Biology subjects

Lalwani, P.

Publications and source records attributed to Lalwani, P..

8 recordsLinked to original sources

bioRxiv2025

Aperiodic neural dynamics define a novel signature of glioma-induced excitation-inhibition dysregulation

Diffuse gliomas remodel neuronal circuits with prognostic and therapeutic significance for patients. Electrophysiologic measures of cortical excitability hold promise for monitoring disease progression and evaluating therapeutic responses. The power law exponent (aperiodic slope) reflects the balance between excitatory and inhibitory activity within neuronal networks, a critical aspect of normal brain function often disrupted in neurological conditions. Despite its potential, the significance of the aperiodic slope in glioma-infiltrated tissue and its underlying cellular processes has not been fully investigated. Here, we integrate multi-modal electrophysiological analysis with transcriptomic profiling to analyze the aperiodic slope in both normal and glioma-infiltrated cortex. We determine that glioma infiltration induces a flattening of the aperiodic slope, indicating a shift toward excitation dominance that varies according to tumor subtype and correlates with impairments in semantic naming. Single-nucleus RNA sequencing revealed that cortical regions with flat aperiodic slope exhibit transcriptional programs enriched in glutamatergic signaling, membrane depolarization, and excitatory synaptic transmission. The aperiodic slope responds to pharmacologically induced changes in cortical inhibition during propofol administration, a GABAA agonist. Our results establish the aperiodic slope as a robust biomarker of glioma-associated excitation-inhibition imbalance, with potential applications in tumor classification and treatment monitoring.

cancer biology↗

bioRxiv2025

Lower GABA levels in the posterior cingulate are linked with poorer episodic memory in healthy older adults

Age-related deficits in episodic memory and mnemonic discrimination are associated with an increased risk of neurodegenerative diseases, such as Alzheimers disease (AD) (Stark et al., 2013). While much research has focused on hippocampal contributions to these age-related changes (Stark et al., 2019), less is known about the role of posterior cingulate cortex (PCC) especially reduced inhibition in episodic memory deficit. PCC has connections to the medial temporal lobe and is linked to memory declines (Greicius et al., 2004). It is also one of the most vulnerable regions to amyloid deposition in AD (Yokoi et al., 2018). This study hypothesized and found that age-related declines in GABAergic function (brains major inhibitory neurotransmitter) within the PCC contributes to individual differences in memory performance in healthy older adults. Using Magnetic Resonance Spectroscopy, we measured GABA levels in the PCC in 22 healthy younger and 30 older adults. We assessed episodic memory using Rey Delayed Auditory Verbal Learning Test (RAVLT) and Mnemonic Similarity Task (MST). We found that both raw GABA levels and episodic memory performance are lower in older adults compared to young. This reduction in GABA levels is subserved by age-related changes in tissue-composition as evidenced by no age-group differences in corrected GABA levels. More importantly, lower GABA levels (independent of tissue-correction) were associated with poorer episodic performance including delayed recall and mnemonic discrimination. This research suggests that therapeutically targeting posterior cingulate GABA levels might help slow or alleviate memory decline. Significance StatementThis study provides novel insights into the role of posterior cingulate cortex (PCC) GABA+ levels in age-related memory deficits. Our findings demonstrate that lower PCC GABA+ levels in older adults are associated with poorer performance on episodic memory tasks, particularly those involving mnemonic discrimination and word-list learning. This research expands on the growing body of literature linking GABAergic dysfunction to age-related cognitive impairments and suggests that GABAergic changes in the PCC contribute to episodic memory deficits. Importantly, our results highlight the potential of targeting PCC GABA levels as a therapeutic strategy to slow or mitigate memory decline in aging. These findings also offer promising avenues for future research into early biomarkers for Alzheimers disease and other neurodegenerative conditions.

neuroscience↗

bioRxiv2024

Carboxylated graphene: A novel approach for enhanced IgA-SARS-CoV-2 electrochemical biosensing

Biosensors comprise devices that use a material of biological nature as receptors connected to transducers, these devices are capable of capturing biorecognition signals, called a primary signal, and converting it to a measurable signal. In this study, we report the synthesis of carboxylated graphene (CG) through a carboxylation method in acid medium and further characterization of the materials by different techniques such as scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), Raman spectroscopy, thermal gravimetric analysis (TGA), and X-ray diffraction (DRX). Also, the surface of the screen-printed carbon electrodes (SPCEs) was modified with CG for subsequent immobilization of N-protein of SARS-CoV-2, which allowed the detection of antibodies (IgA-SARS-CoV-2). The electrical properties and response of the biosensor were investigated using electrochemical techniques (cyclic voltammetry and electrochemical impedance spectroscopy). Through the chemical characterization techniques, it was possible to confirm the success of the CG synthesis process. The biosensor fabricated shown to be able to detect IgA-SARS-CoV-2 in the range of 1:1000 to1:200 v/v in phosphate buffer solution (PBS) and the limit of detection calculated was 1:1601 v/v. this perspective they comprise a wide range of applications due to its advantages, such as the possibility of a shorter response time, reproducibility, the miniaturization of detection devices such as the use of screen-printed electrodes, the use of small amounts of sample, the high sensitivity and specificity, low limits of detection and the integration of nano materials that make it possible to improve the detected signal.

bioengineering↗

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 multidimensional functional fitness score is a stronger predictor of type 2 diabetes than obesity parameters in cross sectional data.

ObjectiveWe examine here whether multidimensional functional fitness is a better predictor of type 2 diabetes as compared to morphometric indices of obesity such as body mass index (BMI) and waist to hip ratio (WHR).\n\nResearch design and methodWe analysed retrospective data of 663 volunteer participants (285 males and 378 females between age 28 and 84), from an exercise clinic in which every participant routinely undergoes a health related physical fitness (HRPF) assessment consisting of 15 different tasks examining 8 different aspects of functional fitness.\n\nResultsThe odds of being diabetic in the highest quartile of BMI were not significantly higher than that in the lowest quartile in either of the sexes. The odds of being a diabetic in the highest WHR quartile were significantly greater than the lowest quartile in females (OR = 4.54 (1.95, 10.61) as well as in males (OR = 3.81 (1.75, 8.3). In both sexes the odds of being a diabetic were significantly greater in the lowest quartile of HRPF score than the highest (males OR = 10.52 (4.21, 26.13); females OR = 10.50 (3.53, 31.35)). HRPF was not correlated with BMI in both sexes but was negatively correlated with WHR. After removing confounding, the predictive power of HRPF was significantly greater than that of WHR.\n\nConclusionMultidimensional functional fitness score was a better predictor of type 2 diabetes than obesity parameters in the Indian population.

epidemiology↗

bioRxiv2018

Neural distinctiveness declines with age in auditory cortex and is associated with auditory GABA levels.

Neural activation patterns in the ventral visual cortex in response to different categories of visual stimuli (e.g., faces vs. houses) are less selective, or distinctive, in older adults than in younger adults, a phenomenon known as age-related neural dedifferentiation. Previous work in animals suggests that age-related reductions of the inhibitory neurotransmitter, gamma aminobutyric acid (GABA), may play a role in this age-related decline in neural distinctiveness. In this study, we investigated whether neural dedifferentiation extends to auditory cortex and whether individual differences in GABA are associated with individual differences in neural distinctiveness in humans. 20 healthy young adults (ages 18-29) and 23 healthy older adults (over 65) completed a functional magnetic resonance imaging (fMRI) scan, during which neural activity was estimated while they listened to foreign speech and music. GABA levels in the auditory, ventrovisual and sensorimotor cortex were estimated in the same individuals in a separate magnetic resonance spectroscopy (MRS) scan. Relative to the younger adults, the older adults exhibited both (1) less distinct activation patterns for music vs. speech stimuli and (2) lower GABA levels in the auditory cortex. Also, individual differences in auditory GABA levels (but not ventrovisual or sensorimotor GABA levels) predicted individual differences in neural distinctiveness in the auditory cortex in the older adults. These results demonstrate that age-related neural dedifferentiation extends to the auditory cortex and suggest that declining GABA levels may play a role in neural dedifferentiation in older adults.\n\nSignificance StatementPrior work has revealed age-related neural dedifferentiation in the visual cortex. GABA levels also decline with age in several parts of the human cortex. Here, we report that these two age-related changes are linked; neural dedifferentiation is associated with lower GABA levels in older adults. We also show that age-related neural dedifferentiation extends to auditory cortex, suggesting that it may be a general feature of the aging brain. These findings provide novel insights into the neurochemical basis of age-related neural dedifferentiation in humans and also offer a potential new avenue for investigating age-related declines in central auditory processing.

neuroscience↗

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↗

bioRxiv2018

Foraging theory and the propensity to be obese: an alternative to thrift

The evolutionary origin of obesity is classically believed to be genetic or developmentally induced thrift, as an adaptation to ancestral feast and famine conditions. However, recently the thrift family of hypotheses have attracted serious criticism necessitating alternative thinking. Optimization of foraging behaviour is an important aspect of behavioural evolution. For a species evolved for optimizing nutritional benefits against predation or other foraging risks, reduction in foraging risk below a threshold dramatically increases the steady-state body weight. In modern life where feeding is detached from foraging, the behavioural regulation mechanisms are likely to fail resulting into escalation of adiposity. At a proximate level the signalling pathways for foraging optimization involve fear induced signal molecules in the brain including Cocaine and Amphetamine Regulated Transcript (CART) interacting with adiposity signals such as leptin. While leptin promotes the expression of the fear peptides, the fear peptides promote anorectic action of leptin. This interaction promotes foraging drive and risk tolerance when the stored energy is low and suppresses hunger and foraging drive when the perceived risk is high. The ecological model of foraging optimization and the molecular model of interaction of these peptides converge in the outcome that the steady state adiposity is an inverse square root function of foraging risk. The foraging optimization model is independent of thrift or insurance hypotheses, but not mutually exclusive. We review existing evidence and suggest testable predictions of the model. Understanding obesity simultaneously at proximate and ultimate levels is likely to suggest effective means to curb the obesity epidemic.

evolutionary biology↗