Interaction of synchronized dynamics in cortex and basal ganglia in Parkinson's disease.

Parkinson's disease pathophysiology is marked by increased oscillatory and synchronous activity in the beta frequency band in cortical and basal ganglia circuits. This study explores the functional connections between synchronized dynamics of cortical areas and synchronized dynamics of subcortical areas in Parkinson's disease. We simultaneously recorded neuronal units (spikes) and local field potentials (LFP) from subthalamic nucleus (STN) and electroencephalograms (EEGs) from the scalp in parkinsonian patients, and analysed the correlation between the time courses of the spike-LFP synchronization and inter-electrode EEG synchronization. We found the (non-invasively obtained) time course of the synchrony strength between EEG electrodes and the (invasively obtained) time course of the synchrony between spiking units and LFP in STN to be weakly, but significantly, correlated with each other. This correlation is largest for the bilateral motor EEG synchronization, followed by bilateral frontal EEG synchronization. Our observations suggest that there may be multiple functional modes by which the cortical and basal ganglia circuits interact with each other in Parkinson's disease: not only may synchronization be observed between some areas in cortex and the basal ganglia, but also synchronization within cortex and within basal ganglia may be related, suggesting potentially a more global functional interaction. More coherent dynamics in one brain region may modulate or activate the dynamics of another brain region in a more powerful way, causing correlations between changes in synchrony strength in the two regions.

A Literature Review of Similarities Between and Among Patients With Autism Spectrum Disorder and Epilepsy.

Autism spectrum disorder (ASD) has been shown to be associated with various other conditions, and most commonly, ASD has been demonstrated to be linked to epilepsy. ASD and epilepsy have been observed to exhibit high rates of comorbidity, even when compared to the co-occurrence of other disorders with similar pathologies. At present, nearly one-half of the individuals diagnosed with ASD also have been diagnosed with comorbid epilepsy. Research suggests that both conditions likely share similarities in their underlying disease pathophysiology, possibly associated with disturbances in the central nervous system (CNS), and may be linked to an imbalance between excitation and inhibition in the brain. Meanwhile, it remains unclear whether one condition is the consequence of the other, as the pathologies of both disorders are commonly linked to many different underlying signal transduction mechanisms. In this review, we aim to investigate the co-occurrence of ASD and epilepsy, with the intent of gaining insights into the similarities in pathophysiology that both conditions present with. Elucidating the underlying disease pathophysiology as a result of both disorders could lead to a better understanding of the underlying mechanism of disease activity that drives co-occurrence, as well as provide insight into the underlying mechanisms of each condition individually.

SEM and TEM data of nuclear graphite and glassy carbon microstructures.

Micrographs of multiple nuclear graphite grades were captured using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), complementing the data contained in the related manuscript, "A multi-technique image library of nuclear graphite microstructures of historical and modern grades." The SEM micrographs show the differences among filler particles, binder, and thermal cracks contained in nuclear graphite. This library of microstructures serves as a baseline of as-received material and enables understanding the phases and differences between nuclear grades. TEM micrographs included in this manuscript elucidate the content of a common material contained in the binder phase known as quinoline insoluble (QI) particles. These particles are a phase of graphite that can be used as a forensic fingerprint of the neutron irradiation effects in graphite. The manuscript also contains some data of glassy carbon, an allotrope of carbon that shares similarities with some of the chaotic structures in nuclear graphite. Combined, these micrographs provide a detailed overview of the microstructures of various graphite grades prior to neutron irradiation.

Intermittent neural synchronization in Parkinson's disease.

Motor symptoms of Parkinson's disease are related to the excessive synchronized oscillatory activity in the beta frequency band (around 20Hz) in the basal ganglia and other parts of the brain. This review explores the dynamics and potential mechanisms of these oscillations employing ideas and methods from nonlinear dynamics. We present extensive experimental documentation of the relevance of synchronized oscillations to motor behavior in Parkinson's disease, and we discuss the intermittent character of this synchronization. The reader is introduced to novel time-series analysis techniques aimed at the detection of the fine temporal structure of intermittent phase locking observed in the brains of parkinsonian patients. Modeling studies of brain networks are reviewed, which may describe the observed intermittent synchrony, and we discuss what these studies reveal about brain dynamics in Parkinson's disease. The parkinsonian brain appears to exist on the boundary between phase-locked and nonsynchronous dynamics. Such a situation may be beneficial in the healthy state, as it may allow for easy formation and dissociation of transient patterns of synchronous activity which are required for normal motor behavior. Dopaminergic degeneration in Parkinson's disease may shift the brain networks closer to this boundary, which would still permit some motor behavior while accounting for the associated motor deficits. Understanding the mechanisms of the intermittent synchrony in Parkinson's disease is also important for biomedical engineering since efficient control strategies for suppression of pathological synchrony through deep brain stimulation require knowledge of the dynamics of the processes subjected to control.

Microstructural characterization data of as received IG-110, 2114 and ETU-10 nuclear graphite grades and oxidation characterization data of IG-110.

This manuscript provides optical microscopy, scanning electron microscopy, and transmission electron microscopy micrographs that show the microstructure of three superfine nuclear graphite grades IG-110, 2114 and ETU-10. This collection of microstructural data showcases the microstructure of these materials and helps to differentiate the most important features or phases of these graphite grades. In particular, the microstructural data illustrate the filler and binder morphology of these grades. Moreover, samples of as-received and oxidized IG-110 were characterized via optical microscopy and x-ray computed tomography. The microstructural data of oxidized IG-110 shows the porosity generated by oxidation experiments. These micrographs and data provide a unique insight into the microstructural features and oxidation effects in nuclear graphite and can be used to perform quantitative porosity analysis. This collection of microstructural data complements the modeling and characterization described in the associated manuscript, "Using porous random fields to predict the elastic modulus of unoxidized and oxidized superfine graphite (Arregui-Mena et al., 2022)."

Fine temporal structure of beta oscillations synchronization in subthalamic nucleus in Parkinson's disease.

Synchronous oscillatory dynamics in the beta frequency band is a characteristic feature of neuronal activity of basal ganglia in Parkinson's disease and is hypothesized to be related to the disease's hypokinetic symptoms. This study explores the temporal structure of this synchronization during episodes of oscillatory beta-band activity. Phase synchronization (phase locking) between extracellular units and local field potentials (LFPs) from the subthalamic nucleus (STN) of parkinsonian patients is analyzed here at a high temporal resolution. We use methods of nonlinear dynamics theory to construct first-return maps for the phases of oscillations and quantify their dynamics. Synchronous episodes are interrupted by less synchronous episodes in an irregular yet structured manner. We estimate probabilities for different kinds of these "desynchronization events." There is a dominance of relatively frequent yet very brief desynchronization events with the most likely desynchronization lasting for about one cycle of oscillations. The chances of longer desynchronization events decrease with their duration. The observed synchronization may primarily reflect the relationship between synaptic input to STN and somatic/axonal output from STN at rest. The intermittent, transient character of synchrony even on very short time scales may reflect the possibility for the basal ganglia to carry out some informational function even in the parkinsonian state. The dominance of short desynchronization events suggests that even though the synchronization in parkinsonian basal ganglia is fragile enough to be frequently destabilized, it has the ability to reestablish itself very quickly.

Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy.

PURPOSE: We report a multicenter, double-blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization-related epilepsy. METHODS: Participants were adults with medically refractory partial seizures, including secondarily generalized seizures. Half received stimulation and half no stimulation during a 3-month blinded phase; then all received unblinded stimulation. RESULTS: One hundred ten participants were randomized. Baseline monthly median seizure frequency was 19.5. In the last month of the blinded phase the stimulated group had a 29% greater reduction in seizures compared with the control group, as estimated by a generalized estimating equations (GEE) model (p = 0.002). Unadjusted median declines at the end of the blinded phase were 14.5% in the control group and 40.4% in the stimulated group. Complex partial and "most severe" seizures were significantly reduced by stimulation. By 2 years, there was a 56% median percent reduction in seizure frequency; 54% of patients had a seizure reduction of at least 50%, and 14 patients were seizure-free for at least 6 months. Five deaths occurred and none were from implantation or stimulation. No participant had symptomatic hemorrhage or brain infection. Two participants had acute, transient stimulation-associated seizures. Cognition and mood showed no group differences, but participants in the stimulated group were more likely to report depression or memory problems as adverse events. DISCUSSION: Bilateral stimulation of the anterior nuclei of the thalamus reduces seizures. Benefit persisted for 2 years of study. Complication rates were modest. Deep brain stimulation of the anterior thalamus is useful for some people with medically refractory partial and secondarily generalized seizures.

Connecting concepts in the brain by mapping cortical representations of semantic relations.

In the brain, the semantic system is thought to store concepts. However, little is known about how it connects different concepts and infers semantic relations. To address this question, we collected hours of functional magnetic resonance imaging data from human subjects listening to natural stories. We developed a predictive model of the voxel-wise response and further applied it to thousands of new words. Our results suggest that both semantic categories and relations are represented by spatially overlapping cortical patterns, instead of anatomically segregated regions. Semantic relations that reflect conceptual progression from concreteness to abstractness are represented by cortical patterns of activation in the default mode network and deactivation in the frontoparietal attention network. We conclude that the human brain uses distributed networks to encode not only concepts but also relationships between concepts. In particular, the default mode network plays a central role in semantic processing for abstraction of concepts.

Critical and Ictal Phases in Simulated EEG Signals on a Small-World Network.

Healthy brain function is marked by neuronal network dynamics at or near the critical phase, which separates regimes of instability and stasis. A failure to remain at this critical point can lead to neurological disorders such as epilepsy, which is associated with pathological synchronization of neuronal oscillations. Using full Hodgkin-Huxley (HH) simulations on a Small-World Network, we are able to generate synthetic electroencephalogram (EEG) signals with intervals corresponding to seizure (ictal) or non-seizure (interictal) states that can occur based on the hyperexcitability of the artificial neurons and the strength and topology of the synaptic connections between them. These interictal simulations can be further classified into scale-free critical phases and disjoint subcritical exponential phases. By changing the HH parameters, we can model seizures due to a variety of causes, including traumatic brain injury (TBI), congenital channelopathies, and idiopathic etiologies, as well as the effects of anticonvulsant drugs. The results of this work may be used to help identify parameters from actual patient EEG or electrocorticographic (ECoG) data associated with ictogenesis, as well as generating simulated data for training machine-learning seizure prediction algorithms.

Gamma knife stereotactic radiosurgery for low-grade astrocytomas.

Patients with low-grade astrocytoma (LGA; 8 pilocytic astrocytomas, 2 subependymal giant cell astrocytomas, 2 fibrillary astrocytomas) were selected for treatment with gamma knife stereotactic radiosurgery (GKSRS) based on having a demarcated appearance on CT or MRI and the possibility of dose sparing of adjacent eloquent structures. A median dose of 13 Gy was prescribed to the 50% isodose line, which covered the gross tumor. The median patient age was 17.4 years. The median target volume was 4.4 cm(3). With a median follow-up of 48.2 months, 4-year tumor control and overall survival were 77 and 83%, respectively. Only 2 patients experienced symptomatic treatment-related toxicity. GKSRS can provide local control in cases of unresectable or recurrent LGA with a low incidence of side effects in carefully selected patients.

Endocrine response after gamma knife-based stereotactic radiosurgery for secretory pituitary adenoma.

PURPOSE: To examine treatment outcomes of Gamma Knife-based stereotactic radiosurgery (GK-based SRS) for secretory pituitary adenomas. MATERIALS AND METHODS: 25 patients were treated with GK-based SRS for secretory pituitary adenomas with >or=12 months of follow-up. RESULTS: For prolactinomas, 2 of 4 patients (50%) showed normalization of serum prolactin at a mean time of 18 months. One of 4 had a >or=50% decrease but still abnormal prolactin levels. For adrenocorticotrophic hormone-secreting tumors, 6 of 12 patients (50%) showed normalization of their endocrine levels at a median of 10 months. An additional 2 (17%) had a >or=50% decrease. For growth hormone-secreting tumors, 4 of 9 patients (44%) showed normalization of endocrine levels at a median time of 30 months. Two patients (22%) had >or=50% lower but abnormal endocrine levels. CONCLUSION: GK-based SRS provides a reasonable rate of endocrine normalization of secretory pituitary adenoma. The time to endocrine response is shorter than reported for fractionated external beam radiotherapy. There is a low risk of optic neuropathy.

Hospital Length of Stay and Readmission Rate for Neurosurgical Patients.

BACKGROUND: Hospital readmission rate has become a major indicator of quality of care, with penalties given to hospitals with high rates of readmission. At the same time, insurers are increasing pressure for greater efficiency and reduced costs, including decreasing hospital lengths of stay (LOS). OBJECTIVE: To analyze the authors' service to determine if there is a relationship between LOS and readmission rates. METHODS: Records of patients admitted to the authors' institution from October 2007 through June 2014 were analyzed for several data points, including initial LOS, readmission occurrence, admitting and secondary diagnoses, and discharge disposition. RESULTS: Out of 9409 patient encounters, there were 925 readmissions. Average LOS was 6 d. Univariate analysis indicated a higher readmission rate with more diagnoses upon admission (P < .001) and an association between insurance type and readmission (P < .001), as well as decreasing average yearly LOS (P = .0045). Multivariate analysis indicated statistically significant associations between longer LOS (P = .03) and government insurance (P < .01). CONCLUSION: A decreasing LOS over time has been associated with an increasing readmission rate at the population level. However, at the individual level, a prolonged LOS was associated with a higher risk of readmission. This was attributed to patient comorbidities. However, this increasing readmission rate may represent many factors including patients' overall health status. Thus, the rate of readmission may represent a burden of illness rather than a valid metric for quality of care.

Stereotactic radiosurgery and fractionated stereotactic radiotherapy in the treatment of uveal melanoma.

Uveal melanoma is the most common primary intraocular malignant tumor. Radiation therapy has now replaced enucleation as the treatment of choice, with radioactive eye plaques and proton therapy being the two most studied radiotherapy modalities. More recently, stereotactic radiosurgery and fractionated stereotactic radiotherapy have emerged as promising, non-invasive treatments for uveal melanoma. This review summarizes the available literature on these newer treatment modalities.

Synchronized Beta-Band Oscillations in a Model of the Globus Pallidus-Subthalamic Nucleus Network under External Input.

Hypokinetic symptoms of Parkinson's disease are usually associated with excessively strong oscillations and synchrony in the beta frequency band. The origin of this synchronized oscillatory dynamics is being debated. Cortical circuits may be a critical source of excessive beta in Parkinson's disease. However, subthalamo-pallidal circuits were also suggested to be a substantial component in generation and/or maintenance of Parkinsonian beta activity. Here we study how the subthalamo-pallidal circuits interact with input signals in the beta frequency band, representing cortical input. We use conductance-based models of the subthalamo-pallidal network and two types of input signals: artificially-generated inputs and input signals obtained from recordings in Parkinsonian patients. The resulting model network dynamics is compared with the dynamics of the experimental recordings from patient's basal ganglia. Our results indicate that the subthalamo-pallidal model network exhibits multiple resonances in response to inputs in the beta band. For a relatively broad range of network parameters, there is always a certain input strength, which will induce patterns of synchrony similar to the experimentally observed ones. This ability of the subthalamo-pallidal network to exhibit realistic patterns of synchronous oscillatory activity under broad conditions may indicate that these basal ganglia circuits are directly involved in the expression of Parkinsonian synchronized beta oscillations. Thus, Parkinsonian synchronized beta oscillations may be promoted by the simultaneous action of both cortical (or some other) and subthalamo-pallidal network mechanisms. Hence, these mechanisms are not necessarily mutually exclusive.

Inguinal neurectomy for inguinal nerve entrapment: an experience with 100 patients.

BACKGROUND: Inguinal nerve entrapment is a debilitating postoperative problem. PATIENTS AND METHODS: One hundred patients were treated for inguinal nerve entrapment, including 52 men and 48 women with an average age of 45 +/- 14 years. Most patients had inguinal hernia repairs or Pfannenstiel incisions. Mesh was found in 27% of patients. Symptoms included pain (100%), radiation of pain to the thigh and/or genital area (59%), and postural pain (59%). Diagnosis was made by physical examination, postural maneuvering, and inguinal nerve block. Proximal nerve resection was followed by Mersiline (Ethicon, Inc., Somerville, NJ) ligature and absolute alcohol or phenol application to prevent neuromas. RESULTS: Five percent of patients had minor complications. There was abnormal nerve histopathology in 18%. Total pain relief was attained in 72% of patients, partial relief in 25%, and no relief in 3%. Two patients complained of numbness postoperatively. Multifactorial analysis showed recurrent hernia repair as a significant predictive factor.

A flexible platform for biofeedback-driven control and personalization of electrical nerve stimulation therapy.

Electrical vagus nerve stimulation is a treatment alternative for many epileptic and depressed patients whose symptoms are not well managed with pharmaceutical therapy. However, the fixed stimulus, open loop dosing mechanism limits its efficacy and precludes major advances in the quality of therapy. A real-time, responsive form of vagus nerve stimulation is needed to control nerve activation according to therapeutic need. This personalized approach to therapy will improve efficacy and reduce the number and severity of side effects. We present autonomous neural control, a responsive, biofeedback-driven approach that uses the degree of measured nerve activation to control stimulus delivery. We demonstrate autonomous neural control in rats, showing that it rapidly learns how to most efficiently activate any desired proportion of vagal A, B, and/or C fibers over time. This system will maximize efficacy by minimizing patient response variability and by minimizing therapeutic failures resulting from longitudinal decreases in nerve activation with increasing durations of treatment. The value of autonomous neural control equally applies to other applications of electrical nerve stimulation.

Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy.

OBJECTIVE: To report long-term efficacy and safety results of the SANTE trial investigating deep brain stimulation of the anterior nucleus of the thalamus (ANT) for treatment of localization-related epilepsy. METHODS: This long-term follow-up is a continuation of a previously reported trial of 5- vs 0-V ANT stimulation. Long-term follow-up began 13 months after device implantation with stimulation parameters adjusted at the investigators' discretion. Seizure frequency was determined using daily seizure diaries. RESULTS: The median percent seizure reduction from baseline at 1 year was 41%, and 69% at 5 years. The responder rate (≥50% reduction in seizure frequency) at 1 year was 43%, and 68% at 5 years. In the 5 years of follow-up, 16% of subjects were seizure-free for at least 6 months. There were no reported unanticipated adverse device effects or symptomatic intracranial hemorrhages. The Liverpool Seizure Severity Scale and 31-item Quality of Life in Epilepsy measure showed statistically significant improvement over baseline by 1 year and at 5 years (p < 0.001). CONCLUSION: Long-term follow-up of ANT deep brain stimulation showed sustained efficacy and safety in a treatment-resistant population. CLASSIFICATION OF EVIDENCE: This long-term follow-up provides Class IV evidence that for patients with drug-resistant partial epilepsy, anterior thalamic stimulation is associated with a 69% reduction in seizure frequency and a 34% serious device-related adverse event rate at 5 years.

Failure of single-unit neuronal activity to differentiate globus pallidus internus and externus in Parkinson disease.

OBJECT: The authors examine the validity of single-unit neuronal recordings as a method of differentiating the globus pallidus internus (GPi) from the GP externus (GPe) in Parkinson Disease. METHODS: One hundred twenty-eight recordings of apparent single-unit activity used to help guide final electrode placement in eight patients who underwent pallidotomy were analyzed using sophisticated spike sorting methods, and 185 neurons were characterized for mean firing frequency and percent of firing within bursts. In addition, the total spectral power was calculated on the full measured waveform for each of 128 samples without spike sorting. No correlation was identified between these measures of neuronal activity and depth within the GP. CONCLUSIONS: These results call into question the validity of relying on single-unit activity and microelectrode recordings in the operating room to localize lesion or electrode placement within the GPi during stereotactic pallidal surgery.

A coupled ordinary differential equation lattice model for the simulation of epileptic seizures.

A coupled ordinary differential equation lattice model for the CA3 region of the hippocampus (a common location of the epileptic focus) is developed. This model consists of a hexagonal lattice of nodes, each describing a subnetwork consisting of a group of prototypical excitatory pyramidal cells and a group of prototypical inhibitory interneurons connected via on/off excitatory and inhibitory synapses. The nodes communicate using simple rules to simulate the diffusion of extracellular potassium. Both the integration time over which a node's trajectory is integrated before the diffusional event is allowed to occur and the level of inhibition in each node were found to be important parameters. Shorter integration times lead to total synchronization of the lattice (similar to synchronous neural activity occurring during a seizure) whereas longer times cause more random spatiotemporal behavior. Moderately diminished levels of inhibition lead to simple nodal oscillatory behavior. It is postulated that both the lack of inhibition and an alteration in conduction time may be necessary for the development of a behaviorally manifest seizure. (c) 1999 American Institute of Physics.

Failure of delayed feedback deep brain stimulation for intermittent pathological synchronization in Parkinson's disease.

Suppression of excessively synchronous beta-band oscillatory activity in the brain is believed to suppress hypokinetic motor symptoms of Parkinson's disease. Recently, a lot of interest has been devoted to desynchronizing delayed feedback deep brain stimulation (DBS). This type of synchrony control was shown to destabilize the synchronized state in networks of simple model oscillators as well as in networks of coupled model neurons. However, the dynamics of the neural activity in Parkinson's disease exhibits complex intermittent synchronous patterns, far from the idealized synchronous dynamics used to study the delayed feedback stimulation. This study explores the action of delayed feedback stimulation on partially synchronized oscillatory dynamics, similar to what one observes experimentally in parkinsonian patients. We employ a computational model of the basal ganglia networks which reproduces experimentally observed fine temporal structure of the synchronous dynamics. When the parameters of our model are such that the synchrony is unphysiologically strong, the feedback exerts a desynchronizing action. However, when the network is tuned to reproduce the highly variable temporal patterns observed experimentally, the same kind of delayed feedback may actually increase the synchrony. As network parameters are changed from the range which produces complete synchrony to those favoring less synchronous dynamics, desynchronizing delayed feedback may gradually turn into synchronizing stimulation. This suggests that delayed feedback DBS in Parkinson's disease may boost rather than suppress synchronization and is unlikely to be clinically successful. The study also indicates that delayed feedback stimulation may not necessarily exhibit a desynchronization effect when acting on a physiologically realistic partially synchronous dynamics, and provides an example of how to estimate the stimulation effect.