Jul 2026· NeuroImage· pp.
122095
· 0 citations· 375 references
MedicineComputer Science
TL;DR
A scoping, narrative roadmap of SSVEP applications organized into three primary domains is provided, highlighting the versatility of SSVEPs in investigating neural mechanisms, supporting diagnosis and treatment of neurological and psychiatric conditions, and advancing brain-computer interface technology.
Abstract
The steady-state visual evoked potential (SSVEP), the brain's oscillatory response to repetitive visual stimulation (RVS), has emerged as a powerful tool in neuroscience with wide-ranging applications in multiple disciplines. This review provides a scoping, narrative roadmap of SSVEP applications organized into three primary domains: fundamental research in vision and cognition, clinical neuroscience, and neural engineering. Although these fields differ in focus, they often converge in their use of similar research questions, stimulation paradigms, analysis techniques, and application scenarios. At the same time, specialization may have created knowledge silos that limit cross-disciplinary transfer of methods and insights. By bridging findings from seemingly disparate domains, this review highlights the versatility of SSVEPs in investigating neural mechanisms, supporting diagnosis and treatment of neurological and psychiatric conditions, and advancing brain-computer interface technology. We conclude with cross-field insights on how stimulus and analysis choices affect interpretation and usability, and we outline directions for improving the comparability and transferability of SSVEP research and applications.
Gamma-band oscillations centered around 40 Hz play an important role in cortical communication, and their disruption has been documented as a neurophysiological feature of several neurodegenerative and neuropsychiatric disorders. This narrative review synthesizes preclinical and early-phase clinical evidence for 40 Hz non-invasive brain stimulation across five delivery modalities: (1) auditory stimulation, which leverages the 40 Hz auditory steady-state response (ASSR) to probe parvalbumin-positive (PV+) interneuron circuits and serves as a validated neurophysiological biomarker in schizophrenia; (2) visual stimulation, using luminance or invisible spectral flicker to induce steady-state visually evoked potentials (SSVEPs) and, in animal models, to activate microglial phagocytosis; (3) transcranial alternating current stimulation (tACS), which delivers sinusoidal sub-threshold membrane polarization at gamma frequency, with preliminary case-series evidence suggesting tau burden reduction and EEG-based biomarker changes in Alzheimer’s disease; (4) repetitive transcranial magnetic stimulation (rTMS), offering focal cortical entrainment that, when combined with tACS in phase-synchronized protocols, produces sustained gamma enhancement in the dorsolateral prefrontal cortex; and (5) multisensory combined stimulation, which engages multiple convergent pathways and currently represents the approach with the most promising early translational signal, including cognitive stabilization and hippocampal volume preservation in small AD trials. While single-session entrainment does not reliably yield cognitive gains, multi-week applications have shown neurophysiological and preliminary biomarker-level changes in selected populations. It should be emphasized, however, that the human evidence base remains early-phase and largely derived from small, often uncontrolled studies; 40 Hz stimulation should accordingly be regarded as a biologically plausible and well-tolerated investigational approach rather than an established therapeutic intervention. Adequately powered, randomized, sham-controlled trials are required before clinical conclusions can be drawn.
Parkinson's disease (PD) can disrupt retinal, early cortical, oscillatory, and distributed visuoperceptual processing. This structured integrative review synthesized human evidence from pattern electroretinography (PERG), electroretinography (ERG), optical coherence tomography (OCT)-linked and conventional visual evoked potentials (VEPs), visual event-related potentials (ERPs), electroencephalography (EEG), steady-state visual evoked potentials (ssVEPs), and occipital transcranial magnetic stimulation-electroencephalography (TMS-EEG), with searches verified up to 18 July 2026. Findings were organized into four domains: 1) Retinal and retinocortical contributions: retinal dysfunction can delay or attenuate afferent input, yet concurrent retinal physiology is rarely measured; therefore VEP abnormalities cannot generally be assigned specifically to cortex. 2) Early visual encoding: prolonged pattern-reversal P100 latency is the most reproducible finding, including a pooled 6.04-ms delay across 20 case-control studies, whereas amplitude findings are inconsistent. 3) Oscillatory dynamics: PD-specific ssVEP evidence suggests altered contextual gain, but it derives from one small unreplicated study; gamma-band and task-EEG findings remain sparse and confound-sensitive. 4) Higher-order and network-level processing: visual ERPs, resting microstates, and occipital TMS-EEG indicate possible associations with hallucinations, cognition, and network connectivity, but current studies are cross-sectional or unreplicated. Overall, PD is characterized by multilevel visual-pathway dysfunction rather than a single cortex-specific biomarker. Ophthalmic status, retinal physiology, medication state, cognition, mood, sleep, and recording quality should be controlled before electrophysiological measures are used for localization, stratification, or prognosis.
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It is demonstrated that spectral correction can elevate the FVEP-P2 to clinically acceptable reliability levels, supporting the continued clinical utility of the FVEP, particularly in patients for whom pattern-reversal stimuli are unsuitable.
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