Karen A. Sigvardt

Modelling of intersegmental coordination in the lamprey central pattern generator for locomotion

Rhythmic motor activity requires coordination of different muscles or muscle groups so that they are all active with the same cycle duration and appropriate phase relationships. The neural mechanisms for such phase coupling in vertebrate locomotion are not known. Swimming in the lamprey is accomplished by the generation of a travelling wave of body curvature in which the phase coupling between segments is so controlled as to give approximately one full wavelength on the body at any swimming speed. This article reviews work that has combined mathematical analysis, biological experimentation and computer simulation to provide a conceptual framework within which intersegmental coordination can be investigated. Evidence is provided to suggest that in the lamprey, ascending coupling is dominant over descending coupling and controls the intersegmental phase lag during locomotion. The significance of long-range intersegmental coupling is also discussed.

Activation of NMDA receptors elecits fictive locomotion and bistable membrane properties in the lamprey spinal cord

The motor pattern underlying locomotion in the lamprey can be elicited in the spinal cord in vitro by applying excitatory amino acids that activate NMDA receptors. When this is done oscillatory membrane potentials phase-linked with the locomotory rhythm can be recorded in different types of neurones. In some spinal neurones large amplitude oscillation continues after elimination of synaptic input with application of TTX. This oscillatory pacemaker-like activity is dependent on an activation of NMDA receptors, and is probably important in the generation of locomotion.

The relationship between executive function and verbal memory in Parkinson's disease.

A growing body of evidence suggests that the various cognitive symptoms found in Parkinsons disease (PD) are secondary to executive dysfunction. Studies addressing this possibility for memory impairment specifically have not included measures of working memory nor have they ruled-out potential mediating variables such as overall level of cognitive impairment or depression. The purpose of this study was to include measures of these variables in determining the relationship between multiple aspects of executive function and delayed verbal recall in 32 idiopathic PD patients. Results were consistent with the original hypothesis and further suggest that working memory is a key factor in recall memory and may mediate the relationship between other executive measures and recall in PD.

Recognition Memory in Parkinson’s Disease With and Without Dementia: Evidence Inconsistent with the Retrieval Deficit Hypothesis

Parkinson’s disease (PD) has been associated with a pattern of performance on memory tests in which free recall is impaired but recognition and cued recall are intact, indicating problems with memory retrieval. Recent findings suggest that PD patients exhibit deficits in recognition as well as free recall, however. The current study set outto provide clear evidence that recognition and cued recall are not intact in PD. Ninety-nine idiopathic PD patients were administered the California Verbal Learning Test and their performance was compared to a well-matched normative sample. A profile analysis revealed that nondemented patients exhibited deficits on measures of cued recall and delayed recognition that were similar in magnitude to that of free recall. This was also the case for the cued recall deficits exhibited by demented patients; however, in this group recognition was worse than free recall. In both groups poor recognition appeared due to an elevated number of false positive errors. These results are inconsistent with the retrieval deficit hypothesis but support the notion that PD memory problems are secondary to prefrontal dysfunction.

Modeling facilitation and inhibition of competing motor programs in basal ganglia subthalamic nucleus–pallidal circuits

The motor symptoms of Parkinsons disease (PD) implicate the basal ganglia (BG) in some aspect of motor control, although the role the BG play in regulation of motor behavior is not completely understood. The modeling study presented here takes advantage of available cellular, systems, and clinical data on BG and PD to begin to build a biophysically based network model of pallidosubthalamic circuits of BG, to integrate this information and better understand the physiology of the normal BG and PD pathophysiology. The model reflects the experimentally supported hypothesis that the BG are involved in facilitation of the desired motor program and inhibition of competing motor programs that interfere with the desired movement. Our model network consists of subthalamic and pallidal (both external and internal segments) neural assemblies, with inputs from cortex and striatum. Functional subsets within each of the BG nuclei correspond to the desired motor program and the unwanted motor programs. A single compartment conductance-based model represents each subset. This network can discriminate between competing signals for motor program initiation, thus facilitating a single motor program. This ability depends on metabotropic γ-aminobutyric acid B projections from the external pallidum to subthalamic nucleus and rebound properties of subthalamic cells, as well as on the structure of projections between pallidum and subthalamus. The loss of this ability leads to hypokinesia, known PD motor deficits characterized by a slowness or inability to switch between motor programs.

Spectral analysis of oscillatory neural circuits

Oscillatory dynamics are found at all levels of the nervous system. The goal of our current research on the control of rhythmic motor output by the lamprey spinal cord is to determine the features of neuronal coupling that lead to stable oscillatory activity and precisely-controlled intersegmental phase. Since our experimental manipulations can greatly increase the variability of the ventral root bursting pattern, it is important for us to employ a data analysis method which remains valid independent of this variability. Traditional analysis approaches which rely on identification of burst event times do not generally satisfy this requirement. In this paper, we illustrate the application of a straightforward statistically-based method for determining important parameters of oscillatory motor circuits using Fourier spectral analysis of spike trains. The frequency, phase, and their variabilities can be quantified; and the relative strength of coupling between different parts of the circuit can be tested for statistical significance. The approach we adopt is highly convenient for neuroscientists who study oscillatory systems as it operates directly on trains of action potentials stored as lists of event times (point-processes). Basic concepts and practical issues concerning use of Fourier analysis are discussed.

Cognitive deficits in essential tremor consistent with frontosubcortical dysfunction

Essential tremor (ET) is increasingly thought to involve a heterogeneous group of patients, with some also exhibiting symptoms of Parkinsons disease (PD), including cognitive deficits. The goal of this study was to utilize a broad battery of neuropsychological measures to compare the cognitive function of 33 ET patients with that of 33 matched PD patients and 21 normal controls. Results indicated that the ET group performed significantly worse than controls across multiple cognitive domains, but performed remarkably similar to PD patients, consistent with frontosubcortical dysfunction.

Intersegmental coordination in the lamprey central pattern generator for locomotion

Two theories have been formulated to explain how intersegmental coordination in the lamprey is produced. Both view the spinal locomotor CPG as a chain of coupled oscillators. One involves the development of a general mathematical framework that allows one to examine how differences in the inherent frequencies and differences in the kinds of coupling affect the phase lags along the chain. The other theory suggests a simple way in which constant phase lags along the chain can be produced from a chain in which the first oscillator has an inherently higher frequency and the coupling between oscillators is symmetrical. The goal of this review is to compare the two theories and to evaluate the available experimental data as it relates to both theories.

Hemispheric asymmetries and prosodic emotion recognition deficits in Parkinson's disease

While Parkinsons disease (PD) has traditionally been described as a movement disorder, there is growing evidence of cognitive and social deficits associated with the disease. However, few studies have looked at multi-modal social cognitive deficits in patients with PD. We studied lateralization of both prosodic and facial emotion recognition (the ability to recognize emotional valence from either tone of voice or from facial expressions) in PD. The Comprehensive Affect Testing System (CATS) is a well-validated test of human emotion processing that has been used to study emotion recognition in several major clinical populations, but never before in PD. We administered an abbreviated version of CATS (CATS-A) to 24 medicated PD participants and 12 age-matched controls. PD participants were divided into two groups, based on side of symptom onset and unilateral motor symptom severity: left-affected (N = 12) or right-affected PD participants (N = 12). CATS-A is a computer-based button press task with eight subtests relevant to prosodic and facial emotion recognition. Left-affected PD participants with inferred predominant right-hemisphere pathology were expected to have difficulty with prosodic emotion recognition since there is evidence that the processing of prosodic information is right-hemisphere dominant. We found that facial emotion recognition was preserved in the PD group, however, left-affected PD participants had specific impairment in prosodic emotion recognition, especially for sadness. Selective deficits in prosodic emotion recognition suggests that (1) hemispheric effects in emotion recognition may contribute to the impairment of emotional communication in a subset of people with PD and (2) the coordination of neural networks needed to decipher temporally complex social cues may be specifically disrupted in PD.

Analysis and Modeling of the Locomotor Central Pattern Generator as a Network of Coupled Oscillators

Abstract: The primary functions of spinal locomotor central pattern generators (CPGs) are to provide oscillatory motor commands to individual joints or segments and to control the precise timing of those commands across all joints or segments for efficient, coordinated locomotor behavior. Our ability to understand the neuronal mechanisms underlying intersegmental coordination has been hampered by the complexity of propriospinal interconnectivity and the paucity of quantitative data on the magnitude and timing of those connections. Theoretical approaches have therefore been employed to discover general roles by which CPG‐like oscillator systems must be constructed to produce appropriate coordinated locomotor behavior; the locomotor CPG is represented as a network of oscillators, where each oscillator generates local motor output and interoscillator coupling provides intersegmental coordination. Mathematical analysis of such coupled oscillator systems has provided a number of experimentally testable predictions regarding the link between coupling and coordination. Application of these network‐level predictions to the results of electrophysiological experiments has required data analysis methods that can relate the behavior of the in vitro spinal cord to the variables employed by the mathematical model. Hence, our most recent work has focused on developing analytic tools for quantifying the changes in locomotor output that result form experimental manipulations of the propriospinal system in terms of frequency, intersegmental phase, and intersegmental correlation. Results of recent experiments can now be used to put further constraints on the allowable kinds of intersegmental coupling provided by mathematical modeling of the system.