In this study, we used a carefully controlled experimental design to test an innovative approach to cognitive training in schizophrenia, delivered as a stand-alone computer-based treatment for 50 hours over 10 weeks. We obtained significant treatment effects in MATRICS-based measures of verbal working memory, verbal learning, and verbal memory, with an overall large effect size of 0.86 in global cognition. In the comprehensive meta-analysis of cognitive remediation trials in schizophrenia by McGurk et al. (7
), only six out of 29 studies showed effect sizes comparable to ours (>0.75), but four of them used 10 or fewer subjects per treatment group, the fifth studied inpatients with a “treatment as usual” comparison condition, and the sixth used a one-on-one therapist-guided approach. Because of these methodological differences, our results are not directly comparable to those in prior studies.
Several factors may have contributed to the enhanced response we obtained using this method. First, prior cognitive remediation approaches have not specifically targeted impaired perceptual processes, although a growing body of research has identified a number of early sensory deficits in schizophrenia and has related them to higher-order cognitive impairments (17
). Second, as would be expected from a program that aims to improve psychophysical responses, the exercises harness the mechanisms of repetitive practice and procedural learning, which appear to be relatively intact in schizophrenia (24
). Third, the exercises are delivered in an attentionally engaging and continuously adaptive manner. This preserves an 85% reward schedule while providing a sufficient number of error trials to ensure the neurological reliability of the desired response (23
). Finally, each exercise is practiced for many thousands of trials.
Indeed, consistent with our study, the meta-analysis by McGurk et al. demonstrated that a higher number of hours of training and drill-and-practice methods show a distinct positive relationship to the remediation of verbal learning and memory in schizophrenia (7
). The large effect sizes obtained in the present study—not only in verbal learning and memory, but also in global cognition—may be due in part to the number of hours of the intervention. It is interesting that only two of the six exercises (or approximately 16 hours) were devoted to tasks that involved word stimuli or had an explicit learning/memory component; the majority (over 30 hours) focused on psychophysical processing of speech elements and on working memory load. At this point, we do not know whether the psychophysical components of the training program are critical or whether similar cognitive improvement could be obtained with sufficiently heavy dosing of simple computerized verbal working memory and verbal learning exercises.
Pursuant to this question, it is important to note that on the most basic exercise, requiring time and frequency resolution of rapidly presented FM sweeps, there was a wide range of progression at the individual level, from subjects who made essentially no performance gains on this exercise to those who became proficient with highly challenging stimuli. This finding indicates that although there was significant improvement on this exercise at a group level, individuals with schizophrenia vary widely in their ability to reliably increase their basic psychophysical auditory processing efficiency in response to training. Consistent with the “neuroplasticity-based” rationale of our approach, subjects who showed the largest training-induced gains in psychophysical performance showed the most improvement in verbal working memory and global cognition. We tentatively speculate that there was a significant relationship specifically between psychophysical gains and working memory because as the auditory cortex responds to the psychophysical training, a more salient verbal signal is “fed forward” into working memory operations; this then permits more efficient and accurate encoding of the verbal information, secondarily leading to improvement in long-term memory. Indeed, the basic neuroscience suggests that increased efficiency in lower-order auditory processes will generalize to higher-order cognitions owing to a more effective engagement of attentional and memory processes (29
). However, the hypothesized neural mechanisms underlying these behavioral observations require direct study, as is currently under way in our laboratory.
We observed no effect of the auditory training exercises on symptoms, but the subjects in this study were clinically stable with mild average PANSS symptom ratings. We also found no benefits for quality of life immediately after training, but patients who have been, on average, ill for 20 years may not show improvements in community functioning as a result of 10 weeks of computerized cognitive training. In a follow-up study of 22 subjects from this study, some of whom received an additional 50 hours of training, we found that many of the neurocognitive gains induced by the training endured 6 months after the intervention; we also found that neurocognitive gains showed a significant positive correlation with improved quality of life at the 6-month assessment point (39
The limitations of this study include our modest number of subjects, their relatively high level of education, and their recruitment through self-referral or clinician referral, which limit the generalizability of our results and likely inflate our effect sizes. Further, we did not conduct an intent-to-treat analysis, although our attrition rate was low, probably because of our subject payment schedule (which may also have produced outcomes different from those in previous studies). Because of these factors, we do not know whether this intervention can be successfully adapted to real-world treatment settings and whether participants can adhere to the demanding training schedule required by this approach outside of a controlled laboratory environment.
We are encouraged by these promising initial results using a “restorative” neuroplasticity-based cognitive training method in schizophrenia, although further research is required to replicate these findings in larger, more clinically representative samples of patients and to investigate the neural processes that underlie the response to training. It will also be important to investigate the utility of this cognitive enhancement approach in patients who are in the earliest phases of schizophrenia, in addition to those who are chronically ill.