Biology subjects

Silverdale, M.

Publications and source records attributed to Silverdale, M..

4 recordsLinked to original sources

bioRxiv2026

Distinct nigral and brainstem pathology markers map onto separable subthalamic electrophysiological signatures in Parkinson's disease

Subthalamic local field potentials (LFPs) are increasingly used as physiomarkers of the symptomatic state in Parkinsons disease, but their relationship to the underlying neurodegenerative pathology remains unclear. Here, we combined OFF-medication subthalamic LFP recordings with quantitative MRI markers of nigral and brainstem pathology in 33 people with Parkinsons disease. Distinct pathological markers mapped onto dissociable electrophysiological components. Substantia nigra pars compacta susceptibility was associated with increased occupancy, duration and rate of low-{beta} bursts, whereas nigral free water was associated with greater low-frequency aperiodic offset and a steeper slope. Pedunculopontine nucleus free-water- corrected axial diffusivity was selectively associated with high-frequency aperiodic activity, and this relationship strengthened with increasing nigral susceptibility, consistent with dopaminergic-state- dependent influences of extranigral pathology on subthalamic physiology. Only low-frequency aperiodic offset was also associated with contralateral bradykinesia. These findings indicate that the subthalamic LFP is not a unitary readout of dopamine loss or motor state, but an integrated physiological signal in which pathology across interconnected systems is expressed through separable oscillatory and aperiodic components. Chronically implanted devices may therefore provide physiological readouts of underlying disease biology alongside control signals for adaptive therapy.

neuroscience↗

bioRxiv2024

Striatal Dopamine Modulates Temporal Surprise P3a

Dopamine is vital in forming mental models of "what" and "when" sensory events occur that essentially guide goal-directed behaviour. However, it remains largely unknown how variations in temporal predictability are incorporated into such mental models. A better understanding of the underlying mechanisms is important, considering dopaminergic depletion in diseases such as Parkinsons Disease and Schizophrenia, where abnormal temporal processing is observed. Some electroencephalographic (EEG) studies indicate that noradrenergic mechanisms, as reflected in the P3b event-related potential, are modulated by temporal predictability, whereas others indicate that dopaminergic mechanisms as reflected in the P3a, underlie surprise. In this study, resting-state and task-dependent EEG was recorded from 24 healthy participants who were administered a selective D2 agonist or antagonist before they performed a pure tone auditory "oddball" task. Two oddball sequences included either partially predictable, with inter-stimulus intervals (ISIs) of 400ms/1200ms; or fully temporally predictable tones, with a consistent ISI of 600ms. Tones following 400ms ISIs were perceived as surprising, or "early", as shown in an enhanced P3a response; tones following a 1200ms ISIs showed a much reduced P3a response ("late"). The agonist accentuated the "late" effect, demonstrating that drugs targeting D2 receptors modulate temporal prediction. These findings differentiate the role of the dopaminergic system in temporal processing and model-based auditory predictions.

neuroscience↗

bioRxiv2023

Investigation of Volatile Metabolites in Sebum as Prodromal Indicators of Parkinson's Disease

Parkinsons Disease (PD) has been associated with a distinct odour, which emanates from the skin and is strongest in sebum-rich areas. In this study, sebum was sampled from participants using cotton gauze and the volatile components emanating from these swabs were analysed directly with thermal desorption gas chromatography - mass spectrometry (TD GC-MS). We analysed subjects with clinically established PD (n=46) along with healthy controls (n=28) sampled from two sites. The volatilome profiles obtained for PD and control cohorts were compared with the profile of participants (n=9) with isolated REM sleep behaviour disorder (iRBD) to investigate metabolite changes in probable prodromal PD. We also compared PD participants sampled at yearly intervals for a total of three years. Volatile compounds from TD GC-MS analysis were found in different quantities between PD, control and iRBD subjects. We found 55 significant features where abundance in samples from individuals with iRBD was intermediate between that found for PD and control samples. Significant features were found to be alkanes and fatty acid methyl esters (FAMEs), with other metabolites identified as an aldehyde, purine and tropinone. In olfactory analysis of the iRBD samples three out of nine were classified PD, and on clinical follow up two of these showed PD symptoms. Further, when analysing the volatilome from longitudinal PD sampling, almost two-thirds of the significant features showed differential regulation over the three visits. Our findings support the use of sebum as an accessible biofluid rich with measurable volatile compounds which alter in abundance in individuals with PD and iRBD, as the disease progresses.

neuroscience↗

bioRxiv2018

Discovery of volatile biomarkers of Parkinsons disease from sebum

Parkinsons disease (PD) is a progressive, neurodegenerative disease that presents with significant motor symptoms, for which there is no diagnostic test (1-3). We have serendipitously identified a hyperosmic individual, a Super Smeller that can detect PD by odor alone, and our early pilot studies have indicated that the odor was present in the sebum from the skin of PD subjects(4). Here, we have employed an unbiased approach to investigate the volatile metabolites of sebum samples obtained non-invasively from the upper back of 64 participants in total (21 controls and 43 PD subjects). Our results, validated by an independent cohort, identified a distinct volatiles-associated signature of PD, including altered levels of perillic aldehyde and eicosane, the smell of which was then described as being highly similar to the scent of PD by our Super Smeller.\n\n1 sentence summaryMetabolomics identifies volatile odorous compounds from patient sebum that associate with the smell of Parkinsons.

neuroscience↗