Using cortico-cerebellar structural patterns to classify early- and late-trained musicians.

A body of current evidence suggests that there is a sensitive period for musical training: people who begin training before the age of seven show better performance on tests of musical skill, and also show differences in brain structure-especially in motor cortical and cerebellar regions-compared with those who start later. We used support vector machine models-a subtype of supervised machine learning-to investigate distributed patterns of structural differences between early-trained (ET) and late-trained (LT) musicians and to better understand the age boundaries of the sensitive period for early musicianship. After selecting regions of interest from the cerebellum and cortical sensorimotor regions, we applied recursive feature elimination with cross-validation to produce a model which optimally and accurately classified ET and LT musicians. This model identified a combination of 17 regions, including 9 cerebellar and 8 sensorimotor regions, and maintained a high accuracy and sensitivity (true positives, i.e., ET musicians) without sacrificing specificity (true negatives, i.e., LT musicians). Critically, this model-which defined ET musicians as those who began their training before the age of 7-outperformed all other models in which age of start was earlier or later (between ages 5-10). Our model's ability to accurately classify ET and LT musicians provides additional evidence that musical training before age 7 affects cortico-cerebellar structure in adulthood, and is consistent with the hypothesis that connected brain regions interact during development to reciprocally influence brain and behavioral maturation.

Early musical training shapes cortico-cerebellar structural covariation.

Adult abilities in complex cognitive domains such as music appear to depend critically on the age at which training or experience begins, and relevant experience has greater long-term effects during periods of peak maturational change. Previous work has shown that early trained musicians (ET; < age 7) out-perform later-trained musicians (LT; > age 7) on tests of musical skill, and also have larger volumes of the ventral premotor cortex (vPMC) and smaller volumes of the cerebellum. These cortico-cerebellar networks mature and function in relation to one another, suggesting that early training may promote coordinated developmental plasticity. To test this hypothesis, we examined structural covariation between cerebellar volume and cortical thickness (CT) in sensorimotor regions in ET and LT musicians and non-musicians (NMs). Results show that ETs have smaller volumes in cerebellar lobules connected to sensorimotor cortices, while both musician groups had greater cortical thickness in right pre-supplementary motor area (SMA) and right PMC compared to NMs. Importantly, early musical training had a specific effect on structural covariance between the cerebellum and cortex: NMs showed negative correlations between left lobule VI and right pre-SMA and PMC, but this relationship was reduced in ET musicians. ETs instead showed a significant negative correlation between vermal IV and right pre-SMA and dPMC. Together, these results suggest that early musical training has differential impacts on the maturation of cortico-cerebellar networks important for optimizing sensorimotor performance. This conclusion is consistent with the hypothesis that connected brain regions interact during development to reciprocally influence brain and behavioral maturation.

Bipolar disorder risk gene FOXO6 modulates negative symptoms in schizophrenia: a neuroimaging genetics study.

BACKGROUND: Despite being diagnostically associated uniquely with schizophrenia, negative symptoms are also observed in bipolar disorder (BD). Genome-wide association studies (GWAS) have uncovered a number of shared risk genes between schizophrenia and BD. The objectives of this study were to examine whether previously identified risk genes for BD are associated with negative symptom severity within a first-episode schizophrenia (FES) cohort and to examine whether such genes influence brain morphology. METHODS: Patients experiencing FES were genotyped for 21 previously identified BD risk genes; a series of univariate analyses of covariance examined the association between negative symptom severity, as measured using the Scale for the Assessment of Negative Symptoms (SANS), and genotype. A subset of participants underwent a structural 1.5 T MRI T1 scan, analyzed for surface area and cortical thickness changes via the CIVET pipeline and LPBA40 atlas. RESULTS: We included 133 patients with FES in our analysis; 61 of them underwent structural MRI. We observed a significant association between negative symptom severity and the BD risk gene FOXO6 (rs4660531). Individuals with the CC genotype presented significantly higher negative symptoms (Cohen d = 0.46, F = 5.854, p = 0.017) and significantly smaller surface area within the right middle orbitofrontal gyrus (Cohen d = 0.69, F = 7.289, p = 0.009) than carriers of allele A. LIMITATIONS: Limitations of this study include its modest sample size and lack of a control sample. CONCLUSION: Lacking the FOXO6 risk allele was associated with an increase in negative symptoms and surface area reduction in the right orbitofrontal gyrus - an area previously associated with negative symptoms - suggesting that presence of the FOXO6 risk allele confers resistance against negative symptoms and associated neuroanatomical changes in individuals with FES.