bioRxiv Science⌕ Search

Biology subjects

Cosgrove, R.

Publications and source records attributed to Cosgrove, R..

3 recordsLinked to original sources

Impact of stimulation location relative to grey and white matter on single pulse electrical stimulation responses in the human brain

BackgroundElectrical neuromodulation is an increasingly common therapy for a wide variety of neuropsychiatric diseases. Unfortunately, therapeutic efficacy is inconsistent, possibly a result of our limited understanding of the mechanisms and the massive stimulation parameter space. Objective/HypothesisTo better understand the role different parameters play in inducing a response, we systematically examined single pulse-induced cortico-cortico evoked potentials (CCEP) as a function of stimulation amplitude, duration and location in the brain and relative to grey and white matter. MethodsWe measured voltage peak amplitudes and area under the curve of intracranially recorded stimulation responses as a function of distance from the stimulation site, pulse width, current injected, location relative to grey and white matter, and brain region stimulated (N=52, n=719 stimulation sites). ResultsIncreasing stimulation pulse width increased response values near the stimulation location. Increasing stimulation amplitude (current) increased responses nonlinearly. Locally (<15 mm from the stimulation site), stimulation closer to the grey matter-white matter boundary induced larger responses. In contrast, for distant sites (>15 mm), white matter stimulation consistently produced larger responses than stimulation in or near grey matter. These relationships were different between cingulate, lateral prefrontal, and lateral temporal cortical stimulation. ConclusionThese results demonstrate the importance of location and stimulation parameters in inducing a specific output and indicate that a stronger local response may require stimulation in the grey-white boundary while stimulation in the white matter may be needed for network activation, suggesting that stimulation location can be tailored for a specific outcome, key to informed neuromodulatory therapy. HighlightsO_LIIntracranial single pulse electrical stimulation (SPES) response increases with increased pulse duration mostly near the stimulation site C_LIO_LISPES response varies nonlinearly with injected current with an effect of distance from the stimulation site. C_LIO_LISPES near the grey-white boundary and 90{degrees} to the nearest cortical axis induces larger local responses, but white matter stimulation produces larger distant responses. C_LIO_LIThe relationship between SPES location and responses depends on brain region stimulated C_LI

neuroscience↗

Detecting genes associated with pathogenicity and antimicrobial resistance in three New Zealand waterways.

BO_SCPLOWACKGROUNDC_SCPLOWMore than 100 zoonoses may be transmitted via water, among them enteric diseases are leading causes of human mortality. Traditional monitoring for zoonoses relies on culturing of indicator species, but environmental DNA (eDNA) provides an alternative, allowing direct testing for genetic loci associated with pathogenicity and/or antimicrobial resistance in zoonotic bacteria. OO_SCPLOWBJECTIVESC_SCPLOWTo evaluate whether genes associated with Shiga toxin producing Escherichia coli (STEC) and antimicrobial resistance can be monitored in waterways using culture-free sampling of eDNA combined with PCR-based testing. MO_SCPLOWETHODSC_SCPLOWWater and sediment samples were collected from two sites on each of three rivers in Canterbury, New Zealand; sample sites were situated above and below reaches bordered by intensive dairy farming. Samples from each site were tested for genes typically associated with Escherichia coli, STEC serogroups O26 and O157, human pathogenic strains of STEC, and resistance to a broad range of antibiotics. RO_SCPLOWESULTSC_SCPLOWBoth culturing and genetic testing confirmed the presence of E. coli in all samples. In contrast, presence of genes associated with STEC and antibiotic resistance varied by season and substrate. The O157 serogroup was identified at more than twice as many sites as O26, with the latter more common in autumn samples. In autumn, genes associated with pathogenic STEC were detected in one Ashley and both Rangitata River samples but were present in all spring samples, except one Ashley and one Selwyn River collection. The antibiotic resistance gene was only identified in spring, predominantly at sites downstream of intensive dairying. DO_SCPLOWISCUSSIONC_SCPLOWWhile our sample is small this study indicates that genetic testing of eDNA can be a useful tool for monitoring the presence and persistence of zoonoses in waterways. How the presence of these genetic elements is related to that of pathogenic STEC and incidence of disease in humans now needs to be examined.

ecology↗

Intracortical neural activity distal to seizure-onset-areas predicts human focal seizures

The apparent unpredictability of epileptic seizures has a major impact in the quality of life of people with pharmacologically resistant seizures. Here, we present initial results and a proof-of-concept of how focal seizures can be predicted early in advance based on intracortical signals recorded from small neocortical patches away from identified seizure onset areas. We show that machine learning algorithms can discriminate between interictal and preictal periods based on multiunit activity (i.e. thresholded action potential counts) and multi-frequency band local field potentials recorded via 4 X 4 mm2 microelectrode arrays. Microelectrode arrays were implanted in 5 patients undergoing neuromonitoring for resective surgery. Post-implant analysis revealed arrays were outside the seizure onset areas. Preictal periods were defined as the 1-hour period leading to a seizure. A 5-minute gap between the preictal period and the putative seizure onset was enforced to account for potential errors in the determination of actual seizure onset times. We used extreme gradient boosting and long short-term memory networks for prediction. Prediction accuracy based on the area under the receiver operating characteristic curves reached 90% for at least one feature type in each patient. Importantly, successful prediction could be achieved based exclusively on multiunit activity. This result indicates that preictal activity in the recorded neocortical patches involved not only subthreshold postsynaptic potentials, perhaps driven by the distal seizure onset areas, but also neuronal spiking in distal recurrent neocortical networks. Beyond the commonly identified seizure onset areas, our findings point to the engagement of large-scale neuronal networks in the neural dynamics building up toward a seizure. Our initial results obtained on currently available human intracortical recordings warrant new studies on larger datasets, and open new perspectives for seizure prediction and control by emphasizing the contribution of multiscale neural signals in large-scale neuronal networks.

neuroscience↗