# Abstract

 Deficits in social cognition including facial affect recognition and their detrimental effects on functional outcome are well established in schizophrenia. Structured training can have substantial effects on social cognitive measures including facial affect recognition. Elucidating training effects on cortical mechanisms involved in facial affect recognition may identify causes of dysfunctional facial affect recognition in schizophrenia and foster remediation strategies. In the present study, 57 schizophrenia patients were randomly assigned to (a) computer-based facial affect training that focused on affect discrimination and working memory in 20 daily 1-hour sessions, (b) similarly intense, targeted cognitive training on auditory-verbal discrimination and working memory, or (c) treatment as usual. Neuromagnetic activity was measured before and after training during a dynamic facial affect recognition task (5 s videos showing human faces gradually changing from neutral to fear or to happy expressions). Effects on 10--13 Hz (alpha) power during the transition from neutral to emotional expressions were assessed via MEG based on previous findings that alpha power increase is related to facial affect recognition and is smaller in schizophrenia than in healthy subjects. Targeted affect training improved overt performance on the training tasks. Moreover, alpha power increase during the dynamic facial affect recognition task was larger after affect training than after treatment-as-usual, though similar to that after targeted perceptual--cognitive training, indicating somewhat nonspecific benefits. Alpha power modulation was unrelated to general neuropsychological test performance, which improved in all groups. Results suggest that specific neural processes supporting facial affect recognition, evident in oscillatory phenomena, are modifiable. This should be considered when developing remediation strategies targeting social cognition in schizophrenia. # Results *Clinical status*improved in all three SZ groups independent of type of intervention: general function (GAF *F* (2,53) = 16.92, *p*  \< .001), positive symptoms (PANSS-P *F* (2,53) = 17.92, *p*  \< .001), and general symptoms (PANSS-G *F* (2,53) = 10.30, *p*  \< .001; PANSS-N n.s.). There were no effects involving Intervention. 

## MEG during FAR criterion task prior to intervention [Fig. 2](#)illustrates time--frequency representation (TFR) of power during face morphing prior to intervention. The HC19 group TFR showed an increase from baseline in the 10--13 Hz range between 1 s (morph onset) and 3.5 s after stimulus onset, with maximum around 3 s. This increase was not evident in any SZ group. Statistical comparisons ( [Fig. 2](#) , bottom) confirmed significant differences between HC19 and pre-intervention SZ in alpha-power increase over a central sensor cluster in the time course from 2.5 to 3.5 s after stimulus onset. *FAT task performance*was poorer in SZ during their first FAT session than in the HC24 group during their one FAT session (same-different task *F* (1,41) = 7.69, *p* = .008; blended emotion task *F* (1,41) = 8.24, *p* = .006; emotion sequence task *F* (1,41) = 16.11, *p*  \< .001; emotion location task *F* (1,41) = 16.19, *p*  \< .001; [Fig. 3](#) A). Performance improved with training on all four tasks in the FAT group, significantly in three tasks ( [Fig. 3B](#) , left): same/different, *F* (1,18) = 4.99, *p* = .04; blended emotion *F* (1,18) = 10.17, *p* = .005; emotion sequence *F* (1,18) = 3.28, *p* = .09; emotion location *F* (1,18) = 13.12, *p* = .002. In the last FAT training session, SZ no longer differed significantly from HC24 on three of the four tasks. SZ still performed worse in the emotion location task ( *F* (1,41) = 6.72, *p* = .01; see also effect sizes in [Fig. 3B](#) , right). 

## FAT impact on MEG during FAR criterion task An Emotion × Time analysis of the FAT group produced a main effect of Time, *F* (1,18) = 5.61, *p* = .03 ( *p* = .02), reflecting a greater increase in alpha power from prestimulus baseline during the pre-recognition period of the FAR criterion task after training than before training ( [Fig. 4](#) , left). Here and below, no effects involving Emotion emerged. Pre-training, a Group (FAT pre-training vs. HC19) × Emotion analysis indicated smaller alpha power increase in SZ than in HC19 ( *F* (1,36) = 22.05, *p*  \< .001; [Fig. 3](#) ). A similar comparison of FAT post-training vs. HC19 verified this effect (Group *F* (1,36) = 5.73, *p* = .02). Effect sizes indicated larger differences in alpha power modulation prior to FAT (fearful condition *g* = 1.29, happy condition *g* = 1.08) than after FAT (fearful condition *g* = .66, happy condition *g* = .58). Thus, dysfunctional oscillatory dynamics can be improved by FAT, though not to full normalization. 

## Specificity of intervention effects [Fig. 4](#)illustrates the change in alpha power increase after intervention in the three patient groups. An Intervention (FAT vs. TAU) × Emotion × Time analysis produced a marginal effect of Time, *F* (1,36) = 2.80, *p* = .1 ( *p*  > .1), reflecting some general improvement over time in the pooled sample, and an Intervention × Time interaction, *F* (1,36) = 4.78, *p* = .04 ( *p* = .05), reflecting improvement in the FAT group ( [Fig. 4](#) , left) vs. a nonsignificant decline in the TAU group ( [Fig. 4](#) , right). Thus, changes in alpha power modulation were specific to training. Here and below, no main effects of Intervention emerged. That was as anticipated, given random assignment to group, with group variance therefore expected only in Intervention × Time effects. The final a priori ANOVA assessed whether this improvement in alpha response with active training was specific to FAT. An Intervention (FAT vs. CE) × Emotion × Time analysis produced an effect of Time, *F* (1,36) = 8.54, *p* = .006 ( *p* = .008), reflecting improvement with training, but no Intervention × Time interaction, indicating similar improvement in the two active treatment groups ( [Fig. 4](#) ). 

## Omnibus test An omnibus Intervention (FAT, CE, TAU) × Emotion × Time analysis is of some value as a control for experiment-wise error. Because the primary relevant hypothesis such an analysis addresses, that intervention improves brain function, is directional, a one-tailed test of the Time effect would be appropriate, or equivalently a *p* = .10 criterion for the ANOVA effect. The Time effect exceeded that criterion, *F* (1,54) = 4.81, *p* = .03 ( *p* = .06), with alpha power increase from prestimulus baseline during the pre-recognition period of the FAR criterion task larger after training than before training. A secondary hypothesis that an omnibus test could address is that interventions differed in their impact, thus a nondirectional Intervention × Time effect, which was marginal, *F* (2,54) = 2.44, *p*  \< .10 ( *p* = .10). However, the motivation for the present study was the series of specific, directional, a priori hypotheses provided above, which, to achieve partial experiment-wise error protection, were tested with a two-tailed criterion. 

## Relationship of FAT performance and alpha activity on the FAR criterion task In the FAT group, alpha power increase in a left fronto-central sensor cluster ( [Fig. 5](#) left panel) varied with performance improvement during the blended emotion task ( *r* = .46, *p*  \< .05; [Fig. 5](#) right panel). 

## Neuropsychological test performance As expected in an SZ sample (e.g., [Kern et al., 2008, 2011](#) ), patient performance was below the normative *T* -score of 50 and varied by MCCB Domain ( *F* (6,324) = 12.83, *p*  \< .001, HF = .94). MCCB performance generally improved after intervention (Time *F* (1,54) = 28.45, *p*  \< .001). A Domain × Time interaction ( *F* (6,324) = 4.05, *p* = .001, HF = .91) reflected improvement in Processing Speed ( *F* (1,56) = 33.56, *p*  \< .01), Attentional Vigilance ( *F* (1,56) = 15.82, *p*  \< .01), and Visual Learning ( *F* (1,56) = 11.99, *p* = .001) but not in Working Memory, Verbal Learning, Reasoning, or Social Cognition (see [Table 2](#) for normative *T* -scores). There was a Time × Intervention effect, *F* (2,54) = 3.70, *p* = .03, resulting from significant performance improvement on Reasoning after CE, *t* (18) = 2.06, *p* = .05, not after FAT or TAU. There was no Time × Intervention × Domain effect ( *F* (12, 324) = 1.28, *p*  > .1). Thus, these improvements did not depend on type of treatment. Change in alpha power increase from baseline between pre- and post-intervention was not related to changes in neuropsychological test performance (MCCB) or in clinical status (symptom severity, GAF). ::::table-wrap

::: caption
Demographic and clinical data (means ± standard deviation), before (pre)
and after (post) treatment for schizophrenia patients per treatment
group ( *n* = 19 per group) together with statistical differences.
:::

```
                       Gender (m/f)         Age                   Years of education    IQ            LQ             CPZ pre         CPZ post
```

______________________________________________________________________

FAT 11/8 39.6 ± 7.9 11.5 ± 1.7 108.1 ± 16.3 70.7 ± 59.0 617.2 ± 327.1 539.6 ± 289.2
CE 12/7 36.0 ± 8.5 10.8 ± 1.7 102.3 ± 13.6 60.7 ± 59.1 544.6 ± 490.1 506.1 ± 344.3
TAU 15/4 35.9 ± 10.6 11.3 ± 1.8 108.7 ± 17.4 59.0 ± 67.5 646.2 ± 393.9 637.9 ± 280.9
Statistical difference Chi ^2^ = 2.0 n.s. *F*2,54 = 1.04 n.s. *F*2,50 \< 1 n.s. *F*2,54 \< 1 *F*2,54 \< 1 *F*2,53 \< 1 *F*2,50 \< 1

```
                       PANSS-P        PANSS-N        PANSS-G        GAF                                                               
```

______________________________________________________________________

Pre Post Pre Post Pre Post Pre Post\
FAT 16.1 ± 5.2 14.4 ± 4.6 19.2 ± 6.6 17.9 ± 6.2 36.9 ± 8.4 33.2 ± 8.2 42.5 ± 12.4 46.3 ± 13.4
CE 15.6 ± 5.2 12.6 ± 4.2 18.0 ± 6.5 17.4 ± 6.8 35.4 ± 5.5 30.5 ± 7.1 44.7 ± 13.6 50.1 ± 13.5
TAU 14.7 ± 4.9 13.6 ± 6.0 19.6 ± 6.1 18.3 ± 6.2 35.1 ± 9.0 34.3 ± 9.9 41.2 ± 13.4 43.0 ± 12.2
Statistical difference *F*2,54 \< 1 *F*2,53 \< 1 *F*2,54 \< 1 *F*2,52 \< 1 *F*2,54 \< 1 *F*2,53 = 1.0 n.s. *F*2,54 \< 1 *F*2,53 = 1.4 n.s.

Note: FAT: facial affect training, CE: cognitive exercise, TAU:
treatment as usual; LQ: laterality quotient; CPZ: chlorpromazine
equivalents; PANSS: Positive and Negative Symptom Scale (26); GAF:
Global Assessment of Functioning (DSM-IV axis V); pre: before
intervention onset; post: after 4-week intervention period; n.s.: *p*
\> .1.:::: ::::table-wrap
::: caption
MATRICS consensus cognitive battery (MCCB) test scores (means ± standard
deviation of normative *T* -scores) for the seven MCCB domains before
(pre) and after (post) intervention period for the three schizophrenia
patients group ( *n* = 19 per group).
:::

```
                                         Processing speed   Attentional vigilance   Working memory   Verbal learning   Visual learning   Reasoning     Social cognition   Overall composite
```

______________________________________________________________________

FAT Pre  39.5 ± 10.6 33.6 ± 11.5 44.6 ± 10.2 46.2 ± 9.9 42.8 ± 12.8 44.5 ± 10.7 39.3 ± 11.1 36.1 ± 10.5
Post 44.6 ± 12.2 38.5 ± 11.8 48.2 ± 9.2 47.1 ± 10.0 49.4 ± 14.0 47.9 ± 8.8 39.3 ± 10.4 41.6 ± 11.5\
CE Pre  40.1 ± 14.4 38.8 ± 10.3 48.9 ± 10.7 45.9 ± 11.3 42.3 ± 17.5 46.3 ± 10.6 39.1 ± 8.5 38.6 ± 14.0
Post 44.2 ± 13.5 41.7 ± 13.7 48.9 ± 14.7 45.0 ± 12.0 50.3 ± 13.8 49.7 ± 10.4 38.5 ± 10.8 42.3 ± 15.9\
TAU Pre 41.8 ± 11.1 36.6 ± 10.5 47.9 ± 13.0 48.2 ± 10.7 43.9 ± 13.0 49.3 ± 10.1 40.2 ± 11.3 39.9 ± 12.3
Post 48.2 ± 12.3 41.3 ± 10.1 50.8 ± 12.1 47.3 ± 10.4 46.5 ± 9.8 45.4 ± 7.7 42.8 ± 11.7 43.3 ± 10.8\
Time *F*~1,56~ 33.56 [\*\*](#) 15.82 [\*\*](#) n.s. \<1 11.99 [\*\*](#) \<1 \<1 28.32 [\*\*](#)\
Group *F*~2,54~ \<1 \<1 \<1 \<1 \<1 \<1 \<1 \<1\
Group × Time *F*~2,54~ \<1 \<1 1.1 \<1 \<1 3.70 [\*](#) \<1 \<1

Note: n.s.: *p*  > .1.

*p*\< .05.

*p*\< .01.::::


Extracted trial result:
Outcome: MCCB performance : Visual Learning (continuous)
Intervention: facial affect training (FAT) in 20 daily 1-hour sessions
Comparator: baseline
Intervention group size: 19
Intervention mean: 49.4
Intervention standard deviation: 12.8
Comparator group size: 19
Comparator mean: 46.5
Comparator standard deviation: 9.8
Notes: used post values and Treatment as Usual as Baseline