Why are some people left-handed?
About 10.6% of people are left-handed (Papadatou-Pastou et al., 2020) but what causes left-handedness is still not well understood. One thing that is clear is that handedness is not caused by the hands. It is completely impossible to tell whether a person is left-handed or right-handed just by looking at their hands. There are no obvious differences between the bones, muscles, tendons, and other parts that make up the hands of left-handers and right-handers.
Instead, handedness is caused by the central nervous system, e.g. the brain and the spinal cord. Handedness is one of many functional left-right differences in the brain. Specifically, in left-handers, the motor cortex in the right side of the brain (the left side of the body is controlled by the right side of the brain, and vice versa) is dominant for fine motor behavior such as writing with a pen. In contrast, in right-handers, the left motor cortex is better at such tasks.
Investigating the link between left-handedness and asymmetries in brain structure
This finding led handedness researchers to an intriguing question: Could those asymmetries in brain structure be relevant for asymmetries in brain function, such as handedness?
A new study, now uploaded on the preprint server bioRxiv, focused on answering this question by looking both at brain structural differences between left-handers and right-handers and the genetic link between handedness and brain structure (Sha et al., 2021). In the study, the researchers analyzed brain imaging data from 28,802 right-handers and 3,062 left-handers that were obtained from the UK Biobank. The UK Biobank is a large dataset of psychological and neuroimaging data obtained from volunteers in the UK that is available to qualified scientists worldwide. The UK Biobank has the tremendous advantage that it contains data from much more participants than any single scientist can obtain in a reasonable timeframe when acquiring data from volunteers themselves. Due to this large sample size, researchers can be more confident in the results obtained from data from the UK Biobank than if they would just collect a few dozen datasets themselves. This is due to the fact that results from larger datasets are influenced less by individual participants that show unusual result patterns and therefore they replicate better in other samples.
In the study, the researchers analyzed asymmetries in brain structure across the whole brain for their dataset, as well as genetic variation linked to handedness and brain structure and the overlap between the two.
What did the researchers find out?
The researchers found out the left-handers showed a rightward shift in structural hemispheric asymmetries in cortical surface area for eight brain areas and a rightward shift in structural hemispheric asymmetries in cortical thickness in two brain areas. This rightward shift of asymmetries in left-handers suggests that left-handedness is associated with a shift of neuronal resources towards the motor-dominant right hemisphere (the right side of the brain controls the left side of the body and vice versa). Functionally, these brain areas were linked to motor functions, but also to so-called executive functions, e.g. a range of higher cognitive abilities such as decision making, vision, and language.
In a second step, the researchers investigated which genetic factors were linked to asymmetries in brain structure in brain areas that showed differences between left-handers and right-handers. They found that for two brain regions, increased genetic disposition for left-handedness was significantly associated with a rightward shift in brain asymmetries, suggesting a genetic link between left-handedness and asymmetries in brain structure. Furthermore, 18 different locations in the genome that had previously been associated with left-handedness were associated with asymmetries in brain structure. Interestingly, six of the genes (called TUBB, TUBA1B, TUBB3, TUBB4A, MAP2, and NME7) associated with the identified locations in the genome were functionally relevant for so-called microtubules. Microtubules play a role in early brain development as they are important for the cytoskeleton, which provides structure and shape to nerve cells and other cells. Importantly, microtubules have also been associated with left-right axis determination in the brain during early development. This suggests that early developmental processes that determine the left and the right side of the brain link left-handedness and asymmetries in brain structure.
Conclusion
In conclusion, the study showed that left-handedness and asymmetries in brain structure are linked. Left-handers show a shift of brain asymmetries towards their motor-dominant right side. The genetic analyses suggest that developmental processes that determine the left and right sides of the nervous system represent the functional link between left-handedness and asymmetries in brain structure.