Differential relationship of frontal pole and whole brain volumetric measures with age in neuroleptic-naïve schizophrenia and healthy subjects.

Brodmann's area (BA) 10, which occupies the frontal pole (FP) of the human brain, has been proven to play a central role in the executive control of cognitive operations. Previous in vivo morphometric studies of the FP have been limited by the lack of an accepted boundary of its posterior limit. We studied the FP gray matter volume in 23 healthy subjects who were age-, sex-, and education-matched to 23 neuroleptic-naïve recent-onset schizophrenia subjects in the age span 20-40 years, using a cytoarchitectonically and functionally valid landmark-based definition of its posterior boundary that we proposed recently (John, J.P., Yashavantha, B.S., Gado, M., Veena, R., Jain, S., Ravishankar, S., Csernansky, J.G., 2007. A proposal for MRI-based parcellation of the frontal pole. Brain Struct. Funct. 212, 245-253. 2007). Additionally, we examined the relationship between FP volume and age in both healthy and schizophrenia subjects to examine evidence for a possible differential relationship between these variables across the samples. A major finding of the study was the absence of a group-level difference in frontal pole gray volumes between the healthy and schizophrenia participants. However, a more complex finding emerged in relation to age effects. The healthy participants showed an inverse relationship of FP gray volume with age, even after taking total brain volume differences into account. But this age effect was completely absent in the schizophrenia group. Moreover, all the volumetric measures in schizophrenia subjects showed substantially higher range, variance, skewness and kurtosis when compared to those of healthy subjects. These findings have implications in understanding the possible role of FP in the pathophysiology of schizophrenia.

Spinocerebellar ataxias type 1, 2 and 3: a study of heart rate variability.

OBJECTIVE: To detect cardiac autonomic dysfunction, using analysis of heart rate variability in genetically defined spinocerebellar ataxias (SCA). MATERIALS AND METHODS: Consecutive RR intervals were analyzed for time- and frequency-domain parameters in 22 genotypically proven SCA patients (SCA1 = 11, SCA2 = 6 and SCA3 = 5) and compared with that of age- and gender-matched controls. RESULTS: Reduction in the standard deviation of RR interval (RR_SD) was seen in 72.7% of SCA patients. There was a reduction in both the parasympathetic and sympathetic parameters in SCA without any change in the ratio of low- to high-frequency power. In SCA1, there was a significant negative correlation between RR_SD and duration of illness but not with the CAG repeat lengths of the abnormal allele. Small sample size of SCA2 and SCA3 precluded similar comparison. CONCLUSIONS: Cardiac autonomic dysfunction, predominantly parasympathetic, was seen in SCA, and the severity correlated with the duration of illness in SCA1.

SCA 1, SCA 2 & SCA 3/MJD mutations in ataxia syndromes in southern India.

BACKGROUND & OBJECTIVE: Spinocerebellar ataxias (SCAs) are often caused by expansions of CTG/ CAG trinucleotide repeat in the genome. Expansions at the SCA1, 2 and 3 loci are the most frequent, but differences in their relative proportion in regions occur across the world. We carried out this study to assess the occurrence of SCA1, 2 and 3, at a tertiary neuro-psychiatric center in Bangalore, Karnataka. METHODS: Probands (N=318) who were diagnosed to have an ataxia syndrome (progressive degenerative ataxia of unknown cause) attending the clinical services of the National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore, were evaluated over a period of three years. Standard protocols were used for both clinical and molecular diagnosis. RESULTS: Genotyping established that SCA1, 2 and 3 accounted for more than one third of the ataxia cases seen in the clinic. In the cases with established family history and autosomal dominant inheritance SCA1 was most prevalent followed by SCA2 and SCA3. INTERPRETATION & CONCLUSION: Our findings suggested SCA1 rather than SCA2 to be the more common mutation in southern India. Large numbers of SCA3 probands were also identified. Differences in prevalence of these syndromes within India need to be explored further for founder effects, correlations with phenotype, and patterns of outcome. Family history was not apparent in almost a fifth of those tested positive, highlighting the value of testing even in the absence of family history. Molecular testing should be extended to cover the other forms of ataxia, of which a large number are now known. Combined efforts to confirm the presence of these less common forms, as well as family studies to detect novel mutations, are necessary in this context in India.

A proposal for MRI-based parcellation of the frontal pole.

The frontal pole (FP), which largely overlaps with Brodmann's area (BA) 10, is the rostral-most part of the hominid cerebral cortex, and plays a critical role in complex aspects of human cognition. The existing conventions suggested for MRI-based parcellation of this important frontal subdivision have limited cytoarchitectonic meaning with regard to the demarcation of the FP from adjacent prefrontal subdivisions. In this paper, we propose the coronal section containing the anterior termination of the olfactory sulcus (ATOS) as an easy-to-identify landmark for FP parcellation that largely overlaps with the cytoarchitectonic distinction between BA 10 and the more posterior cytoarchitectonic subdivisions of the PFC. Manual segmentation-based parcellation of the FP using the proposed landmark in 20 healthy volunteers yielded highly reliable (standardized item alpha = 0.92) volumetric estimates [right FP volume = 8.421 cm3 (SE = 0.773, range 3.107-15.741); left FP volume = 8.039 cm3 (SE = 0.708, range 2.234-12.956)]. The volumetric measurements of right FP generated in the present study were comparable to those reported in a prior study of BA 10 using histological sections and stereological techniques (Semendeferi et al. In: Am J Phys Anthropol 114:224-241, 2001). Therefore, in the absence of a naturally occurring sulcal boundary, the proposed method for parcellation of the FP can provide unbiased volume estimations for studies of healthy and disordered populations of subjects.