Regional homogeneity differences between the brains of young men and young women: A resting-state functional magnetic resonance imaging study

Abstract

Objective

The aim of the study was to investigate gender differences in the brains of young healthy adults, by calculating the regional homogeneity (ReHo) values of resting-state functional magnetic resonance imaging (rs-fMRI). Thereby providing candidate imaging biomarkers for risk stratification of neurodegenerative diseases and offering a basis for their early screening and targeted intervention.

Methods

Forty-two (42) healthy young adults (21males and 21females) were examined using resting-state fMRI. We employed the statistical method of regional homogeneity (ReHo) to compare the brains of males and females.

Results

The female group exhibited higher activity intensity in the right supramarginal gyrus, but significantly lower activity intensity in the left dorsolateral prefrontal cortex, the right frontal eye field, the right premotor cortex and the right superior temporal gyrus compared to the male group.

Conclusion

Males have greater advantages in working memory, conscious decision-making behavior, visual-motor skills, physical reaction speed, rhythmic perception and language perception, while females show better episodic memory and visual imagination. High ReHo in the left DLPFC of men is a screening marker for high-risk groups of men with AD. High ReHo in the right superior marginal gyrus of women is an early warning biomarker for PTSD or depression.

1. Introduction

There are obvious gender differences in the anatomical structure and physiological functions of the human brain. Previous studies have shown that, on average, the size of a male brain is larger than that of a female (Cosgrove et al., 2007). The ratio of white matter to cerebrospinal fluid is higher in males than in females, while the ratio of gray matter is higher in females (Voskuhl et al., 2020). Females perform better than males in memory, language, facial expression recognition, emotion processing, and fine motor skills, whereas males excel in mathematics and visual-spatial information processing. Gender differences in the brain, especially in terms of function, have always been one of the key foci in the field of brain science studies.

Functional magnetic resonance imaging (fMRI) reflects the activity intensity in brain regions through the magnetic resonance signal generated by changes in blood oxygen levels. This technique offers great maneuverability and high accuracy, facilitating a deeper and noninvasive exploration of the brain's operating mechanisms. Resting-state fMRI was first proposed by S, O. and L.T. M (1990), and Zang et al. (2004) subsequently introduced the regional homogeneity (ReHo) algorithm to assess the functional activity of the brain in the resting state. ReHo is a data-driven fMRI data analysis algorithm that assumes that within an active or activated brain area, the blood oxygenation level-dependent (BOLD) signal values of neighboring voxels exhibit a certain similarity or consistency over time. By calculating Kendall’s coefficient of concordance (KCC), the similarity or consistency of spontaneous neural activities, as reflected by changes in the time series signal within a local region, can be quantitatively measured. A higher KCC value for a voxel indicates greater consistency with the neuronal activity of neighboring voxels. Conversely, a lower KCC value suggests lower temporal consistency.

In this study, we aimed to use the ReHo algorithm to investigate rs-fMRI data from 42 healthy young adults, with the goal of exploring the differences in brain region activities between different genders, the value of research results for the risk stratification of neurodegenerative diseases is investigated, providing a basis for the early screening and targeted intervention of such diseases.

2. Materials and methods

2.1. Data sources

All experimental data adopted in this study were obtained from the Affiliated Nanjing Brain Hospital of Nanjing Medical University. Forty-two healthy volunteers were enrolled as study subjects, including 21 females aged 22–26 years (mean age 23.55 ± 1.10 years) and 21 males aged 22–26 years (mean age 24.09 ± 1.27 years). All participants were right-handed, with no mental or neurological symptoms or signs, and no serious physical diseases. This study was approved by the Medical Ethics Committee of Nanjing Medical University, and all participants provided signed written informed consent.

We used G*Power software (https://www.psychologie.hhu.de/) for statistical power analysis. By selecting F-test, ANOVA mode, with input parameters Effect size= 0.25 (conservative estimate), α= 0.05, Power= 0.8, the output result is that each group needs ≥ 26 people. The current sample size is 21 people per group, and the statistical power is approximately 0.72. Statistical power analysis suggests that the ability of this study to detect moderate effect sizes is limited. Therefore, negative results, such as brain regions where no differences were found, should be interpreted with caution. We will expand the sample bank for verification in the future.

All the volunteers underwent the Wechsler Scale cognitive test, which consists of seven parts: number breadth, memory measurement, visuospatial, arithmetic test, number symbol, mapping, and similarity. Table 1 was obtained by analyzing the cognitive test data of the Wechsler Scale through Statistical Product Service Solutions 26.0 (https://www.ibm.com/products/spss-statistics, SPSS 26.0). From this table, it can be known that all the data used in this paper are young men and women who are in good health and have normal cognition.

Table 1.

Wechsler scale male and female group statistics.

Cognitive tests	Gender	number	average	Standard deviation	Average standard error
digital breadth	men	21	18.33	0.73	0.159
	women	21	17.38	0.74	0.161
memory measurement	men	21	14.05	0.74	0.161
	women	21	13.86	0.91	0.199
visual-spatial aspects	men	21	13	0.632	0.138
	women	21	13.14	0.793	0.173
arithmetic test	men	21	15.19	1.078	0.235
	women	21	15.29	1.189	0.26
numerical symbols	men	21	16.19	1.167	0.255
	women	21	15.95	1.117	0.244
graph filling	men	21	9.14	1.014	0.221
	women	21	9.38	1.284	0.28
similarity	men	21	11.19	1.47	0.321
	women	21	11.19	1.806	0.394

Independent sample testing of this cognitive test yields Table 2, which is divided into two parts: F-test and t-test. When the significance (Sig) is greater than 0.1, there is no significant difference in variance. With equal variance, it can be known from the F-test that when Sig is less than 0.1 in visuospatial and mapping aspects, there is a significant difference in variance. It can be known from the t-test that Sig is less than 0.1 in terms of number breadth, and there is a significant difference in variance. From this, it can be concluded that there are gender differences between men and women in terms of visual space, mapping, and digital breadth, and men have more advantages over women.

Table 2.

Wechsler scale independent sample test.

Cognitive tests	Levene's Test for Equality of Variances		Mean equivalence t-test
	F	Sig	t	DOF	Sig. (Two-tailed)	Average value difference	Standard error difference	95 % confidence interval of difference
								Lower limit	Upper limit
digital breadth	0.007	0.9337	4.1978	40	0.0001	0.952	0.2269	0.4938	1.4109
memory measurement	1.529	0.2235	0.7441	40	0.4612	0.191	0.256	−0.3269	0.7079
visual-spatial aspects	3.63	0.064	−0.6455	40	0.5223	−0.14	0.2213	−0.5901	0.3044
arithmetic test	0.252	0.6183	−0.2719	40	0.7871	−0.1	0.3503	−0.8031	0.6126
numerical symbols	0.421	0.5202	0.6754	40	0.5033	0.238	0.3525	−0.4744	0.9505
graph filling	3.744	0.0601	−0.667	40	0.5086	−0.24	0.357	−0.9596	0.4834
similarity	1.82	0.1849	0	40	1	0	0.5082	−1.0271	1.0271

2.2. Data acquisition

fMRI scans were performed using a German Siemens 3.0-T MRI scanner to collect data. During the scanning process, the subjects were secured to minimize involuntary head movements and were instructed to lie supine, remain awake, and keep their eyes closed. The BOLD function images were obtained using an echo-planar imaging (EPI) sequence with the following parameters: TR/TE = 2000/30ms, flip angle = 90°, field of view (FOV) = 256 mm× 256 mm, acquisition matrix = 64 mm× 64 mm, slice thickness = 3 mm, scan layer = 30 layers and sampled voxel point = 1. T1-weighted whole brain magnetization-prepared rapid gradient-echo (MPRAGE) images were obtained with the following parameters: TR/TE = 1900/2.49ms, flip angle= 9°, TI = 900 ms, field of view (FOV) = 250 mm× 250 mm, acquisition matrix = 256 mm× 256 mm, slice thickness = 1 mm, voxel size= 1 mm× 1 mm× 1 mm.

2.3. Data processing

Data preprocessing was performed on Matlab (R2014a) using the Data Processing Assistant for Resting-State fMRI (DPARSF) software (http://rfmri.org/DPARSF). The preprocessing steps included: (1) removing the first 10 time points to eliminate initial magnetic field inhomogeneity and the participant instability, retaining 130 time points for subsequent processing; (2) converting the image format from DICOM to NIFTI; (3) performing slice timing and head-motion corrections, and excluding participants whose translation or rotation parameters exceeded 2 mm or 2° during the entire fMRI scan; (4) normalizing the images into the Montreal Neurological Institute (MNI) space and resample to 3 mm× 3 mm× 3 mm voxels; (5) applying Gaussian kernel with a full-width at half maximum (FWHM) of 4 mm to improve signal-to-noise ratio (SNR); 6) perform linear drift elimination.

The ReHo method can conduct imaging analysis on the functional magnetic resonance imaging data of the brain, thereby exploring the differences in brain function between groups of subjects. Assuming that the selected voxels are similar to the surrounding adjacent voxels in time, and the locally identical voxels show the same changes in the same time series, the KCC of a specific voxel can be obtained through the above method. The following is the formula for calculating KCC:

$$W=\frac{\sum _{i=1}^n{(R_i)}^2-n{(\stackrel{\circledR }{R})}^2}{\frac{1}{2}{K}^2\left(n^3-n\right)}$$

As shown in the above formula, W represents KCC at a specific position, ranging from 0 to 1. n represents the number of time points, which is 130 in this article. K represents the number of a specific voxel and its adjacent voxels. $R_i$ is the total number of grades of each voxel value at the i-th time point. $\stackrel{\circledR }{R}$ is the average of R over the full time series. When the value of W, that is the KCC, tends to 1, it indicates that the activity of local neurons is more ordered. The KCC is used to calculate the time synchronization of the voxel neighborhood (27 adjacent voxels), with a frequency band of 0.01–0.08 Hz.

mReHo is obtained by dividing ReHo by the mean of the whole brain. zReHo is obtained by subtracting the whole-brain mean from ReHo and then dividing by the standard deviation. sReHo is the result obtained by smoothing after calculating ReHo. smReHo is obtained by dividing sReHo by the mean of the whole brain. szReHo is obtained by subtracting the whole-brain mean from sReHo and then dividing by the standard deviation.

2.4. Statistical analysis

To investigate the statistical differences in ReHo values between males and females during the resting-state, an independent two-sample t-test was performed on the brain maps of mReHo, ReHo, smReHo, sReHo, szReHo and zReHo for both groups. A threshold of 2.3 (uncorrected) was applied, and the results were then corrected using the AlphaSim program (P < 0.05).

3. Results

3.1. mReHo

Compared to the male group, the female group exhibited lower mReHo values in the left dorsolateral prefrontal cortex, right frontal eye field, and right premotor cortex, whereas the right supramarginal gyrus showed significantly increased mReHo values in the female group (shown in Fig. 1 and Table 3).

Fig. 1.

Differences in mReHo value between young male and female groups.

Table 3.

Differential brain regions based on mReHo between young male and female groups.

Brain regions with altered mReHo		MNI		BA	Voxel	Peak t (F-M)
	X	Y	Z
Supramarginal gyrus(R)	60	−27	33	40	54	5.234
Dorsolateral prefrontal cortex(L)	−24	39	42	9	60	−3.6702
Frontal eye field(R)	3	42	51	8	174	−3.9902
Premotor cortex(R)	9	−21	75	6	99	−4.9183

Note: The threshold was set at p < 0.05 corrected by AlphaSim program. Voxel values＞52. Abbreviations: BA, Brodmann's Area; MNI, Montreal Neurological Institute.

3.2. ReHo

Compared to the male group, the female group exhibited lower ReHo values in the left dorsolateral prefrontal cortex, right frontal eye field, and right premotor cortex (shown in Fig. 2 and Table 4).

Fig. 2.

Differences in ReHo value between young male and female groups.

Table 4.

Differential brain regions based on ReHo between young male and female groups.

Brain regions with altered ReHo		MNI		BA	Voxel	Peak t (F-M)
	X	Y	Z
Dorsolateral prefrontal cortex(L)	−24	39	42	9	57	−3.5807
Frontal eye field(R)	3	42	51	8	138	−3.9938
Premotor cortex(R)	9	−21	75	6	88	−4.7057

Note: The threshold was set at p < 0.05 corrected by AlphaSim program. Voxel values＞56. Abbreviations: BA, Brodmann's Area; MNI, Montreal Neurological Institute.

3.3. smReHo

Compared to the male group, the female group exhibited significantly lower smReHo values in the right premotor cortex (shown in Fig. 3 and Table 5).

Fig. 3.

Differences in smReHo value between young male and female groups.

Table 5.

Differential brain regions based on smReHo between young male and female groups.

Brain regions with altered smReHo		MNI		BA	Voxel	Peak t (F-M)
	X	Y	Z
Premotor cortex(R)	21	−9	69	6	895	−5.6364

Note: The threshold was set at p < 0.05 corrected by AlphaSim program. Voxel values＞123. Abbreviations: BA, Brodmann's Area: MNI, Montreal Neurological Institute.

3.4. sReHo

Although there existed differences in sReHo values, our analysis found no significant difference in Brodmann's area after correction by the AlphaSim program (shown in Fig. 4).

Fig. 4.

Differences in sReHo value between young male and female groups.

3.5. szReHo

Compared to the male group, the female group exhibited significantly lower szReHo value in the right superior temporal gyrus and right premotor cortex (shown in Fig. 5 and Table 6).

Fig. 5.

Differences in szReHo value between young male and female groups.

Table 6.

Differential brain regions based on szReHo between young male and female groups.

Brain regions with altered szReHo		MNI		BA	Voxel	Peak t (F-M)
	X	Y	Z
Superior temporal gyrus(R)	69	−39	12	22	121	−3.5456
Premotor cortex(R)	21	−9	69	6	779	−5.4014

Note: The threshold was set at p < 0.05 corrected by AlphaSim program. Voxel values＞115. Abbreviations: BA, Brodmann's Area: MNI, Montreal Neurological Institute.

3.6. zReHo

Compared to the male group, the female group exhibited lower zReHo values in the right frontal eye field and right premotor cortex, and significantly higher zReHo in the right supramarginal gyrus (shown in Fig. 6 and Table 7).

Fig. 6.

Differences in zReHo value between young male and female groups.

Table 7.

Differential brain regions based on zReHo between young male and female groups.

		MNI		BA	Voxel	Peak t (F-M)
	X	Y	Z
Supramarginal gyrus(R)	60	−27	33	40	61	5.5374
Frontal eye field(R)	3	42	51	8	135	−4.2543
Premotor cortex(R)	9	−21	75	6	88	−4.9942

Note: The threshold was set at p < 0.05 corrected by AlphaSim program. Voxel values＞51. Abbreviations: BA, Brodmann's Area: MNI, Montreal Neurological Institute.

In conclusion, as shown in Table 8, there was no inconsistency in the corresponding indicators for each brain region. The female group exhibited higher activity intensity in the right supramarginal gyrus and lower activity intensity in the left dorsolateral prefrontal cortex, right frontal eye field, right premotor cortex and right superior temporal gyrus compared to the male group. Based on the experimental results, particularly in the right premotor cortex, we can infer from all the changed indices under the current standards that males have an advantage over females in the corresponding functions of this brain region, such as motor function. In the right frontal eye field, mReHo, ReHo and zReHo indices suggest that males have a greater advantage than females in visual sensation. In the left dorsolateral prefrontal cortex, mReHo and ReHo indices indicate that males show better cognitive ability than females. However, regarding the right supramarginal gyrus, mReHo and zReHo indices demonstrate that females possibly have a greater advantage in imagination. In the right superior temporal gyrus, only szReHo indices show changes, which possibly indicate little significance in the differences in brain functions between males and females in this brain region. We will discuss this in more depth in the next section.

Table 8.

Altered brain regions between young male and female groups.

Altered brain region under the BA standard	mReHo	ReHo	smReHo	sReHo	szReHo	zReHo
Supramarginal gyrus(R)	↑					↑
Dorsolateral prefrontal cortex(L)	↓	↓
Frontal eye field(R)	↓	↓				↓
Premotor cortex(R)	↓	↓	↓		↓	↓
Superior temporal gyrus(R)					↓

Note: Abbreviations: BA, Brodmann's Area.

4. Discussion

4.1. Dorsolateral prefrontal cortex

Our rs-fMRI results revealed that the male group exhibited higher mReHo and ReHo values localized in the left dorsolateral prefrontal cortex compared to the female group. The dorsolateral prefrontal cortex (DLPFC) is a core region of human executive function, associated with higher cognitive functions and emotional regulation. It is involved in the performance and control of cognitive functions such as spatial working memory, memory retrieval, selective attention and programming strategies, and is sensitive to the outcome of execution.

Previous studies have shown that the dorsolateral prefrontal cortex, in the context of working memory, can be associated with the frontal eye field and the para-visual area (Anja et al., 2011). The spatial location of visual cues is programmed to generate spatial working memory, and the processing of working memory is regulated through the dopamine "reward mechanism" (Kobayashi, 2009), thus influencing behavioral decision-making. Patients with damage to this region may show cognitive difficulties and executive dysfunction syndrome (Zgaljardic et al., 2010). For example, the results of brain function and brain structure MRI in patients with spinal cord injury by Zhu et al (Ling, 2015). showed a significant decrease in ReHo values in the bilateral dorsolateral prefrontal cortex. Meanwhile, the dorsolateral prefrontal cortex supports the basic cognitive choices and reactions to sensory information through its connection with the parietal cortex and may influence emotional responses by altering the higher-order perceptual system.

We speculated that males are superior to females in mass spatial visual processing and benefit from different mechanisms in processing complex visual tasks compared to females. Voyer et al. (2017) using a multi-level and mixed-effects model, performed statistical analyses on different task subgroups of 98 samples from healthy men and women with an average age range of 3–86. Their results revealed that, despite age and specific tasks, men still have an advantage over women in visual-spatial working memory. Our results are consistent with theirs and provide valid radiological evidence.

4.2. Frontal eye field

The male group showed higher mReHo, ReHo, and zReHo values in the right frontal eye field than the female group. The frontal eye field (FEF) is a part of the visual system, which is closely related to oculomotor control, chasing movement, and the selection of visual search targets. Most neurons in the frontal eye field participate in visual response (including a large number of visual motor neurons), but unlike the extra striate cortex, FEF visual neurons do not show selectivity to specific features such as color or shape. Instead, it exhibits selective activation related to visual saliency (Thompson, 2005). FEF neurons are divided into two groups, including a group of neurons activated during saccades and the other group activated during fixation after eye shift and smooth pursuit movement.

Existing studies have demonstrated that more than 30 % of FEF neurons exhibit characteristic burst of discharge before saccades (Bruce and Friedman, 2002). FEF neurons produce saccades after electrical activity through the movement of the receptive field mediated by visual short-term memory (Optican et al., 2019). This process also reflects the significant correlation between the frontal eye field and the prefrontal cortex when performing visual spatial tasks. Furthermore, studies have also indicated that FEF damage often leads to saccadic dysfunction, for example, the frontal lobe epilepsy lesion may cause skew deviation and nystagmus (Liu, 2003); moreover, it will also slow down the speed of the eyeball chasing movement, especially affecting the tracking ability target after the receptive field prediction (Krauzlis, 2013).

Based on our imaging results and existing research results, we speculated that men have faster visual motion perception and visual responses than women. This difference may be related to the male superiority in visual spatial working memory, which allows men to mobilize visual memory quickly, thereby shifting the receptive field and produce faster saccade amplitude.

4.3. Premotor cortex

The premotor cortex (preMC) is located in front of the primary motor cortex and participates in planning and organizing movement. According to our results, the male group revealed significantly higher mReHo, ReHo, smReHo, szReHo, and zReHo values in the right premotor cortex than the female group. During the process of movement planning and organization, the premotor cortex receives input from the cortical sensory area and projects to the primary motor cortex (MI), spinal cord, and reticular formation. The reticular formation produces fibers that extend to the spinal cord, which in turn affect the spinal motor neurons that innervate the paravertebral and proximal limb muscle tissues (Mihailoff and Haines, 2018). This process regulates the control of proximal limb muscles by the premotor cortex and guides the physical movement (Pressman and Rosen, 2015).

In addition, studies have indicated that the premotor cortex can be compensate for dyskinesia following damage to the descending fibers of neurons or MI (Nudo and McNeal, 2013). Recent studies have also shown that during complex rhythm processing, the degree of coupling between the premotor cortex and the auditory sensation increases. It is activated consistently with the supplementary motor area in the time with the rhythm and during the period of rhythmic perception (Moore, 2018).

Therefore, we speculated that men have an advantage in the planning and organization of physical movement, as well as in the functional compensation of motor-related nerve damage. Furthermore, men may have better rhythmic perception, which may be relevant to existing resting-state fMRI results indicating that male hearing has an advantage in distinguishing tone and loudness (Yu et al., 2019).

4.4. Comprehensive analysis of dorsolateral prefrontal cortex, frontal eye field, and premotor cortex

The higher activity intensity observed in men in the left dorsolateral prefrontal cortex, right frontal eye field, and right premotor cortex may indicate that men have a greater advantage in visual-motor and body coordination response. Murray et al. (2018) randomly divided 263 healthy male and female subjects between 18 and 30 years of age into three groups to undergo a visual perception test and evaluate their reaction time. The results showed that female participants spent 25–75 % more time to make decisions than males, and the gender differences in reaction speed among the three groups were 42 %, 38 %, and 27 %, respectively. Males showed faster visual motion processing and better eye-hand coordination abilities.

However, the MRI scanning results did not reveal significant differences in brain morphology and function. Our resting-state fMRI results demonstrated significant differences between male and female brains in the left dorsolateral prefrontal cortex, right frontal eye field, and right premotor cortex which were consistent with existing experimental results and provided a supplement to the relevant imaging evidence.

4.5. Superior temporal gyrus

The male group exhibited a higher szReHo value in right superior temporal gyrus than the female group. The superior temporal gyrus (STG) is a part of the auditory cortex and integrates multiple sensations, processing complex functions including the perception and processing of speech, the processing of oculomotor control and the regulation of visual consciousness, as well as social cognition.

Yu et al., (2020) reported that when Chinese-English bilingual participants performed the English voice naming tasks, the activation of the right superior temporal gyrus reached its peak activation with a voxel count of 5862 and the maximum activation intensity of 9.62; Wang et al (Xiaoyi et al., 2005). reported that the right superior temporal gyrus may be a specific region of Chinese tone processing; Feng et al (Xiang et al., 2017). found through VBM-MRI analysis that the volume of the right superior temporal gyrus increased in bilingual subjects compared with non-bilinguals. Recent studies have revealed that abnormalities of language areas in the superior temporal gyrus and frontal lobe have become the most prominent indicators in schizophrenia research (Magneticcndenberg et al., 2015). For example, Chen et al (Xudong et al., 2019). conducted clinical evaluations and resting-state functional magnetic resonance scans on all subjects and used the primary auditory cortex and secondary auditory cortex brain regions as seed points to construct a whole-brain functional connectivity map from which the authors compared and analyzed the connectivity differences among three groups, finding that the functional connectivity of the superior temporal gyrus could significantly decrease.

Therefore, we inferred that males have certain advantages over females in speech perception, language understanding and eye movement processing, and the differences in ReHo values between men and women in the right superior temporal gyrus may be related to men’s and women’s different mechanisms of distinguishing the mental state of others. Our speculation may explain the findings of the Icahn School of Medicine at Mount Sinai which found significant gender differences in the way of schizophrenia and healthy individuals distinguishing the mental state of others.

4.6. Supramarginal gyrus

However, mReHo and zReHo values in the right supramarginal gyrus of the female group are significantly higher than those of the male group. The supramarginal gyrus (SMG) is considered to have functional differences in the left and right hemispheres. The traditional "Wernicke" area includes the left supramarginal gyrus, which reveals the important role of the left supramarginal gyrus in participating in the speech center. However, the latest research indicated that related areas of the right brain are involved in singing which assists the language function of the left brain and helps stutterers and aphasiacs speak more fluently (Dongyan., 2016). A study has demonstrated that the left supramarginal gyrus plays a key role in processing spatial language (Struiksma and Postma, 2017). And for the right supramarginal gyrus, some studies have also shown that the supramarginal gyrus and the angular gyrus, especially in the right hemisphere, are crucial to visual-spatial awareness (Edward et al., 2017). These areas may generate fictitious dream spaces which are necessary for dream perception.

Therefore, based on our findings on the right supramarginal gyrus, we speculated that women have greater advantages over men in the episodic memory and establishment of imaginary visual space. Our study results may provide some evidence for the study of Scott et al. that females have better position judgment ability than males (Murray et al., 2018). However, there are relatively few studies on the function of the right supramarginal gyrus, so the relevant function is not clear. Therefore, the functional differences between males and females in the right supramarginal gyrus still need to be further studied.

4.7. Value of translational medicine

The gender-specific ReHo patterns discovered in this study, such as high synchricity of the left DLPFC in males and high activity of the right superior marginal cortex in females, provide candidate imaging biomarkers for risk stratification of neurodegenerative diseases. Take Alzheimer's disease (AD) as an example: Hampel et al (Wood, 2021). found a male protective marker, high ReHo in the left DLPFC, which may delay the decline in executive function caused by tau protein deposition. Its quantitative threshold (ReHo > 0.35) can be included in the screening system for high-risk AD men. Koch et al. (2023) found that an elevated ReHo in the right superior marginal gyrus, a female risk marker, is associated with excessive activation of episodic memory and may accelerate the clearance disorder of beta-amyloid protein. High ReHo in the left DLPFC of men is a screening marker for high-risk groups of men with AD. High ReHo in the right superior marginal gyrus of women is an early warning biomarker for PTSD or depression.

5. Conclusions

In this study, we compared the brain differences between young men and women by calculating the ReHo of the resting-state fMRI data. Our results suggested that men exhibit greater advantages in working memory, conscious decision-making behavior, visual motion, physical reaction speed, rhythm, sense perception as well as language sense, while women show better episodic memory and visual imagination. High ReHo in the left DLPFC of men is a screening marker for high-risk groups of men with AD. High ReHo in the right superior marginal gyrus of women is an early warning biomarker for PTSD or depression. In a sense, these results can explain the gender differences in behavior, emotion, and cognition to some extent. In our future studies, we will expand the sample size and test specific behaviors of men and women to further deepen our research and make it more focused.

Ethics approval

The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of the Affiliated Nanjing Brain Hospital of Nanjing Medical University.

Funding

This work was supported by the Yangzhou Municipal Health Commission 2023 Medical Scientific Research Project (Grant no. 2023–2–32), the Nantong Science and Technology Bureau (No. MS12021036) and the National Natural Science Foundation of China (grant numbers: 1220221).

CRediT authorship contribution statement

Lingling Sun: Writing – review & editing, Writing – original draft, Supervision. Xiaoci Li: Project administration, Methodology, Funding acquisition, Conceptualization. Shihong Yan: Writing – review & editing, Resources, Data curation. Ziyu Zeng: Writing – original draft, Validation, Software, Formal analysis. Abao Rui: Validation, Formal analysis. Qingyu Wang: Supervision, Software. Jian Cai: Software, Formal analysis. Yun Yu: Validation, Resources, Project administration, Funding acquisition, Data curation, Conceptualization. Jian Mei: Resources, Data curation. Yue Yu: Methodology.

Declaration of Competing Interest

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Data availability

The data presented in this study are available on request from the corresponding author. The data are not publicly available for data protection reasons.