Polycystic ovarian syndrome (PCOS) is a multifactorial endocrine disorder affecting approximately 3–10% of women in the reproductive age group, with global estimates suggesting over 116 million affected individuals . Characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology, PCOS represents one of the leading causes of infertility and metabolic dysregulation in women.

Beyond its reproductive manifestations, PCOS is increasingly recognized as a systemic disorder associated with insulin resistance, dyslipidemia, hypertension, and cardiovascular risk . Insulin resistance plays a central role in its pathophysiology, contributing to hyperinsulinemia and subsequent androgen excess, thereby perpetuating the disease process.

While metabolic and endocrine aspects have been extensively studied, emerging evidence suggests that PCOS also affects neurocognitive and psychological domains. Women with PCOS exhibit higher prevalence of anxiety (up to 39%) and depression (approximately 25%), along with reduced quality of life . Cognitive impairments, particularly involving executive function, memory, and attention, have also been reported, although findings remain inconsistent

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The neurobiological basis for these alterations is not fully understood. Hormonal imbalances, particularly hyperandrogenism and hypoestrogenism, along with insulin resistance, may influence neural functioning and cognition. Structural and functional brain changes, including alterations in white matter microstructure and cortical activity, have been documented in PCOS

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Traditional cognitive assessment methods rely primarily on subjective tools such as questionnaires, which may be influenced by psychological factors. Objective techniques such as electroencephalography (EEG) and event-related potentials (ERP), particularly the P300 component, offer real-time insights into neural processing and cognitive function. These tools provide high temporal resolution and allow precise evaluation of cortical activity associated with cognition.

Despite these advancements, there is a paucity of comprehensive studies integrating both objective neurophysiological measures and subjective cognitive assessments in PCOS. Moreover, the correlation between psychological distress and cognitive impairment remains unclear.

Therefore, the present study was undertaken to evaluate neurocognitive and psychological parameters in women with PCOS using a combination of EEG, VERP (P300), and standardized cognitive and psychological assessment tools, and to explore their interrelationships.

This case-control prospective observational study was conducted in the Department of Physiology at AIIMS Raipur . The study included 30 women diagnosed with PCOS and 37 age-matched healthy controls. Ethical approval was obtained from the Institutional Ethics Committee, and informed consent was secured from all participants.

Participants were recruited based on predefined inclusion and exclusion criteria. PCOS diagnosis was established using standard clinical criteria, and controls were selected from healthy individuals without endocrine or neurological disorders.

Anthropometric and physiological parameters were recorded for all participants. Psychological status was evaluated using standardized tools for anxiety and depression assessment. Cognitive function was assessed both subjectively and objectively. Subjective assessment included the Montreal Cognitive Assessment (MoCA), which evaluates multiple cognitive domains including memory, attention, executive function, and visuospatial ability

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Objective neurocognitive evaluation was performed using electroencephalography (EEG) and visual event-related potentials (VERP). EEG recordings were obtained during resting state and during an oddball paradigm. Spectral power of alpha, beta, and theta waves and their ratios were analyzed

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VERP recordings focused on the P300 component, where latency and amplitude were measured. P300 latency reflects cognitive processing speed, while amplitude reflects attentional resource allocation

All recordings were performed under standardized laboratory conditions. Data analysis included comparison between PCOS and control groups using appropriate statistical tests such as ANOVA. Correlation analysis was performed to assess relationships between EEG parameters, P300 indices, and cognitive scores

1. Anthropometric and Physiological Parameters

Baseline characteristics of the study population are presented in Table 1. Both groups were comparable in terms of age (p>0.05), confirming appropriate matching. However, women with PCOS demonstrated significantly higher BMI (27.39 ± 3.85 vs 21.87 ± 1.78 kg/m²; p<0.001) and waist-hip ratio (0.85 ± 0.07 vs 0.76 ± 0.04; p<0.001), indicating increased adiposity. Among physiological parameters, diastolic blood pressure was significantly elevated in the PCOS group (p<0.05), while systolic blood pressure and pulse rate showed no significant differences

Table 1. Anthropometric and Physiological Variables

2. Psychological Profile (Anxiety and Depression)

Psychological assessment findings are summarized in Table 2. Women with PCOS exhibited significantly higher anxiety and depression scores. Total STAI scores were significantly elevated (p<0.01), with both trait and state anxiety components also showing significant differences (p<0.05). Depression scores (BDI) were markedly higher in the PCOS group (p<0.001), indicating substantial psychological burden

Table 2. Psychological Assessment (STAI & BDI Scores)

3. EEG Spectral Power Alterations (Resting State)

EEG spectral analysis revealed significant neurophysiological alterations in PCOS subjects, as shown in Table 3. Alpha power was significantly reduced at both Fz and Pz locations (p<0.001), indicating impaired cortical relaxation. Beta power showed partial alterations, while theta activity and derived ratios demonstrated significant changes, reflecting increased cortical slowing and impaired attentional processing

Table 3. EEG Spectral Power and Ratios (Resting State)

4. Relative EEG Power Distribution

Relative power distribution analysis (Table 4) further confirmed reduced alpha dominance in PCOS patients, particularly at both cortical locations (p<0.05). Beta and theta relative powers showed no statistically significant differences, suggesting selective impairment in cortical inhibitory rhythms.

Table 4. Relative EEG Power (Resting State)

5. Event-Related Potentials (P300 Amplitude and Latency)

Event-related potential analysis demonstrated significant impairment in cognitive processing among PCOS patients, as shown in Table 5. P300 amplitude was significantly reduced, particularly during rare stimulus conditions (p<0.01), indicating decreased attentional resource allocation. Latency values were prolonged in the PCOS group, reflecting delayed cognitive processing, although not all differences reached statistical significance

Table 5. P300 Amplitude and Latency

6. Cognitive Function (MoCA Scores)

Cognitive performance assessed using MoCA is presented in Table 6. The PCOS group demonstrated significantly lower total MoCA scores (24.97 ± 2.84 vs 27.59 ± 1.64; p<0.001). Domain-wise analysis revealed significant impairments in attention, language, abstraction, delayed recall, and orientation, indicating widespread cognitive dysfunction

Table 6. MoCA Scores and Cognitive Domains

Principal Findings

The present study demonstrates that women with PCOS exhibit significant metabolic, psychological, neurophysiological, and cognitive alterations. PCOS, first described by Irving F Stein and Michael L Leventhal [1], is now recognized as a complex endocrine-metabolic disorder with systemic implications. The diagnostic framework used in contemporary studies is based on the Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group criteria [3], with further refinements by the Androgen Excess and PCOS Society [4].

In the present study, anthropometric findings (Table 1) showed significantly higher BMI and waist-hip ratio in PCOS subjects, reflecting central obesity. These findings are consistent with previous reports highlighting insulin resistance and metabolic syndrome as core features of PCOS [5,6]. Elevated diastolic blood pressure further supports early cardiovascular risk in these patients, as also described in epidemiological and clinical studies [8,9,]

Metabolic and Psychological Interrelationship

PCOS is strongly associated with insulin resistance, which plays a central role in its pathogenesis and systemic manifestations [5,11]. Studies have shown that metabolic abnormalities, including impaired glucose tolerance and type 2 diabetes risk, are significantly higher in PCOS populations [9,12]. The findings of increased adiposity and metabolic alterations in this study (Table 1) align with these established observations.

Psychological assessment (Table 2) revealed significantly higher anxiety and depression scores in PCOS patients. This is in agreement with meta-analyses demonstrating a significantly increased prevalence of mood disorders in PCOS [13,14]. The interplay between metabolic dysfunction and psychological distress may be mediated through neuroendocrine pathways,

Neurophysiological Alterations (EEG Findings)

The EEG findings in this study (Table 3) demonstrated reduced alpha power and altered theta activity in PCOS subjects, indicating impaired cortical regulation. Alpha oscillations are closely associated with cognitive efficiency and inhibitory control, and their reduction suggests disrupted neural processing [15]. Increased slow-wave activity, particularly theta oscillations, is often linked to reduced attentional capacity and cognitive slowing [16]

These findings suggest that PCOS may be associated with functional alterations in cortical activity, possibly mediated by hormonal imbalance and metabolic dysregulation. Previous studies have shown that endocrine factors, particularly hyperandrogenism and insulin resistance, can influence brain function and neural oscillations [18].

Relative EEG power analysis (Table 4) further confirmed selective reduction in alpha dominance, suggesting impaired cortical inhibition without global neuronal dysfunction

Cognitive Processing and Event-Related Potentials

Event-related potential analysis (Table 5) demonstrated reduced P300 amplitude and prolonged latency in PCOS subjects. The P300 component is a well-established marker of cognitive processing, with amplitude reflecting attentional resource allocation and latency indicating processing speed [17]. The observed reduction in amplitude suggests decreased attentional engagement, while increased latency indicates delayed cognitive processing

These findings are consistent with previous neurocognitive studies in PCOS, which have reported subtle impairments in attention and executive function [18]. The absence of statistical significance in some latency parameters may be attributed to sample size limitations; however, the overall trend supports the presence of neurocognitive dysfunction

Cognitive Impairment (MoCA Findings)

Cognitive assessment using MoCA (Table 6) revealed significantly lower total scores in the PCOS group, with deficits across multiple domains, including attention, language, abstraction, and delayed recall. These findings indicate that cognitive impairment in PCOS is multidomain rather than focal.

Previous studies have demonstrated similar cognitive deficits in PCOS, particularly in executive function and memory domains, which have been attributed to hormonal imbalance and metabolic factors [18,19]. Additionally, insulin resistance has been implicated in cognitive decline through mechanisms involving impaired neuronal signaling and neurodegeneration [20].

A key strength of the present study is the integration of objective and subjective measures. The concordance between elevated psychological distress (Table 2), altered EEG patterns (Tables 3–4), impaired P300 responses (Table 5), and reduced cognitive performance (Table 6) suggests a unified neurocognitive dysfunction in PCOS.

This multidimensional impairment likely reflects the combined effects of endocrine, metabolic, and neurobiological factors. Chronic insulin resistance, hyperandrogenism, and low-grade inflammation may collectively contribute to altered brain function and cognitive decline in PCOS

Significance of Theta-Based Ratios in Neurocognitive Dysfunction

particularly important and novel observation in the present study is the significant alteration in theta-based ratios, especially the theta/alpha and theta/beta ratios, which provide deeper insight into cortical functional balance beyond absolute spectral power measures. While individual frequency bands reflect localized neural activity, ratio metrics are considered more sensitive indicators of global cortical regulation, integrating both excitatory and inhibitory dynamics [15,16].

In this study, the theta/alpha ratio was significantly elevated in women with PCOS, particularly at the Pz region (0.94 ± 0.09 vs 0.63 ± 0.25; p<0.001) . This increase indicates a relative dominance of slower oscillatory activity over faster alpha rhythms, suggesting impaired cortical efficiency and reduced neural synchronization. Alpha activity is typically associated with inhibitory control and efficient information processing, whereas theta activity is linked to cognitive effort and compensatory mechanisms [15]. Therefore, an increased theta/alpha ratio reflects a shift toward a less efficient and more effortful mode of cognitive processing.

Similarly, the theta/beta ratio, although less prominently altered in resting state, demonstrated significant variations during task-related conditions, reinforcing the concept of impaired attentional regulation. Elevated theta/beta ratio has been widely interpreted as a marker of reduced attentional control and executive dysfunction [16,17]. In the present study, its alteration during oddball paradigms suggests that PCOS subjects require greater neural effort to process stimuli, consistent with the observed reductions in P300 amplitude and cognitive scores [17].

Importantly, correlation analysis further strengthens the significance of these ratios. Negative correlations between theta-based ratios and cognitive domains such as abstraction and orientation indicate that higher ratio values are associated with poorer cognitive performance . This establishes theta-based ratios not merely as electrophysiological findings but as functionally relevant biomarkers of neurocognitive impairment.

The novelty of this finding lies in the fact that previous studies in PCOS have primarily focused on absolute EEG power changes or hormonal correlations, with limited emphasis on derived ratio metrics. By demonstrating significant alterations in theta-based ratios alongside cognitive and ERP abnormalities, the present study provides a more integrated understanding of cortical dysregulation in PCOS [18,19].

From a clinical perspective, theta-based ratios may serve as sensitive, non-invasive biomarkers for early detection of cognitive dysfunction in PCOS. Their ability to reflect subtle shifts in cortical processing makes them particularly valuable in identifying early neurocognitive involvement, even before overt clinical impairment becomes apparent. This aligns with emerging concepts linking metabolic dysfunction and neural efficiency, particularly in insulin resistance-related cognitive decline [20]

Clinical Implications:

Findings of this study emphasize that PCOS extends beyond reproductive and metabolic dysfunction to include significant neurocognitive and psychological components. Routine screening for cognitive impairment and mental health disorders should be considered in clinical practice.

The use of objective tools such as EEG and P300, alongside standardized cognitive assessments, provides a comprehensive framework for evaluation and may facilitate early intervention and improved patient outcomes

The present study demonstrates that women with polycystic ovarian syndrome exhibit significant alterations across metabolic, psychological, neurophysiological, and cognitive domains. PCOS subjects showed increased adiposity and early cardiovascular changes, along with markedly elevated anxiety and depression scores. Objective neurophysiological assessment revealed altered EEG patterns characterized by reduced alpha activity and increased slow-wave dominance, indicating impaired cortical regulation. Event-related potential analysis further demonstrated reduced P300 amplitude and delayed latency, reflecting compromised cognitive processing

Importantly, subjective cognitive evaluation using MoCA confirmed significant multidomain impairment, particularly in attention, executive function, and memory. The concordance between psychological distress, electrophysiological abnormalities, and cognitive decline suggests a unified neurocognitive dysfunction in PCOS.

These findings highlight that PCOS is not merely a reproductive or metabolic disorder but also involves significant neurocognitive involvement. Integration of objective and subjective assessment tools may facilitate early detection and targeted interventions, thereby improving overall clinical outcomes and quality of life in affected women

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