The efficacy of transcranial magnetic stimulation (TMS) for negative symptoms in schizophrenia: a systematic review and meta-analysis

Abstract

Several trials have shown preliminary evidence for the efficacy of transcranial magnetic stimulation (TMS) as a treatment for negative symptoms in schizophrenia. Here, we synthesize this literature in a systematic review and quantitative meta-analysis of double-blind randomized controlled trials of TMS in patients with schizophrenia. Specifically, MEDLINE, EMBASE, Web of Science, and PsycINFO were searched for sham-controlled, randomized trials of TMS among patients with schizophrenia. The effect of TMS vs. sham on negative symptoms in each study was quantified by the standardized mean difference (SMD, Cohen’s d) with 95% confidence intervals (95%CI) and pooled across studies using an inverse variance random effects model. We identified 57 studies with a total of 2633 participants that were included in the meta-analysis. The pooled analysis showed statistically significant superiority of TMS (SMD = 0.41, 95%CI: 0.26; 0.56, p-value < 0.001), corresponding to a number needed to treat of 5. Furthermore, stratified analyses suggested that TMS targeting the left dorsolateral prefrontal cortex and using a stimulation frequency >1 Hz was most efficacious. There was, however, substantial heterogeneity and high risk of bias among the included studies. In conclusion, TMS appears to be an efficacious treatment option for patients with schizophrenia suffering from negative symptoms, but the optimal TMS parameters are yet to be established.

Cerebellar stimulation in schizophrenia: A systematic review of the evidence and an overview of the methods

“…Previous brain stimulation studies in schizophrenia have typically targeted cortical regions, such as the frontal cortex and the motor cortex, in an effort to improve positive symptoms (38,39), negative symptoms (40)(41)(42), and cognitive deficits (42,43). The rationale for the cerebellum as a brain stimulation target in schizophrenia is at least twofold: first, there is increased knowledge documenting relationships between cerebellum abnormalities and clinical features of schizophrenia (8)(9)(10), and second, the cerebellum has several unique attributes that make it an attractive stimulation site, such as its immense and distributed connections throughout the cortex, impressive processing capabilities, and inherent plasticity (33,(44)(45)(46).…”

Language Network Dysfunction and Formal Thought Disorder in Schizophrenia

“…Manipulating brain activity and observing its effect on language behavior, will strengthen causal inferences. Many LN and non-language sites (the temporo-parietal junction, inferior parietal lobe (social cognition network), inferior frontal gyrus and superior or middle temporal gyrus (language), middle frontal gyrus (executive), anterior prefrontal cortex (salience) and the cerebellum [Figure 1]) are well established as safe targets for transcranial magnetic stimulation (TMS) for positive [124,125] and negative symptoms [126]; these offer feasible targets to study causal circuits of FTD (Figure 1).…”

“…Pink nodes represent core language areas based on a probabilistic Language Atlas (LanA[144]). Blue nodes are rTMS stimulation sites used in prior clinical trials in schizophrenia, summarised from two recent meta-analytical syntheses[124,126]. The purple nodes represent an overlap between the blue and pink nodes (LanA+rTMS), thus providing possible sites for applying rTMS for perturb-and-measure causal mapping and clinical trials aimed at Language Network Modulation in schizophrenia.…”

Language Network Dysfunction and Formal Thought Disorder in schizophrenia

“…Manipulating brain activity and observing its effect on language behavior, i.e, focal perturbation studies of LN sites to evaluate the effect on FTD are required to move further towards causal inferences. Many LN sites (STG, TPJ) have already been utilized in noninvasive brain stimulation (NIBS), particularly transcranial magnetic stimulation (TMS) trials for positive [105,106] and negative symptoms [107], with proven safety profiles demonstrating feasibility to study FTD (Fig 1). Causal claims can be further strengthened if early developmental deviations in the LN can be linked to later FTD burden.…”

“…Figure 1: Most probable non-invasive brain stimulation targets for FTD.Pink nodes represent core language areas based on a probabilistic Language Atlas (LanA[136]). Blue nodes are rTMS stimulation sites used in prior clinical trials in schizophrenia, summarised from two recent meta-analytical syntheses[105,107]. The purple nodes represent an overlap between the blue and pink nodes, thus providing possible sites for applying rTMS for perturband-measure causal mapping and clinical trials aimed at Language Network Modulation in schizophrenia.…”