Emergence of structures in neuronal network activities.

Nonlinear responses of individual neurons are both experimentally established and considered fundamental for the functioning of neuronal circuitry. Consequently, one may envisage the collective dynamics of large networks of neurons exhibiting a large repertoire of nonlinear behaviors. However, an ongoing and central challenge in the modeling of neural dynamics involves the trade-off between tractability and biological realism.

Spectrum dependency to rate and spike timing in neuronal spike trains.

Background: Spike trains are series of interspike intervals in a specific order that can be characterized by their probability distributions and order in time which refer to the concepts of rate and spike timing features. Periodic structure in the spike train can be reflected in oscillatory activities. Thus, there is a direct link between oscillator activities and the spike train.

Challenges for future theories of Parkinson pathophysiology.

Current theories on the basal ganglia-thalamic-cortical circuitry address the phenomena of hypokinesia and hyperkinesia. In this Perspective, we question whether the current models can address the orchestration of the motor units which is the common final pathway of the motor system. We conclude that the current theories do not to address this orchestration in health and disease.

Modeling and Theories of Pathophysiology and Physiology of the Basal Ganglia-Thalamic-Cortical System: Critical Analysis.

Theories impact the movement disorders clinic, not only affecting the development of new therapies but determining how current therapies are used. Models are theories that are procedural rather than declarative. Theories and models are important because, as argued by Kant, one cannot know the thing-in-itself (das Ding an sich) and only a model is knowable.

Deep Brain Stimulation Frequency-A Divining Rod for New and Novel Concepts of Nervous System Function and Therapy.

The efficacy of Deep Brain Stimulation (DBS) for an expanding array of neurological and psychiatric disorders demonstrates directly that DBS affects the basic electroneurophysiological mechanisms of the brain. The increasing array of active electrode configurations, stimulation currents, pulse widths, frequencies, and pulse patterns provides valuable tools to probe electroneurophysiological mechanisms. The extension of basic electroneurophysiological and anatomical concepts using sophisticated computational modeling and simulation has provided relatively straightforward explanations of all the DBS parameters except frequency.

Computer-Guided Deep Brain Stimulation Programming for Parkinson's Disease.

Objective: Pilot study to evaluate computer-guided deep brain stimulation (DBS) programming designed to optimize stimulation settings using objective motion sensor-based motor assessments.

Materials And Methods: Seven subjects (five males; 54-71 years) with Parkinson's disease (PD) and recently implanted DBS systems participated in this pilot study. Within two months of lead implantation, the subject returned to the clinic to undergo computer-guided programming and parameter selection.

Neuronal Complexity in Subthalamic Nucleus is Reduced in Parkinson's Disease.

Several theories posit increased Subthalamic Nucleus (STN) activity is causal to Parkinsonism, yet in our previous study we showed that activity from 113 STN neurons from two epilepsy patients and 103 neurons from nine Parkinson's disease (PD) patients demonstrated no significant differences in frequencies or in the coefficients of variation of mean discharge frequencies per 1-s epochs. We continued our analysis using point process modeling to capture higher order temporal dynamics; in particular, bursting, beta-band oscillations, excitatory and inhibitory ensemble interactions, and neuronal complexity. We used this analysis as input to a logistic regression classifier and were able to differentiate between PD and epilepsy neurons with an accuracy of 92%.

Therapeutic mechanisms of high-frequency stimulation in Parkinson's disease and neural restoration via loop-based reinforcement.

High-frequency deep brain stimulation (HFS) is clinically recognized to treat parkinsonian movement disorders, but its mechanisms remain elusive. Current hypotheses suggest that the therapeutic merit of HFS stems from increasing the regularity of the firing patterns in the basal ganglia (BG). Although this is consistent with experiments in humans and animal models of Parkinsonism, it is unclear how the pattern regularization would originate from HFS.

Development of a clinician worn device for the evaluation of abnormal muscle tone.

Neurological disorders such as cerebral palsy commonly result in abnormal muscle hyperactivity that negatively effects functional use of the affected limbs. Individuals with cerebral palsy often present with a mix of spasticity and dystonia, and it can be difficult to distinguish between the effects of these types of abnormal tone. Different types of abnormal tone respond differently to treatments such as deep brain stimulation and baclofen.

The rationale driving the evolution of deep brain stimulation to constant-current devices.

Objective: Deep brain stimulation (DBS) is an effective therapy for the treatment of a number of movement and neuropsychiatric disorders. The effectiveness of DBS is dependent on the density and location of stimulation in a given brain area. Adjustments are made to optimize clinical benefits and minimize side effects.

Effects of deep brain stimulation frequency on bradykinesia of Parkinson's disease.

Deep brain stimulation (DBS) in Parkinson's disease (PD) is frequency-dependent. Past studies of the effect of DBS frequency, however, involved scrutiny of too few frequencies to eliminate risk of undersampling. Also, these studies presented averaged measures across subjects; high intersubject variability makes these measures problematic.

Reinforcement mechanisms in putamen during high frequency STN DBS: A point process study.

Despite a pivotal role in the motor loop, dorsolateral striatum (putamen) has been poorly studied thus far under Parkinsonian conditions and Deep Brain Stimulation (DBS). We analyze the activity of the putamen in a monkey by combining single unit recordings and point process models. The animal received DBS (30-130 Hz) in the subthalamic nucleus (STN) while at rest and recordings were acquired both before and after treatment with 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP), which induced Parkinsonian-like motor disorders.

Randomized trial of deep brain stimulation for Parkinson disease: thirty-six-month outcomes; turning tables: should GPi become the preferred DBS target for Parkinson disease?

Weaver et al. and Tagliati mistakenly infer clinical equivalence between globus pallidus interna vs subthalamic nucleus deep brain stimulation based on failure to demonstrate statistically significant differences. A clinically meaningful-not statistically significant-difference in outcome should be decided a priori, after which the sample size necessary to have a reasonable probability of detecting the difference could be determined.

A Point Process Model-based Framework Reveals Reinforcement Mechanisms in Striatum during High Frequency STN DBS.

Striatum is a major stage of the motor loop but, despite a pivotal role in the execution of movements, it has been poorly studied thus far under Parkinsonian conditions and Deep Brain Stimulation (DBS). We propose a computational framework to analyze the spiking activity of striatal neurons under several conditions. This framework combines point process models and single unit recordings, and separately evaluates the effects of the spiking history, DBS frequency, and other cells on the neuronal discharge pattern, thus giving a full characterization of non-stationary neuronal dynamics and inter-neuronal dependencies.