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136 result(s) for "Grayden, David B"
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Circadian and circaseptan rhythms in human epilepsy: a retrospective cohort study
Epilepsy has long been suspected to be governed by cyclic rhythms, with seizure rates rising and falling periodically over weeks, months, or even years. The very long scales of seizure patterns seem to defy natural explanation and have sometimes been attributed to hormonal cycles or environmental factors. This study aimed to quantify the strength and prevalence of seizure cycles at multiple temporal scales across a large cohort of people with epilepsy. This retrospective cohort study used the two most comprehensive databases of human seizures (SeizureTracker [USA] and NeuroVista [Melbourne, VIC, Australia]) and analytic techniques from circular statistics to analyse patients with epilepsy for the presence and frequency of multitemporal cycles of seizure activity. NeuroVista patients were selected on the basis of having intractable focal epilepsy; data from patients with at least 30 clinical seizures were used. SeizureTracker participants are self selected and data do not adhere to any specific criteria; we used patients with a minimum of 100 seizures. The presence of seizure cycles over multiple time scales was measured using the mean resultant length (R value). The Rayleigh test and Hodges-Ajne test were used to test for circular uniformity. Monte-Carlo simulations were used to confirm the results of the Rayleigh test for seizure phase. We used data from 12 people from the NeuroVista study (data recorded from June 10, 2010, to Aug 22, 2012) and 1118 patients from the SeizureTracker database (data recorded from Jan 1, 2007, to Oct 19, 2015). At least 891 (80%) of 1118 patients in the SeizureTracker cohort and 11 (92%) of 12 patients in the NeuroVista cohort showed circadian (24 h) modulation of their seizure rates. In the NeuroVista cohort, patient 8 had a significant cycle at precisely 1 week. Two others (patients 1 and 7) also had approximately 1-week cycles. Patients 1 and 4 had 2-week cycles. In the SeizureTracker cohort, between 77 (7%) and 233 (21%) of the 1118 patients showed strong circaseptan (weekly) rhythms, with a clear 7-day period. Between 151 (14%) and 247 (22%) patients had significant seizure cycles that were longer than 3 weeks. Seizure cycles were equally prevalent in men and women, and peak seizure rates were evenly distributed across all days of the week. Our results suggest that seizure cycles are robust, patient specific, and more widespread than previously understood. They align with the accepted consensus that most epilepsies have some diurnal influence. Variations in seizure rate have important clinical implications. Detection and tracking of seizure cycles on a patient-specific basis should be standard in epilepsy management practices. Australian National Health and Medical Research Council.
Critical slowing down as a biomarker for seizure susceptibility
The human brain has the capacity to rapidly change state, and in epilepsy these state changes can be catastrophic, resulting in loss of consciousness, injury and even death. Theoretical interpretations considering the brain as a dynamical system suggest that prior to a seizure, recorded brain signals may exhibit critical slowing down, a warning signal preceding many critical transitions in dynamical systems. Using long-term intracranial electroencephalography (iEEG) recordings from fourteen patients with focal epilepsy, we monitored key signatures of critical slowing down prior to seizures. The metrics used to detect critical slowing down fluctuated over temporally long scales (hours to days), longer than would be detectable in standard clinical evaluation settings. Seizure risk was associated with a combination of these signals together with epileptiform discharges. These results provide strong validation of theoretical models and demonstrate that critical slowing down is a reliable indicator that could be used in seizure forecasting algorithms. Critical slowing (associated with increased variance and autocorrelation) can precede critical state transitions. Here, the authors show critical slowing can be used as a marker in seizure forecasting algorithms.
State transitions through inhibitory interneurons in a cortical network model
Inhibitory interneurons shape the spiking characteristics and computational properties of cortical networks. Interneuron subtypes can precisely regulate cortical function but the roles of interneuron subtypes for promoting different regimes of cortical activity remains unclear. Therefore, we investigated the impact of fast spiking and non-fast spiking interneuron subtypes on cortical activity using a network model with connectivity and synaptic properties constrained by experimental data. We found that network properties were more sensitive to modulation of the fast spiking population, with reductions of fast spiking excitability generating strong spike correlations and network oscillations. Paradoxically, reduced fast spiking excitability produced a reduction of global excitation-inhibition balance and features of an inhibition stabilised network, in which firing rates were driven by the activity of excitatory neurons within the network. Further analysis revealed that the synaptic interactions and biophysical features associated with fast spiking interneurons, in particular their rapid intrinsic response properties and short synaptic latency, enabled this state transition by enhancing gain within the excitatory population. Therefore, fast spiking interneurons may be uniquely positioned to control the strength of recurrent excitatory connectivity and the transition to an inhibition stabilised regime. Overall, our results suggest that interneuron subtypes can exert selective control over excitatory gain allowing for differential modulation of global network state.
Balancing prior knowledge and sensory data in a predictive coding model of coherent motion detection
This study introduces a neurobiologically inspired computational model based on the predictive coding algorithm, providing insights into coherent motion detection processes. The model is designed to reflect key principles observed in the visual system, particularly MT neurons and their surround suppression mechanisms, which play a critical role in detecting global motion. By integrating these principles, the model simulates how motion structures are decomposed into individual and shared sources, mirroring the brain’s strategy for extracting coherent motion patterns. The results obtained from random dot stimuli underscore the delicate balance between sensory data and prior knowledge in motion detection. Model testing across varying noise levels reveals that, as noise increases, the model takes longer to stabilize its motion estimates, consistent with psychophysical experiments showing that response duration (e.g., reaction time or decision-making time) also increases under higher noise conditions. The model suggests that an excessive emphasis on prior knowledge prolongs the stabilization time for motion detection, whereas an optimal integration of prior expectations enhances detection accuracy and efficiency by preventing excessive disturbances due to noise. These findings contribute to potential explanations for motion detection deficiencies observed in schizophrenia.
Towards developing brain-computer interfaces for people with Multiple Sclerosis
Multiple Sclerosis (MS) can be a severely disabling condition that leads to various neurological symptoms. A Brain-Computer Interface (BCI) may substitute some lost function; however, there is a lack of BCI research in people with MS. Present BCI designs have also overlooked the unique pathological changes associated with MS and have not considered needs of users within their home environments. To progress this research area effectively and efficiently, we aimed to evaluate user needs and assess the feasibility and user-centric requirements of a BCI for people with MS. We hypothesised that (i) people with MS would be interested in adopting BCI technology and (ii) those with reduced independence would prefer a higher-performing invasive BCI. We conducted an online survey of people with MS to describe user preferences and establish the initial steps of user-centred design. The survey aimed to understand their interest in BCI applications, bionic applications, device preferences, and development considerations and related these to symptoms and assistance needs. We demonstrated widespread interest for BCI applications in all stages of MS, with a preference for a non-invasive (n = 12) or minimally invasive (n = 15) BCI over carer assistance (n = 6). Descriptive analysis indicated that level of independence did not influence preference towards the higher performing but highly invasive BCI. The needs of end users reported in this study are crucial for efficient development of BCI systems that can be effectively translated into the home environment. Considering the potential to enhance independence and quality of life for people living with MS, the results emphasise the importance of user-centred design for future advancement of BCIs that account for the unique pathological changes associated with MS.
Frequency set selection for multi-frequency steady-state visual evoked potential-based brain-computer interfaces
Objective Multi-frequency steady-state visual evoked potential (SSVEP) stimulation and decoding methods enable the representation of a large number of visual targets in brain-computer interfaces (BCIs), but it is not yet widely used. One of the key reasons is that the redundancy in the input options requires an additional selection process to define an effective set of frequencies for the interface. This study investigates systematic frequency set selection methods. Methods An optimization strategy based on the analysis of the frequency components in the resulting multi-frequency SSVEP is proposed, investigated and compared to existing methods, which are constructed based on the analysis of the stimulation (input) signals. We hypothesized that minimizing the occurrence of common sums in the multi-frequency SSVEP improves the performance of the interface, and that selection by pairs further increases the accuracy compared to selection by frequencies. An experiment with 12 participants was conducted to validate the hypotheses. Results Our results demonstrated a statistically significant improvement in decoding accuracy with the proposed optimization strategy based on multi-frequency SSVEP features compared to conventional techniques. Both hypotheses were validated by the experiments. Conclusion Minimizing the number of common sums and performing selection by pairs are effective ways to select suitable frequency sets that improve multi-frequency SSVEP-based BCI accuracies. Significance This study provides guidance on frequency set selection in multi-frequency SSVEP. The proposed method in this study shows significant improvement in BCI performance (decoding accuracy) compared to existing methods in the literature.
Dynamic multiday seizure cycles and evolving rhythms in a tetanus toxin rat model of epilepsy
Epilepsy is characterized by recurrent, unpredictable seizures that impose significant challenges in daily management and treatment. One emerging area of interest is the identification of seizure cycles, including multiday patterns, which may offer insights into seizure prediction and treatment optimization. This study investigated multiday seizure cycles in a Tetanus Toxin (TT) rat model of epilepsy. Six TT-injected rats were observed over a 40-day period, with continuous EEG monitoring to record seizure events. Wavelet transform analysis revealed significant multiday cycles in seizure occurrences, with periods ranging from 4 to 7 days across different rats. Synchronization Index (SI) analysis demonstrated variable phase locking, with some rats showing strong synchronization of seizures with specific phases of the cycle. Importantly, the study revealed that these seizure cycles are dynamic and evolve over time, with some rats exhibiting shifts in cycle periods during the recording period. This suggests that the underlying neural mechanisms driving these cycles may change as the epileptic state progresses. The identification of stable and evolving multiday rhythms in seizure activity, independent of external factors, highlights a potential intrinsic biological basis for seizure timing. These findings offer promising avenues for improving seizure forecasting and designing personalized, timing-based therapeutic interventions in epilepsy. Future research should explore the underlying neural mechanisms and clinical applications of multiday seizure cycles.
GABA-mediated tonic inhibition differentially modulates gain in functional subtypes of cortical interneurons
The binding of GABA (γ-aminobutyric acid) to extrasynaptic GABAA receptors generates tonic inhibition that acts as a powerful modulator of cortical network activity. Despite GABA being present throughout the extracellular space of the brain, previous work has shown that GABA may differentially modulate the excitability of neuron subtypes according to variation in chloride gradient. Here, using biophysically detailed neuron models, we predict that tonic inhibition can differentially modulate the excitability of neuron subtypes according to variation in electrophysiological properties. Surprisingly, tonic inhibition increased the responsiveness (or gain) in models with features typical for somatostatin interneurons but decreased gain in models with features typical for parvalbumin interneurons. Patch-clamp recordings from cortical interneurons supported these predictions, and further in silico analysis was then performed to seek a putative mechanism underlying gain modulation. We found that gainmodulation in models was dependent upon the magnitude of tonic current generated at depolarized membrane potential—a property associated with outward rectifying GABAA receptors. Furthermore, tonic inhibition produced two biophysical changes in models of relevance to neuronal excitability: 1) enhanced action potential repolarization via increased current flow into the dendritic compartment, and 2) reduced activation of voltage-dependent potassium channels. Finally, we show theoretically that reduced potassium channel activation selectively increases gain in models possessing action potential dynamics typical for somatostatin interneurons. Potassium channels in parvalbumin-type models deactivate rapidly and are unavailable for further modulation. These findings show that GABA can differentially modulate interneuron excitability and suggest a mechanism through which this occurs in silico via differences of intrinsic electrophysiological properties.
Seizure pathways: A model-based investigation
We present the results of a model inversion algorithm for electrocorticography (ECoG) data recorded during epileptic seizures. The states and parameters of neural mass models were tracked during a total of over 3000 seizures from twelve patients with focal epilepsy. These models provide an estimate of the effective connectivity within intracortical circuits over the time course of seizures. Observing the dynamics of effective connectivity provides insight into mechanisms of seizures. Estimation of patients seizure dynamics revealed: 1) a highly stereotyped pattern of evolution for each patient, 2) distinct sub-groups of onset mechanisms amongst patients, and 3) different offset mechanisms for long and short seizures. Stereotypical dynamics suggest that, once initiated, seizures follow a deterministic path through the parameter space of a neural model. Furthermore, distinct sub-populations of patients were identified based on characteristic motifs in the dynamics at seizure onset. There were also distinct patterns between long and short duration seizures that were related to seizure offset. Understanding how these different patterns of seizure evolution arise may provide new insights into brain function and guide treatment for epilepsy, since specific therapies may have preferential effects on the various parameters that could potentially be individualized. Methods that unite computational models with data provide a powerful means to generate testable hypotheses for further experimental research. This work provides a demonstration that the hidden connectivity parameters of a neural mass model can be dynamically inferred from data. Our results underscore the power of theoretical models to inform epilepsy management. It is our hope that this work guides further efforts to apply computational models to clinical data.
Learning receptive field properties of complex cells in V1
There are two distinct classes of cells in the primary visual cortex (V1): simple cells and complex cells. One defining feature of complex cells is their spatial phase invariance; they respond strongly to oriented grating stimuli with a preferred orientation but with a wide range of spatial phases. A classical model of complete spatial phase invariance in complex cells is the energy model, in which the responses are the sum of the squared outputs of two linear spatially phase-shifted filters. However, recent experimental studies have shown that complex cells have a diverse range of spatial phase invariance and only a subset can be characterized by the energy model. While several models have been proposed to explain how complex cells could learn to be selective to orientation but invariant to spatial phase, most existing models overlook many biologically important details. We propose a biologically plausible model for complex cells that learns to pool inputs from simple cells based on the presentation of natural scene stimuli. The model is a three-layer network with rate-based neurons that describes the activities of LGN cells (layer 1), V1 simple cells (layer 2), and V1 complex cells (layer 3). The first two layers implement a recently proposed simple cell model that is biologically plausible and accounts for many experimental phenomena. The neural dynamics of the complex cells is modeled as the integration of simple cells inputs along with response normalization. Connections between LGN and simple cells are learned using Hebbian and anti-Hebbian plasticity. Connections between simple and complex cells are learned using a modified version of the Bienenstock, Cooper, and Munro (BCM) rule. Our results demonstrate that the learning rule can describe a diversity of complex cells, similar to those observed experimentally.