Temporal control of glucocorticoid neurodynamics and its relevance for brain homeostasis,neuropathology and glucocorticoid-based therapeutics

Glucocorticoids mediate plethora of actions throughout the human body. Within the brain, they modulate aspects of immune system and neuroinflammatory processes, interfere with cellular metabolism and viability, interact with systems of neurotransmission and regulate neural rhythms. The influence of glucocorticoids on memory and emotional behaviour is well known and there is increasing evidence for their involvement in many neuropsychiatric pathologies. These effects, which at times can be in opposing directions, depend not only on the concentration of glucocorticoids but also the duration of their presence, the temporal relationship between their fluctuations, the co-influence of other stimuli, and the overall state of brain activity. Moreover, they are region- and cell type-specific. The molecular basis of such diversity of effects lies on the orchestration of the spatiotemporal interplay between glucocorticoid- and mineralocorticoid receptors, and is achieved through complex dynamics, mainly mediated via the circadian and ultradian pattern of glucocorticoid secretion. More sophisticated methodologies are therefore required to better approach the study of these hormones and improve the effectiveness of glucocorticoid-based therapeutics.     

Synchrony in the Eye of the Beholder: An Analysis of the Role of Neural Synchronization in Cognitive Processes

We discuss the role of synchrony of activationin higher-level cognitive processes. Inparticular, we analyze the question of whethersynchrony of activation provides a mechanismfor compositional representation in neuralsystems. We will argue that synchrony ofactivation does not provide a mechanism forcompositional representation in neural systems.At face value, one can identify a level ofcompositional representation in the models thatintroduce synchrony of activation for thispurpose. But behavior in these models isalways produced by means conjunctiverepresentations in the form of coincidencedetectors. Therefore, models that rely onsynchrony of activation lack the systematicityand productivity of true compositional systems.As a result, they cannot distinguish betweentype and token representations, which resultsin misrepresentations of spatial relations andpropositions. Furthermore, higher-levelcognitive processes will likely integrateinformation from widely distributed areas inthe brain, which puts severe restrictions onthe underlying neural dynamics if synchrony ofactivation is to play a role in theseprocesses. We will briefly discuss theserestrictions in the case of feature binding invisual cognition.     

Effect of splinting and exercise on intraneural edema of the median nerve in carpal tunnel syndrome--an MRI study to reveal therapeutic mechanisms

Splinting and nerve and tendon gliding exercises are commonly used to treat carpal tunnel syndrome (CTS). It has been postulated that both modalities reduce intraneural edema. To test this hypothesis, 20 patients with mild to moderate CTS were randomly allocated to either night splinting or a home program of nerve and tendon gliding exercises. Magnetic resonance images of the wrist were taken at baseline, immediately after 10 min of splinting or exercise, and following 1 week of intervention. Primary outcome measures were signal intensity of the median nerve at the wrist as a measure of intraneural edema and palmar bowing of the carpal ligament. Secondary outcome measures were changes in symptom severity and function. Following 1 week of intervention, but not immediately after 10 min, signal intensity of the median nerve was reduced by ≈ 11% at the radioulnar level for both interventions (p = 0.03). This was accompanied by a mild improvement in symptoms and function (p < 0.004). A similar reduction in signal intensity is not observed in patients who only receive advice to remain active. No changes in signal intensity were identified further distally (p > 0.28). Ligament bowing remained unchanged (p > 0.08). Intraneural edema reduction is a likely therapeutic mechanism of splinting and exercise.     

A computational neuroscience approach to schizophrenia and its onset

Computational neuroscience integrate-and-fire attractor network models can be used to understand the factors that alter the stability of cortical networks in the face of noise caused for example by neuronal spiking times. A reduction of the firing rates of cortical neurons caused for example by reduced NMDA receptor function (present in schizophrenia) can lead to instability of the high firing rate attractor states that normally implement short-term memory and attention, contributing to the cognitive and negative symptoms of schizophrenia. Reduced cortical inhibition caused by a reduction of GABA neurotransmission (present in schizophrenia) can lead to instability of the spontaneous firing states of cortical networks, leading to a noise-induced jump to a high firing rate attractor state even in the absence of external inputs, contributing to the positive symptoms of schizophrenia. We consider how effects occurring at the time of late adolescence including synaptic pruning, decreases in grey matter volume, and changes in GABA-mediated inhibition and dopamine may contribute to the onset in some individuals of schizophrenia at this time.     

Aperiodic phase re-setting in scalp EEG of beta-gamma oscillations by state transitions at alpha-theta rates

We evaluated the rapid changes in regional scalp EEG synchronization in normal subjects with spatial and temporal resolution exceeding prior art 10-fold with a high spatial density array and the Hilbert transform. A curvilinear array of 64 electrodes 3 mm apart extending 18.9 cm across the scalp was used to record EEG at 200/sec. Analytic amplitude (AA) and phase (AP) were calculated at each time step for the 64 traces in the analog pass band of 0.5-120 Hz. AP differences approximated the AP derivative (instantaneous frequency). The AP from unfiltered EEG revealed no reproducible patterns. Filtering was necessary in the beta and gamma ranges according to a technique that optimized the correlation of the AP differences with the activity band pass filtered in the alpha range. The sizes of temporal AP differences were usually within +/-0.5 radian from the average step corresponding to the center frequency of the pass band. Large AP differences were often synchronized over distances of 6 to 19 cm. An optimal pass band to detect and measure these recurring jumps in AP in the beta and gamma ranges was found by maximizing the alpha peak in the cospectrum of the correlation between unfiltered EEG and the band pass AP differences. Synchronized AP jumps recurred in clusters (CAP) at alpha and theta rates in resting subjects and with EMG. Cortex functions by serial changes in state. The Hilbert transform of EEG from high-density arrays can visualize these state transitions with high temporal and spatial resolution and should be useful in relating EEG to cognition.     

On the 'Dynamic Brain' Metaphor

Dynamic systems theory offers conceptual andmathematical tools for describing the performance ofneural systems at very different levels oforganization. Three aspects of the dynamic paradigmare discussed, namely neural rhythms, neural andmental development, and macroscopic brain theories andmodels.