# Sex-Related Variations in the Brain Motor-Network Connectivity at Rest during Puberty
## 4 Discussion  
Puberty is an essential stage in sexual development as sexual hormones reach their highest levels. Sexual hormones influence metabolism in a variety of tissues, including the brain. Four major findings from this study will be discussed: (1) Comparative changes in motor network connectivity between males and females during puberty, (2) sex-related changes in MsN connectivity at rest, (3) asymmetry of the cerebellar-mouth and cerebellar-hand MsN, and (4) the centrality variation of MsN regions in by age and sex.  
(1) Comparative changes in MsN connectivity in males and females during puberty.  
When comparing same sex groups by age we found that there were changes in node strength values in the male group and no significant change in the female group between ages 12 and 16. A close examination of the PDFs between ages 12 and 16 shows there was an increase in node strength. Puberty is characterized by two main phases: adrenarche and gonadarche. Both phases have different onset ages depending on sex, normally occurring earlier in females. As a result, the concentration and influence of released hormones in the brain are sex-specific between ages 12 and 16. In males, adrenarche begins around 7 years old and in females around 6 years old, while gonadarche can begin between 10-15 years of age and in females between 9-14 years of age [32; 33]. Adrenarche and gonadarche are associated with the secretion of adrenal androgen, which is indexed by a rise in dehydropiandrosterone sulfate (DHEAS) and testosterone secretion.  
The differences observed in our results between the MsN connectivity of males at age 12 and 16 may be associated with the levels of DHEAS and testosterone, since it has been reported to be lower in males between 6 and 13 years old compared to males between ages  
Figure 10: Male and female hub nodes at each age group. Coronal view of the nodes that were a hub in at least 45% of the population in each group. Hand regions (blue spheres) and cerebellar regions (red spheres). (**A**) male groups, (**B**) female groups.  
13 and 16 [33; 34]. Brain DHEAS concentration participates in several neurodevelopmental processes, such as modulation of neurotransmitter synaptic transmission, postsynaptic receptor activity, dendrite outgrowth, neuronal motility, and formation of gap junctions [35]. Also, testosterone increases the volume of motor-related regions such as the cerebellar cortex, caudate, putamen, and pallidum [34].  
In females, no significant change occurred between the ages of 12 and 16. This result must be carefully interpreted, since DHEAS and estradiol levels are higher at age 16 and estrogen and progesterone cycles are regular when compared to age 12 in females. The connectivity of the MsN observed in this study is consistent with changes during the maturation of the cerebellum in the pubertal female [34; 36], where cerebellar trajectories to the anterior lobe (primarily concerned with motor function), superior posterior, and inferior posterior lobes reach their highest volume at 11.8 years of age [36]. During this peak, volumetric changes are caused by increased neuropil, neuronal size, dendritic or axonal arborization, glia, and angiogenesis [37]. After this point, cerebellar volume decreases, which can be related to our observed decrease in cerebellar connectivity in females between these ages. Cerebellar structural change along with concentrations of hormones resulted in no significant differences in MsN connectivity when compared to females at age 12 and 16.