety moderate the relationship between time since injury and FA trajectory/recovery?

Hypotheses:

  • Time since injury has a positive effect on FA.
  • The positive effect of FA on time since injury is stronger for individuals with lower anxiety symptoms.
Proposed Linear Mixed Effects Model

time.Anx.FA.lme.model <- nlme::lme(zFA ~ zTime.since.injury*zAnx_BAI,random=list(ParticipantID=~1, Tract.ID=~1), data=tbi)

Checking Model Assumptions

ASSUMPTION 1: Linearity

ASSUMPTION 2: Normal Distribution of Residuals

ASSUMPTION 3: Homoscedasticity of model and random effects

## OK: Error variance appears to be homoscedastic (p = 0.883).

ASSUMPTION 4: No Auto-Correlation of Residuals

ASSUMPTION 5: NO MULTI-COLLINEARITY

## # Check for Multicollinearity
## 
## Low Correlation
## 
##                         Term  VIF   VIF 95% CI Increased SE Tolerance
##           zTime.since.injury 1.36 [1.25, 1.50]         1.16      0.74
##                     zAnx_BAI 1.95 [1.76, 2.18]         1.39      0.51
##  zTime.since.injury:zAnx_BAI 1.51 [1.39, 1.68]         1.23      0.66
##  Tolerance 95% CI
##      [0.67, 0.80]
##      [0.46, 0.57]
##      [0.60, 0.72]
Final Model Output
## Linear mixed-effects model fit by REML
##   Data: tbi 
##         AIC       BIC   logLik
##   -957.5886 -925.3991 485.7943
## 
## Random effects:
##  Formula: ~1 | ParticipantID
##          (Intercept)
## StdDev: 0.0001030225
## 
##  Formula: ~1 | Tract.ID %in% ParticipantID
##         (Intercept)  Residual
## StdDev:   0.9652455 0.1027296
## 
## Fixed effects:  zFA ~ zTime.since.injury * zAnx_BAI 
##                                    Value  Std.Error  DF   t-value p-value
## (Intercept)                 -0.025654550 0.16094147 699 -0.159403  0.8734
## zTime.since.injury          -0.027729077 0.00441384 699 -6.282304  0.0000
## zAnx_BAI                     0.015299363 0.00678076 699  2.256292  0.0244
## zTime.since.injury:zAnx_BAI -0.006003478 0.00419150 699 -1.432297  0.1525
##  Correlation: 
##                             (Intr) zTm.s. zA_BAI
## zTime.since.injury          0.006               
## zAnx_BAI                    0.013  0.491        
## zTime.since.injury:zAnx_BAI 0.013  0.154  0.565 
## 
## Standardized Within-Group Residuals:
##          Min           Q1          Med           Q3          Max 
## -4.194119185 -0.561723620 -0.001038555  0.564403242  4.297677826 
## 
## Number of Observations: 738
## Number of Groups: 
##               ParticipantID Tract.ID %in% ParticipantID 
##                           2                          36
##                             numDF denDF  F-value p-value
## (Intercept)                     1   699  0.02735  0.8687
## zTime.since.injury              1   699 84.26891  <.0001
## zAnx_BAI                        1   699 13.79525  0.0002
## zTime.since.injury:zAnx_BAI     1   699  2.05147  0.1525