Experiences of using the Theoretical Domains Framework across diverse clinical environments: a qualitative study.

BACKGROUND: The Theoretical Domains Framework (TDF) is an integrative framework developed from a synthesis of psychological theories as a vehicle to help apply theoretical approaches to interventions aimed at behavior change. PURPOSE: This study explores experiences of TDF use by professionals from multiple disciplines across diverse clinical settings. METHODS: Mixed methods were used to examine experiences, attitudes, and perspectives of health professionals in using the TDF in health care implementation projects. Individual interviews were conducted with ten health care professionals from six disciplines who used the TDF in implementation projects. Deductive content and thematic analysis were used. RESULTS: Three main themes and associated subthemes were identified including: 1) reasons for use of the TDF (increased confidence, broader perspective, and theoretical underpinnings); 2) challenges using the TDF (time and resources, operationalization of the TDF) and; 3) future use of the TDF. CONCLUSION: The TDF provided a useful, flexible framework for a diverse group of health professionals working across different clinical settings for the assessment of barriers and targeting resources to influence behavior change for implementation projects. The development of practical tools and training or support is likely to aid the utility of TDF.

Treatment of neurolept-induced tardive dyskinesia.

Tardive dyskinesia (TDK) includes orobuccolingual movements and "piano-playing" movements of the limbs. It is a movement disorder of delayed onset that can occur in the setting of neuroleptic treatment as well as in other diseases and following treatment with other drugs. The specific pathophysiology resulting in TDK is still not completely understood but possible mechanisms include postsynaptic dopamine receptor hypersensitivity, abnormalities of striatal gamma-aminobutyric acid (GABA) neurons, and degeneration of striatal cholinergic interneurons. More recently, the theory of synaptic plasticity has been proposed. Considering these proposed mechanisms of disease, therapeutic interventions have attempted to manipulate dopamine, GABA, acetylcholine, norepinephrine and serotonin pathways and receptors. The data for the effectiveness of each class of drugs and the side effects were considered in turn.

Pathophysiology of HNPP explored using axonal excitability.

OBJECTIVE: Hereditary liability to pressure palsies (HNPP) is an autosomal dominant disorder of myelination resulting in susceptibility to pressure palsies from compression or stretching of peripheral nerves. PATIENTS AND METHODS: This study examined axonal excitability at two sites (one distal and one proximal) in five patients with biopsy and genetically proven HNPP to understand the pathophysiology of the disease. Comparisons were made with age-matched control subjects as well as five Charcot-Marie-Tooth type 1A patients to contrast the findings and explain the different phenotypes of diseases affecting the same gene. RESULTS: Changes in axonal excitability were found in HNPP subjects, but these were not uniform along the nerve: at the wrist there were prominent alterations in threshold electrotonus, whereas at the elbow there were only subtle alterations in the recovery cycle and the response to strong long-lasting hyperpolarisation. Threshold was raised at both sites, but the nerves were probably not hyperpolarised. Not unexpectedly, changes in CMT1A subjects were more marked than those in HNPP subjects and were uniform along the nerve. CONCLUSIONS: Structural abnormalities at the node of Ranvier are sufficient to explain the changes in axonal excitability in HNPP, and these abnormalities would predispose the nerves to conduction block when subjected to pressure or stretch.

Do the motor manifestations of Parkinson disease alter motor axon excitability?

BACKGROUND: Axonal excitability is altered in common medical conditions such as stroke, multiple sclerosis, and spinal cord injury. Given the motor neuron changes in the presence of rigidity and tremor in Parkinson disease, we examine whether there are also changes in motor axon excitability. METHODS: Axonal excitability studies were performed in 15 Parkinson subjects and 12 age-matched control subjects. RESULTS: There was no significant difference in excitability indices between Parkinson subjects and control subjects. CONCLUSIONS: It is unlikely that the lack of change in the excitability indices reflects a balance between the effects of bradykinesia ("underactivity") and the effects of rigidity and tremor ("overactivity") on the motoneuron and its axon. It is more likely that plastic changes in motoneuron properties do not occur symmetrically with decreases and increases in activity, being more profound when activity levels are interrupted and less obvious when they are enhanced.

Threshold behaviour of human axons explored using subthreshold perturbations to membrane potential.

The present study explores the threshold behaviour of human axons and the mechanisms contributing to this behaviour. The changes in excitability of cutaneous afferents in the median nerve at the wrist were recorded to a long-lasting subthreshold conditioning stimulus, with a waveform designed to maximize the contribution of currents active in the just-subthreshold region. The conditioning stimulus produced a decrease in threshold that developed over 3-5 ms following the end of the depolarization and then decayed slowly, in a pattern similar to the recovery of axonal excitability following a discharge. To ensure that the conditioning stimulus did not activate low-threshold axons, similar recordings were then made from single motor axons in the ulnar nerve at the elbow. The findings were comparable, and behaviour with the same pattern and time course could be reproduced by subthreshold stimuli in a model of the human axon. In motor axons, subthreshold depolarizing stimuli, 1 ms long, produced a similar increase in excitability, but the late hyperpolarizing deflection was less prominent. This behaviour was again reproduced by the model axon and could be explained by the passive properties of the nodal membrane and conventional Na+ and K+ currents. The modelling studies emphasized the importance of leak current through the Barrett-Barrett resistance, even in the subthreshold region, and suggested a significant contribution of K+ currents to the threshold behaviour of axons. While the gating of slow K+ channels is slow, the resultant current may not be slow if there are substantial changes in membrane potential. By extrapolation, we suggest that, when human axons discharge, nodal slow K+ currents will be activated sufficiently early to contribute to the early changes in excitability following the action potential.

Postactivation depression of the soleus H reflex measured using threshold tracking.

The interpretation of changes in the soleus H reflex is problematic in the face of reflex gain changes, a nonlinear input/output relationship for the motoneuron pool, and a nonhomogeneous response of different motoneurons to afferent inputs. By altering the stimulus intensity to maintain a constant reflex output, threshold tracking allows a relatively constant population of alpha-motoneurons to be studied. This approach was used to examine postactivation ("homosynaptic") depression of the H reflex (HD) in 23 neurologically healthy subjects. The H reflex was elicited by tibial nerve stimulation at 0.05, 0.1, 0.3, 1, and 2 Hz at rest and during voluntary plantar flexion at 2.5, 5, and 10% of maximum. A computerized threshold tracking procedure was used to set the current needed to generate a target H reflex 10% of M(max). The current needed to produce the target reflex increased with stimulus rate but not significantly beyond 1 Hz. In three subjects, the current needed to produce H reflexes of 5, 10, 15, and 20% M(max) at 0.3, 1, and 2 Hz increased with rate and with the size of the test H reflex. HD was significantly reduced during voluntary contractions. Using threshold tracking, HD was maximal at lower frequencies than previously emphasized, probably because HD is greater the larger the test H reflex. This would reinforce the greater sensitivity of small motoneurons to reflex inputs.

Plasticity of inwardly rectifying conductances following a corticospinal lesion in human subjects.

This study investigated whether there are changes in the excitability of motor axons in peripheral nerves of patients with corticospinal lesions, reflecting plasticity of the motoneuron due to altered descending drives and/or changes in afferent feedback. The excitability of motor and sensory axons in peripheral nerves of the affected limb of 11 patients with unilateral hemiparesis due to stroke was compared with that for the unaffected limbs and with data for 12 age-matched controls. There was significantly less accommodation to hyperpolarizing currents in motor axons on the affected side. There were small differences between the data for the unaffected side and that of the control subjects but these were not statistically significant. Other findings indicate that there was no change in resting membrane potential. There was no comparable alteration in the excitability of sensory axons. The changes in response of motor axons to hyperpolarizing currents could be reproduced in a computer model of the human motor axon by reducing the hyperpolarization-activated conductance, IH, by 30% and the quantitatively small leak conductance by 77%. The data for the uninvolved side matched the data for control subjects best when IH was increased. These findings are consistent with modulation of IH by activity. They demonstrate a change in the biophysical properties of motor axons not directly affected by the pathology and synaptically remote from the lesion, and have implications for 'trans-synaptic' changes in central nervous system pathways. In human subjects studies of motor axon properties may allow insight into processes affecting the motoneuron.

Athetosis II: the syndrome of mild athetoid cerebral palsy.

We describe 8 patients who presented with continuous, irregular movements occurring independently in individual fingers and, in some cases, toes, in the setting of mild dystonia present since early childhood and not associated with major disability. The finger movements varied from low-amplitude quivering or wriggling to larger amplitude movements in the plane of abduction-adduction as well as flexion-extension; they were asymmetrical but not unilateral. Quivering or working of the facial muscles was seen in 5 patients. Most patients reported worsening of the movements over the years, but there was no other evidence of a progressive neurological disease. We classify the movement disorder as athetosis as described by Hammond and Shaw and the syndrome as mild athetoid cerebral palsy.