Clinical highlights – March 2025
In this article, we explore the differences between voluntary and reflexive saccades, the neural pathway involved, and how they can provide interesting clues about brain health.
Now officially CE-marked as a Class IIa medical device, neuroClues® is available for clinical use across Europe. To mark this milestone, we’ll be highlighting in the coming months how neuroClues® can enhance your practice by focusing on the biomarkers it captures and the scientific research that supports their diagnostic value.
Enjoy the reading!
1. EYE MOVEMENTS
Throughout our lives, we trigger an astonishing 2.5 saccades per second, a frequency even higher than our heartbeats. Saccades are among the fastest movements the human body can perform.
Our eye movements are stereotypical, as we all move our eyes in similar patterns. This is advantageous because it makes any abnormalities highly noticeable.
Since different brain regions control these eye movements, abnormalities in eye behavior often point to specific areas of the brain that may not be functioning properly. This connection is why research has linked eye movement abnormalities to malfunctions in particular brain regions.
Klein & Ettinger (2019)
Eye Movement Assessment
To assess these movements, we rely on paradigms, a structured sequence of visual stimuli that prompts specific eye behaviors. These paradigms are vital for evaluating how the eyes respond to various targets, typically presented on a screen. Common examples of paradigms include visually guided saccades (also known as pro-saccades), anti-saccades, and others—see figure below.
Each paradigm follows a defined set of parameters, such as the position and timing of the visual target, collectively forming a protocol.
Within these protocols, we extract biomarkers. Examples include latency—the time between the appearance of a target and the initiation of a saccade—and error rate, which measures the frequency of incorrect eye movements. These biomarkers offer objective insights into eye behavior, allowing us to analyze multiple aspects of eye movement with precision.
Leng et al. (2024)
2. Saccades and Neural Pathway
Eye movements are classified based on their neural pathways into two types: low-level reflexive movements and high-level voluntary movements.
Leng et al. (2024)
Reflexive Eye Movements
Reflexive saccades are rapid, automatic eye movements directed toward a visual stimulus that suddenly appears in the peripheral field.
Neural Pathway
Reflexive saccades require minimal cognitive effort and are primarily controlled by neural circuits in the brainstem, with the superior colliculus in the midbrain playing a central role. The superior colliculus processes sensory information (such as location, size, shape, or brightness) to determine the saccade target and ensure accuracy in direction and endpoint. This exogenous information, linked to attentional processes, guides the initiation of reflexive saccades.
Paradigm
To study reflexive eye movements, Visually Guided Saccades (VGS) are used. In this task, the patient is asked to perform a saccadic eye movement toward a visual target (pro-saccades).
Additionally, the anti-saccade task is another method to study reflexive eye movements, as it relies on the ability to suppress reflexive saccades.
Voluntary Eye Movements
Voluntary saccades are intentional eye rotations that require more complex processes than simple reflexive responses.
Neural pathway
Voluntary saccades engage various cortical areas, including pathways through the frontal lobe, to control eye movements. Unlike reflexive saccades, which primarily rely on a quick loop between the parietal cortex and the superior colliculus, voluntary movements require active input from frontal cortical regions [Link]
Different tasks have been shown to involve specific brain areas:
Pro-saccades engage regions like the prefrontal cortex (PFC), frontal eye field (FEF), supplementary eye field (SEF), and parietal eye field (PEF).
Antisaccades involve the FEF, SEF, dorsolateral prefrontal cortex (DLPFC), PEF, and anterior cingulate cortex (ACC). Damage to the DLPFC and cingulate eye fields (CEF) increases errors, while FEF damage increases latency.
Memory-guided saccades are linked to the FEF, SEF, and PEF, which are crucial for spatial working memory. Extraretinal signals, such as vestibular input, also contribute.
Predictive saccades involve the FEF, SEF, DLPFC, and cerebellum.
Gap and overlap saccades mainly engage the FEF, PEF, and superior colliculus (SC), which are associated with visual attention shifts.
Paradigm
To study voluntary eye movements, several tasks can be used:
- Visually Guided Saccades (VGS) (overlap)
- Anti-saccades (AS)
- Delayed saccades (DS)
- Self-Generated Saccades (SGS)
- Memory-Guided Saccades (MGS)
- Predictive Saccades
- Adaptive Saccades
In essence, reflexive saccades are more stimulus-driven and involve lower-level motor pathways, whereas voluntary saccades are goal-directed, often require the suppression of reflexive responses, involve higher-level cognitive functions like executive control, working memory, and learning, and depend more heavily on cortical input, particularly from the frontal lobe.
3. neuroClues Technology
neuroClues offers a comprehensive tool for evaluating both voluntary and reflexive saccades, including Visually Guided Saccades and Antisaccades, allowing for the extraction of key biomarkers such as errors and latency.
As we highlight in this month’s review, these biomarkers can provide information about potential brain structure impairments.
For example, increased pro-saccade latency can indicate impairment in the PFC, FEF, SEF and PEF. On the other hand, increased anti-saccade latency could be indicative of damage in the FEF and increased anti-saccade error rates have been associated with damage to the DLPFC and CEF.
Stay tuned for next month, where we’ll dive into studies demonstrating the link between eye movement abnormalities and cognitive impairments.
Upcoming Newsletters
Over the coming months, we’ll be providing insights on how neuroClues® can elevate your consultations, supported by compelling studies and research.
Here’s a preview of the upcoming newsletters:
- April — Exploring Anti-Saccades and Frontal Lobe Function
- May — The Science Behind our Biomarker Computation
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