Interictal and Ictal Cognitive Performance in Episodic and Chronic Migraine

ABSTRACT

Background

Cognitive dysfunction is a disabling feature of migraine, affecting attention, memory, and executive functions. Differences between episodic and chronic migraine, as well as between interictal and ictal periods, remain unclear. We aimed to compare interictal cognitive performance in episodic and chronic migraine with healthy controls and to evaluate intra‐individual changes during attacks.

Methods

In this cross‐sectional study with within‐subject repeated measures, migraine patients (32 EM, 32 CM) and 30 matched healthy controls underwent standardized cognitive testing (Mini Mental State Examination, Clock Drawing Test, Stroop Test, Digit Span Forward/Backward Tests) assessing attention, short‐term and working memory, and executive function along with Beck Depression Inventory. Migraine cohorts were evaluated interictally (≥ 72 h attack‐free) and again within the first 3 h of an untreated spontaneous migraine attack.

Results

Interictally, CM patients demonstrated significant impairments in attention, short‐term memory, and working memory compared to healthy controls. EM patients, however, showed no cognitive dysfunction except for working memory. During migraine attacks, all cognitive domains deteriorated significantly in both groups. The magnitude of cognitive decline during an attack did not differ between EM and CM. Attack severity was associated with greater cognitive decline during attacks in the general migraine group, but this association was more pronounced in EM than in CM.

Conclusions

Migraine is a neurobiological disorder with cognitive consequences that extend beyond pain. Our findings highlight the importance of incorporating cognitive assessment into routine migraine management and reveal the need for longitudinal studies to elucidate the underlying mechanisms of cognitive dysfunction in migraine.

Migraine is not only a pain disorder but a dynamic network disorder with measurable cognitive consequences. Interictally, working memory impairment was observed in episodic migraine, while chronic migraine showed broader deficits in attention and executive functions. During attacks, both subtypes demonstrated significant cognitive decline across all domains, independent of migraine type. Attack severity was associated with cognitive worsening, particularly in episodic migraine. Our findings highlight the clinical importance of incorporating routine cognitive assessment into migraine management.

1. Introduction

Migraine is a primary headache disorder affecting millions of people worldwide, involving complex neurobiological processes and profoundly impacting quality of life [1]. The disease causes a significant global economic and social burden and remains the second leading cause of disability worldwide [2].

The pathophysiology of migraine is complex and multifactorial. While migraine is often perceived as solely a pain disorder, the disease is a multidimensional clinical entity with autonomic, sensory, and neurological symptoms that can encompass prodromal, aura, pain, postdrome, and interictal phases. The disabling impact of migraine on the individual can occur not only during attacks but also between them. Cognitive dysfunction is one of the significant yet underrecognized disabling consequences of migraine. Indeed, studies have shown that cognitive symptoms are second only to pain in terms of disability [3]. Patients with migraine may experience cognitive complaints that persist not only during attacks but also during the interictal period, significantly impacting daily functioning and social interaction. The link between migraine and cognitive impairment is complex and involves many different pathophysiological processes [4]. Neuroimaging and electrophysiological studies suggest that migraine is associated with altered functional connectivity within frontoparietal, salience, and default mode networks, which are critically involved in attention, working memory, and executive control. Recurrent cortical spreading depression, trigeminovascular activation, central sensitization, and neuroinflammatory mechanisms may transiently or persistently disrupt these cognitive networks. These network‐level alterations provide a plausible biological basis for both ictal and interictal cognitive dysfunction observed in migraine [5]. Attention and memory problems, as well as difficulties with concentration and executive functions, are commonly reported in people with migraine. Despite their prevalence and impact, such complaints are often overlooked in clinical assessments because current diagnostic and treatment frameworks primarily focus on pain relief.

Studies have shown that migraine can cause cognitive impairments both during and between attacks [5, 6]. However, results vary due to differences in methodology, population, and the lack of a homogeneous group.

To address cognitive dysfunction, which is often overlooked in the management of migraine patients but can be a significant cause of disability, we assessed cognitive status in migraine patients between and during attacks using a homogeneous cohort and clinically applicable cognitive tests. Our aim is to emphasize the importance of screening for cognitive dysfunction in migraine patients, to increase the applicability of this screening in clinical practice, and to make cognitive function one of the important targets in migraine treatment.

2. Materials and Methods

2.1. Study Design and Participants

This study employed a cross‐sectional design complemented by a within‐subject repeated‐measures comparison in the migraine group. It included 64 patients with episodic (n = 32) and chronic (n = 32) migraine without aura, recruited between 2022 and 2025. The control group consisted of 30 healthy individuals without migraine. All participants' migraine diagnosis, neurological examinations, and cognitive assessments were conducted by the same neurologist (E.K.K.).

The inclusion criteria were as follows:

1. Meeting the diagnostic criteria for episodic or chronic migraine according to the International Classification of Headache Disorders, third edition (ICHD‐3), and the absence of any other type of headache except for medication‐overuse headache [7].

2. Having at least 4 years of formal education

3. Absence of any prophylactic treatment in the last 3 months (e.g., topiramate, valproate, amitriptyline).

4. In cognitive tests performed during the interictal period in migraine patients, the patient must have been free from attacks for the last 3 days (72 h).

Exclusion criteria of the study were set as follows:

1. Age < 18 or > 65 years.

2. Being diagnosed with dementia or similar neurological diseases.

3. Abnormal or suspicious neurological findings.

4. Patients who have severe depression with a score of 30 or higher on the baseline Beck Depression Inventory (BDI).

5. Alcohol/substance abuse or use of cognition‐affecting drugs.

6. Presence of pregnancy or breastfeeding.

2.2. Demographic Data and Headache Characterization

Demographic data and headache characteristics of the patients included in the study were obtained using a structured survey. Demographic data included gender, age, education level, history of other diseases and medications used. Regarding headache characteristics, data were collected on disease duration, pain localization, pain character, monthly headache frequency, duration of pain, average pain intensity score, presence of nausea/vomiting‐photo phonophobia, use of painkillers. Pain intensity was evaluated using the 10‐point Visual Analog Scale (VAS), where 0 indicates no pain and 10 the worst imaginable pain, based on both the average headache severity over the past 3 months and the current attack severity before the cognitive assessment [8]. VAS was used to evaluate pain intensity twice: as the average attack severity based on headache episodes over the past 3 months, and during the ongoing attack immediately before the cognitive assessment.

The Headache Impact Test (HIT‐6) is a six‐item self‐report measure of headache‐related disability [9]. Total scores range from 36 to 78, with higher scores indicating greater impairment.

2.3. Cognitive and Mood Assessments

All cognitive tests were administered by a trained clinician in a fixed order and lasted approximately 40–45 min. They were conducted in a quiet outpatient clinic room, free from external distractions. In all migraine patients, cognitive tests were first administered during the interictal period (at least 72 h after the last attack) and subsequently repeated within the first 3 h of a spontaneous untreated migraine attack (ictal period).

In patients diagnosed with episodic or chronic migraine, interictal cognitive evaluation was performed only if the patient had been attack‐free for at least 72 h. These patients were subjected to the same cognitive tests again within the first 3 h of the migraine attack. Ictal cognitive testing was performed before the administration of any acute migraine medications to avoid pharmacological effects on cognitive performance.

For each patient, the hour of the attack at which testing occurred (1st–3rd hour), attack severity (ictal VAS), and associated symptoms were recorded before administering cognitive assessments.

The tests administered are detailed below in the order in which they were applied in the study.

• Mini Mental State Examination (MMSE) is a brief screening tool that provides a general measure of cognitive impairment, is easy to administer, and is therefore the best known and most frequently used in clinical settings and research. The maximum score possible is 30 and the lower the score, the worse the cognitive functioning [10].

• Digit Span Tests (DST): Forward and backward DSTs are subtests of the Wechsler scales which are used to assess working memory and attention. Forward digit span (DST‐f) is considered a measure of verbal short‐term memory, while backward digit span (DST‐b) involves additional working memory and executive control [11]. The maximum range of numbers that the participants are asked to repeat in direct and reverse order form DST‐f and DST‐b scores, respectively. The higher the scores of DST‐f and DST‐b, the better the cognitive functioning.

• Stroop Test is a neuropsychological test extensively used to measure attention, information processing speed, selective attention, and cognitive flexibility. The Stroop effect occurs when individuals are presented with incongruent color‐word stimuli (e.g., the task involves reading the word “red” printed in blue ink or naming the color of the ink instead of reading the word). There are various subtypes and scoring systems for the test [12]. In this study, the color‐naming interference condition was administered. Participants were presented with incongruent color–word stimuli and were instructed to verbally report the ink color while inhibiting the written word. To ensure standardization, the words were presented sequentially with a fixed interval between each item. The primary outcome measure was the total number of incorrect responses. An error was defined as incorrect naming of the ink color, initial incorrect responses followed by immediate self‐correction, verbalization of the written word, or marked hesitations that disrupted response fluency. All such responses were counted as errors to maintain scoring consistency. Higher error counts were interpreted as poorer inhibitory control performance

• Clock Drawing Test (CDT) is a brief cognitive screening tool primarily assessing visuospatial construction and basic executive planning abilities. In this study, participants were given a pre‐drawn circle and were verbally instructed to draw a clock face set to a specified time. The test was scored using the 13‐point Caffarra system, with higher scores indicating better performance [13].

• BDI is a 21‐item self‐reporting questionnaire used in the evaluation of the severity of depressive symptoms. Scores range from 0 to 63 points, with higher scores indicating greater severity [14]. BDI was used to assess depressive symptom severity and to control for the potential influence of mood on cognitive performance.

The participant flow throughout the study is illustrated in Figure 1.

FIGURE 1.

Participant flow diagram of the study population.

2.4. Statistical Analysis

Statistical analyses were performed using R 4.5.2 on RStudio 2025.09.2. Descriptive statistics were calculated for all study variables. Hypothesis testing was performed using Pearson's Chi‐squared test and Fisher's exact test for categorical data and non‐parametric tests (Wilcoxon rank‐sum and Kruskal–Wallis tests) for non‐normally distributed continuous data. Dunn's test with Benjamini‐Hochberg correction was used for post hoc subgroup analyses of significant Kruskal–Wallis results. Correlations were assessed using Spearman's correlation test. Wilcoxon signed‐rank test was used for paired data. Wilcoxon r effect sizes were reported for comparing difference levels in cognitive tests. To evaluate the influence of migraine subtype (chronic vs. episodic) on test score differences, score change values (delta scores) were calculated for each test. Wilcoxon rank sum tests were used to compare delta scores between episodic and chronic migraine groups. Robust ANCOVA (package: {WRS2}) was used to control covariates and determine if the difference in a specific test remained significant when the covariate was controlled. Assumptions were checked for all tests before analysis. To account for potential effects of education on baseline cognitive performance, raw baseline test scores were transformed into education‐adjusted z‐scores. For each cognitive measure, z‐scores were calculated using the mean and standard deviation of the healthy control group within each education stratum. All baseline group comparisons were performed using these standardized scores. A p value below 0.05 was considered statistically significant.

3. Results

3.1. Demographic and Migraine Characteristics

The study cohort consisted of 32 episodic and 32 chronic migraine patients and 30 healthy controls. Groups with episodic and chronic migraine patients included 28 females each (88%), along with 26 females (87%) in the healthy control group. Mean ages for episodic, chronic, and control groups were respectively 38.2 (range: 21–52), 38.9 (range: 18–58), and 36.3 (range: 20–49) years. Levels of education, grouped in four‐year bins, showed no clear trend within the groups. No statistically significant differences were found among the groups in terms of sex, age, or education level (p > 0.05; Table 1).

TABLE 1.

Demographic overview and migraine‐related findings.

Characteristic	Migraine		Healthy control N = 30	p
	Chronic N = 32	Episodic N = 32
Sex (n [%])				> 0.91
Female	28 (88%)	28 (88%)	26 (87%)
Male	4 (13%)	4 (13%)	4 (13%)
Age (years, Mean [SD])	38.2 (12.0)	38.9 (8.4)	36.3 (7.8)	0.4 b
Level of Education (n [%])				0.8 c
University (16+ years)	8 (25%)	6 (19%)	9 (30%)
High school (12 years)	8 (25%)	10 (31%)	5 (17%)
Middle school (8 years)	5 (16%)	7 (22%)	7 (23%)
Primary school (4 years)	11 (34%)	9 (28%)	9 (30%)
Baseline beck depression inventory score (Mean [SD])	15.0 (8.2)	11.7 (7.0)	8.8 (5.5)	0.010* b
Years since migraine diagnosis (Mean [SD])	8.7 (7.4)	7.4 (6.1)		0.5 d
Age of migraine diagnosis (Mean [SD])	29.5 (11.8)	31.5 (7.9)		0.5 d
Laterality (n [%])				0.5 c
Bilateral	15 (47%)	9 (38%)
Unilateral	17 (53%)	15 (63%)
Unknown	0	8
Attack per month (Mean [SD])	15.2 (6.7)	3.8 (1.2)		< 0.001*** d
Average attack severity (last 3 months) (VAS score, Mean [SD])	8.4 (0.8)	7.9 (0.9)		0.027* d
Attack duration (hours, mean [SD])	41.6 (20.7)	36.2 (33.9)		0.10 d
Nausea (n [%])	29 (91%)	29 (91%)		> 0.9 a
Vomiting (n (%)]	16 (50%)	11 (34%)		0.2 c
Photophonophobia (n [%])	32 (100%)	30 (94%)		0.5 a
Sleeplessness (n [%])	21 (66%)	14 (44%)		0.079 c
Stress (n [%])	28 (88%)	24 (75%)		0.2 c
Analgesic use per month (tablet count, Mean [SD])	14.5 (9.5)	3.3 (2.1)		< 0.001*** d
HIT‐6 score (Mean [SD])	69.3 (8.1)	48.3 (8.0)		< 0.001*** d

Note: * = p < 0.05, ** = p < 0.01, and *** = p < 0.001.

^a Fisher's exact test.

^b Kruskal–Wallis rank‐sum test.

^c Pearson's Chi‐squared test.

^d Wilcoxon rank‐sum test.

Patients with chronic migraine had longer mean years of migraine history (mean: 8.7 ± 7.4 years) than patients with episodic migraine (mean: 7.4 ± 6.1 years), but this difference was not statistically significant. Significant differences were observed between the episodic and chronic migraine groups regarding attack frequency (p < 0.001), analgesic consumption (p < 0.001), and HIT‐6 scores (p < 0.001), all of which were higher in the chronic group. BDI scores were statistically different among three groups (p = 0.010). Post hoc analysis showed that patients with chronic migraine had higher BDI scores than healthy controls (p = 0.007), while no other significant differences were found. In patients with chronic migraine, the mean attack severity (VAS) over the last 3 months was higher than in patients with episodic migraine (p = 0.027). There were no significant differences among the groups regarding other clinical parameters (p > 0.05; Table 1).

3.2. Relationship Among Baseline Cognitive Tests and BDI in Episodic, Chronic Migraine, and Healthy Controls

At baseline, education‐adjusted z‐scores revealed significant differences between individuals with migraine (episodic and chronic combined) and healthy controls in BDI (p = 0.007), DST‐f (p = 0.023), and DST‐b (p = 0.001). In the three‐group comparison, significant differences were observed in BDI (p = 0.006), DST‐f (p = 0.020), and DST‐b (p = 0.003). Post hoc analyses showed that the chronic migraine group had higher BDI scores (p = 0.004) and lower DST‐f and DST‐b scores (p = 0.016 and p = 0.004, respectively) compared to healthy controls. After adjustment for education level, the episodic migraine group also demonstrated significantly lower DST‐b scores compared to healthy controls (p = 0.018), whereas this difference was not observed in the unadjusted analysis (p = 0.07). Baseline MMSE, CDT, and Stroop scores did not differ significantly among the three groups (MMSE: p = 0.3; CDT: p = 0.4; Stroop: p = 0.2; Table 2).

TABLE 2.

Comparison of Baseline Education‐Adjusted Z‐Scores for Cognitive Performance and Depression Between Migraine Cohorts and Healthy Controls.

Characteristic—Mean (SD)	Migraine vs. Healthy control			Three group comparison
	Migraine N = 64	Healthy control N = 30	p	Chronic N = 32	Episodic N = 32	Healthy control N = 30	p
Standardized mini mental examination	−0.7 (2.4)	0.0 (0.9)	0.5 a	−0.9 (2.6)	−0.5 (2.1)	0.0 (0.9)	0.3 b
Beck depression inventory	1.1 (1.8)	0.0 (0.9)	0.007** a	1.4 (1.9)	0.7 (1.7)	0.0 (0.9)	0.006** b
Clock drawing test	−0.3 (1.3)	0.0 (0.9)	0.3 a	−0.4 (1.4)	−0.1 (1.3)	0.0 (0.9)	0.4 b
Stroop test	1.0 (2.5)	0.0 (0.9)	0.11 a	1.1 (2.4)	1.0 (2.7)	0.0 (0.9)	0.2 b
Digit span forward test	−0.4 (0.8)	0.0 (0.9)	0.023* a	−0.5 (0.8)	−0.2 (0.8)	0.0 (0.9)	0.020* b
Digit span backward test	−0.9 (1.3)	0.0 (0.9)	0.001** a	−1.0 (1.3)	−0.9 (1.4)	0.0 (0.9)	0.003** b

Note: * = p < 0.05, ** = p < 0.01***, and = p < 0.001.

^a Wilcoxon rank‐sum test.

^b Kruskal–Wallis rank‐sum test.

3.3. Effect of Baseline BDI Scores on Baseline Digit Span Tests

DST‐f and DST‐b were the only cognitive measures that showed a significant difference among the three groups. To determine whether this difference could be attributed to depressive symptoms, robust ANCOVA tests were constructed with BDI scores included as a covariate. After adjusting for depressive symptom severity, the group effect remained significant, particularly among participants with low‐to‐moderate BDI scores (DST‐b p value < 0.05 between BDI scores 4 to 9, range = 0.007 to 0.024. DST‐f p value < 0.05 between BDI scores 5 to 13, range = 0.003 to 0.024). This finding indicates that the impairment observed in digit span test performances cannot be explained solely by depressive symptoms and suggests an independent cognitive effect of migraine. Within this adjusted BDI range, migraine patients scored approximately one point lower on average than healthy controls.

3.4. Comparison of Baseline and Ictal Test Results

Across all cognitive tests, migraine patients showed significantly poorer performance during the ictal phase compared with their baseline interictal scores. In episodic migraine, MMSE (p = 0.017) and CDT (p = 0.048) showed smaller but statistically significant declines, whereas all other cognitive tests demonstrated highly significant worsening (p < 0.001). In chronic migraine, CDT was significantly reduced during the ictal period (p = 0.001), with all remaining cognitive measures again showing p < 0.001. Violin plots illustrating these changes are presented in Figure 2, results detailed in Table S1. The largest effect sizes were observed for Stroop error counts (r = 0.81–0.82) and for DST‐f and DST‐b (r = 0.63–0.80), while MMSE and CDT demonstrated smaller effect sizes consistent with their ceiling properties. Across all measures, ictal scores were consistently worse than baseline scores.

FIGURE 2.

Comparison of baseline and ictal cognitive tests. Wilcoxon signed‐rank test for all Baseline and Ictal comparisons within Episodic, Chronic, and Overall groups were statistically significant. Besides standardized mini mental examination (p = 0.017*) and clock drawing test (p = 0.048*) in episodic group, and clock drawing test (p = 0.001**) in chronic group, p‐values of all comparisons were p < 0.001***. * = p < 0.05, ** = p < 0.01, and *** = p < 0.001.

No significant differences were found between episodic and chronic migraine groups in terms of attack severity (ictal VAS score), accompanying symptoms (photophonophobia), and time from pain onset to cognitive testing (p = 0.082, p = 0.52, p = 0.648, respectively).

3.5. Comparison of Ictal Cognitive Decline Between Episodic and Chronic Migraine

Comparisons of delta scores (ictal—baseline) using Wilcoxon rank sum test revealed no significant differences between the two groups (MMSE p = 0.35, DST‐f p = 0.36, DST‐b p = 0.56, Stroop p = 0.79, CDT p = 0.70). This finding demonstrates a robust effect of migraine attack on cognitive performance regardless of underlying migraine subtype (episodic vs. chronic).

3.6. Relationship Between Attack Severity and Ictal Cognitive Worsening

Attack severity (ictal VAS score) was significantly correlated with the magnitude of cognitive decline across the entire migraine cohort. Specifically, higher pain intensity (VAS) correlated with greater decreases in CDT, MMSE, and DST scores, as well as an increase in Stroop test errors. Subgroup analyses revealed in the chronic migraine group that significant correlations were observed only for the DST‐f (decreasing scores) and Stroop test (increasing errors). Scatterplots and trend lines showing these correlations can be found in Figure 3 with correlation coefficients and p‐values.

FIGURE 3.

Correlation between the attack's severity and the score difference between baseline and ictal cognitive test results. Note that each facet uses independent scales to enhance the clarity of within‐group variations. Dashed black line shows overall correlation.

4. Discussion

Migraine is a common and disabling neurological disorder which leads to reduced quality of life and significant functional impairments. Cognitive dysfunction, in particular, is increasingly recognized as a significant contributing factor to disability, occurring not only during attacks but also in the interictal period [6]. Studies have shown that cognitive disruption spans the entire migraine cycle, beginning in the prodromal phase [15], and persisting into the postdrome period [16].

Previous studies evaluating ictal and interictal cognition have yielded inconsistent results, likely due to methodological differences, varying patient populations, and the use of different neuropsychological batteries. Furthermore, failure to control for key confounders, such as depression, anxiety, and the presence of prophylactic drugs that may affect cognition, has complicated the interpretation of prior findings.

In the present study, we aimed to address these limitations by recruiting a homogeneous cohort matched for age, gender, and education. Those with evidence of severe depression and those receiving any prophylactic treatment that might impair cognition were excluded. To minimize the effect of the presence of psychiatric comorbidities on cognition, patients with severe depression according to the BDI (scores of 30 and above) were not included in the study. Since patients experience serious disability due to pain during the attack period, an attempt was made to select tests that would be easy to apply and cooperate with. All tests were applied to the patients by the same person to minimize differences in results.

4.1. Interictal Period Evaluation

In our study, migraine patients showed a decrease in working memory assessed with DST compared to the healthy control group. While cognitive impairment is widely documented in the literature, particularly during the ictal phase, there is less consensus on its presence during headache‐free periods, and the data are conflicting. Some studies report that migraine patients have worse cognitive performance during the interictal phase compared to healthy controls [17, 18], while other studies have found no significant difference among groups [19, 20]. The reported domains of cognitive dysfunction are also diverse, with most reporting areas such as memory, attention, and executive functions [17, 18]. Studies have shown that cortical excitability and pain processing in migraine patients differ from controls, even during the interictal period. The decreased functional connectivity found, particularly in frontoparietal networks, may explain the executive dysfunction experienced in migraine patients [21, 22].

Contrary to some previous reports, our study found no statistically significant difference in global cognition between the episodic and chronic migraine groups [23, 24]. Another study published in 2025 showed similar findings to our study and found no difference in cognitive impairment between the episodic and chronic groups [25]. However, patients with chronic migraine exhibited impairments in short‐term memory, attention, working memory, and executive functions assessed with DST‐B and DST‐f compared to healthy individuals. In a study comparing chronic migraine and healthy controls, cognitive deficits were found in chronic migraine patients, regardless of the presence of comorbidities or medication use [26]. In the study conducted by Lozano‐Soto et al. [27], cognitive retardation was found in chronic migraine patients during the interictal period compared to controls. In this study, more than half of the chronic migraine patients demonstrated mild to severe neuropsychological impairment, with the most frequent impairments being in short‐ and long‐term verbal episodic memory and inhibitory control. To eliminate a possible confounding effect of depression, patients with high scores on the BDI were excluded from the study and patients receiving prophylactic treatment that could affect cognition were not included in our study. Group differences in DST‐f and DST‐b remained statistically significant even after adjustment for the existing mild‐to‐moderate BDI. Our findings suggest that cognitive impairment in migraine cannot be fully explained by psychiatric comorbidities such as depression. Cognitive dysfunction may occur independently of psychiatric disorders or medications [5, 20, 28, 29, 30, 31]. Mongini and colleagues also reported that neuropsychological findings in migraine patients are partially independent of psychological characteristics [30]. Moreover, several studies that controlled for depression observed either a reduced or no effect of migraine on cognitive performance [28, 29].

Although overall cognitive performance was largely preserved in patients with episodic migraine, adjusted analyses revealed a selective working memory deficit compared to healthy controls. In contrast, chronic migraine was associated with more consistent impairments in digit span measurements. These findings suggest a gradient of interictal cognitive involvement across the migraine spectrum, with chronic migraine exhibiting greater impairment. The selective impairment observed in episodic migraine on the backward digit span task is particularly noteworthy. Unlike the forward condition, the backward digit span task requires not only short‐term storage but also active manipulation and executive control, placing greater demands on frontoparietal working memory networks [11]. The presence of this subtle deficit in episodic migraine, despite the preservation of general cognitive function, suggests that interictal cognitive vulnerability may primarily affect the executive components of working memory rather than simple verbal span capacity. In this context, episodic migraine may represent an early or milder stage of network‐level dysfunction, while chronic migraine is associated with more extensive cognitive involvement. This gradual pattern supports conceptualizing migraine not merely as an attack‐related phenomenon, but as a spectrum disorder with a progressive impact on cognitive control systems.

Factors that could potentially account for the disparity between episodic and chronic migraine include attack frequency and NSAID overuse. In our study, however, the independent effect of NSAID overuse on cognitive function could not be statistically assessed. Therefore, it remains unclear to what extent the differences observed between episodic and chronic migraine groups may be attributable to medication overuse. This represents an important limitation of our study.

Previous studies on interictal cognitive function in migraine have shown inconsistent results. While some suggest that higher attack frequency and longer duration are linked to greater executive deficits [21, 32], others report that factors like longer disease duration and social support may protect cognitive function [25]. Furthermore, no significant associations were found between executive dysfunction and headache features in some studies, suggesting attack‐independent cognitive alterations [17].

Cognitive impairment in migraine is likely influenced by neurobiological mechanisms beyond attack frequency alone. Instead, several migraine‐specific neurobiological mechanisms appear to contribute to interictal cognitive dysfunction. Cortical spreading depression, neuroinflammation, altered cortical excitability, and deficits in habituation and sensitization may disrupt the function of frontal and parietal networks involved in attention and executive control [33]. Electrophysiological studies have demonstrated that migraine patients show reduced sustained attention, hypersensitivity to external stimuli, and general inefficiency within attention networks even during attack‐free periods [34].

Migraine patients exhibit reduced activation within key executive‐function regions, including the right middle frontal gyrus and dorsal anterior cingulate cortex, during the interictal period, even when neuropsychological test results appear normal [22, 35]. This dissociation suggests that neural network alterations may precede or exceed behavioral manifestations of cognitive dysfunction. Taken together, these findings indicate that interictal cognitive impairment in migraine reflects widespread alterations in pain‐ and attention‐related brain networks, rather than being solely a consequence of attack frequency or intensity. The deficits observed in attention, working memory, and executive functions in our study are consistent with these neurobiological mechanisms.

4.2. Ictal–Interictal Period Evaluation

In our study, we observed impairments across several cognitive domains during migraine attacks, including attention, visuospatial processing, processing speed, short‐term memory, and working memory. These findings are consistent with the existing literature and indicate that executive functions appear to be the most prominently affected domain during the ictal phase [36, 37]. Functional neuroimaging studies reporting increased activation in executive‐function–related regions—such as the cingulate cortex, insula, prefrontal cortex, and temporal areas—further support this observation [38].

Acute pain processing is mediated by a broad neural network that includes sensorimotor (SI, SII, insula, thalamus), emotional (anterior cingulate gyrus, prefrontal cortex), and cognitive (parietal and prefrontal) components. Because these regions are critically involved not only in pain modulation but also in attentional control, memory, inhibition, and executive functioning, their heightened activation during pain may interfere with cognitive performance and lead to measurable declines in these domains [39]. Consistently, reduced task‐related neural suppression during acute pain—reflecting an inability to downregulate pain‐related brain regions while engaging in a cognitive task—has also been demonstrated [40].

Furthermore, an fMRI study conducted during a migraine attack revealed increased activation in the left frontal pole and orbitofrontal cortex during a working memory task, suggesting that patients must recruit inhibitory control regions more intensively to maintain task performance during the attack [41].

However, like the interictal period, ictal cognitive dysfunction in migraine cannot be fully explained by pain alone. The absence of comparable cognitive impairment in other non‐migraine headache disorders argues against a purely distraction‐based mechanism [16, 42]. Additionally, the frequent occurrence of cognitive complaints in the prodromal phase further indicates that pain is not the sole contributor to cognitive decline [15, 43]. Taken together, these findings suggest that the cognitive impairment observed during migraine attacks is not only pain‐related but also mediated by migraine‐specific neurobiological processes. Cortical spreading depression can induce transient dysfunction in frontal and parietal regions involved in attention and executive processing [44]. In parallel, attack‐related cerebral hypoperfusion may reduce metabolic efficiency within frontoparietal cognitive networks, contributing to slowed processing and impaired executive function [45]. Trigeminovascular activation and associated neuroinflammatory responses, mediated by CGRP and other neuropeptides, may further disrupt synaptic processing and attentional control. Functional imaging studies have also demonstrated early involvement of the hypothalamus and limbic structures, as well as altered connectivity within large‐scale brain networks, including the default mode, salience, and attention networks, even before pain onset [46, 47]. Taken together, these mechanisms suggest that the attentional, working memory, and executive deficits observed during attacks represent a widespread and transient disruption of migraine‐sensitive brain networks rather than a secondary consequence of nociceptive distraction alone [36].

Although we were unable to directly assess prodromal or interictal mechanisms, existing evidence suggests that alterations in multiple brain networks throughout the migraine cycle may contribute to the cognitive dysfunction observed during attacks. Future multicenter and prospective studies are needed to clarify the relative contributions of these mechanisms in episodic and chronic migraine.

In our study, the magnitude of ictal cognitive worsening was not dependent on migraine type (episodic or chronic). This finding suggests that the primary determinant of acute cognitive impairment is the attack itself. Although episodic and chronic migraine are known to have different neurophysiological characteristics, our results indicate that these differences do not lead to a meaningful divergence in cognitive performance during the attack. The observation that the extent of impairment in attention, working memory, and executive functions was similar across migraine types suggests that the acute cognitive changes are more likely related to attack‐specific transient disruptions in neural networks. Since there are no previous studies directly comparing episodic and chronic migraine during attacks, this finding provides a novel contribution to the existing literature. Overall, our results demonstrate that an acute migraine attack exerts a strong and comparable impact on cognitive performance, independent of migraine type.

Given that cognitive testing was performed first in the interictal phase and subsequently during the ictal phase, a potential test–retest (practice) effect should be considered. However, practice effects typically result in performance improvement, whereas we observed consistent and significant deterioration across all cognitive domains during the second (ictal) assessment. This pattern strongly suggests that the observed differences reflect genuine attack‐related cognitive impairment rather than a learning effect.

4.3. Attack Severity and Cognitive Impairment During the Attack

In our study, higher attack severity was associated with greater cognitive impairment during the ictal phase in migraine patients. When migraine type was considered, this association was more pronounced in episodic migraine than in chronic migraine. Chronic migraine is characterized by persistent abnormalities in cortical pain processing, including habituation deficits and sustained central sensitization [48]. These long‐standing alterations reduce the flexibility of the nervous system and limit its ability to modulate responses according to varying levels of symptom severity. As a result, patients with chronic migraine tend to remain in a persistently aroused state, and increases in attack severity do not produce additional physiological or cognitive changes. In contrast, episodic migraine involves less entrenched sensitization and relatively preserved cortical adaptability. Therefore, the nervous system in episodic migraine remains more dynamic, allowing symptom severity to exert a greater modulatory effect on neurocognitive functioning. In this context, more severe attacks lead to larger changes in cognitive performance. Consistent with this interpretation, an electrophysiological study by De Tommaso et al. [49] demonstrated a strong relationship between pain intensity and brain responses in episodic migraine but not in chronic migraine. This finding, in line with our results, supports the notion that attack severity is more tightly coupled to cognitive changes in episodic migraine.

We should acknowledge the limitations of the study. This study has several limitations. The small sample size and difficulty in administering tests during migraine attacks limited data diversity. Since most participants were female, findings related to male patients should be interpreted with caution. Radiological imaging could not be performed during attacks, so the data lacked imaging support. Advanced and comprehensive neuropsychological assessments, including episodic memory measures, were not performed, which limits the breadth of cognitive domains evaluated in this study. In addition, performance in the Stroop task was assessed solely using an error‐based metric, and reaction time parameters were not recorded; therefore, sensitivity to processing speed and subtle executive slowing may have been limited. The interval between the interictal and ictal assessments was not standardized due to the unpredictable nature of spontaneous migraine attacks. Long‐term cognitive effects of migraine were not evaluated through follow‐up.

5. Conclusions

Migraine is a complex neurobiological disorder with cognitive consequences extending beyond pain. Our findings demonstrate that migraine attacks impair attention and executive functions regardless of subtype. During attacks, cognitive decline was associated with attack severity in episodic migraine but not in chronic cases. Interictally, working memory was affected in both episodic and chronic migraine, with broader cognitive involvement observed in the chronic form. These results underscore the importance of incorporating cognitive assessment into migraine management and support the development of interventions targeting attention and executive dysfunction to improve patients' quality of life.

Author Contributions

E.K.K.: concept; E.K.K.: design; E.K.K.: supervision; E.K.K, S.U.Y.: data collection and/or processing; B.B.K., E.K.K.: analysis and interpretation; E.K.K., B.B.K.: literature search; E.K.K, B.B.K.: writing; E.K.K.: critical review.

Funding

The authors have nothing to report.

Ethics Statement

The study was approved by the Local Ethics Committee of Prof. Dr. Cemil Taşcıoğlu City Hospital (Approval No: 22/05/2022‐156). All participants provided written informed consent, and all procedures complied with the Declaration of Helsinki.

Consent

All participants provided written informed consent, and all procedures complied with the Declaration of Helsinki.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Table S1: Baseline and Ictal test comparison with significance levels.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.