Cross-frequency coupling in deep brain structures upon processing the painful sensory inputs.

Cross-frequency coupling has been shown to be functionally significant in cortical information processing, potentially serving as a mechanism for integrating functionally relevant regions in the brain. In this study, we evaluate the hypothesis that pain-related gamma oscillatory responses are coupled with low-frequency oscillations in the frontal lobe, amygdala and hippocampus, areas known to have roles in pain processing. We delivered painful laser pulses to random locations on the dorsal hand of five patients with uncontrolled epilepsy requiring depth electrode implantation for seizure monitoring. Two blocks of 40 laser stimulations were delivered to each subject and the pain-intensity was controlled at five in a 0-10 scale by adjusting the energy level of the laser pulses. Local-field-potentials (LFPs) were recorded through bilaterally implanted depth electrode contacts to study the oscillatory responses upon processing the painful laser stimulations. Our results show that painful laser stimulations enhanced low-gamma (LH, 40-70 Hz) and high-gamma (HG, 70-110 Hz) oscillatory responses in the amygdala and hippocampal regions on the right hemisphere and these gamma responses were significantly coupled with the phases of theta (4-7 Hz) and alpha (8-1 2 Hz) rhythms during pain processing. Given the roles of these deep brain structures in emotion, these findings suggest that the oscillatory responses in these regions may play a role in integrating the affective component of pain, which may contribute to our understanding of the mechanisms underlying the affective information processing in humans.

Fear conditioning is associated with dynamic directed functional interactions between and within the human amygdala, hippocampus, and frontal lobe.

The current model of fear conditioning suggests that it is mediated through modules involving the amygdala (AMY), hippocampus (HIP), and frontal lobe (FL). We now test the hypothesis that habituation and acquisition stages of a fear conditioning protocol are characterized by different event-related causal interactions (ERCs) within and between these modules. The protocol used the painful cutaneous laser as the unconditioned stimulus and ERC was estimated by analysis of local field potentials recorded through electrodes implanted for investigation of epilepsy. During the prestimulus interval of the habituation stage FL>AMY ERC interactions were common. For comparison, in the poststimulus interval of the habituation stage, only a subdivision of the FL (dorsolateral prefrontal cortex, dlPFC) still exerted the FL>AMY ERC interaction (dlFC>AMY). For a further comparison, during the poststimulus interval of the acquisition stage, the dlPFC>AMY interaction persisted and an AMY>FL interaction appeared. In addition to these ERC interactions between modules, the results also show ERC interactions within modules. During the poststimulus interval, HIP>HIP ERC interactions were more common during acquisition, and deep hippocampal contacts exerted causal interactions on superficial contacts, possibly explained by connectivity between the perihippocampal gyrus and the HIP. During the prestimulus interval of the habituation stage, AMY>AMY ERC interactions were commonly found, while interactions between the deep and superficial AMY (indirect pathway) were independent of intervals and stages. These results suggest that the network subserving fear includes distributed or widespread modules, some of which are themselves "local networks." ERC interactions between and within modules can be either static or change dynamically across intervals or stages of fear conditioning.

Direct cardiac and peripheral vascular effects of intracoronary and intravenous nifedipine.

The hemodynamic effects of a new parenteral formulation of nifedipine administered by the intravenous (1 mg) and intracoronary (IC) (0.1 and 0.2 mg) routes were studied in 10 patients with symptomatic coronary artery disease undergoing diagnostic right- and left-sided cardiac catheterization. Intravenous nifedipine (1 mg) reduced systemic vascular resistance by 34% (p less than 0.01), increased cardiac output by 28% (p less than 0.01) and decreased mean arterial pressure by 10% (p less than 0.01). It had less effect on peak positive dP/dt (-8% p less than 0.025) and on peak negative dP/dt (-15% p less than 0.01). Coronary blood flow increased 20% (p less than 0.025). In contrast, IC nifedipine (0.2 mg) increased coronary blood flow 46% (p less than 0.025), depressed contractility as assessed by peak positive dP/dt (-26% p less than 0.01) and prolonged diastolic relaxation time. The effect of 0.1 mg was similar but less pronounced. These data suggest that the primary therapeutic effect of nifedipine administered systemically to patients at rest results from an increase in coronary blood flow and, to a lesser extent, from afterload reduction; its myocardial depressant effects are small, transient and masked by reflex catecholamine release. IC nifedipine increases coronary blood flow, has a transient negative inotropic effect and prolongs relaxation. The relative importance of these myocardial effects in preventing myocardial ischemia is not known.