Publications by authors named "Southwell D"

Reliable and systematic experimental access to diverse cell types is necessary for understanding the neural circuit organization, function, and pathophysiology of the human brain. Methods for targeting human neural populations are scarce and currently center around identifying and engineering transcriptional enhancers and viral capsids. Here we demonstrate the utility of CellREADR, a programmable RNA sensor-effector technology that couples cellular RNA sensing to effector protein translation, for accessing, monitoring, and manipulating specific neuron types in human cortical tissues.

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Article Synopsis
  • The study presents two cases of sleep-related hypermotor epilepsy (SHE) linked to the occipital lobe in young females who experienced frequent sleep seizures and occasional tonic-clonic seizures with hypermotor movements.
  • SEEG monitoring revealed an epileptogenic zone in the occipital lobe, highlighting that most seizures occurred during NREM sleep.
  • This research suggests that occipital lobe seizures should be considered in diagnosing SHE, particularly when there are unique symptoms like visual aura and delayed motor responses.
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Quantifying the cost-effectiveness of alternative sampling methods is crucial for efficient biodiversity monitoring and detection of population trends. In this study, we compared the cost-effectiveness of three novel sampling methods for detecting changes in koala () occupancy: thermal drones, passive acoustic recorders and camera trapping. Specifically, we fitted single-season occupancy-detection models to data recorded from 46 sites in eight bioregions of New South Wales, Australia, between 2018 and 2022.

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This brief review summarizes presentations at the Temporal Lobe Club Special Interest Group session held in December 2022 at the American Epilepsy Society meeting. The session addressed newer methods to treat temporal epilepsy, including methods currently in clinical use and techniques under investigation. Brief summaries are provided for each of 4 lectures.

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Current epilepsy surgical techniques, such as brain resection, laser ablation, and neurostimulation, target seizure networks macroscopically, and they may yield an unfavorable balance between seizure reduction, procedural invasiveness, and neurologic morbidity. The transplantation of GABAergic interneurons is a regenerative technique for altering neural inhibition in cortical circuits, with potential as an alternative and minimally invasive approach to epilepsy treatment. This article (1) reviews some of the preclinical evidence supporting interneuron transplantation as an epilepsy therapy, (2) describes a first-in-human study of interneuron transplantation for epilepsy, and (3) considers knowledge gaps that stand before the effective clinical application of this novel treatment.

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Patients suffering from debilitating neurodegenerative diseases often lose the ability to communicate, detrimentally affecting their quality of life. One solution to restore communication is to decode signals directly from the brain to enable neural speech prostheses. However, decoding has been limited by coarse neural recordings which inadequately capture the rich spatio-temporal structure of human brain signals.

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Objective: Effective surgical treatment of drug-resistant epilepsy depends on accurate localization of the epileptogenic zone (EZ). High-frequency oscillations (HFOs) are potential biomarkers of the EZ. Previous research has shown that HFOs often occur within submillimeter areas of brain tissue and that the coarse spatial sampling of clinical intracranial electrode arrays may limit the accurate capture of HFO activity.

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Monitoring trends in animal populations in arid regions is challenging due to remoteness and low population densities. However, detecting species' tracks or signs is an effective survey technique for monitoring population trends across large spatial and temporal scales. In this study, we developed a simulation framework to evaluate the performance of alternative track-based monitoring designs at detecting change in species distributions in arid Australia.

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RNA is a central and universal mediator of genetic information underlying the diversity of cell types and cell states, which together shape tissue organization and organismal function across species and lifespans. Despite numerous advances in RNA sequencing technologies and the massive accumulation of transcriptome datasets across the life sciences, the dearth of technologies that use RNAs to observe and manipulate cell types remains a bottleneck in biology and medicine. Here we describe CellREADR (Cell access through RNA sensing by Endogenous ADAR), a programmable RNA-sensing technology that leverages RNA editing mediated by ADAR to couple the detection of cell-defining RNAs with the translation of effector proteins.

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Background: Musicogenic epilepsy (ME) is a rare reflex epilepsy in which seizures are triggered by musical stimuli. Prior descriptions of ME have suggested localization to the nondominant temporal lobe, primarily in neocortex. Although resection has been described as a treatment for ME, other surgical modalities, such as laser ablation, may effectively disrupt seizure networks in ME while incurring comparatively lower risks of morbidity.

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One-third of epilepsy patients suffer from medication-resistant seizures. While surgery to remove epileptogenic tissue helps some patients, 30-70% of patients continue to experience seizures following resection. Surgical outcomes may be improved with more accurate localization of epileptogenic tissue.

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Brain functions such as perception, motor control, learning, and memory arise from the coordinated activity of neuronal assemblies distributed across multiple brain regions. While major progress has been made in understanding the function of individual neurons, circuit interactions remain poorly understood. A fundamental obstacle to deciphering circuit interactions is the limited availability of research tools to observe and manipulate the activity of large, distributed neuronal populations in humans.

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Article Synopsis
  • Developers legally need to offset environmental impacts, often using vegetation condition metrics, but their effectiveness for maintaining biodiversity is uncertain.
  • A study in the Hunter Region of New South Wales simulated development and restoration to assess how different offset strategies affected three species, showing that habitat gains didn't always support species persistence.
  • The findings highlight the importance of considering specific species needs and population dynamics in offset policies, as relying solely on vegetation metrics can mislead efforts to achieve no net loss in biodiversity.
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Brain tumors, such as low grade gliomas (LGG), are molecularly classified which require the surgical collection of tissue samples. The pre-surgical or non-operative identification of LGG molecular type could improve patient counseling and treatment decisions. However, radiographic approaches to LGG molecular classification are currently lacking, as clinicians are unable to reliably predict LGG molecular type using magnetic resonance imaging (MRI) studies.

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Monitoring of threatened species and threatened ecosystems is critical for determining population trends, identifying urgency of management responses, and assessing the efficacy of management interventions. Yet many threatened species and threatened ecosystems are not monitored and for those that are, the quality of the monitoring is often poor. Here we provide a checklist of factors that need to be considered for inclusion in robust monitoring programs for threatened species and threatened ecosystems.

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Excitatory-inhibitory imbalance is central to epilepsy pathophysiology. Current surgical therapies for epilepsy, such as brain resection, laser ablation, and neurostimulation, target epileptic networks on macroscopic scales, without directly correcting the circuit-level aberrations responsible for seizures. The transplantation of inhibitory cortical interneurons represents a novel neurobiological method for modifying recipient neural circuits in a physiologically corrective manner.

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Manipulations that enhance GABAergic inhibition have been associated with improved behavioral phenotypes in autism models, suggesting that autism may be treated by correcting underlying deficits of inhibition. Interneuron transplantation is a method for increasing recipient synaptic inhibition, and it has been considered a prospective therapy for conditions marked by deficient inhibition, including neuropsychiatric disorders. It is unknown, however, whether interneuron transplantation may be therapeutically effective only for conditions marked by reduced inhibition, and it is also unclear whether transplantation improves behavioral phenotypes solely by normalizing underlying circuit defects.

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Assessing the statistical power to detect changes in wildlife populations is a crucial yet often overlooked step when designing and evaluating monitoring programs. Here, we developed a simulation framework to perform spatially explicit statistical power analysis of biological monitoring programs for detecting temporal trends in occupancy for multiple species. Using raster layers representing the spatial variation in current occupancy and species-level detectability for one or multiple observation methods, our framework simulates changes in occupancy over space and time, with the capacity to explicitly model stochastic disturbances at monitoring sites (i.

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Background: Intraoperative stimulation of the posterior inferior frontal lobe (IFL) induces speech arrest, which is often interpreted as demonstration of essential language function. However, prior reports have described "negative motor areas" in the IFL, sites where stimulation halts ongoing limb motor activity.

Objective: To investigate the spatial and functional relationship between IFL speech arrest areas and negative motor areas (NMAs).

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Understanding where species occur and how difficult they are to detect during surveys is crucial for designing and evaluating monitoring programs, and has broader applications for conservation planning and management. In this study, we modelled occupancy and the effectiveness of six sampling methods at detecting vertebrates across the Top End of northern Australia. We fitted occupancy-detection models to 136 species (83 birds, 33 reptiles, 20 mammals) of 242 recorded during surveys of 333 sites in eight conservation reserves between 2011 and 2016.

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Targeted threatened species management is a central component of efforts to prevent species extinction. Despite the development of a range of management frameworks to improve conservation outcomes over the past decade, threatened species management is still commonly characterised as ad hoc. Although there are notable successes, many management programs are ineffective, with relatively few species experiencing improvements in their conservation status.

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Background And Importance: Skull base surgery involves the microdissection and intraoperative monitoring of cranial nerves, including cranial nerve XI (CN XI). Manipulation of CN XI can evoke brisk trapezius contraction, which in turn may disturb the surgical procedure and risk patient safety. Here we describe a method for temporarily silencing CN XI via direct intraoperative application of 1% lidocaine.

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Hypothalamic hamartomas (HHs) are benign lesions that cause medically refractory seizures, behavioral disturbances, and endocrine dysfunction. Open resection of HHs does not guarantee seizure freedom and carries a relatively high risk of morbidity. Minimally invasive stereotactic laser ablation has recently been described as an effective and safe alternative for HH treatment.

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