Electroretinography and Mental Health Research
There is a fascinating intersection of ERG technology and the fields of neuroscience, neurology, and mental health, with differences in ERG results helping to articulate biomarkers with diagnostic potential. We at LKC Technologies are proud to see our technology being used at the frontier of this research.
Here are some relevant studies that have been recently published.
- Cabrera DeBuc, D. et al ‘Investigating Multimodal Diagnostic Eye Biomarkers of Cognitive Impairment by Measuring Vascular and Neurogenic Changes in the Retina’ in Frontiers in Physiology, December 2018, Volume 9, Article 1721
- Cabrera DeBuc, D. et al. 2020. ‘Investigating Vascular Complexity and Neurogenic Alterations in Sectoral Regions of the Retina in Patients With Cognitive Impairment’. 2020
- Constable P.A. et al ‘Light-Adapted Electroretinogram Differences in Autism Spectrum Disorder’ in Journal of Autism and Developmental Disorders, 2020
- Demmin D.L. et al ’ Electroretinographic Anomalies in Schizophrenia’ in Journal of Abnormal Psychology 2018, Vol. 127, No. 4, 417–428
- Demmin D.L. et al ‘People with current major depression resemble healthy controls on flash Electroretinogram indices associated with impairment in people with stabilized schizophrenia’ in Schizophrenia Research (Article in Press) 2019
- Kazakos C.T. et al ‘Retinal Changes in Schizophrenia: A Systematic Review and Meta-analysis Based on Individual Participant Data’ in Schizophrenia Bulletin 2019
Cabrera DeBuc, D. et al ‘Investigating Multimodal Diagnostic Eye Biomarkers of Cognitive Impairment by Measuring Vascular and Neurogenic Changes in the Retina’
In Frontiers in Physiology, December 2018, Volume 9, Article 1721
PURPOSE: In this pilot study, we investigated the extent to which measures of vascular complexity and neurodegenerative changes in the retinal tissue contribute to differences in cognitive function using a low-cost multimodal approach. Our central hypothesis is that multivariate eye biomarkers reflect distinctive eye-brain signatures of cognitive impairment that might be associated with the onset and progression of cognitive decline.
METHOD: Prospective subjects with cognitive impairment were identified in a non-systematic fashion as they appeared in the clinic or identified from a population attending adult care centers and community clinics with a diagnosis of AD.
Quantification of the retinal structure and function were conducted for every subject (n = 69) using advanced retinal imaging, full-field electroretinogram (ERG) and visual performance exams.
Of the 69 participants, 32 had CI (46%).
RESULTS/ CONCLUSION: Our preliminary findings show that our multimodal approach to evaluating visual capacities in elderly individuals may add predictive value of early visual pathway injury associated with cognitive decline and facilitate the introduction of novel multimodal eye biomarkers for early detection of cognitive impairment at a low-cost.
(…) Also, drusen-like regions in the peripheral retina along with pigment dispersion were noted in subjects with mild CI. Functional loss in color vision, as well as smaller ERG amplitudes and larger peak times, were observed in the subjects with CI.
Cabrera DeBuc, D. et al. 2020. ‘Investigating Vascular Complexity and Neurogenic Alterations in Sectoral Regions of the Retina in Patients With Cognitive Impairment’
In Frontiers in Physiology, 2020
PURPOSE: In this pilot study, we investigated whether multifractal dimension and lacunarity analyses performed in sectoral regions of the retina may reveal changes in patients with cognitive impairment (CI)[…].
METHODS: Prospective age-matched subjects (n = 69) with and with no CI and without the presence of any ophthalmic history were recruited (age > 55C years). The Montreal Cognitive Assessment (MoCA) was used to measure CI, and full-field electroretinogram (ERG) was performed. Also, visual performance exams were conducted using the Rabin cone contrast test (CCT). Quantification of the retinal structure was performed […]. The multifractal behavior was analyzed by calculating the generalized dimension Dq (Do, D1, and D2), the lacunarity parameter (3), and singularity spectrum f(a) in the nine sectoral skeletonized images as well as in the skeletons that comprised the whole branching pattern observable in the full 45_ FOV.
RESULTS: Significant correlations between multifractal and 3 parameters with the MoCA and implicit time ERG-parameter were observed in the regional analysis. In contrast, no trend was found when considering the whole retinal branching pattern. [alpha2 and Implicit time of ERG were included in a single model to obtain a robust predictive index being the Predictive probability of CI. The AUROC for this predictive model was 0.90 (SE = 0.050) and was highly significant (p < 0.001).]
CONCLUSION: Analysis of combined structural-functional parameters in sectoral regions of the retina, instead of individual retinal biomarkers, may provide a useful clinical marker of CI.
Constable P.A. et al ‘Light - Adapted Electroretinogram Differences in Autism Spectrum Disorder’
In Journal of Autism and Developmental Disorders, 2020
PURPOSE: The ERG offers the potential to help our understanding of neurodevelopmental and neurodegenerative conditions as a non-invasive and objective measure of retinal activity in response to brief flashes of light.
There are presently no biomarkers for ASD. Differences in the ERG waveform in ASD may help our understanding of the biology of factors contributing to ASD.
(…) the present study sought to explore the nature and frequency of differences in LA-ERGs with sufficient power in a large group of young individuals with ASD from multiple centers.
METHOD: This study comparison between children and young adults with ASD and the control group was conducted across three sites based in London (UK), New Haven (USA) and Adelaide (Australia).
Light-adapted (LA) electroretinograms (ERGs) from 90 individuals with autism spectrum disorder (ASD), mean age (13.0 ± 4.2), were compared to 87 control subjects, mean age (13.8 ± 4.8). LA-ERGs were produced by a random series of nine different Troland based, full-field flash strengths and the ISCEV standard flash at 2/s on a 30 cd m·2 white background.
RESULTS/ CONCLUSION: A random effects mixed model analysis showed the ASD group had smaller b- and a-wave amplitudes at high flash strengths (p < .001) and slower b-wave peak times (p < .001). Photopic hill models showed the peaks of the component Gaussian (p = .035) and logistic functions (p = .014) differed significantly between groups. Retinal neurophysiology assessed by LA-ERG provides insight into neural development in ASD.
The main finding is that the primary outcome, the LA ERG b-wave amplitude was reduced in the ASD group.
For the secondary outcomes, the b-wave time to peak and a-wave amplitude were delayed and reduced at the higher flash strengths respectively, along with a reduced b:a wave amplitude ratio.
This large, multicenter study of children shows the LA-ERG is a potential marker for neurodevelopmental conditions such as ASD in children. By providing a reproducible, non-invasive and robust measure of CNS activity the ERG can help our understanding of the impact of genetic interaction and complexity in ASD and aid drug discovery that targets CNS development of signaling pathways common to the CNS and retina.
Demmin D.L. et al. ‘ Electroretinographic Anomalies in Schizophrenia’
In Journal of Abnormal Psychology 2018, Vol. 127, No. 4, 417–428
PURPOSE: In this study, we recorded light- (photopic) and dark-adapted (scotopic) fERG data from 25 schizophrenia patients and 25 healthy control subjects to (1) determine if past key findings on abnormal photoreceptor and bipolar cell signaling could be replicated; (2) for the first time, examine retinal ganglion cell functioning using the photopic negative response of the fERG; (3) also for the first time, determine responsiveness of schizophrenia patients to a flickering stimulus, as an additional method to isolate cone photoreceptor function; and (4) determine if schizophrenia-related changes in the fERG could be detected using a portable hand-held ERG device.
METHOD: ERG data were collected on 25 patients with schizophrenia and 25 healthy controls. At the time of testing all but one patient was prescribed psychiatric medication. All participants were between the ages of 18 and 60 years old.
RESULTS/ CONCLUSION: In both photopic and scotopic conditions, schizophrenia patients demonstrated weakened photoreceptor and bipolar cell activations that were most pronounced in response to the most intense stimuli. A reduced cone response to a flicker stimulus and attenuation in ganglion cell activity were also observed in the schizophrenia group. In general, groups did not differ in implicit time of retinal cell responses. These findings (1) replicate and extend prior studies demonstrating reduced photoreceptor (both rod and cone) and bipolar cell functioning in schizophrenia; (2) indicate that retinal ganglion function abnormality can also be detected using fERG; and (3) indicate that these anomalies can be detected using a portable testing device, thereby opening up possibilities for more routine administration of ERG testing.
Demmin D.L. et al. ‘People with current major depression resemble healthy controls on flash Electroretinogram indices associated with impairment in people with stabilized schizophrenia’
In Schizophrenia Research (Article in Press) 2019
PURPOSE: In this study we directly compared the fERG performance of MDD patients experiencing a current major depressive episode to that of stabilized, but not symptom-free, schizophrenia patients, and that of healthy controls, in order to clarify the extent of changes in acute MDD relative to both groups, thereby addressing both the issues of presence of MDD-related abnormality and diagnostic specificity.
METHOD: ERG data were recorded from 25 patients with schizophrenia (SCZ), 25 patients with major depressive disorder (either single episode or recurrent; MDD) in a current major depressive episode, and 25 healthy controls (HC). At the time of testing, all MDD patients and all but one SCZ patient were prescribed psychiatric medication. In the MDD group, 72% of patients (n = 18) had recurrent major depressive episodes and 28% (n = 7) met criteria for a single episode. All patients in the MDD group were experiencing a current major depressive episode (past month). No patients in the MDD group reported experiences of psychotic symptoms. Healthy control participants were recruited from the community. All participants were between the ages of 18 and 60 years old.
RESULTS/ CONCLUSION: These data indicate that MDD patients currently experiencing a
major depressive episode requiring hospitalization resemble psychiatrically healthy controls on fERG indices that have previously been shown to discriminate stabilized schizophrenia patients from controls. While we cannot rule out the possibility that MDD is associated with retinal functioning anomalies on other fERG indices or test parameters, prior research on this issue suggests that if/when such anomalies exist they are likely to be less severe than those observed in schizophrenia, and possibly much less severe if compared to a schizophrenia group with an equal proportion of hospitalized cases.
Demmin D.L. et al. ‘Retinal functioning and reward processing in schizophrenia’
In Schizophrenia Research (Article in Press) 2019
PURPOSE: We aimed to determine whether ERG amplitudes would be sensitive to the well-documented reward processing impairment in schizophrenia.
METHOD: Flash ERG data from15 clinically stable people with schizophrenia or schizoaffective disorder and 15 healthy controls were collected under three conditions: baseline, the anticipation of a food reward, and immediately after consuming the food reward. At the group level, data indicated that controls’ ERG responses varied as a function of salience of the food reward (baseline vs. anticipation vs. consumption) whereas patients’ ERG responses did not vary significantly across conditions.
RESULTS/ CONCLUSION: These data suggest that flash ERG amplitudes may be a sensitive indicator of the integrity of reward processing mechanisms. However, several differences in the direction of findings between this and a prior study in controls point to the need for further investigation of the contributions of a number of key variables to the observed effects.
Kazakos C.T. et al. ‘Retinal Changes in Schizophrenia: A Systematic Review and Meta-analysis Based on Individual Participant Data’
In Schizophrenia Bulletin 2019
PURPOSE: In this study, we aimed to investigate the potential role of 3 non-invasive retinal evaluation methods in SZ detection: OCT, fundus photography, and electroretinography (ERG).
METHOD: e searched MEDLINE, SCOPUS, clinicaltrials.gov, PSYNDEX, Cochrane Controlled Register of Trials (CENTRAL), WHO International Clinical Trials Registry Platform, and Google Scholar, up to October 30, 2018. Authors were contacted and invited to share anonymized participant-level data. Aggregate data were pooled using random-effects models. Diagnostic accuracy meta-analysis was based on multiple cut-offs logistic generalized linear mixed modeling. This study was registered with PROSPERO, number CRD42018109344.
RESULTS/ CONCLUSION: Pooled mean differences of peripapillary retinal nerve fiber layer thickness in micrometer between 694 eyes of 432 schizophrenia patients and 609 eyes of 358 controls, from 11 case-control studies, with corresponding 95% confidence intervals (CIs) by quadrant were the following: −4.55, 95% CI: −8.28, −0.82 (superior); −6.25, 95% CI: −9.46, −3.04 (inferior); −3.18, 95% CI: −5.04, −1.31 (nasal); and −2.7, 95% CI: −4.35, −1.04 (temporal). Diagnostic accuracy, based on 4 studies, was fair to poor, unaffected by age and sex; macular area measurements performed slightly better.
The notion of structural and functional changes in retinal integrity of patients with schizophrenia is supported with current evidence, but diagnostic accuracy is limited. The potential prognostic, theranostic, and preventive role of retinal evaluation remains to be examined
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