The Journal of neuroscience : the official journal of the Society for Neuroscience
-
Randomized Controlled Trial Clinical Trial
Corticotropin-releasing factor receptor 1 antagonist alters regional activation and effective connectivity in an emotional-arousal circuit during expectation of abdominal pain.
Alterations in corticotropin-releasing factor (CRF) signaling pathways have been implicated in irritable bowel syndrome (IBS) pathophysiology. We aimed to (1) determine the effect of the selective CRF receptor 1 antagonist (CRF(1)) GW876008 relative to placebo, on regional activation and effective connectivity of a stress-related emotional-arousal circuit during expectation of abdominal pain using functional magnetic resonance imaging in human subjects with a diagnosis of IBS and healthy controls (HCs), and (2) examine GW876008 effects on state-trait anxiety and hypothalamic-pituitary-adrenal (HPA) axis response. Although there were no drug-related effects on peripheral HPA activity, significant central effects were observed in brain regions associated with the stress response. ⋯ The inhibitory effects of GW876008 in the hypothalamus in patients were moderated by anxiety; patients having average and high levels of state anxiety showed drug-related BOLD decreases. GW876008 represents a novel tool for elucidating the neuronal mechanisms and circuitry underlying hyperactivation of CRF/CRF(1) signaling and its role in IBS pathophysiology. The unique state anxiety effects observed suggest a potential pathway for therapeutic benefit of CRF(1) receptor antagonism for patients with stress-sensitive disorders.
-
Randomized Controlled Trial Comparative Study
The phase of ongoing oscillations mediates the causal relation between brain excitation and visual perception.
Why does neuronal activity in sensory brain areas sometimes give rise to perception, and sometimes not? Although neuronal noise is often invoked as the key factor, a portion of this variability could also be due to the history and current state of the brain affecting cortical excitability. Here we directly test this idea by examining whether the phase of prestimulus oscillatory activity is causally linked with modulations of cortical excitability and with visual perception. Transcranial magnetic stimulation (TMS) was applied over human visual cortex to induce illusory perceptions (phosphenes) while electroencephalograms (EEGs) were simultaneously recorded. ⋯ This effect was observed in occipital regions around the site of TMS, as well as in a distant frontocentral region. In both regions, we found a systematic relationship between prepulse EEG phase and perceptual performance: phosphene probability changed by ∼15% between opposite phases. In summary, we provide direct evidence for a chain of causal relations between the phase of ongoing oscillations, neuronal excitability, and visual perception: ongoing oscillations create periodic "windows of excitability," with sensory perception being more likely to occur at specific phases.
-
Randomized Controlled Trial Comparative Study
TMS perturbs saccade trajectories and unmasks an internal feedback controller for saccades.
When we applied a single pulse of transcranial magnetic stimulation (TMS) to any part of the human head during a saccadic eye movement, the ongoing eye velocity was reduced as early as 45 ms after the TMS, and lasted ∼32 ms. The perturbation to the saccade trajectory was not due to a mechanical effect of the lid on the eye (e.g., from blinks). When the saccade involved coordinated movements of both the eyes and the lids, e.g., in vertical saccades, TMS produced a synchronized inhibition of the motor commands to both eye and lid muscles. ⋯ TMS disrupted saccades regardless of the location of the coil on the head, suggesting that the coil discharge engages a nonhabituating startle-like reflex system. This system affects ongoing motor commands upstream of the oculomotor neurons, possibly at the level of the superior colliculus or omnipause neurons. Therefore, a TMS pulse centrally perturbs saccadic motor commands, which are monitored possibly via efference copy and are corrected via internal feedback.