Sex differences in electrophysiology: P200 event-related potential evidence

Introduction

Significant evidence exists for sex differences in behavior and neuropsychiatric disorders [1]. There are many examples of female-biased conditions that include depression, anxiety disorders, and emotional disorders. On the same note, examples of male-biased conditions include dyslexia, autism, and schizophrenia. Also, there has been identification of sex-biased differences in biological functions that influence pharmacokinetic determinations. Furthermore, there exists different vulnerability of males and females to addictive disorders [1,2,3]. However, despite the overwhelming evidence of sexbiased behavior, neuropsychiatric disorders, and biological influences, studies investigating the effects of sex on electrophysiological event-related potentials (ERPs) remain limited, and investigations into the P200 ERP are even more limited.

Although there are studies that did not show sex-related differences in the human brain [4,5], there are other studies, some of which are more recent, that provided significant evidence of the existence of sexual dimorphism in the human brain [6,7,8]. Conflicting evidence also exists with regards to event-related potential (ERP), electroencephalography (EEG), and electrophysiology in general. Some ERP studies did not show any sex-bias in ERP(9,10), while other and more recent evidence shows that sex differences in ERP exist [11,12,13].

Jiajin Yuan et al. (2008) used an oddball task in an ERP study to investigate sex-related behavioral inhibitory control. They recorded ERP signals from 15 male and 15 female participants, while the participants performed a two-choice oddball task (standard/target distinction) by pressing keys within 1000 ms. Their results indicated that men exhibited smaller amplitudes and longer latencies than women for P200 ERP. Therefore showing a general sex difference in behavioral control for adult humans [14]. In another study, Oliver-Rodriguez et al. found that the P300 ERP amplitude to be smaller among females compared to males [15]. There are also other studies (11,12) that have shown sex differences in ERP.

On the other hand, Sangal and Sangal in a 1996 publication showed no ERP difference across sex. In that study [10] they used a 32 channel EEG system to record the evoked potentials. Using a pseudo-random presentation, the participants were asked to press a button at each rare/target stimulus. The results of this study suggested that sex had no significant effect on amplitude or latency of the ERP signal. Other research work also showed no significant difference in ERP signal between males and females [9].

As portrayed above, there is overwhelming evidence on the existence of sex-biased behavior, neuropsychiatric disorders, and biological influence. Also, as portrayed above, there is still no consensus on the effects of sex on electrophysiology, more specifically event-related potentials, and relevant studies are very limited. Given all of that, we have conducted an electrophysiological ERP study to investigate the effect of sex (female vs. male) on both amplitude and latency of P200 ERP.

Methods

Results

The average ERP head models of both sexes were inspected by careful visualization using Net Station 5.1 (Electrical Geodesics, Inc.). Both sexes showed a clear peak in the electrophysiological signal intensity at frontalcentral scalp locations between 150-250 ms after event onset. This peak resembles the P200 ERP. The averaged female ERP head model showed a peak in ERP signal intensity around 200 ms for the standard (high-probability) stimuli at frontal-central scalp locations (Figure 1). As for the target (low-probability) stimuli, the averaged female ERP head model showed a peak in ERP signal intensity around 193 ms at frontal-central scalp locations (Figure 2). For the males, the averaged ERP head model showed a peak in signal intensity around 188 ms and 181 ms respectively for standard and target stimuli at frontal-central scalp locations (Figure 3, Figure 4). These signal intensity peaks at the 150-250 ms temporal domain are P200 ERP amplitude peaks.

Figure 1

Two-dimensional voltage map of the averaged female P200 waveforms at 200 ms peak latency for the standard (high-probability) stimuli. Bright yellow is positive and dark red is negative (scaled from -2.5μV to 2.5μV). The orientation of the figure is looking down at the top of the head with the nose at the top of the figure.

Figure 2

Two-dimensional voltage map of the averaged female P200 waveforms at 193 ms peak latency for the target (low-probability) stimuli. Bright yellow is positive and dark red is negative (scaled from -5.3μV to 5.3μV). The orientation of the figure is looking down at the top of the head with the nose at the top of the figure.

Figure 3

Two-dimensional voltage map of the averaged male P200 waveforms at 188 ms peak latency for the standard (high-probability) stimuli. Bright yellow is positive and dark red is negative (scaled from -3.0μV to 3.0μV). The orientation of the figure is looking down at the top of the head with the nose at the top of the figure.

Figure 4

Two-dimensional voltage map of the averaged male P200 waveforms at 181 ms peak latency for the target (low-probability) stimuli. Bright yellow is positive and dark red is negative (scaled from -8.0μV to 8.0μV). The orientation of the figure is looking down at the top of the head with the nose at the top of the figure.

The results of the two-sample t test showed significant difference across sexes in both the mean P200 peak amplitude for all participants as well as the mean P200 latency for all participants. Females had a lower mean P200 peak amplitude (M = 2.06 μV, SD = 1.81) compared to males’ mean P200 peak amplitude (M = 2.79 μV, SD = 2.09) for the standard (high-probability) stimuli (p = 0.013). As for the target (low-probability) stimuli, females, also, showed lower mean P200 peak amplitude (M = 5.01 μV, SD = 3.46) compared to males’ mean P200 peak amplitude (M = 6.93 μV, SD = 3.41) at p<0.001. Furthermore, the results of the two-sample t test also showed that females had significantly longer mean latency for P200 compared to males. For the standard stimuli, females’ mean P200 latency was 200 ms (SD = 28.0) compared to 188 ms (SD = 32.5) that of males (p = 0.008). As for the target stimuli’s P200 mean latency, the females’ P200 mean latency was 193 ms (SD = 38.2) compared to 181 ms (SD = 31.8) for the males (p = 0.028). Figures 1–4 show the P200 ERP signal intensities for the respective study categories, and Figure 5 shows single-subject waveforms associated with stimuli type across sex, at the Fz electrode site.

Figure 5

Single-subject ERP waveforms at Fz (A: Female and standard stimuli, B: Female and target stimuli, C: Male and standard stimuli, D: Male and target stimuli).

Discussion

In the present study, participants were required to distinguish between high-probability stimuli (standard) and low-probability stimuli (target). They did so by accurately pressing a key, on which their right index finger was comfortably situated, and in response to the target stimuli. The oddball task, as the one used in this study, demonstrates adaptive reflexive processing whereby processes of inhibitory control must be recruited on the response to the standard (high-probability) stimuli during the presentation of the target (low-probability) stimuli in order for participants to provide a correct response to the target stimuli [14,17].

The P200 ERP is an attention-related component that usually peaks between 150-250 ms after the onset of a stimulus. It appears as a positive going electrical potential in the frontal-central areas of the scalp. The P200 is believed to form the basis for later cognitive processing by indexing early attentional recruitment, and is a reflection of perceptual processing [14,18,19,20]. Furthermore, a P200 peak appearing within 200 ms in the frontal scalp region is indicative of rapid detection of stimulus features [20,21].

The females showed a lower mean P200 peak compared to males. The females also had a longer mean P200 latency compared to males. Therefore, in the present study, we found that the P200 ERP is sensitive to sex in both high-probability (standard) and low-probability (target) stimuli. The present study supports the notion that sex does affect ERP.

Furthermore, our study is consistent with previous studies that did show sex sensitivity to ERP [11,12,15,22,23].

Males essentially elicited larger P200 amplitudes and shorter P200 latencies than females. Therefore, suggesting that males were faster at detecting the occurrence of the low-probability (target) stimuli and that they also directed more attentional resources to the features of the low-probability (target) stimuli compared to females. The faster detection of the low-probability (target) stimuli onset forms the bases of the succeeding recognition and resolution of response conflicts. Correspondingly, the observed sex effect on the P200 ERP during low-probability recognition further entails the probable existence of sex differences in the recognition and resolution of response conflicts subsequent phases [19,24,25].

Given that the females in the present study exhibited lower mean P200 amplitude along with longer mean P200 latency compared to males, suggests that the attentional recruitment in the brain of males may be both larger and faster than that of females. Furthermore, results of the present study suggest that low-probability or infrequent stimuli may differentially activate attentional frontal-central brain circuits and/or regions in females compared to males. This further implies a sexually dimorphic disposition that may account for various sex-specific novelties in brain function and behavior, and that can be used to aid in better understanding sex-biased biological influences and neuropsychiatric disorders.