Cognitive deficits are commonly observed in patients with schizophrenia. Converging lines of evidence suggest that these deficits are associated with impaired long-term potentiation (LTP). In our systematic review, this hypothesis is evaluated using neuroimaging literature focused on proton magnetic resonance spectroscopy, positron emission tomography, and single-photon emission computed tomography. The review provides evidence for abnormal dopaminergic, GABAergic, and glutamatergic neurotransmission in antipsychotic-naive/free patients with schizophrenia compared with healthy controls. The review concludes with a model illustrating how these abnormalities could lead to impaired LTP in patients with schizophrenia and consequently cognitive deficits.

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SummaryObjectiveTo perform a systematic review and meta‐analysis of real‐world evidence for the use of low‐frequency repetitive transcranial magnetic stimulation (rTMS) in the treatment of drug‐resistant epilepsy.MethodsWe systematically searched PubMed, Scopus, Medline, and clinicaltrials.gov for all relevant articles. Relevant patient and stimulation predictors as well as seizure outcomes were assessed. For studies with and without individual participant data (IPD), the primary outcomes were the rate of “favorable response” (reduction in seizure frequency ≥50%) and pooled event rate of mean reduction in seizure frequency, respectively. Outcomes were assessed with comparative statistics and random‐effects meta‐analysis models.ResultsOf 3,477 identified articles, 12 met eligibility and were included in this review. We were able to obtain IPD for 5 articles constituting 34 participants. Univariate analysis on IPD identified greater favorable response event rates between participants with temporal seizure focus versus extratemporal (50% vs. 14%, p = 0.045) and between participants who were stimulated with a figure‐8 coil versus other types (47% vs. 0%, p = 0.01). We also performed study‐level meta‐analysis on the remaining 7 studies without IPD, which included 212 participants. The pooled mean event rate of 50% seizure reduction using low‐frequency rTMS was 30% (95% confidence interval [CI] 12–57%). Sensitivity analysis revealed that studies with a mean age ≤21 years and studies using targeted stimulation had the highest seizure reduction rates compared to studies with a mean age >21 years (69% vs. 18%) and not using a targeted stimulation (47% vs. 14–20%). Moreover, we identified high interstudy heterogeneity, moderate study bias, and high publication bias.SignificanceReal‐world evidence suggests that low‐frequency rTMS using a figure‐8 coil may be an effective therapy for the treatment of drug‐resistant epilepsy in pediatric patients. This meta‐analysis can inform the design and expedite recruitment of a subsequent randomized clinical trial.