Biology subjects

Petrou, M.

Publications and source records attributed to Petrou, M..

3 recordsLinked to original sources

bioRxiv2019

GABA levels in ventral visual cortex decline with age and are associated with neural distinctiveness

Age-related neural dedifferentiation - a decline in the distinctiveness of neural representations in the aging brain-has been associated with age-related declines in cognitive abilities. But why does neural distinctiveness decline with age? Based on prior work in non-human primates and more recent work in humans, we hypothesized that the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) declines with age and is associated with neural dedifferentiation in older adults. To test this hypothesis, we used magnetic resonance spectroscopy (MRS) to measure GABA and functional MRI (fMRI) to measure neural distinctiveness in the ventral visual cortex in a set of older and younger participants. Relative to younger adults, older adults exhibited lower GABA levels and less distinct activation patterns for faces and houses in the ventral visual cortex. Furthermore, individual differences in GABA within older adults positively predicted individual differences in neural distinctiveness. These results provide novel support for the view that age-related reductions of GABA contribute to age-related reductions in neural distinctiveness (i.e., neural dedifferentiation) in the human ventral visual cortex.

neuroscience↗

bioRxiv2019

A method for non-invasive prenatal diagnosis of monogenic autosomal recessive disorders

Non-invasive prenatal testing (NIPT) to date is used in the clinic primarily to detect foetal aneuploidy. Few studies so far have focused on the detection of monogenic autosomal recessive disorders where mother and foetus carry the same mutation. In particular, NIPT is currently not available for the detection of Sickle Cell Anaemia (SCA), the most common monogenic disorder world-wide and the most common indication for invasive prenatal testing in high-income countries. Here, we report the clinical validation of a novel diagnostic approach that combines ultra-sensitive amplicon-based sequencing of cell-free DNA (cfDNA) with internal controls and bias factor correction to calculate the probability for the presence of allelic imbalance from maternal plasma without prior knowledge of the paternal genotype. Identification of the foetal genotype was determined using a hierarchical probabilistic model based on the relative number of reads from the sequencing, along with the foetal fraction. NIPT was performed on a cohort of 57 patients, all of whom had previously undergone invasive prenatal testing so that the foetal genotype was known. Overall, NIPT demonstrated 100% sensitivity and negative predictive value for foetal fractions higher than 0.5%, and 100% specificity and positive predictive value for foetal fractions higher than or equal to 4%. Our methodology can be used as a safe, non-invasive screening tool in any clinical scenarios where early prenatal diagnosis of SCA or other recessive disorders is important.

genomics↗

bioRxiv2018

Michigan Neural Distinctiveness (MiND) project: Investigating the scope, causes, and consequences of age-related neural dedifferentiation

BackgroundAging is often associated with behavioral impairments, but some people age more gracefully than others. Why? One factor that may play a role is individual differences in the distinctiveness of neural representations. Previous research has found that neural activation patterns in visual cortex in response to different visual stimuli are often more similar (i.e., less distinctive) in older vs. young participants, a phenomenon referred to as age-related neural dedifferentiation. Furthermore, older people whose neural representations are less distinctive tend to perform worse on a wide range of behavioral tasks. The Michigan Neural Distinctiveness (MiND) project aims to investigate the scope of neural dedifferentiation (e.g., does it also occur in auditory, motor, and somatosensory cortex?), one potential cause (age-related reductions in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)), and the behavioral consequences of neural dedifferentiation. This protocol paper describes the study rationale and methods being used in complete detail, but not the results (data collection is currently underway).\n\nMethods/DesignThe MiND project consists of two studies: the main study and a drug study. In the main study, we are recruiting 60 young and 100 older adults to perform behavioral tasks that measure sensory and cognitive function. They also participate in functional MRI (fMRI), MR spectroscopy (MRS), and diffusion weighted imaging (DWI) sessions, providing data on neural distinctiveness and GABA concentrations. In the drug study, we are recruiting 25 young and 25 older adults to compare neural distinctiveness, measured with fMRI, after participants take (1) a benzodiazepine (lorazepam) that should increase GABA activity or (2) a placebo.\n\nDiscussionBy collecting multimodal imaging measures (fMRI, MRS, DWI) along with extensive behavioral measures from the same subjects, we are linking individual differences in neurochemistry, neural representation, and behavioral performance, rather than focusing solely on group differences between young and old participants. Our findings have the potential to inform new interventions for age-related declines.

neuroscience↗