A systematic review of brain stimulation in functional seizures

Functional (dissociative) seizures (FDS) are disabling neurological disorders characterized by significant diagnostic and therapeutic challenges. Brain stimulation (BS) techniques are being investigated as potential, neurobiologically-grounded interventions. This systematic review aims to synthesize and evaluate the existing evidence on the therapeutic and diagnostic applications of various BS modalities in patients with FDS.

Following PRISMA 2020 guidelines, a systematic search was conducted across PubMed, Scopus, and Web of Science databases from their inception. We included all original research studies, regardless of design, that investigated invasive or non-invasive brain stimulation for therapeutic or diagnostic purposes in patients with a confirmed diagnosis of FDS. Due to substantial clinical and methodological heterogeneity across studies, a narrative synthesis was performed instead of a quantitative meta-analysis.

The search yielded 4963 records, from which 19 studies (11 therapeutic, 8 diagnostic) met the inclusion criteria after screening. Therapeutic studies, predominantly case reports and small series, indicated that non-invasive techniques such as repetitive transcranial magnetic stimulation (rTMS), intermittent theta-burst stimulation (iTBS), and transcranial direct current stimulation (tDCS) have been associated with reductions in seizure frequency and comorbid psychiatric symptoms in preliminary reports. The right temporoparietal junction (rTPJ) emerged as a commonly targeted region, with preliminary reports suggesting potential benefit. Reported modulation of other regions, including the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC), lends support to a network-based pathophysiology for FDS. Diagnostic studies confirmed the utility of provocative techniques like photic stimulation in inducing events during video-EEG monitoring. Adverse effects were generally mild and transient, with headache being the most common.

Brain stimulation, particularly non-invasive modalities targeting key nodes within fronto-limbic-motor circuits, represents a field of significant research interest and a potential future therapeutic avenue for FDS. The evidence supports a shift towards conceptualizing FDS as a heterogeneous network disorder, necessitating phenotype-guided treatment strategies. Future research must prioritize large-scale, sham-controlled randomized clinical trials with standardized protocols and long-term follow-up to definitively establish efficacy and optimize treatment parameters.