Exploring Anti-Saccades and Frontal Lobe Function

May 6, 2025

Learn more about how neuroClues® eye movement biomarkers could support early detection of cognitive impairments.

Clinical highlights – April 2025

neuroClues has officially received its CE-marking as a Class IIa medical device, available for clinical use in Europe.

For this occasion, we have decided to highlight how neuroClues can elevate your practice by focusing on the biomarkers it extracts and how proven research demonstrates their diagnostic value.

In the previous blog, we explored saccadic eye movements and the neural structures involved. In this blog, we take it a step further by linking abnormalities in those movements to valuable insights into brain health, particularly cognitive impairments.

Enjoy the reading!

– The neuroClues^® Team

1. Quick recap

Saccades—rapid, precise eye movements—occur around 2.5 times per second and are regulated by distinct brain circuits.

Reflexive saccades are automatic responses, relying on lower-level pathways such as the brainstem and superior colliculus. In contrast, voluntary saccades are intentional and engage higher-order regions, including the prefrontal cortex (1).

1. Leng Q, Deng B, Ju Y. Application and progress of advanced eye movement examinations in cognitive impairment. Front Aging Neurosci [Internet]. 2024 Apr 17 [cited 2025 Feb 19];16. Available from:https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2024.1377406/full

Abnormalities in these eye movements can be captured through biomarkers like latency and error rates, measured using tasks such as Visually Guided Saccades and Antisaccades.

These biomarkers offer insight into specific neural pathway dysfunctions, making saccade assessment a powerful, non-invasive window into brain health.

→ We touched on this in last month’s newsletter. Need a refresher? Click here to take another look.

2. Link to Cognitive Impairment

Several recent studies suggest that measuring saccadic eye movements biomarkers may serve as valuable clinical tools for assessing cognitive impairments.

In this section, we will explore four of these studies in greater detail.

Behavioral Variant Frontotemporal Dementia (bvFTD)

Saccadic testing can offer valuable insights into frontal lobe dysfunction in bvFTD patients. A study found that, compared to healthy controls, bvFTD patients tend to show a general slowing in the initiation of eye movements, with increased latency due to motor pathway issues or delays in saccadic commands from higher cortical areas (2).

Voluntary saccades, such as antisaccades, displayed relatively more specific impairments, including a higher error rate, which may suggest poor inhibitory control and the reliance on frontal lobe function (2).

2. Douglass A, Walterfang M, Velakoulis D, Abel L. Behavioral Variant Frontotemporal Dementia Performance on a Range of Saccadic Tasks. Savage S, editor. JAD [Internet]. 2018 Aug 7 [cited 2025 Feb 27];65(1):231–42. Available from: https://journals.sagepub.com/doi/full/10.3233/JAD-170797

Mild Cognitive Impairment & Dementia

Anti-saccade tasks, both horizontal and vertical, were showned in this study to outperform horizontal pro-saccades in distinguishing between mild cognitive impairment (MCI) and dementia, with stronger associations to neuropsychological test results (3).

While vertical pro-saccades show promise, the study also highlights that anti-saccades, with their more consistent reaction times and high accuracy in clustering, may serve as sensitive markers of cognitive decline (3).

As illustrated in the figure above, reaction times (latencies) in visual saccade tasks, particularly vertical and anti-saccade, appear to effectively differentiate healthy older adults, individuals with MCI, and those with dementia, with notable distinctions observed between groups.

3. Rane D, Dash DP, Dutt A, Dutta A, Das A, Lahiri U. Distinctive visual tasks for characterizing mild cognitive impairment and dementia using oculomotor behavior. Front Aging Neurosci [Internet]. 2023 Jul 20 [cited 2025 Mar 12];15:1125651. Available from: https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1125651/full

Amnestic (aMCI) & Non-Amnestic (naMCI) Cognitive Impairment

Saccadic eye movements have been found to help differentiate between subtypes of mild cognitive impairment (MCI) and healthy controls (HCs), with distinct variations in eye movement metrics being associated with specific cognitive functions (4).

This study demonstrated that individuals with aMCI tend to exhibit longer saccadic reaction times (SRTs), in other words latency, and a higher proportion of express saccades during anti-saccade tasks, which may reflect impairments in inhibitory control (4).

These saccadic abnormalities were linked to executive function and attention deficits, suggesting that they could serve as a valuable tool for identifying cognitive decline in the early stages of dementia (4).

4. Koçoğlu K, Hodgson TL, Eraslan Boz H, Akdal G. Deficits in saccadic eye movements differ between subtypes of patients with mild cognitive impairment. Journal of Clinical and Experimental Neuropsychology [Internet]. 2021 Feb 7 [cited 2025 Feb 27];43(2):187–98. Available from: https://pubmed.ncbi.nlm.nih.gov/33792489/

Amnestic (aMCI) Cognitive Impairment & Alzheimer’s Disease

Objective saccadic eye movement tasks have been shows to effectively assess executive function deficits in individuals with amnestic mild cognitive impairment (aMCI) and mild Alzheimer’s disease (AD) (5).

Findings from this study suggest that both patient groups exhibit slower initiation of correct antisaccades and make more direction errors compared to healthy controls, highlighting impairments in inhibitory control and voluntary saccade generation (5).

The authors found a correlation between antisaccade performance and neuropsychological tests, such as the Stroop task, which further underscores the task’s sensitivity in detecting early cognitive decline. This suggests that evaluating antisaccade performance would be a valuable tool for assessing executive dysfunction in a non-invasive manner (5).

5. Peltsch A, Hemraj A, Garcia A, Munoz DP. Saccade deficits in amnestic mild cognitive impairment resemble mild Alzheimer’s disease. Eur J of Neuroscience [Internet]. 2014 Jun [cited 2025 Feb 7];39(11):2000–13. Available from:https://pubmed.ncbi.nlm.nih.gov/24890471/

3. Clinical Implications with neuroClues

The literature examples discussed above indicate that analyzing error rates and latencies from Visually Guided Saccades and Antisaccades may offer valuable insights into:

distinguishing subtypes of Mild Cognitive Impairment (MCI),
estimating the likelihood of clinical progression in amnestic MCI (aMCI) and assessing the risk of conversion to Alzheimer’s disease, potentially enabling earlier intervention,
detecting subtle deficits in executive function.

Therefore, leveraging neuroClues^® to automatically extract error rates and latency data from Visually Guided Saccades and Antisaccades could support the evaluation of cognitive impairments in a clinical setting.

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