Mangin et al. (2020) conducted a study to better understand and expand on the
progression of Huntington's Disease (HD) and its consequences on the brain. The research is
extensive and analyzes an aspect of HD that had not been researched on before, but, due to its
depth and reach, the research makes several question that relate brain development and
neuropsychological disorders arise. According to Mangin et al. (2020), despite cellular and
molecular evidence that HD could affect normal development, there has been a scarcity of
systems-level data from in vivo human research to support this idea. This idea was the spark for
the entirety of the research by Mangin et al. (2018). The researchers hypothesized that sulcus-
specific morphometry analysis could aid in disentangling the contribution of concurrent
neurodegenerative and neurodevelopmental processes, but this approach had never been applied
in HD research before (Mangin et al., 2020). The scientists looked at a relatively commonly
research aspect of neuroscience: cortical sulcal depth (Mangin et al., 2018). This specific
component is linked to the degenerative process, and cortical sulcal length, which is linked to the
developing process, in early-stage HD patients and age-matched healthy controls (Mangin et al.,
2020). The central and intra-parietal sulcus, as well as the left intermediate frontal sulcus and
calcarine fissure, showed significant changes in the HD individuals compared to the healthy
controls in the morphometric study (Mangin et al., 2020). The fact that the primary visual cortex
was not connected to the striatum was also discovered, adding to the growing body of evidence
showing initial cortical degeneration in HD in vivo (Mangin et al., 2020). The authors of the
research (2020) discovered that the sulcal measurements that changed among HD and healthy
people were mostly atrophy-related, with HD people having shallower sulci. In contrast, sulcal
morphometry revealed a critical difference in the Sylvian fissure imprint that could not be linked
to reduction of grey matter volume: the lack of asymmetry in the length of the fissure in HD
patients (Mangin et al., 2020). In normal development, there is a significant amount of
asymmetry in the cortical region (Kong et al., 2020). This unexpected finding likely reflects the
fetal onset of a disease-specific, genetic interplay with neurodevelopment, as the Sylvian fissure
emerges early in pregnancy and marked asymmetry is specifically detected in this region of the
neocortex in newborns (Pooh et al., 2019).
These findings are critical to expanding on the subject and research of HD as cortical
sulcal analysis has relied entirely on the empirical description of postmortem cortical foldings up
until this point (Mangin et al., 2020). Two fundamental steps were observed in the antenatal
stage, which are now thought to be common to higher order mammals: initially, the
operculisation of the insula at 6 months, usually accompanied by a gradual gyrification allowing
the neocortical surface to increase and become even more intricate during the last three months
of development (Whittle et al., 2020). These prior observation foreshadowed a theory that
placed the consistency of these sulcal "roots" across people, which was confirmed in vivo in
neonates (Meng et al., 2018). Furthermore, numerous developmental defects resulting to cerebral
sulci malformations have been linked to sensorimotor, cognitive, and behavioral impairments
since the early nineteenth century (Mangin et al., 2018) (Babik, 2022). Mangin et al. (2020) are
able to shed some light on this topic with their innovative results. Sulcal morphometry research
might potentially detect defects that emerge during neocortical development, either concurrently
with the creation of sulcal roots or later in the cortical maturation process (Mangin et al., 2018).
Despite the fact that Mangin et al., (2018)'s research is extensive and includes several
findings and discoveries about HD and its relationship with cortical morphologies that have
never been analyzed before, let alone have a team of scientists perform extensive research on the
subject, the authors leave some unanswered questions about the relationship between brain
References
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Sabidussi, E., & Mochel, F. (2021). Multiparametric characterization of white matter
alterations in early stage Huntington disease. Scientific Reports, 11(1).
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https://doi.org/10.3390/sym14020345
formation and cognitive development, as previously mentioned. In addition, questions regarding
the relationship between cortical sulcal length and central and intra-parietal sulcus, as well as the
left intermediate frontal sulcus and calcarine fissure arise. Since these particular regions of the
brain are directly related to the development of HD, as examined by Mangin et al., (2018), the
research leaves the audience wanting more answers. Given the similarities of the disorders, could
the research findings further expand on the relationship between Amyotrophic Lateral Sclerosis
(ASL) or Multiple Sclerosis (MS) and neocortical morphometry? The research is also left lacking
some minor details such as the involvement of the white matter in Huntington’s disease and the
damage it undergoes in an individual affected by Hungtington’s disease as better explained by
Adanyeguh et al. (2021). Often, explaining the basis of a research and the normal physiology of
a disease are just as important as the novelty findings that stem from the research itself, and this
is what the research by Mangin et al. (2018) is lacking.
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