Martin Tobias Huber

Sleep deprivation affects thermal pain thresholds but not somatosensory thresholds in healthy volunteers.

Objective: Sleep disturbances have been thought to augment pain. Sleep deprivation has been proven to produce hyperalgesic effects. It is still unclear whether these changes are truly specific to pain and not related to general changes in somatosensory functions. The aim of the present study was to evaluate the effect of total sleep deprivation on thermal pain thresholds (heat, cold) and pain complaints. Thermal detection thresholds (warmth, cold) were included as covariates to determine the contribution of somatosensory functions to changes in pain processing. Methods: Twenty healthy volunteers were randomly assigned either to two nights of total sleep deprivation or to two nights of undisturbed night sleep. Sleep deprivation nights were separated by two days with normal night sleep. Heat and cold pain thresholds as well as warmth and cold detection thresholds were measured by use of a peltier thermode in the evening before and the morning after each deprivation or control night. Pain complaints were examined by use of a questionnaire in parallel. Results: During treatment nights, sleep deprivation produced a significant overnight decrease in heat pain thresholds. Cold pain thresholds tended to decrease also during sleep deprivation, whereas the warmth and cold detection thresholds remained unaffected. Accordingly, no substantial contributions of the changes in thermal detection thresholds to the changes in thermal pain thresholds were determined by regression analyses. Pain complaints were not induced by sleep deprivation. Conclusions: The present findings suggest that sleep deprivation produces hyperalgesic changes that cannot be explained by nonspecific alterations in somatosensory functions. REM = rapid eye movement; SEM = standard error of the mean.

Homoclinic bifurcation in a Hodgkin-Huxley model of thermally sensitive neurons.

We study global bifurcations of the chaotic attractor in a modified Hodgkin-Huxley model of thermally sensitive neurons. The control parameter for this model is the temperature. The chaotic behavior is realized over a wide range of temperatures and is visualized using interspike intervals. We observe an abrupt increase of the interspike intervals in a certain temperature region. We identify this as a homoclinic bifurcation of a saddle-focus fixed point which is embedded in the chaotic attractors. The transition is accompanied by intermittency, which obeys a universal scaling law for the average length of trajectory segments exhibiting only short interspike intervals with the distance from the onset of intermittency. We also present experimental results of interspike interval measurements taken from the crayfish caudal photoreceptor, which qualitatively demonstrate the same bifurcation structure. (c) 2000 American Institute of Physics.

Effects of total sleep deprivation in major depression: overnight improvement of mood is accompanied by increased pain sensitivity and augmented pain complaints.

Objective: Major depressive disorder (MDD) is associated with more pain complaints and an altered pain perception. Studies regarding the longitudinal relationship between depressive symptoms and pain processing have rarely been performed and have produced inconsistent results. To clarify how short-term alleviation of depressive mood is linked to changes in pain processing, the effect of sleep deprivation (SD) on pain and somatosensory thresholds, pain complaints, and mood was investigated in MDD patients. Methods: Nineteen drug-free inpatients with Diagnostic and Statistical Manual of Mental Disorders, fourth edition, diagnosis of MDD were investigated for 3 weeks. All patients received cognitive-behavioral therapy and were randomized to obtain either additional SD therapy (six nights of total SD, separated by recovery sleep) or no SD therapy (control group). Heat/cold pain thresholds, warmth/cold thresholds, measures of current pain complaints, and mood were assessed the evening before and the morning after SD as well as before and after a normal night sleep in the control group. Long-term changes of depressive symptomatology were assessed by weekly mood ratings. Results: Both treatment groups improved markedly in mood over the 3-week treatment period. SD regularly induced a moderate but statistically nonsignificant overnight improvement of mood, which was abolished by recovery sleep. Compared with the control condition, SD significantly decreased heat pain thresholds and nearly significantly cold pain thresholds; SD significantly augmented pain complaints the next morning. No such effects were observed for somatosensory thresholds. Conclusions: SD induced differential short-term effects on mood and pain, with the patients being less depressed but more pain vulnerable. MDD = major depressive disorder; SD = sleep deprivation; CDT = cold detection threshold; WDT = warmth detection threshold; CPT = cold pain threshold; HPT = heat pain threshold; BDI = Beck Depression Inventory; HDRS = Hamilton Depression Rating Scale; ANOVA = analysis of variance; GG = Greenhouse-Geisser; D-S = Depression Scale; Bf-S = Scale of Well-Being.

Oscillations, resonances and noise: basis of flexible neuronal pattern generation

Modulation of neuronal impulse pattern is examined by means of a simplified Hodgkin-Huxley type computer model which refers to experimental recordings of cold receptor discharges. This model essentially consists of two potentially oscillating subsystems: a spike generator and a subthreshold oscillator. With addition of noise the model successfully mimics the major types of experimentally recorded impulse patterns and thereby elucidate different resonance behaviors. (1) There is a range of rhythmic spiking or bursting where the spike generator is strongly coupled to the subthreshold oscillator. (2) There is a pacemaker activity of more complex interactions where the spike generator has overtaken part of the control. (3) There is a situation where the two subsystems are decoupled and only resonate with the help of noise.

Stimulus sensitivity and neuromodulatory properties of noisy intrinsic neuronal oscillators

Intrinsic subthreshold oscillations in the membrane potential are a common property of many neurons in the peripheral and central nervous system. When such oscillations are combined with noise, interesting signal encoding and neuromodulatory properties are obtained which allow, for example, sensitivity adjustment or differential encoding of stimuli. Here we demonstrate that a noisy Hodgkin/Huxley-model for subthreshold oscillations, when tuned to maximum sensitivity, can be significantly modulated by even minor physiological changes in the oscillation parameters amplitude or frequency. Given the ubiquity of subthreshold oscillating neurons, it can be assumed that these findings reflect principle encoding properties which are relevant for an understanding of sensitivity and neuromodulation in peripheral and central neurons.

Noise-induced impulse pattern modifications at different dynamical period-one situations in a computer model of temperature encoding.

We used a minimal Hodgkin-Huxley type model of cold receptor discharges to examine how noise interferes with the non-linear dynamics of the ionic mechanisms of neuronal stimulus encoding. The model is based on the assumption that spike-generation depends on subthreshold oscillations. With physiologically plausible temperature scaling, it passes through different impulse patterns which, with addition of noise, are in excellent agreement with real experimental data. The interval distributions of purely deterministic simulations, however, exhibit considerable differences compared to the noisy simulations especially at the bifurcations of deterministically period-one discharges. We, therefore, analyzed the effects of noise in different situations of deterministically regular period-one discharges: (1) at high-temperatures near the transition to subthreshold oscillations and to burst discharges, and (2) at low-temperatures close to and more far away from the bifurcations to chaotic dynamics. The data suggest that addition of noise can considerably extend the dynamical behavior of the system with coexistence of different dynamical situations at deterministically fixed parameter constellations. Apart from well-described coexistence of spike-generating and subthreshold oscillations also mixtures of tonic and bursting patterns can be seen and even transitions to unstable period-one orbits seem to appear. The data indicate that cooperative effects between low- and high-dimensional dynamics have to be considered as qualitatively important factors in neuronal encoding.

Pain sensitivity in major depression and its relationship to central serotoninergic function as reflected by the neuroendocrine response to clomipramine

Several studies reported a decreased pain sensitivity in patients with depression, but the underlying neurobiological mechanisms of this phenomenon are unclear. While there is extensive evidence that the serotoninergic system plays a key role in pain modulation, especially in pain inhibitory mechanisms via descending pathways, as well as in the pathophysiology of depression, no study so far has examined its potential relevance in mediating the alteration of pain processing. The present study addresses the question of whether indices of serotoninergic dysfunction, as investigated by a neuroendrocine challenge paradigm, are related to pain sensitivity. Nineteen drug-free inpatients with unipolar major depression underwent a neuroendocrine challenge test by measuring cortisol and prolactin in response to intravenously administered clomipramine (12.5mg). Heat/cold pain thresholds, warmth/cold detection thresholds, measures of current pain complaints and mood were assessed the day before and three day after challenge procedure. When patients were classified in subgroups based on a median split of their cortisol response values, the low-responsive group showed significantly elevated heat pain thresholds and nearly significantly elevated cold pain thresholds compared to the high-responsive group. No such group differences were found with regard to somatosensory thresholds, measures of pain complaints and mood. Subgrouping on the basis of prolactin responsiveness did not reveal significant differences in any parameter. In summary, a decreased pain sensitivity was demonstrated in patients characterized by a reduced neuroendocrine responsiveness to clomipramine, suggesting an involvement of serotoninergic dysfunction underlying altered pain perception in depression.

Interactions between slow and fast conductances in the Huber/Braun model of cold-receptor discharges

Abstract Transitions between different types of impulse patterns, according to experimentally recorded cold-receptor discharges, can successfully be mimicked with a minimal Hodgkin–Huxley-type simulation, here referred to as the Huber/Braun cold-receptor model. The model consists of two sets of simplified de- and repolarizing ionic conductances responsible for spike generation and slow-wave potentials, respectively. Over a broad temperature range, spike patterns are determined by the periodicity of subthreshold oscillations. At low temperatures, however, the periodicity of the pattern is destroyed and then appears again but with different patterns of different rhythmicity. We demonstrate that these complex transitions originate from the interactions between slow-wave and spike-generating currents.

Effects of noise on different disease states of recurrent affective disorders.

BACKGROUND Nonlinear dynamics are currently proposed to explain the course of recurrent affective disorders. Such a nonlinear disease model predicts complex interactions with stochastic influences, in particular, because both disease dynamics and stochastic influences, such as psychosocial stressors, will vary during the course of the disease. We approach this problem by investigating general effects of noise intensity on different disease states of a nonlinear model for recurrent affective disorders. METHODS A recently developed neurodynamic model is studied numerically. RESULTS Noise can cause unstructured randomness or can maximize periodic order. The frequency of episode occurrence can increase with noise but it can also remain unaffected or even can decrease. The observed effects, thereby, depend critically on both the noise intensity and the internal nonlinear dynamics of the disease model. CONCLUSIONS Our findings indicate that altered stochastic influences can significantly affect the outcome of a dynamic disease. To evaluate the effects of noise, it is essential to know about the underlying dynamics of respective disease states. Therefore, characterization of low-dimensional dynamics might become valuable for disease prediction and control.

Stimulus-response curves of a neuronal model for noisy subthreshold oscillations and related spike generation

We investigate the stimulus-dependent tuning properties of a noisy ionic conductance model for intrinsic subthreshold oscillations in membrane potential and associated spike generation. Upon depolarization by an applied current, the model exhibits subthreshold oscillatory activity with an occasional spike generation when oscillations reach the spike threshold. We consider how the amount of applied current, the noise intensity, variation of maximum conductance values, and scaling to different temperature ranges alter the responses of the model with respect to voltage traces, interspike intervals and their statistics, and the mean spike frequency curves. We demonstrate that subthreshold oscillatory neurons in the presence of noise can sensitively and also selectively be tuned by the stimulus-dependent variation of model parameters.