Abstract
Stroboscopic light stimulation (SLS) on closed eyes reliably evokes vivid geometric
visual phenomena, and in some contexts, altered-state experiences, motivating its
increasing use across research, public installations, recreational use, and exploratory
clinical contexts. The main medical risk for SLS is a photosensitive epileptic
response. In contrast, non-epileptic sensitivities (e.g., migraine/photophobia, anxiety,
autism/ADHD, psychosis) typically induce discomfort or distress rather than
medical emergencies. Here, we integrate a multi-laboratory safety survey (24
studies; n = 1,070 participants, including cohorts with major depressive disorder),
and operational data from two commercial SLS providers, with a focused review of
SLS and sensory-intolerance evidence, to refine safety screening and characterise
adverse events. Across laboratory studies, there were 20 minor side-effects (e.g.,
early withdrawal due to discomfort; ~18.7 per 1,000), with no severe incidents
requiring medical attention. From two commercial datasets (~4.2 million closed-eye
SLS sessions), 14 major adverse events requiring medical attention were documented
(~3.3 per million); minor reactions were not systematically captured. Synthesising
these strands, we developed an evidence-based tool: the Sussex Strobe Safety
Screening Questionnaire (4SQ), which uses non-specialist language to identify
known sensitivities to SLS, alongside practical recommendations for risk mitigation
across research, clinical, commercial, and public contexts. Together, these findings
suggest that the absolute risk under SLS is low but non-zero. Screening tools can
help exclude pre-existing conditions, while graded exposure (e.g., a short ‘taster’
session, after which participants may opt out) and trained staff can mitigate the risk
of first-episode events. Nonetheless, such events should be anticipated and
minimised through clear screening pathways and their impact reduced through
rehearsed on-site response plans.
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1.0 Introduction
Stroboscopic light stimulation (SLS), usually delivered to closed eyes at frequencies
between ~5-50 Hz, evokes stroboscopically induced visual hallucinations (SIVHs)
comprising dynamic geometric patterns and colours, with occasional reports of
complex visual hallucinations and altered-state experiences 1–3. Comparable
phenomena occur with open-eye stimulation using diffusion goggles 4. As SLS use
expands beyond specialist research laboratories, clear safety frameworks are
required.
Contemporary SLS research has so far addressed multiple, partly overlapping aims,
such as investigating the neural correlates of SIVHs using fMRI and EEG,
particularly in relation to neural entrainment and thalamocortical dynamics 1,5–13.
Many of these studies combine electrophysiological and phenomenological
measures, linking entrainment and thalamocortical dynamics to the subjective
features of SLS-induced visual experiences. SLS has also been used to examine
altered states of consciousness (ASCs; Bartossek et al., 2021; Beauté et al., 2025;
Montgomery et al., 2024; Schwartzman et al., 2019), and to model simple visual
hallucinations 7,16,17.
Interest has grown in the potential therapeutic applications of SLS, particularly at
gamma (~40 Hz) and alpha (9–11 Hz) frequencies, for conditions such as Alzheimer’s
disease and depression 18–21. However, the evidence for any benefit remains
preliminary and inconclusive 18,22.
Against this backdrop, we aim to synthesise cross-laboratory practice and
operational data from two commercial SLS providers, alongside a focused review of
SLS and sensory-intolerance evidence1. Our goal is not only to characterise risk, but
to develop a broadly applicable, evidence-based screening tool that reflects best
practices across research, clinical, commercial and public domains. As use broadens,
understanding who is at risk—and why— becomes increasingly important. We
therefore begin by outlining the principal medical risks and discomfort-related
sensitivities relevant to SLS.
1 Several of the present authors worked with Collective Act Ltd (CAL) on a large-scale public-oriented
experience called Dreamachine, which used SLS and music to induce SIVHs in a large number of
people. DJS, AKS, JWS, and TH provided scientific input; FM provided philosophical input; see
Hewitt et al., 2025 and https://dreamachine.world. The collaboration with CAL informed aspects of
our approach to SLS safety advocated here. However, this collaboration brings some legal
considerations, so we’re not able to report the Dreamachine data at present.
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1.1 Medical risks and sensitivities associated with SLS
Primary risk factor: photosensitive seizure
The main medical risk associated with SLS is photosensitive convulsive seizures
(PSE). While the lifetime risk of any epilepsy is relatively common (~1 in 26 in
developed countries), PSE is comparatively uncommon, representing only a small
proportion of epilepsy diagnoses 23. General-population estimates indicate an annual
incidence of ~1 per 100,000 and a lifetime prevalence of ~1 in 10,000 24. Importantly,
not all people with epilepsy are at risk from SLS exposure. Photophobia, defined by
a sensitivity or intolerance to bright light, is relatively common in people with
epilepsy, but true PSE remains rare. Given the rarity of this risk factor, SLS can be
delivered with minimal risk when appropriate precautions are taken for PSE, along
with the following secondary risk factors. In practice, the principal concern is
undetected PSE, first-episode reactions in individuals who screen negative, since
most known PSE cases (typically in adolescence) are aware and self-exclude. We
examine this topic in greater depth in the Discussion.
Several factors, however, may increase the risk of a participant having PSE or
suffering from a seizure more generally. The most notable of these factors are family
history, age, sleep deprivation, and pregnancy, recent alcohol or recreational drug
use, and medications that lower seizure threshold. PSE is most concentrated in
younger age groups—up to six times more common in children and adolescents (7–
19 years) than in adults 23. Epilepsy, including the photosensitive variant, is
heterogeneous but widely recognised as heritable, often occurring in multiple
members of the same family 25.
Sleep deprivation is a well-established factor that increases the risk of seizures in
people with epilepsy 26,27. Mechanistically, observational and experimental work
indicates that reduced sleep increases both cortical excitability and the frequency of
epileptiform discharges, particularly in idiopathic generalised epilepsies 26–29. Diary-
based and prospective studies show that acute sleep loss can raise seizure risk by as
much as threefold 30,31. Similarly, several prescribed medications, such as smoking
cessation drugs (e.g., bupropion), antipsychotics, opioid analgesics, and stimulants,
are associated with increased seizure susceptibility (see Supplementary Material for
a summary list).
Pregnancy involves physiological, hormonal, and psychological changes that may
influence seizure threshold across trimesters 32, with additional factors, including
altered drug metabolism, disrupted sleep, stress, and fatigue, potentially increasing
susceptibility to seizure provocation. Given this potential for greater vulnerability,
SLS exposure during pregnancy is not recommended.
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Secondary risk factors: sensory sensitivities and photophobia
Setting PSE aside, several conditions may increase an individual’s sensitivity to SLS,
not because they are typically linked to serious medical events, but because they can
heighten discomfort or distress under high-intensity sensory stimulation. These
include anxiety, migraine, autism spectrum disorder (ASD), attention-deficit
hyperactivity disorder (ADHD), and psychosis.
Here, we summarise these sensitivities along with their prevalence.
Anxiety. In the U.K., medical consultations for anxiety have recently increased
markedly 33, with prevalence estimates ranging from 3.8% to 25% of the population
34. Individuals with heightened anxiety may be more susceptible to discomfort from
specific lighting conditions, and SLS can be anxiety-inducing 35,36.
Migraine. Current estimates put the global prevalence of migraine at ~14–15%; in
terms of burden, migraine accounts for about ~4.9% of global years lived with
disability 37. Photophobia is common, and bright or flickering light is frequently
reported as a trigger. However, it has been argued that much of this ‘provocation’
reflects photophobia during the premonitory phase rather than an independent
external trigger (Schulte et al., 2015). Whether such stimuli act as true triggers or
reflect premonitory hypersensitivity, high-contrast SLS can exacerbate discomfort in
people with migraine.
ASD. Prevalence estimates vary considerably depending on age, diagnostic criteria,
and methods. The National Institute for Health and Care Excellence estimates the
global prevalence of ASD in children to be around 1-2%, and ~1.1% of U.K. adults 39.
ASD is often associated with sensory hypersensitivity, heightened arousal, and
elevated physiological stress responses, though these traits are heterogeneous and
not universal 40,41. For some, high-intensity visual stimuli, such as bright light or SLS,
may induce a stress response, particularly in those with heightened sensory
reactivity 41.
ADHD. ADHD affects roughly 3–4% of U.K. adults (NICE, 2021), and photophobia
appears markedly over-represented, with ~69% of adults with ADHD reporting light
sensitivity versus ~28% of controls 42. While ADHD per se is not a contraindication
for SLS exposure, self-reported photophobia suggests a higher likelihood of
discomfort under SLS.
Psychosis. Psychotic disorders, including schizophrenia, are relatively uncommon
(global prevalence of schizophrenia ~0.28% 43; broader psychotic disorders ~0.3%-
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0.7% 44). Because SLS can evoke vivid visual phenomena, interactions with active
positive symptoms may increase distress or confusion, warranting additional
caution.
1.2 Public Incidents Shaping Perceived Risk and Regulation
Several widely publicised cultural incidents have shaped risk perception and
regulation of SLS exposure, largely due to them unintentionally triggering
photosensitive epileptic seizures. The infamous 1997 “Pokémon incident” in Japan
involved rapidly alternating red–blue flashes at ~12 Hz shown on television to an
audience mainly of children. There were seizures in hundreds of viewers, many
without prior epilepsy history 45. In response, Japan introduced broadcasting
regulations in 1999, limiting flash frequency to <3 Hz, restricting high-intensity
flashes, and prohibiting saturated-red flicker 45. Similar concerns have arisen
elsewhere: a Dutch cohort study found seizures were over three times more likely at
night-time electronic dance music events with intense stroboscopic lighting
compared with daylight events 46. In the U.K., Ofcom guidance, operationalised via
the Harding Flash and Pattern Analyser (‘Harding test’), which algorithmically
screens broadcast images for luminance, colour, and spatial pattern flicker likely to
provoke photosensitive seizures, to restrict flashing imagery. Even with these tests
the London 2012 Olympic logo promo had to be withdrawn after seizure concerns 47.
1.3 Current Screening Practice
Across contexts, screening protocols vary widely in scope, design, and their
evidence base. Laboratory studies typically use bespoke self-report questionnaires to
exclude known PSE and other neurological/psychiatric vulnerabilities. In contrast,
public installations often rely on simplified health declarations or verbal briefings
with varying degrees of formality. Both approaches have their limitations: many
focus narrowly on epilepsy, overlooking other clinically relevant sensitivities, and
protocols are often context-specific and insufficiently documented to allow
replication or cross-study comparisons.
To address these gaps, we integrate three strands: (i) a cross-laboratory SLS safety
survey, (ii) operational data from two commercial providers, and (iii) a focused
review of photic-stimulation and sensory-intolerance research. Together, these
strands quantify absolute and operational risk under SLS, identify where risk
concentrates, and translate the evidence into practical, proportionate guidance. For
each safety consideration, we assess currently available data and specify screening
and operating procedures that prioritise phenotypic risk markers (photophobia,
migraine/visual aura, seizure history, sensory intolerance, light-triggered
discomfort) over diagnostic labels. We condense these into a simple, implementable
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pathway suitable for research, commercial use, clinical feasibility, and public
installations—including the Sussex Strobe Safety Screening Questionnaire (4SQ) for
pre-screening and clear escalation/opt-out steps. Our aim is a standardised,
platform-agnostic safety architecture that enables safe inclusion at scale while
acknowledging that absolute risk of adverse events is low but non-zero.
2.0 Methods
2.1 Cross-laboratory and commercial data acquisition on SLS safety and
practice
A structured Qualtrics portal was created to capture SLS safety practices and
outcomes across four research laboratories and two commercial providers. The
portal recorded: (i) submitter identifiers; (ii) reporting scope (whole group/platform
vs. individual studies, programmes, or product sessions); (iii) date range and total
number of experiments conducted; (iv) technical parameters of the SLS used (e.g.,
device type, stimulation mode, eye state, frequency range, brightness, duty cycle,
music synchrony); (v) participant/user counts; (vi) counts of major incidents (e.g.,
epileptic seizures, panic attacks, events with medical implications) and minor side-
effects (e.g., discomfort leading to early withdrawal without medical consequences);
(vii) number of epileptic seizures; (viii) participant/user demographics (where
available); (ix) supporting documents (safety protocols, participant information,
incident reports). Laboratory and supplier datasets were provided in anonymised
form, and their identities are anonymised throughout the paper.
Research laboratories
Data were contributed by four research laboratories, based in the UK, Germany, the
Netherlands, and Australia, which conducted SLS studies between 2020 and 2025
and included healthy and clinical participants. Lab A provided data from one study
(N = 20); Lab B contributed twelve studies (N = 461), including two with participants
with Major Depressive Disorder (MDD; N = 105); Lab C contributed six studies (N =
480); and Lab D provided five studies (N = 109). Where available, laboratories
provided summary information on screening procedures and adverse-event logging.
SLS characteristics. Across laboratories, SLS was delivered using commercial and
custom hardware. Devices included commercial stroboscopes (Lucia N003, Light
Attendance GmbH, Innsbruck, Austria; Roxiva RX1, roXiva Ltd); custom-built
stroboscopes (one constructed by Lumenate Growth Ltd, Bristol, UK, and another
developed at the University of Sussex); a projector (Epson EB-G7400U); and
standard computer monitors at maximum brightness.
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Commercial SLS providers
Data were also obtained from two commercial providers of SLS. Commercial
Provider A is a mobile-app platform that delivers closed-eye SLS experiences using
the smartphone flashlight. Frequency, brightness, and duty cycle are modulated in
synchrony with audio content, with many sessions designed to complement music
and enhance user-reported impact. The sessions comprise dynamic SLS sequences
with frequencies of 3–13.5 Hz and duty cycles of ~0.0–0.7. The platform has been in
operation since 2021 and, to date, has delivered ~3.8 million closed-eye SLS sessions
to a large international user base.
Commercial Provider B is a manufacturer of a dedicated SLS device designed to
support wellbeing and to reliably induce vivid SIVHs. The device delivers controlled
SLS via high-intensity LEDs, with configurable frequency, brightness, and duty cycle
parameters, and is used in both group settings and individual sessions. Users can
create their own SLS sessions within a frequency envelope of 0.01–200.00 Hz and a
duty cycle of 1–99% or select from the lamp’s built-in pre-set sessions. Some SLS
sessions are tuned to align with music, with rhythmic modulation of light
parameters designed to enhance the subjective experience. According to the
company's operational figures, ~400,000 closed-eye SLS sessions have been
conducted over the past five years. This conservative total excludes additional usage
from consumer (non-professional) units and likely underestimates total exposures.
Commercial providers developed their own safety screening criteria (see Table 1 for
a summary).
3.0 Results: laboratory-based studies
3.1 Laboratory-based SLS survey
Most studies (n = 21) used fixed-frequency SLS with reported frequencies spanning
1–80 Hz; all studies used a square-wave SLS signal. Stimulation protocols typically
used frequencies within the alpha frequency range (8–12 Hz; Mauro et al., 2015),
with one lab also experimenting with 15 Hz stimulation. A subset (n = 3; total n = 95)
used dynamic frequency shifts (3–15 Hz).
Flash duration and inter-flash interval (duty cycle) varied: most protocols adopted a
50% duty cycle (equal flash/inter-flash), with values ranging from 25% to 75%.
Brightness levels varied by device: mean luminous flux for stroboscope-based setups
was ~5,373 lumens (SD = 326); the projector operated at 447.2 cd/m²; monitor setups
typically delivered ~300 cd/m². Because luminous flux (lumens) and luminance
(cd/m²) quantify different properties, these figures are not directly comparable and
are reported as provided by each laboratory.
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Session duration ranged from brief exposures (8 s) to extended stimulation (≤ 25
min), with some protocols including ramp-up periods and rest intervals.
3.2 Participants
Across studies, 1,070 unique participants took part (mean age = 25.04 years, SD =
2.68). Of these, 389 (36.4%) identified as male, 680 (63.6%) as female, and 1 (<0.1%) as
non-binary. 105 participants self-reported symptoms consistent with MDD, assessed
using the Patient Health Questionnaire-9 (PHQ-9).
3.3 SLS Safety Screening Across Laboratories
Screening and risk-management procedures varied across groups, reflecting
differences in populations, aims, and institutional requirements (Table 1). We
collated safety protocols from all four laboratories (Labs A-D) and identified a
common “minimum set”, alongside areas of divergence.
All laboratories set a minimum age criterion (18 or 21 years) for participation,
reflecting the higher incidence of photosensitive epilepsy in those aged 7–18 23 and
consent and safeguarding requirements for minors. Every protocol excluded a
personal history of epilepsy, particularly photosensitive subtypes, and most (A, B,
D) also screened for first-degree family history as a precaution. All laboratories
assessed sensitivity to bright and flashing light (including migraine history or
photophobia), and pregnancy was a common exclusion in these research settings.
Despite convergence on core exclusions, laboratories differed on several dimensions:
Anxiety. All laboratories acknowledged potential discomfort in individuals with
heightened anxiety, but screening approaches varied. Lab A used the State–Trait
Anxiety Inventory, Trait version (STAI-T; Spielberger, 2012) with an exclusion cut-
off >50. Lab B excluded self-reported severe anxiety within the past 3 years. Lab C
used a broad “severe psychiatric condition” criterion. Lab D did not screen
specifically for anxiety.
Psychiatric disorders. Labs A and C applied broad exclusions (“any psychiatric
disorder”; “any severe psychiatric condition”). Lab D excluded psychosis or a first-
degree family history of schizophrenia. Lab B excluded self-reported severe anxiety
or psychosis within 3 years, with less emphasis on broader or lifetime history.
Importantly, these broad exclusions reflect standard good practice in laboratory-
based experiments to reduce heterogeneity and outcome variability, rather than SLS-
specific risk.
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Alcohol and recreational drug use. Labs A, C, and D asked about recent use and
instructed participants not to attend under the influence to reduce adverse-reaction
risk and preserve data quality. Lab B did not formally assess recent substance use.
Psychotropic medication use. Labs A, C, and D excluded current psychoactive
medications (e.g., antipsychotics, anxiolytics), to avoid agents that may lower seizure
threshold or alter SLS responsiveness. Lab B did not specify medication status.
Sleep deprivation. Labs A, C, and D excluded recent sleep loss, while Lab B did not.
Current major medical issues. Lab A excluded active major medical conditions (e.g.,
cardiovascular, metabolic, neurological) that could increase vulnerability to intense
stimulation 49, citing examples such as unstable hypertension, significant
arrhythmias, and multiple sclerosis. Other laboratories did not.
Traumatic brain injury (TBI). Lab A excluded any history of TBI, including
concussion or post-concussive syndrome, given the common post-TBI photophobia,
headache, and sensory overload.
Unexplained loss of consciousness: Lab B uniquely screened for unexplained,
repeated losses of consciousness to identify possible absence seizures.
Heart disease/pacemakers: Only Lab C explicitly excluded people with heart disease
or cardiac pacemakers, including those without neuroimaging components, to
maintain consistency in safety screening and minimise any potential cardiovascular
risk.
Aphantasia: Lab C excluded aphantasia (inability to voluntarily generate visual
imagery). This was a study-design choice to maintain comparable phenomenological
reporting. Data on SLS-induced experiences in aphantasia remains limited 50.
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Table 1. Comparison of screening criteria for SLS across four laboratories (Labs A–D), and
two commercial providers (Provider A = app-based; Provider B = device-based). Each row
lists a specific exclusion criterion, with columns indicating whether it is explicitly included
in the Lab’s screening protocol. Symbols are defined as follows: ‘✓ ’ Criterion explicitly
included in the screening procedure. ‘—’ Criterion not included in the screening procedure.
‘○’ Criterion included in a qualified or partial form. PSE = photosensitive epilepsy; ‘≤3y’ =
within last 3 years; FHx = family history; u/wk = units per week; psych. = psychiatric.
3.4 Additional Risk Management Strategies
Here we note additional risk management strategies beyond screening, identifying
common strategies across laboratories, as well as areas of divergence.
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First-aid training and on-site readiness. The majority of laboratories ensured that
staff conducting studies had current first-aid training, including recognising and
managing seizures. In Lab C, not all staff were first-aid trained; however, a
designated first-aid warden was always on call and immediately available during
data collection sessions.
Taster SLS exposure. Every site implemented ‘graded exposure’, including a brief
‘taster’ session before the main experiment to confirm tolerability and identify
adverse responses before full participation.
EEG pre-screening. In two studies, Lab D required first-time SLS participants to
undergo a 10-minute EEG with SLS to assess photosensitivity. Although this
approach is a clinically accepted method for identifying photosensitive epilepsy, its
effectiveness is low in asymptomatic, pre-screened adults 51. Where thorough
medical and migraine/photophobia history, clear risk information, supervised
‘graded exposure’, and trained staff are in place, routine SLS-EEG is unlikely to add
Material
benefit and increases cost and participant burden.
3.5 Adverse responses to SLS
Across all surveyed laboratories, no severe adverse reactions were observed,
specifically, no seizures, and no syncope (transient loss of consciousness). Among
1,070 participants, there were 20 non-serious minor side-effects reported: 0/20 in Lab
A (0.0 per 1,000), 7/461 in Lab B (15.2 per 1,000), 11/480 in Lab C (22.9 per 1,000), and
2/109 in Lab D (18.3 per 1,000), yielding a pooled prevalence of ~18.7 per 1,000
(1.87%). Events clustered into five main themes: anxiety/distress (n = 5; e.g.,
misinterpreting bodily sensations, uncertainty about session duration), eye
discomfort/photophobia (n = 5), dizziness/vertigo/motion distortion (n = 3),
headache/migraine (n = 3; including one mild migraine with prior history), and non-
specific unpleasantness/early withdrawal (n = 4; e.g., “unpleasant,” “did not enjoy”).
Where multiple symptoms were reported, we coded the primary reason for
withdrawal. All events were resolved on-site without medical transfer. For context,
this pooled prevalence (~1.87%) sits at the low end of routine MRI terminations in
screened adults due to anxiety or claustrophobia (~1–3%; Munn et al., 2015).
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4.0 Results: Commercial SLS Providers
4.1 Commercial providers screening procedures
Compared with laboratory protocols, commercial SLS screening procedures overlap
on the core exclusions, notably a history of epilepsy/PSE and age ≥18, as well as
caution around migraine, photophobia and significant psychiatric histories (Table 1).
There are, however, clear divergences from laboratory-based screening. Provider A:
asked for information about migraine or photophobia, cardiac issues, sleep
deprivation cut-offs, and neurodiversity-related sensory intolerance. A novel feature
was the inclusion, for users, of a detailed list of medications that increase the
likelihood of seizures. In contrast, while Provider B included core exclusions (e.g.,
epilepsy, pregnancy, recent alcohol/drugs, sleep deprivation, head injury), there was
no formal photophobia or migraine screening, syncope history, cardiac or
pacemaker checks, or neurodiversity accommodations.
4.2 Commercial providers adverse responses to SLS
Provider A. Across approximately 3.8 million closed-eye SLS sessions delivered via
a mobile platform, based on ad hoc feedback and incident reporting, nine major
adverse events were recorded. Major events were defined as those requiring medical
attention (e.g., a primary care doctor visit), and these highlighted events encompass
all reports judged to have probable or higher causation related to the SLS experience.
This equates to an incidence of roughly 2.4 per million sessions, underscoring the
rarity of such outcomes. Minor side-effects (e.g., transient discomfort,
unpleasantness, or session withdrawal) were not systematically recorded and
therefore are challenging to quantify. Given this limitation, the reported data
primarily reflect serious events where users actively sought medical attention, rather
than the broader spectrum of tolerability issues.
Provider B. Based on operational figures, more than 400,000 closed-eye SLS sessions
have been run with this device over the past five years. This conservative total
excludes additional usage from consumer (non-professional) units and therefore
likely underestimates total exposures. Data availability on adverse reactions from
this source was minimal: as a commercial provider, they receive limited user
feedback and incident reporting is largely ad hoc. Two recent cases were directly
reported: one instance of transient memory loss over several days after repeated
home use, and one seizure at a public event. Historical accounts from earlier
operations describe a prolonged trance-like unresponsive state (resolved on-site) and
two additional seizures assessed by emergency services, including one with short-
lived cognitive disorientation. This leads to a total of 5 adverse events. While low
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(incident rate of ~12.5 per million sessions), this number should be treated with
caution given the lack of systematic reporting.
5.0 Discussion
Across the laboratory and commercial datasets, adverse events associated with SLS
were extremely rare and generally non-serious. Laboratory studies (n = 1,070)
reported 20 minor withdrawals due to discomfort, with no severe adverse events.
Commercial provider data (~4.2 million sessions) reported 14 severe adverse events
requiring medical attention (~3.3 per million). These convergent data indicate that
the absolute risk of serious adverse outcomes under controlled, closed-eye SLS is
low but non-zero, and that proportionate pre-screening effectively mitigates the
majority of predictable risks.
To facilitate risk management and ensure proportionate, practical safeguards for
SLS, we created the Sussex Strobe Safety Screening Questionnaire (4SQ). This is a
brief, plain-language tool that flags established SLS sensitivities and is paired with
actionable guidance for risk management across research, clinical, commercial, and
public settings. The 4SQ prioritises phenotypic risk markers (photosensitivity, light-
triggered discomfort, migraine/visual aura, seizure history, sensory intolerance) over
diagnostic labels. It provides a simple, implementable screening pathway for
research, clinical, and public contexts.
5.1 Development of the Sussex Strobe Safety Screening Questionnaire (4SQ)
To translate our findings into practical screening guidance, we synthesise evidence
from laboratory protocols, operational data from two commercial SLS providers, and
the clinical/safety materials, balancing participant inclusion with risk reduction
using clear, operational decision rules. In the sections that follow, we examine each
safety-relevant sensitivity to SLS in turn, and (a) state the rationale linking the factor
to elevated risk or intolerance for SLS, (b) specify screening questions phrased for
non-specialists, and (c) give a default decision (exclude/include with caution and
accommodations). Where evidence is limited or heterogeneous, we adopt
conservative exclusion criteria.
1) Age (minimum age & safeguarding)
Rationale: Photosensitive epilepsy is up to ~6× more common in those aged 7–19
than in adults (Quirk et al., 1995), and participation by minors carries additional
consent and safeguarding requirements. Although photosensitivity declines with
age, large-scale epidemiological evidence shows that the likelihood of seizures
becoming prolonged or non-self-limiting (i.e., status epilepticus) increases from
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around 60 years of age 53. Accordingly, ≥60 years is recommended as a conservative
upper-age threshold for unsupervised SLS, with medical clearance and enhanced
safeguards advised above this age.
Screening: Confirm age is ≥18 or older at booking or consent.
Default decision: Exclude.
2) Neurological history
Photosensitive epilepsy or seizure history (including first-degree family history)
Rationale: SLS can provoke epileptic seizures in susceptible individuals. The risk is
higher in younger people and in families with a history of photosensitivity. A
personal history of any unprovoked seizure (not only epileptic) indicates a lowered
seizure threshold and uncertainty about individual triggers, and “non-
photosensitive” epilepsy may still be precipitated by interacting factors (e.g., high
arousal, anxiety, hyperventilation, sleep loss, recent illness, or medicines that may
reduce seizure threshold). Given this diagnostic ambiguity, a conservative approach
is to treat any prior seizure history as a contraindication.
Screening: Personal epilepsy/seizure history; first-degree family history; prior
visually triggered events.
Default decision: Exclude.
Migraine (especially with photophobia or aura)
Rationale: Bright or flickering light is a common migraine trigger; visual aura
indicates cortical hyper-excitability, and marked photophobia predicts discomfort
and early withdrawal.
Screening: History of migraine or frequent headaches; photophobia/visual aura.
Default decision: Exclude when aura or marked photophobia is present or migraine;
otherwise, include with caution and enhanced monitoring.
Traumatic brain injury (TBI), concussion, or head injury (past 12 months)
Rationale: Post-concussive symptoms (photophobia, headache, sensory overload,
dizziness) can be aggravated by high-intensity SLS; recent TBI also carries an
uncertain seizure risk.
Screening: Any head injury/TBI in the prior 12 months; persistent post-concussive
symptoms.
Default decision: Exclude (12-month exclusion window).
Unexplained loss of consciousness/episodes of altered awareness
Rationale: May indicate undiagnosed epilepsy (e.g., absence seizures) or other
instability. SLS could precipitate adverse events in such cases.
Screening: History of fainting/blackouts/brief unresponsiveness without a clear
medical explanation.
Default decision: Exclude (or defer pending medical evaluation).
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3) Neurodevelopmental conditions & sensory sensitivity
Autism spectrum disorder (ASD)
Rationale: Higher rates of photophobia and sensory intolerance mean intense SLS
may be overwhelming for some autistic individuals; the relevant risk marker is
sensory sensitivity, and not the diagnosis itself.
Screening: Brief, direct questions on light sensitivity and sensory intolerance.
Default decision: Do not blanket-exclude. Include by default within an environment
designed to be tolerable for neurotypical and neurodivergent participants. Exclude
only if marked photophobia or sensory intolerance persists despite these provisions,
or if the participant prefers not to proceed.
Attention-deficit/hyperactivity disorder (ADHD)
Rationale: Photophobia/light discomfort is commonly reported in ADHD. Again,
sensory sensitivity, not the diagnostic label, is the risk marker.
Screening: As above, focus on photophobia and sensory intolerance.
Default decision: Do not blanket-exclude. Exclude when significant photophobia or
sensory intolerance is reported; otherwise, include with accommodations.
4) Psychiatric history
Anxiety disorders / high anxiety
Rationale: SLS can elevate arousal and alter perception, potentially precipitating
panic or distress. However, evidence is limited, so we take a conservative stance.
Screening: STAI-T where feasible (suggested cut-off > 50) or self-reported severe
anxiety/panic history.
Default decision: Exclude if STAI-T >50 or severe anxiety disorder is reported,
otherwise include with caution (enhanced briefing, easy exit, close monitoring).
Psychosis (current or recent)
Rationale: SLS-evoked visual phenomena may interact with positive symptoms,
increasing distress or confusion. However, evidence is limited, so we take a
conservative stance.
Screening: Current psychotic symptoms; recent episodes.
Default decision: Exclude with active symptoms; consider only with clinical
clearance in stable remission.
5) Other medical conditions
Pregnancy
Rationale: Direct evidence on SLS in pregnancy is lacking; physiological changes
during pregnancy may alter seizure threshold. Apply precautionary exclusion in
research/public settings.
Screening: Current pregnancy.
Default decision: Exclude.
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Heart disease / implanted cardiac devices / unstable medical conditions
Rationale: SLS sessions can elicit autonomic arousal, pre-existing cardiac instability
or serious systemic illness increases risk.
Screening: History of arrhythmias, unstable angina, heart failure, implanted devices;
uncontrolled hypertension; demyelinating disease with active symptoms, etc.
Default decision: Exclude.
6) Substances & sleep
Alcohol or recreational drug use (recent)
Rationale: Intoxication might alter neural responsiveness (depending on substance),
judgment and undermine reliable self-report and timely withdrawal.
Screening: Ask (i) Have you used alcohol or recreational drugs recently? and (ii) Do
you feel any current or residual effects (e.g., “high”, hangover, withdrawal, unusual
fatigue, poor sleep)?
Default decision: Exclude or reschedule if any current or residual effects are
reported or observed.
Operational note. Sites should pre-specify conservative wash-out guidance by class
(e.g., alcohol, cannabis, stimulants, MDMA, psychedelics).
Sleep deprivation (recent)
Rationale: Acute sleep loss raises seizure risk and impairs self-monitoring of
distress.
Screening: Hours slept in the past 24 hours; acute restriction (e.g., < 4 hours).
Default decision: Exclude/reschedule; proceed when sleep normalises.
7) Medications
Psychotropic/psychoactive medications
Rationale: Some medications may alter neural responsiveness and lower seizure
threshold, complicating risk estimation.
Screening: Current use of antipsychotics, bupropion (for smoking cessation), opioid
analgesics, benzodiazepines, stimulants, or other psychoactive agents (see the
Supplementary Material for a full list of medications that may lower the seizure
threshold).
Default decision: Exclude, unless a protocol explicitly permits specific classes with
clinical oversight.
Drawing on these sensitivities, we developed the Sussex Strobe Safety Screening
Questionnaire (4SQ; Figure 2), a plain-language tool to identify known SLS
sensitivities. A ‘YES’ response to any item signals the need for further assessment
and eligibility decisions based on context-specific exclusion criteria.
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Figure 2. The 4SQ is a brief, plain-language pre-participation screener for stroboscopic light
stimulation (SLS). It comprises five sections covering (1) Neurological history (epilepsy/PSE,
seizures, first-degree family history, unexplained loss of awareness, neurological diagnoses,
recent head injury), (2) Psychiatric and mental health (diagnoses, recent difficulties, current
psychotropic medication, first-degree family history of psychosis), (3) Heart conditions
(cardiac disease, implanted devices), (4) Sensory sensitivities (migraine/photophobia, strong
discomfort/panic with bright or flashing lights), and (5) Lifestyle and substance use
(alcohol/recreational drugs in the last 24 h, significant sleep restriction, pregnancy).
Responses are recorded YES/NO. Any YES flags the need for further assessment and a
context-specific eligibility decision (exclude, include with caution, or include with
accommodations). The 4SQ is not diagnostic and is intended to support proportionate risk
management across research, clinical, commercial, and public settings.
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5.2 Practical Risk Mitigation for SLS
Mitigating the risks associated with SLS delivery requires trained staff,
proportionate screening, and controlled exposure parameters. We recommend that
staff should receive regular first-aid training (including seizure first aid, syncope,
panic response, and post-event documentation), with annual refreshers and
scenario-based drills to maintain readiness. In our cross-laboratory synthesis, we
found that a small set of procedural safeguards provided an effective balance
between safety and accessibility: proportionate screening, brief supervised ‘graded
exposure’ with explicit opt-out, plain-English stop-signals, and continuous
monitoring. In contexts where direct supervision is not possible, such as app-based
or home-use SLS, additional safety measures are recommended. These include
providing a simple and immediate way for users to stop the SLS through direct
interaction (e.g., a clear “stop” control, automatic termination of SLS if sudden
movement is detected where feasible and allowing brightness adjustment to enhance
comfort and minimise minor side-effects. Clear guidance should be provided to
users on safe usage (e.g., not using the device near water, in the bath, or at height),
and incident-reporting mechanisms should be in place so that users can easily report
adverse reactions. On report of major incidents, users shall be guided towards
suitable medical attention, ideally under the oversight of medical professionals or
designated safety officers.
Clinically, photosensitivity is typically assessed using intermittent photic
stimulation (IPS) during EEG, normally spanning ~1–65 Hz to elicit abnormal EEG
responses. Seizure-provoking SLS frequencies tend to cluster between 15 and 25 Hz
(Fisher et al., 2005). While we do not think clinical IPS assessment is needed for
general SLS use, to mitigate risk we encourage that stimulation should generally not
exceed 15 Hz, with conservative sequences capped at 15 Hz and minimal dwell time
above 15 Hz. This avoids the highest-risk frequency range while preserving the
vividness of SLS experiences.
Prolonged direct exposure to high-intensity light sources can cause retinal damage.
Appropriate exposure limit values (ELVs) defined in the International Commission
on Non-Ionizing Radiation Protection (ICNIRP) guidelines and adopted by the
European Directive 2006/25/EC sets a maximum safe exposure of ~2.4 s at 7,000 lux
with eyes open. In practice, the eyelid reflex (~0.1 s; Pearce, 2008) provides rapid
protection, so exposure under controlled conditions is unlikely to be harmful. We
recommend verifying peak luminance at the participant position with a light meter
and documenting compliance with European Directive 2006/25/EC. For commercial
providers, photobiological safety must also comply with the IEC 62471 standard
(“Photobiological safety of lamps and lamp systems”), which classifies devices by
risk group. Only devices rated as Risk Group 1 (“low risk”) or below should be used
for SLS applications, confirming that normal use poses no hazard to the eye or skin.
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5.3 First-Episode Risk Without Screening: Benchmarks and Context
Even with a robust screening tool, a residual risk of first-episode reactions persists
among individuals who screen negative, so it is essential to contextualise baseline
risk in unscreened or minimally screened populations. While this paper focuses on
developing a screening measure to mitigate SLS-related risk, our results relate to
pre-screened samples. To quantify the baseline risk of a first-episode adverse
reaction to SLS, we draw on safety-critical occupational screening (e.g., aircrew),
where intermittent photic stimulation (IPS) is routinely administered, and on mass
public exposures to strobe at electronic dance music events. As a proxy for base-rate
first-episode seizure risk, we compared the rate of adverse events across three large
cohorts where screening did not take place: U.K. aircrew candidates (N = 13,658;
adverse events: 322 per 100,000; 54), electronic dance-music event attendees (N =
400,343; adverse events: 9 per 100,000, likely under-ascertained; Salet et al., 2019),
and Danish air-force recruits (N = 5,893; adverse events: 1,103 per 100,000; 55.
Counting either an IPS-evoked photoparoxysmal response (PPR) or an observed
seizure as a first-episode adverse event, reported rates range from 9 to 1,103 per
100,000. Due to differences in outcome measures (EEG PPR vs clinically observed
seizures) and contexts (military screening, public events), we report both an
exposure-weighted pooled estimate and a deliberately conservative unweighted
mean. The pooled rate across all exposures is ~34.5 per 100,000 (145/419,894; 95% CI
~28.9–40.1), which likely underestimates the risk of first-time seizures in public
settings and overestimates risk during IPS screening (not all PPRs translate to
clinical seizures during SLS). The intentionally conservative unweighted mean (~478
per 100,000) should be treated as a worst-reasonable planning figure, not a
population estimate.
These rates should be treated as worst-case estimates from unscreened contexts.
With adequate screening, the likelihood of a first-episode photosensitive reaction is
substantially lower than these worst-case estimates. In addition to screening for
seizure history, migraine/photophobia, and relevant medications, asking explicitly
about prior exposure to strobe or flickering lights (e.g., nightclub lights, EEG IPS,
SLS sessions), as a documented history of symptom-free exposure makes a first-
episode reaction unlikely. Coupled with clear information with an opt-out option,
brief, closely monitored ‘graded exposure’, and trained staff, this combination
significantly reduces the chance of enrolling an undiagnosed photosensitive
participant. Consistent with this view, no seizures were observed in our surveyed
laboratories, and operational data from our commercial partners indicate that
seizure events under closed-eye SLS are extremely rare.
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6.0 Conclusion
We present a practical, evidence-based framework to make stroboscopic light
stimulation (SLS) safe, scalable, and replicable. Screening is centred on phenotypic
risk markers (photophobia, migraine/aura, seizure history, sensory intolerance)
rather than diagnostic labels. The Sussex Strobe Safety Screening Questionnaire
(4SQ) provides a concise, non-specialist tool for pre-screening sensitivities to SLS.
External benchmarks indicate low but non-zero absolute risk from SLS; operational
risk is further reduced by using sub-15 Hz SLS, graded exposure, and trained on-site
response. The framework is platform-agnostic and suited to research, clinical
feasibility studies, commercial delivery, and public installations moving the field
towards a standardised, evidence-informed safety architecture that enables
responsible and scalable inclusion.
Funding
D.J.S. is supported by a Medical Research Council Grant UKRI083. A.K.S. is
supported by the European Research Council (ERC) Advanced Investigator Grant
101019254, under the European Union’s Horizon 2020 programme. T.H. is supported
by the Margaret Boden PhD scholarship from the University of Sussex. R.B. is
funded by the Be.AI Leverhulme PhD scholarship, from the Leverhulme Trust.
Acknowledgements
DJS, AKS, FM, TH and JWS are grateful to Collective Act Ltd for the opportunity to
collaborate on the Dreamachine project, which informed aspects of our approach to
stroboscopic-light safety described here. The authors are also grateful to Devraj Joshi
(Whatever Together) and Cecelia Schwartzman for helpful discussions.
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7.0 References
1. Amaya IA, Behrens N, Schwartzman DJ, Hewitt T, Schmidt TT. Effect of
frequency and rhythmicity on flicker light-induced hallucinatory phenomena.
Spitschan M, ed. PLOS ONE. 2023;18(4):e0284271.
doi:10.1371/journal.pone.0284271
2. Beauté R, Schwartzman DJ, Dumas G, et al. Mapping of Subjective Accounts
into Interpreted Clusters (MOSAIC): Topic Modelling and LLM applied to
Stroboscopic Phenomenology. arXiv. Preprint posted online February 25, 2025.
doi:10.48550/arXiv.2502.18318
3. Hewitt T, Amaya I, Beauté R, Seth AK, Schmidt TT, Schwartzman DJ.
Stroboscopically induced visual hallucinations: historical, phenomenological,
and neurobiological perspectives. Neurosci Conscious. 2025;2025(1):niaf020.
doi:10.1093/nc/niaf020
4. Shenyan O, Lisi M, Greenwood JA, Skipper JI, Dekker TM. Visual
hallucinations induced by Ganzflicker and Ganzfeld differ in frequency,
complexity, and content. Sci Rep. 2024;14:null. doi:10.1038/s41598-024-52372-1
5. Amaya IA, Schmidt ME, Bartossek MT, et al. Flicker light stimulation induces
thalamocortical hyperconnectivity with LGN and higher-order thalamic nuclei.
Imaging Neurosci. 2023;1:1-20. doi:10.1162/imag_a_00033
6. Becker C, Gramann K, Müller H, Elliott M. Electrophysiological correlates of
flicker-induced color hallucinations. Conscious Cogn. 2009;18:266-276.
doi:10.1016/j.concog.2008.05.001
7. Ffytche D. The hodology of hallucinations. Cortex. 2008;44(8):1067-1083.
doi:10.1016/j.cortex.2008.04.005
8. Heller NH, Patel N, Faustin VM, Tse PU, Störmer VS. Neural correlates of
stroboscopic stimulation to test a model of psychedelic hallucination. PsyArXiv.
Preprint posted online December 4, 2023. doi:10.31234/osf.io/dex5v
9. Mauro F, Raffone A, VanRullen R. A Bidirectional Link between Brain
Oscillations and Geometric Patterns. J Neurosci. 2015;35(20):7921-7926.
doi:10.1523/JNEUROSCI.0390-15.2015
10. Pütz P, Braeunig M, Wackermann J. EEG correlates of multimodal ganzfeld
induced hallucinatory imagery. Int J Psychophysiol. 2006;61(2):167-178.
doi:10.1016/j.ijpsycho.2005.09.002
11. Schwartzman DJ, Schartner M, Ador BB, Simonelli F, Chang AYC, Seth AK.
Increased spontaneous EEG signal diversity during stroboscopically-induced
. CC-BY-NC 4.0 International licenseIt is made available under a
perpetuity.
is the author/funder, who has granted medRxiv a license to display the preprint in(which was not certified by peer review)preprint
The copyright holder for thisthis version posted November 19, 2025. ; https://doi.org/10.1101/2025.11.17.25340398doi: medRxiv preprint
altered states of consciousness. Preprint posted online January 4, 2019.
doi:10.1101/511766
12. Sumich A, Anderson JD, Howard CJ, et al. Reduction in lower-alpha power
during Ganzfeld flicker stimulation is associated with the production of imagery
and trait positive schizotypy. Neuropsychologia. 2018;121:79-87.
doi:10.1016/j.neuropsychologia.2018.11.004
13. Wackermann J, Pütz P, Allefeld C. Ganzfeld-induced hallucinatory
experience, its phenomenology and cerebral electrophysiology. Cortex.
2008;44:1364-1378. doi:10.1016/j.cortex.2007.05.003
14. Bartossek MT, Kemmerer J, Schmidt TT. Altered states phenomena induced
by visual flicker light stimulation. Eisenbarth H, ed. PLOS ONE.
2021;16(7):e0253779. doi:10.1371/journal.pone.0253779
15. Montgomery C, Amaya IA, Schmidt TT. Flicker light stimulation enhances the
emotional response to music: a comparison study to the effects of psychedelics.
Front Psychol. 2024;15:1325499. doi:10.3389/fpsyg.2024.1325499
16. Pearson J, Chiou R, Rogers S, Wicken M, Heitmann S, Ermentrout B. Sensory
dynamics of visual hallucinations in the normal population. eLife. 2016;5:e17072.
doi:10.7554/eLife.17072
17. Rule M, Stoffregen M, Ermentrout B. A Model for the Origin and Properties of
Flicker-Induced Geometric Phosphenes. Sporns O, ed. PLoS Comput Biol.
2011;7(9):e1002158. doi:10.1371/journal.pcbi.1002158
18. Agger MP, Danielsen ER, Carstensen MS, et al. Safety, Feasibility, and
Potential Clinical Efficacy of 40 Hz Invisible Spectral Flicker versus Placebo in
Patients with Mild-to-Moderate Alzheimer’s Disease: A Randomized, Placebo-
Controlled, Double-Blinded, Pilot Study. J Alzheimers Dis. 2023;92(2):653-665.
doi:10.3233/JAD-221238
19. Huang F, Huang Q, Zheng L, et al. Effect of 40 Hz light flicker on behaviors of
adult C57BL/6J mice. Brain Res. 2023;1814:148441.
doi:10.1016/j.brainres.2023.148441
20. Kim S, Kim S, Khalid A, et al. Rhythmical Photic Stimulation at Alpha
Frequencies Produces Antidepressant-Like Effects in a Mouse Model of
Depression. Svenningsson P, ed. PLOS ONE. 2016;11(1):e0145374.
doi:10.1371/journal.pone.0145374
. CC-BY-NC 4.0 International licenseIt is made available under a
perpetuity.
is the author/funder, who has granted medRxiv a license to display the preprint in(which was not certified by peer review)preprint
The copyright holder for thisthis version posted November 19, 2025. ; https://doi.org/10.1101/2025.11.17.25340398doi: medRxiv preprint
21. Martorell AJ, Paulson AL, Suk HJ, et al. Multi-sensory Gamma Stimulation
Ameliorates Alzheimer’s-Associated Pathology and Improves Cognition. Cell.
2019;177(2):256-271.e22. doi:10.1016/j.cell.2019.02.014
22. Yang YL, Lai TW. Chronic Visual Stimulation with LED Light Flickering at 24,
40, or 80 Hz Failed to Reduce Amyloid β Load in the 5XFAD Alzheimer’s
Disease Mouse Model. eneuro. 2023;10(8):ENEURO.0189-23.2023.
doi:10.1523/ENEURO.0189-23.2023
23. Quirk JA, Fish DR, Smith SJM, Sander JWAS, Shorvon SD, Allen PJ. Incidence
of photosensitive epilepsy: a prospective national study. Electroencephalogr Clin
Neurophysiol. 1995;95(4):260-267. doi:10.1016/0013-4694(95)00118-I
24. De Bittencourt PRM. Photosensitivity: The Magnitude of the Problem.
Epilepsia. 2004;45(s1):30-34. doi:10.1111/j.0013-9580.2004.451010.x
25. Perucca P, Bahlo M, Berkovic SF. The Genetics of Epilepsy. Annu Rev
Genomics Hum Genet. 2020;21(1):205-230. doi:10.1146/annurev-genom-120219-
074937
26. Badawy RAB, Curatolo JM, Newton M, Berkovic SF, Macdonell RAL. Sleep
deprivation increases cortical excitability in epilepsy: Syndrome-specific effects.
Neurology. 2006;67(6):1018-1022. doi:10.1212/01.wnl.0000237392.64230.f7
27. Moore JL, Carvalho DZ, St Louis EK, Bazil C. Sleep and Epilepsy: a Focused
Review of Pathophysiology, Clinical Syndromes, Co-morbidities, and Therapy.
Neurotherapeutics. 2021;18(1):170-180. doi:10.1007/s13311-021-01021-w
28. Giorgi FS, Maestri M, Guida M, et al. Controversial Issues on EEG after Sleep
Deprivation for the Diagnosis of Epilepsy. Epilepsy Res Treat. 2013;2013:1-5.
doi:10.1155/2013/614685
29. Giorgi FS, Guida M, Caciagli L, et al. What is the role for EEG after sleep
deprivation in the diagnosis of epilepsy? Issues, controversies, and future
directions. Neurosci Biobehav Rev. 2014;47:533-548.
doi:10.1016/j.neubiorev.2014.10.005
30. Dell’Aquila JT, Soti V. Sleep deprivation: a risk for epileptic seizures. Sleep Sci.
2022;15(02):245-249. doi:10.5935/1984-0063.20220046
31. Haut SR, Hall CB, Masur J, Lipton RB. Seizure occurrence: Precipitants and
prediction. Neurology. 2007;69(20):1905-1910.
doi:10.1212/01.wnl.0000278112.48285.84
. CC-BY-NC 4.0 International licenseIt is made available under a
perpetuity.
is the author/funder, who has granted medRxiv a license to display the preprint in(which was not certified by peer review)preprint
The copyright holder for thisthis version posted November 19, 2025. ; https://doi.org/10.1101/2025.11.17.25340398doi: medRxiv preprint
32. Li Y, Meador KJ. Epilepsy and Pregnancy. Continuum. 2022;28(1):34-54.
doi:10.1212/CON.0000000000001056
33. Slee A, Nazareth I, Freemantle N, Horsfall L. Trends in generalised anxiety
disorders and symptoms in primary care: UK population-based cohort study. Br
J Psychiatry. 2021;218(3):158-164. doi:10.1192/bjp.2020.159
34. Remes O, Brayne C, Van Der Linde R, Lafortune L. A systematic review of
reviews on the prevalence of anxiety disorders in adult populations. Brain Behav.
2016;6(7):e00497. doi:10.1002/brb3.497
35. Digre KB, Brennan KC. Shedding Light on Photophobia. J Neuroophthalmol.
2012;32(1):68-81. doi:10.1097/WNO.0b013e3182474548
36. Patterson Gentile C, Aguirre GK. A neural correlate of visual discomfort from
flicker. J Vis. 2020;20(7):11. doi:10.1167/jov.20.7.11
37. Steiner T, Scher A, Stewart W, Kolodner K, Liberman J, Lipton R. The
Prevalence and Disability Burden of Adult Migraine in England and their
Relationships to Age, Gender and Ethnicity. Cephalalgia. 2003;23(7):519-527.
doi:10.1046/j.1468-2982.2003.00568.x
38. Schulte LH, Jürgens TP, May A. Photo-, osmo- and phonophobia in the
premonitory phase of migraine: mistaking symptoms for triggers? J Headache
Pain. 2015;16(1):14. doi:10.1186/s10194-015-0495-7
39. Prevalence | Background information | Autism in adults | CKS | NICE.
Accessed October 10, 2025. https://cks.nice.org.uk/topics/autism-in-
adults/background-information/prevalence/
40. Corbett BA, Schupp CW, Levine S, Mendoza S. Comparing cortisol, stress,
and sensory sensitivity in children with autism. Autism Res. 2009;2(1):39-49.
doi:10.1002/aur.64
41. Corbett BA, Muscatello RA, Blain SD. Impact of Sensory Sensitivity on
Physiological Stress Response and Novel Peer Interaction in Children with and
without Autism Spectrum Disorder. Front Neurosci. 2016;10.
doi:10.3389/fnins.2016.00278
42. Kooij JJS, Bijlenga D. High Prevalence of Self-Reported Photophobia in Adult
ADHD. Front Neurol. 2014;5. doi:10.3389/fneur.2014.00256
43. Charlson FJ, Ferrari AJ, Santomauro DF, et al. Global Epidemiology and
Burden of Schizophrenia: Findings From the Global Burden of Disease Study
2016. Schizophr Bull. 2018;44(6):1195-1203. doi:10.1093/schbul/sby058
. CC-BY-NC 4.0 International licenseIt is made available under a
perpetuity.
is the author/funder, who has granted medRxiv a license to display the preprint in(which was not certified by peer review)preprint
The copyright holder for thisthis version posted November 19, 2025. ; https://doi.org/10.1101/2025.11.17.25340398doi: medRxiv preprint
44. Saha S, Chant D, Welham J, McGrath J. A Systematic Review of the
Prevalence of Schizophrenia. Hyman SE, ed. PLoS Med. 2005;2(5):e141.
doi:10.1371/journal.pmed.0020141
45. Ishiguro Y, Takada H, Watanabe K, Okumura A, Aso K, Ishikawa T. A
Follow-up Survey on Seizures Induced by Animated Cartoon TV Program
“Pocket Monster.” Epilepsia. 2004;45(4):377-383. doi:10.1111/j.0013-
9580.2004.18903.x
46. Salet N, Visser M, Stam C, Smulders YM. Stroboscopic light effects during
electronic dance music festivals and photosensitive epilepsy: a cohort study and
case report. BMJ Open. 2019;9(6):e023442. doi:10.1136/bmjopen-2018-023442
47. Glendinning L. Please look away ... it’s the 2012 logo. The Guardian.
https://www.theguardian.com/media/2007/jun/06/marketingandpr.olympics2012
. June 6, 2007. Accessed October 13, 2025.
48. Spielberger CD. State-Trait Anxiety Inventory for Adults. Published online
July 9, 2012. doi:10.1037/t06496-000
49. Cortese A, Conte A, Ferrazzano G, et al. Photophobia in multiple sclerosis.
Mult Scler Relat Disord. 2018;26:55-57. doi:10.1016/j.msard.2018.09.005
50. Reeder RR. Ganzflicker Reveals the Complex Relationship Between Visual
Mental Imagery and Pseudo-Hallucinatory Experiences: A Replication and
Expansion. Collabra Psychol. 2022;8(1):36318. doi:10.1525/collabra.36318
51. de Pémille CV, Rekik S, Amiel H, et al. Contribution of intermittent photic
stimulation to routine EEG. Neurophysiol Clin Clin Neurophysiol. 2021;51(6):549-
553. doi:10.1016/j.neucli.2021.10.003
52. Munn Z, Moola S, Lisy K, Riitano D, Murphy F. Claustrophobia in magnetic
resonance imaging: A systematic review and meta-analysis. Radiography.
2015;21(2):e59-e63. doi:10.1016/j.radi.2014.12.004
53. Ong CT, Sheu SM, Tsai CF, Wong YS, Chen SCC. Age-Dependent Sex
Difference of the Incidence and Mortality of Status Epilepticus: A Twelve Year
Nationwide Population-Based Cohort Study in Taiwan. Biagini G, ed. PLOS
ONE. 2015;10(3):e0122350. doi:10.1371/journal.pone.0122350
54. Gregory RP, Oates T, Merry RTG. Electroencephalogram epileptiform
abnormalities in candidates for aircrew training. Electroencephalogr Clin
Neurophysiol. 1993;86(1):75-77. doi:10.1016/0013-4694(93)90069-8
. CC-BY-NC 4.0 International licenseIt is made available under a
perpetuity.
is the author/funder, who has granted medRxiv a license to display the preprint in(which was not certified by peer review)preprint
The copyright holder for thisthis version posted November 19, 2025. ; https://doi.org/10.1101/2025.11.17.25340398doi: medRxiv preprint
55. Trojaborg W. EEG Abnormalities in 5,893 Jet Pilot Applicants Registered in a
20-Year Period. Clin Electroencephalogr. 1992;23(2):72-78.
doi:10.1177/155005949202300206
. CC-BY-NC 4.0 International licenseIt is made available under a
perpetuity.
is the author/funder, who has granted medRxiv a license to display the preprint in(which was not certified by peer review)preprint
The copyright holder for thisthis version posted November 19, 2025. ; https://doi.org/10.1101/2025.11.17.25340398doi: medRxiv preprint
8.0 Supplemental Material
8.1 List of medications that may lower seizure threshold
Reviewing the literature on medications known to reduce the seizure threshold, we
arrive at the following list of medications.
Antimicrobials
● β-lactams: penicillins, cephalosporins, carbapenems (dose-related risk;
carbapenems higher relative risk; also rapid, marked reduction of valproate
levels with carbapenems).
● Isoniazid (mechanism via pyridoxal-5-phosphate/GABA; pyridoxine reverses
toxicity).
● Fluoroquinolones (e.g., ciprofloxacin, ofloxacin, levofloxacin; rare but
reported; GABAA_AA antagonism).
Antimalarials
● Mefloquine, chloroquine (seizures reported in people with and without
epilepsy).
Analgesics
● Opioids (class effect is context- and dose-dependent; tramadol,
buprenorphine and pethidine/meperidine most consistently implicated;
others possible under certain conditions).
● NSAIDs: aspirin, diclofenac, indometacin (dose-dependent; uncommon
clinically). Mefenamic acid can be pro-convulsant at toxic doses. Ibuprofen
and paracetamol are not implicated.
Methylxanthines (respiratory)
● Theophylline, aminophylline (adenosine A1 antagonism; can cause difficult-
to-treat seizures in toxicity).
Antipsychotics
● Clozapine (strongest signal; clinical seizures ~3–6%).
● Chlorpromazine and other phenothiazines (other antipsychotics have lower
but present risk).
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● Haloperidol, benperidol, droperidol, melperone, azaperone (butyrophenones)
● Other monoaminergic agents: Venlafaxine and mirtazapine (rare, usually
dose-related pro-convulsant effects, most often reported in overdose or at
higher therapeutic doses).
Antiepileptics (paradoxically)
● Benzodiazepine withdrawal (withdrawal lowers threshold).
● Withdrawal of topiramate, lamotrigine, gabapentin and pregabalin (can lower
seizure threshold and precipitate seizures).
● Carbamazepine (can exacerbate some generalised/myoclonic epilepsies).
Immunosuppressant / Antineoplastic
● Cyclosporine (high epileptogenic potential in review).
● Chlorambucil (intermediate potential).
Radiology contrast
● Iodinated contrast media (low epileptogenic potential; rare events; risk
affected by CNS comorbidity).
Smoking cessation
● Bupropion (clear, dose-dependent risk at therapeutic use for smoking
cessation).
Other
● Interferon-α (minimal/inconclusive pro-convulsant potential).
● Atomoxetine and stimulant medications for ADHD (e.g. methylphenidate,
amphetamine formulations) have a generally low seizure risk once treatment
is established, but caution is advised during initiation or recent dose changes;
unfamiliarity with a recently prescribed stimulant should prompt
conservative screening and, where appropriate, clinical review.
Additional References:
Hitchings, A. W. (2016). Drugs that lower the seizure threshold. Adverse drug
reaction bulletin, 298(1), 1151-1154.
Ruffmann, C., Bogliun, G., & Beghi, E. (2006). Epileptogenic drugs: a systematic
review. Expert review of neurotherapeutics, 6(4), 575-589.
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