Neuroimaging Differences Between Migraine Types: Aura vs. Without Aura

Posted on September 14 2025, By: Cerebral Torque

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Brain Imaging in Migraine

Similarities and differences between migraine with aura and migraine without aura

Based on neuroimaging research by Casillo et al. - Cephalalgia 2025

Introduction: Unraveling Migraine's Brain Mysteries

Migraine affects millions worldwide, yet its underlying brain mechanisms remain complex and not fully understood. One of the most intriguing questions in migraine research is whether migraine with aura (MA) and migraine without aura (MO) represent different conditions or variations of the same disorder.

Recent advances in neuroimaging have allowed researchers to examine both structural and functional differences between these migraine subtypes. Understanding these differences could lead to better treatments and help explain why some people experience aura while others don't.

What is Migraine Aura?

Migraine aura consists of transient neurological symptoms that typically precede or accompany the headache phase. Common manifestations include visual disturbances like flashing lights, zigzag lines (fortification spectra), or blind spots (scotomas). Less frequently, aura may involve sensory disturbances, speech difficulties, or motor symptoms. This is called atypical aura.

30%

Migraine with Aura

Approximately 30% of migraine patients experience aura symptoms

CSD

Cortical Spreading Depression

Key mechanism believed to underlie aura phenomena

Multiple

Imaging Techniques

DTI, fMRI, VBM, SBM, and ASL used to study brain differences

Research Methodology

This comprehensive review analyzed neuroimaging studies comparing migraine with aura and migraine without aura using multiple advanced techniques. The research included studies published through May 2025, examining both structural and functional brain differences.

Neuroimaging Techniques Used

Diffusion Tensor Imaging (DTI) White Matter Analysis

Voxel-Based Morphometry (VBM) Gray Matter Volume

Surface-Based Morphometry (SBM) Cortical Thickness

Functional MRI (fMRI) Brain Connectivity

Arterial Spin Labeling (ASL) Blood Flow

Study Selection Criteria

The review included original neuroimaging studies using MRI that directly compared migraine with aura and migraine without aura. Studies of chronic migraine and pediatric patients were excluded to focus on adult episodic migraine populations.

Structural Brain Imaging Findings

Structural neuroimaging found important differences in brain anatomy between migraine with aura and migraine without aura patients, particularly in white matter integrity and gray matter characteristics.

White Matter Changes in Migraine Subtypes

Brain Region	Migraine with Aura Findings	Migraine without Aura Findings	Clinical Significance
Parieto-occipital White Matter	Decreased radial diffusivity Suggests axonal damage or altered microstructure	Normal values in most studies	May reflect repeated cortical spreading depression effects
Corpus Callosum	Reduced diffusivity markers Altered interhemispheric communication	Generally preserved structure	Could affect bilateral coordination of brain functions
Cingulate White Matter	Microstructural changes Affects emotional and pain processing pathways	Less pronounced changes	May contribute to different pain experiences
Cerebellum	Lower magnetization transfer ratio Suggests myelin-related alterations	Higher values compared to MA	Cerebellum involved in pain modulation

Thalamic Microstructural Differences

Studies revealed that migraine with aura patients showed lower magnetization transfer ratios and altered T1 relaxation times in the thalamus compared to migraine without aura patients. This suggests differences in tissue microstructure that could affect the thalamus's role in processing and filtering sensory information.

Gray Matter Volume and Cortical Thickness

Both migraine subtypes showed decreased gray matter volume in visual regions V3 and V5 compared to healthy controls. However, cortical thickness analyses revealed more complex patterns, with migraine with aura showing specific alterations in areas involved in higher cognitive functions, memory, learning, and arousal.

Functional Brain Imaging Results

Functional neuroimaging studies provided insights into how brain networks operate differently in migraine with aura versus migraine without aura, revealing both similarities and distinct differences in brain connectivity and activation patterns.

Visual

Network Hyperactivity

MA patients show heightened visual pathway activation during tasks

Reduced

Connectivity

MA shows decreased insula-occipital region connectivity

Shared

Alterations

Both subtypes show altered temporal region connections

Key Functional Connectivity Findings

Visual Processing Networks

Migraine with aura patients demonstrated heightened activation of visual processing regions, including the lingual gyrus, inferior parietal lobule, and cerebellum during visual tasks. This hyperresponsiveness strongly correlated with photophobia levels, suggesting a direct link between neural sensitivity and symptom severity.

Salience Network Changes

Both migraine subtypes showed altered connectivity within the salience network, particularly involving the frontal executive network, thalamus, and putamen. However, migraine with aura exhibited additional reductions in cerebellar and brainstem connectivity compared to migraine without aura.

Cerebral Blood Flow Alterations

Arterial spin labeling studies revealed that migraine with aura patients had elevated cerebral blood flow in the superior frontal gyrus, postcentral gyrus, and cerebellum, but reduced flow in the middle frontal gyrus, thalamus, and medioventral occipital cortex. Additionally, reduced neurovascular coupling in the visual cortex was observed.

Key Research Findings

The comprehensive analysis of neuroimaging studies revealed several important patterns that distinguish migraine with aura from migraine without aura, while also identifying shared characteristics between the two conditions.

Primary Differences in Migraine with Aura

Enhanced Visual Processing: Heightened engagement of visual regions, including striate and extrastriate cortices

Cerebellar Changes: Decreased antinociceptive activity and altered connectivity patterns

Thalamic Dysfunction: Impaired information filtering and processing capabilities

Structural Alterations: White matter microstructural changes in key brain regions

Comparative Analysis: MA vs MO Brain Patterns

Neuroimaging Technique	Shared Characteristics	Migraine with Aura Specific
Structural Imaging	Reduced gray matter in visual areas V3, V5 Increased cortical thickness in visual/somatosensory regions	Decreased radial diffusivity in parieto-occipital regions Lower cerebellar magnetization transfer ratio Altered thalamic microstructure
Functional Connectivity	Heightened temporal region connectivity Reduced executive network activity Decreased thalamic/putamen connectivity	Enhanced visual network activation during tasks Reduced insula-occipital connectivity Decreased cerebellar/brainstem connectivity
Blood Flow	Similar baseline perfusion patterns	Elevated cerebral blood flow in frontal regions Reduced neurovascular coupling in visual cortex Decreased flow in thalamus and occipital areas

The Cortical Spreading Depression Connection

The observed differences in migraine with aura may result from cortical spreading depression (CSD), a wave of cortical hyperactivity followed by prolonged neuronal suppression. Whether these brain changes represent consequences of repeated CSD events or a primary predisposition to them remains an open question.

Study Limitations and Research Challenges

While the neuroimaging research provides valuable insights, several methodological limitations affect the reliability and interpretation of findings across studies.

Major Study Limitations Identified

Sample Sizes Small (10-50 patients)

Migraine Phase Timing Often unspecified

Medication Effects Preventive treatments included

Statistical Approaches Inconsistent methodologies

Reproducibility Limited replication studies

Critical Research Gaps

Most studies failed to specify the migraine phase during scanning, potentially capturing patients during peri-ictal periods when brain metabolism and function may be altered. This heterogeneity significantly complicates the interpretation of structural and functional differences between migraine subtypes (Casillo et al., 2025).

Impact of Preventive Medications

Many studies included patients taking preventive migraine medications, which may alter brain structure and function. Beta-blockers, antiepileptics, and CGRP antagonists can all influence neuroimaging findings, potentially confounding study results and making it difficult to determine which changes are disease-related versus treatment-related.

Statistical and Methodological Concerns

Inadequate sample sizes, variability in preprocessing pipelines, and different analytical approaches created challenges for cross-study comparisons. The expanding array of potential analysis methodologies, termed "researcher degrees of freedom," can hinder reproducibility and inter-study reliability (Casillo et al., 2025).

Clinical Implications

Despite study limitations, the neuroimaging findings have important implications for understanding migraine pathophysiology and potentially guiding future treatment approaches.

Key Brain Systems

Visual processing, cerebellar modulation, and thalamic filtering show distinct patterns

Both

Subtypes Affected

Salience network alterations present in MA and MO

Future

Treatment Targets

Findings may guide personalized therapy approaches

Understanding Brain Network Dysfunction

The research suggests that migraine with aura exhibits altered cerebellar antinociceptive capacity, reduced thalamic information filtering, and increased visual processing region engagement compared to migraine without aura. These patterns may explain clinical differences in symptom presentation and treatment response.

Salience Network Involvement

Both migraine subtypes showed involvement of the salience network, which identifies and filters environmental inputs while modulating attention and behavior. This network's dysfunction may contribute to pain perception alterations and emotional responses to migraine attacks in both MA and MO patients.

Potential Clinical Applications

Biomarker Development

The distinct neuroimaging patterns could potentially serve as biomarkers to differentiate migraine subtypes and predict treatment responses, though this requires validation in larger, well-controlled studies.

Personalized Treatment

Understanding brain network differences may guide personalized treatment selection, particularly for patients with treatment-resistant migraine or complex symptom presentations.

Drug Development

Insights into specific brain regions and networks affected in each migraine subtype could inform targeted drug development efforts for more effective treatments.

Future Research Directions

To advance our understanding of migraine brain differences, future research must address current methodological limitations and adopt more rigorous approaches.

Research Priorities

Future studies should employ larger sample sizes, standardized protocols, careful migraine phase classification, and consistent outcome measures. Greater emphasis on clinical phenotyping of aura characteristics is also needed (Casillo et al., 2025).

Recommended Study Design Improvements

Sample Size Larger

Migraine Phase Carefully documented timing

Medication Status Drug-naive or washout periods

Statistical Methods Standardized approaches

Replication Multi-center validation

Conclusions and Clinical Takeaways

The comprehensive analysis of neuroimaging studies reveals both shared characteristics and distinct differences between migraine with aura and migraine without aura, providing important insights into migraine pathophysiology.

Key Research Conclusions

Shared Networks Both subtypes affect salience and visual systems

MA-Specific Changes Visual, cerebellar, and thalamic alterations

Clinical Relevance May guide future treatment approaches

Research Needs Larger, standardized studies required

Clinical Significance

While migraine with aura and migraine without aura share common brain network alterations, migraine with aura demonstrates distinct patterns of enhanced visual processing, altered cerebellar function, and impaired thalamic information processing. These differences may reflect either consequences of repeated cortical spreading depression or primary predisposing factors.

Impact on Patient Care

Understanding these brain differences could eventually lead to more personalized treatment approaches, better patient stratification for clinical trials, and development of targeted therapies. However, current findings require validation through larger, more rigorously designed studies before clinical implementation.

References

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Leão AAP. Spreading depression of activity in the cerebral cortex. J Neurophysiol. 1944;7:359-390.
Lauritzen M. Cortical spreading depression in migraine. Cephalalgia. 2001;21:757-760.
Hadjikhani N, Sanchez del Rio M, Wu O, et al. Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proc Natl Acad Sci USA. 2001;98:4687-4692.
Headache Classification Committee of the International Headache Society. The international classification of headache disorders, 3rd edition. Cephalalgia. 2018;38:1-211.
Granziera C, DaSilva AFM, Snyder J, et al. Anatomical alterations of the visual motion processing network in migraine with and without aura. PLoS Med. 2006;3:e402.
Tessitore A, Russo A, Conte F, et al. Abnormal connectivity within executive resting-state network in migraine with aura. Headache. 2015;55:794-805.
Magon S, May A, Stankewitz A, et al. Cortical abnormalities in episodic migraine: a multi-center 3 T MRI study. Cephalalgia. 2019;39:665-673.
Fu T, Gao Y, Huang X, et al. Brain connectome-based imaging markers for identifiable signature of migraine with and without aura. Quant Imaging Med Surg. 2024;14:194-207.
Silvestro M, Esposito F, De Rosa AP, et al. Reduced neurovascular coupling of the visual network in migraine patients with aura. J Headache Pain. 2024;25:180.

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