TMS Improves Memory in Schizophrenia

Deborah Brauser

March 19, 2013

Repetitive transcranial magnetic stimulation (rTMS) may improve impaired cognitive deficits in patients with schizophrenia, a new pilot study suggests.

The small, randomized controlled trial of 27 adults with schizophrenia showed that those who underwent rTMS, targeted bilaterally to the left and right dorsolated prefrontal cortex, for 4 weeks had greater improvement in scores on working memory tasks than those who underwent a sham procedure.

In addition, the improved performance scores were found to be comparable to those of a group of healthy volunteers.

"Working memory represents a core cognitive domain that is impaired in schizophrenia for which there are currently no satisfactory treatments," write principal investigator Zafiris J. Daskalakis, MD, PhD, from the Department of Psychiatry at the University of Toronto, Ontario, Canada, and colleagues.

However, "we demonstrate that bilateral 20-Hz rTMS...significantly improved working memory compared with sham. Specifically, rTMS selectively improved response accuracy," write the investigators.

They note that the study is the first to demonstrate this type of improvement in this patient population.

"Although previous studies demonstrated small-moderate improvements with cognitive remediation and pharmacological adjunct treatments, none have found a large effect comparable to the present study," they write

"Furthermore, no study has demonstrated a normalization of performance to the level of healthy subjects with any treatment intervention."

The study is published in the March 15 issue of Biological Psychiatry.

Normalizes Memory Performance

As reported by Medscape Medical News, TMS has been shown to be effective in depression and for certain language deficits related to Alzheimer's disease.

Working memory, which includes language comprehension, learning, and reasoning, is often impaired in patients with schizophrenia.

Because previous research has shown that rTMS can improve working memory in healthy volunteers, in the current study, investigators sought to assess whether having patients with schizophrenia undergo this treatment "normalizes performance to healthy subject levels."

A total of 27 adult patients with schizophrenia were enrolled at the Center for Addiction and Mental Health at the University of Toronto between January 2007 and January 2010.

Of these participants, 13 (mean age, 41.2 years) were randomly assigned to undergo 20 treatments of high-frequency rTMS at 20 Hz to the right and then left (or reversed) dorsolateral prefrontal cortex for 4 weeks, and 12 were assigned to undergo a placebo/sham procedure (mean age, 49 years).

The verbal working memory n-back task was given to all participants before and after each treatment procedure. The n-back assesses working memory while participants determine whether the current stimulus shown on a computer monitor matches previously presented stimuli, either 1 trial back (1-back) or 3 trials back (3-back).

Symptom severity was also evaluated at baseline and after every fifth treatment using the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS), and the Calgary Depression Scale (CDS).

In addition, a comparison group of 13 healthy volunteers (mean age, 41.2 years) were also evaluated.

Novel, Efficacious Approach

Results showed that the group receiving the active treatment had significantly improved 3-back accuracy scores compared with the group receiving the sham procedure (P = .04).

In addition, overall mixed model repeated measures suggested that rTMS led to higher scores as difficulty of the memory tasks increased.

Although rTMS was considered well tolerated by the participants who completed the study, 2 did withdraw due to treatment intolerance.

There were no between-group differences found for symptom severity on the PANSS, SANS, or CDS, and no relationship was found between change in 3-back response and patient use of antipsychotic medications.

In further analysis, the rTMS group's working memory performance scores before treatment were significantly worse than those of the healthy volunteers. However, there were no significant differences between the groups after treatment.

"These pilot data suggest that bilateral rTMS might be a novel, efficacious, and safe treatment for working memory deficits in patients with schizophrenia," write the researchers.

They note that more studies are now needed to replicate the findings and to investigate the mechanisms for the improvements.

Still, the results "provide the first compelling method to treat working memory deficits in this disorder. The impact of such findings is considerable."

The study was supported by the Canadian Institutes of Health Research, the Ontario Mental Health Foundation, the Brain and Behaviour Research Foundation, the Grant Family through the Center for Addiction and Mental Health, and by a National Health and Medical Research Council Practitioner Fellowship. The study authors have reported several relevant financial relationships, which are fully listed in the original article.

Biol Psychiatry. 2013;73:510-517. Abstract