PhD student, Hudson Institute of Medical Research
My research interest is in the developmental human brain, but more specifically in how it folds.
When it is first formed in the uterus, the brain of the fetus starts as a simple structure with a smooth surface (like a marble ball), but as it develops in the second and third trimester, it not only starts growing, but also its cortex starts folding, to finally adopt the wrinkly , convoluted shape we know in the adult brain.
The correct folding pattern is very, very important for the future of the owner of this brain, because if it is not properly folded (i.e. the shape is not right) the person can suffer multiple issues, such as hearing, learning, motor and visual impairment, schizophrenia, epilepsy, mental retardation, cerebral palsy, behavioural issues and many more.
In general terms, the brain is pretty similar to an origami figure: it needs to be properly folded to be completely functional. However, instructions for such folding are not found in the bookstore as for origami. The instructions for the brain to fold are hidden inside the cells, and are part of our genes. However, regrettably, only initial understanding of these genes has been obtained, and also many genes affecting the right folding pattern remain unknown.
So, it is very important to understand and keep studying and discovering these important genes, so in the future we can keep our babies and children from suffering the consequences of a misfolded brain origami.
Abstract: Cortical gyrification is not a random process. Instead, the folds that develop are synonymous with the functional organization of the cortex, and form patterns that are remarkably consistent across individuals and even some species. How this happens is not well understood. Although many developmental features and evolutionary adaptations have been proposed as the primary cause of gyrencephaly, it is not evident that gyrification is reducible in this way. In recent years, we have greatly increased our understanding of the multiple factors that influence cortical folding, from the action of genes in health and disease to evolutionary adaptations that characterize distinctions between gyrencephalic and lissencephalic cortices. Nonetheless it is unclear how these factors which influence events at a small-scale synthesize to form the consistent and biologically meaningful large-scale features of sulci and gyri. In this article, we review the empirical evidence which suggests that gyrification is the product of a generalized mechanism, namely the differential expansion of the cortex. By considering the implications of this model, we demonstrate that it is possible to link the fundamental biological components of the cortex to its large-scale pattern-specific morphology and functional organization.
Pub.: 17 Dec '14, Pinned: 28 Jul '17
Abstract: Gyrification brain abnormalities are considered a marker of early deviations from normal developmental trajectories and a putative predictor of poor outcome in psychiatric disorders. The aim of this study was to explore cortical folding morphology in patients with anorexia nervosa (AN). A MRI brain study was conducted on 38 patients with AN, 20 fully recovered patients, and 38 healthy women. Local gyrification was measured with procedures implemented in FreeSurfer. Vertex-wise comparisons were carried out to compare: (1) AN patients and healthy women; (2) patients with a full remission at a 3-year longitudinal follow-up assessment and patients who did not recover. AN patients exhibited significantly lower gyrification when compared with healthy controls. Patients with a poor 3-year outcome had significantly lower baseline gyrification when compared to both healthy women and patients with full recovery at follow-up, even after controlling for the effects of duration of illness and gray matter volume. No significant correlation has been found between gyrification, body mass index, amount of weight loss, onset age, and duration of illness. Brain gyrification significantly predicted outcome at follow-up even after controlling for the effects of duration of illness and other clinical prognostic factors. Although the role of starvation in determining our findings cannot be excluded, our study showed that brain gyrification might be a predictor of outcome in AN. Further studies are needed to understand if brain gyrification abnormalities are indices of early neurodevelopmental alterations, the consequence of starvation, or the interaction between both factors.
Pub.: 17 Sep '15, Pinned: 28 Jul '17
Abstract: Male predominance is a prominent feature of autism spectrum disorders (ASD), with a reported male to female ratio of 4:1. Because of the overwhelming focus on males, little is known about the neuroanatomical basis of sex differences in ASD. Investigations of sex differences with adequate sample sizes are critical for improving our understanding of the biological mechanisms underlying ASD in females.We leveraged the open-access autism brain imaging data exchange (ABIDE) dataset to obtain structural brain imaging data from 53 females with ASD, who were matched with equivalent samples of males with ASD, and their typically developing (TD) male and female peers. Brain images were processed with FreeSurfer to assess three key features of local cortical morphometry: volume, thickness, and gyrification. A whole-brain approach was used to identify significant effects of sex, diagnosis, and sex-by-diagnosis interaction, using a stringent threshold of p < 0.01 to control for false positives. Stability and power analyses were conducted to guide future research on sex differences in ASD.We detected a main effect of sex in the bilateral superior temporal cortex, driven by greater cortical volume in females compared to males in both the ASD and TD groups. Sex-by-diagnosis interaction was detected in the gyrification of the ventromedial/orbitofrontal prefrontal cortex (vmPFC/OFC). Post-hoc analyses revealed that sex-by-diagnosis interaction was driven by reduced vmPFC/OFC gyrification in males with ASD, compared to females with ASD as well as TD males and females. Finally, stability analyses demonstrated a dramatic drop in the likelihood of observing significant clusters as the sample size decreased, suggesting that previous studies have been largely underpowered. For instance, with a sample of 30 females with ASD (total n = 120), a significant sex-by-diagnosis interaction was only detected in 50 % of the simulated subsamples.Our results demonstrate that some features of typical sex differences are preserved in the brain of individuals with ASD, while others are not. Sex differences in ASD are associated with cortical regions involved in language and social function, two domains of deficits in the disorder. Stability analyses provide novel quantitative insights into why smaller samples may have previously failed to detect sex differences.
Pub.: 07 Jul '15, Pinned: 28 Jul '17
Abstract: To introduce a measure of global cortical folding in epilepsy by using stereology. Subtle developmental abnormalities associated with temporal lobe epilepsy may encompass brain morphologic changes such as an aberrant degree of cortical folding.Stereologic methods of volume and surface-area estimation were applied to in vivo MR brain-image data of a cohort of 20 temporal lobe epilepsy (TLE) patients (10 men, 10 women), and 20 neurologically normal controls (10 men, 10 women). Indices of cerebral gyrification and cerebral atrophy were generated. The impact of side of seizure onset, age at onset, history of febrile seizures, presence or absence of lesions, and presence or absence of secondarily generalized seizures on cerebral gyrification was assessed.Although no significant group mean difference was found in the degree of cerebral gyrification between patients and controls, five of 10 of male patients had an abnormal gyrification when compared with male controls. One female patient had a significant change in gyrification compared with female controls. In general, patients with TLE demonstrated a significant degree of global cerebral atrophy compared with controls. Clinical factors were not demonstrated to affect significantly any of the quantitative parameters.The results of this study suggest that an aberrant degree of global cerebral gyrification may occur in certain clinical groups of TLE patients. These findings have implications for general theories of developmental susceptibility in TLE.
Pub.: 14 Feb '07, Pinned: 28 Jul '17
Abstract: There is emerging evidence for a connection between the surface morphology of the brain and its underlying connectivity. The foundation for this relationship is thought to be established during brain development through the shaping influences of tension exerted by viscoelastic nerve fibers. The tension-based morphogenesis results in compact wiring that enhances efficient neural processing. Individuals with schizophrenia present with multiple symptoms that can include impaired thought, action, perception, and cognition. The global nature of these symptoms has led researchers to explore a more global disruption of neuronal connectivity as a theory to explain the vast array of clinical and cognitive symptoms in schizophrenia. If cerebral function and form are linked through the organization of neural connectivity, then a disruption in neural connectivity may also alter the surface morphology of the brain. This paper reviews developmental theories of gyrification and the potential interaction between gyrification and neuronal connectivity. Studies of gyrification abnormalities in children, adolescents, and adults with schizophrenia demonstrate a relationship between disrupted function and altered morphology in the surface patterns of the cerebral cortex. This altered form may provide helpful clues in understanding the neurobiological abnormalities associated with schizophrenia.
Pub.: 26 Jan '11, Pinned: 28 Jul '17
Abstract: Structural and functional abnormalities have been extensively reported in major depressive disorder, but possible changes in cortical folding have not yet been explored in this disorder. This study investigated this issue in major depressive disorder using the local gyrification index. High-resolution magnetic resonance imaging was performed in 18 patients with first-episode major depressive disorder and 18 age-matched and sex-matched healthy individuals. The local gyrification index was applied to detect brain areas with abnormal cortical folding in major depressive disorder. Compared with healthy participants, patients with major depressive disorder showed significantly decreased local gyrification index in the bilateral mid-posterior cingulate, insula, and orbital frontal cortices, the left anterior cingulate cortex, and the right temporal operculum.
Pub.: 17 Feb '09, Pinned: 28 Jul '17
Abstract: Radial glial cells play key roles during cerebral cortex development, as primary stem and progenitor cells giving rise-directly or indirectly-to neurons and glia, but also acting as scaffold for the cerebral cortex architecture and migrating neurons. Recent work led to the discovery of novel types of radial glial cells with key roles in gyrification, the folding of the mammalian cerebral cortex in phylogeny and ontogeny. Here we summarize the cellular and molecular basis of this fascinating process allowing the expansion of the mammalian cerebral cortex with all its functional consequences.
Pub.: 19 Mar '14, Pinned: 28 Jul '17