Computer-assisted cognitive remediation in schizophrenia: What is the active ingredient?

Abstract

An emerging body of research has shown that computer-assisted cognitive remediation, consisting of training in attention, memory, language and/or problem-solving, produces improvement in neurocognitive function that generalizes to untrained neurocognitive tests and may also impact symptoms and work functioning in patients with schizophrenia. The active ingredient of these interventions, however, remains unknown as control groups in these studies have typically included few, if any, of the elements of these complex behavioral treatments. This study compared the effects of an extended (12-month), standardized, computer-assisted cognitive remediation intervention with those of a computer-skills training control condition that consisted of many of the elements of the experimental intervention, including hours spent on a computer, interaction with a clinician and non-specific cognitive stimulation. Forty-two patients with schizophrenia were randomly assigned to one of two conditions and were assessed with a comprehensive neuropsychological test battery before and after treatment. Results revealed that cognitive-remediation training produced a significant improvement in working memory, relative to the computers-skills training control condition, but that there was overall improvement in both groups on measures of working memory, reasoning/executive-function, verbal and spatial episodic memory, and processing speed. Taken together, these findings suggest that specific practice in neurocognitive exercises targeted at attention, memory and language, produce improvements in neurocognitive function that are not solely attributable to non-specific stimulation associated with working with a computer, interacting with a clinician or cognitive challenge, but that non-specific stimulation has a salutary effect on neurocognition as well.

Introduction

Schizophrenia is a chronic and profoundly disabling psychiatric disorder. Current estimates suggest that 70–80% of patients with schizophrenia are unemployed at any one time, and only 1/2 of 1% of patients with schizophrenia who receive Social Security Insurance (SSI/SSDI) ever remove themselves from entitlements (Rupp and Keith, 1993, Torrey, 1999). A growing body of data suggests that deficits in neurocognition are linked to social disability. Evidence over the past 15 years has revealed that as many as 70% of patients with schizophrenia (Palmer et al., 1997) exhibit neurocognitive deficits on measures of attention, learning and memory, problem-solving, language and/or sensory-motor skill (Heinrichs and Zakzanis, 1998, Saykin et al., 1991, Saykin et al., 1994). These neurocognitive deficits are present at disease onset, are resistant to the effects of typical and atypical antipsychotic medication, persist into senescence and are closely linked to poor outcome in this disorder, explaining 20–60% of the variance in measures of clinician-rated community function, social problem-solving, and progress in rehabilitation programs (Green et al., 2000, Kurtz et al., 2005, Revheim et al., 2006). Other studies have linked neurocognitive deficits to competitive work status or tenure (e.g., Gold et al., 2002, McGurk and Meltzer, 2000, McGurk and Mueser, 2003, McGurk and Mueser, 2004) and ability to participate in supported employment programs (McGurk et al., 2003).

In light of these links, a growing number of studies have investigated behavioral methods for improving neurocognitive deficits as a possible mechanism for helping attenuate the profound disability evident in this disorder. These behavioral approaches, while heterogeneous in terms of the degree to which they consist of rote rehearsal or are strategy-based, whether they are individualized or administered in groups, and whether they are paper-and-pencil or computer-assisted, are all focused on the improvement of neuropsychological impairment in schizophrenia and are labeled collectively, cognitive remediation, rehabilitation or training.

While results from one of the first controlled studies of cognitive rehabilitation in schizophrenia failed to show generalization of an attention training program to other neurocognitive measures (Benedict et al., 1994), results of more recent randomized treatment trials have been promising, with selected studies demonstrating effect sizes of over 1.0 for measures of sustained auditory attention, speed visual sequencing, reaction time, susceptibility to distraction, memory and visuospatial function in selected studies (see Twamley et al., 2003). While there have been some exceptions (e.g., Medalia et al., 2000), the majority of studies in this domain have reported rehabilitation-related improvement on neurocognitive instruments that are distinct from those instruments used for rehabilitation training, despite wide differences in sample characteristics, methodological approach and outcome measures selected (see Krabbendam and Aleman, 2003, Twamley et al., 2003, Wykes and van der Gaag, 2001; for reviews).

For example, Bellucci et al. (2002) in a study of 34 patients with schizophrenia, investigated the effects of a 16-session program of computer-assisted cognitive remediation program that targeted attention, visuo-motor skills and memory relative to a wait-list control condition. The results of this study revealed remediation-linked improvement in delayed, but not immediate, prose recall and speeded set-shifting at the termination of treatment, along with an improvement in negative symptoms.

Bell et al. (2001) investigated the effects of a comprehensive and extended 5-month program of computer-assisted cognitive remediation consisting of drill-and-practice exercises in attention, memory, language and problem-solving on performance on a comprehensive neurocognitive test battery in sixty-five patients with schizophrenia. Patients were randomly assigned to a work therapy plus cognitive remediation condition or work therapy alone. Results revealed improvements in executive-function, working memory and affect recognition in the cognitive remediation condition. Follow-up studies have shown that these improvements in cognitive function are durable and accompanied by improved work outcomes (Bell et al., 2003, Bell et al., 2005).

Despite these promising results, the mechanism of treatment effects in these studies remains unclear. An underlying assumption of studies to date is that the “active” ingredient of cognitive remediation interventions is repeated practice on neurocognitive tasks that either directly strengthens the requisite neurocognitive skills to perform these tasks, or enables patients to acquire compensatory strategies to circumvent areas of persistent cognitive difficulties (e.g., semantic grouping for memory deficiencies). This improved neurocognitive skill in turn generalizes to unpracticed neuropsychological tests that make similar neurocognitive demands. An alternative and equally plausible (albeit not mutually exclusive) explanation of these results is that exposure to a computer, consistent interaction with a supervising clinician, and the non-specific cognitive challenge associated with completing demanding computer exercises produces “non-specific” change in neurocognitive function unrelated to specific task practice in attention, memory and problem-solving.

One well-accepted method for understanding the mechanisms of behavioral treatment effects is the “dismantling” or “component-control” design (e.g., Kirsch, 2005) in which elements of a complete therapy are first identified and then contrasted with a therapy that contains a subset of most, but not all of the elements of the complete therapy. This approach has been used effectively for understanding the elements of behavioral therapy crucial for improvement in anxiety disorders (Butler et al., 1991) and allows for specific causal inferences regarding a unique component of treatment that are not possible in the wait-list, or comparative control designs that have characterized many studies in this research domain to date (but see Medalia et al., 2000, Medalia et al., 2001 for an exception). In the absence of such studies, the mechanisms of neurocognitive improvement evident in studies of cognitive remediation remain elusive.

We report the results of a single-blind, randomized study that contrasted the effects of a treatment with computer-assisted cognitive remediation that included explicit training in attention, verbal and non-verbal working and episodic memory, and language processing exercises, with a comparison condition that included an equivalent duration of exposure to and operation of a computer, equivalent interaction with a clinician and non-specific cognitive challenge (acquiring skills in basic computer literacy through multi-modal, computer-based lessons and completion of content exams on an ongoing basis) but without repetitive practice in specific neurocognitive functions. We hypothesized that patients in both conditions would show enhanced performance on non-trained neurocognitive tests at the conclusion of training, but that the cognitive remediation condition would produce a greater improvement in neuropsychological function.