The amygdala has been studied extensively for its critical role in associative fear conditioning in animals and humans. Noxious stimuli, such as those used for fear conditioning, are most effective in eliciting behavioral responses and amygdala activation when experienced in an unpredictable manner. Here, we show, using a translational approach in mice and humans, that unpredictability per se without interaction with motivational information is sufficient to induce sustained neural activity in the amygdala and to elicit anxiety-like behavior. Exposing mice to mere temporal unpredictability within a time series of neutral sound pulses in an otherwise neutral sensory environment increased expression of the immediate-early gene c-fosand prevented rapid habituation of single neuron activity in the basolateral amygdala. At the behavioral level, unpredictable, but not predictable, auditory stimulation induced avoidance and anxiety-like behavior. In humans, functional magnetic resonance imaging revealed that temporal unpredictably causes sustained neural activity in amygdala and anxiety-like behavior as quantified by enhanced attention toward emotional faces. Our findings show that unpredictability per se is an important feature of the sensory environment influencing habituation of neuronal activity in amygdala and emotional behavior and indicate that regulation of amygdala habituation represents an evolutionary-conserved mechanism for adapting behavior in anticipation of temporally unpredictable events.

Neural correlates of electroencephalographic (EEG) alpha rhythm are poorly understood. Here, we related EEG alpha rhythm in awake humans to blood-oxygen-level-dependent (BOLD) signal change determined by functional magnetic resonance imaging (fMRI). Topographical EEG was recorded simultaneously with fMRI during an open versus closed eyes and an auditory stimulation versus silence condition. EEG was separated into spatial components of maximal temporal independence using independent component analysis. Alpha component amplitudes and stimulus conditions served as general linear model regressors of the fMRI signal time course. In both paradigms, EEG alpha component amplitudes were associated with BOLD signal decreases in occipital areas, but not in thalamus, when a standard BOLD response curve (maximum effect at ∼6 s) was assumed. The part of the alpha regressor independent of the protocol condition, however, revealed significant positive thalamic and mesencephalic correlations with a mean time delay of ∼2.5 s between EEG and BOLD signals. The inverse relationship between EEG alpha amplitude and BOLD signals in primary and secondary visual areas suggests that widespread thalamocortical synchronization is associated with decreased brain metabolism. While the temporal relationship of this association is consistent with metabolic changes occurring simultaneously with changes in the alpha rhythm, sites in the medial thalamus and in the anterior midbrain were found to correlate with short time lag. Assuming a canonical hemodynamic response function, this finding is indicative of activity preceding the actual EEG change by some seconds.

Objective: Using resting-state (RS) fMRI, we investigated the functional integrity of the default-mode network (DMN) in cognitively unimpaired patients with Parkinson disease (PD). Methods: RS fMRI at 3 T was collected in 16 cognitively unimpaired patients with PD and 16 age- and gender-matched healthy controls. Single-subject and group-level independent component analysis was used to investigate differences in functional connectivity within the DMN in patients with PD and healthy controls. Statistical analysis was performed using BrainVoyager QX. In addition, we used voxel-based morphometry to test whether between-group differences in RS functional connectivity were related to structural abnormalities. Results: Patients with PD compared with controls showed a decreased functional connectivity of the right medial temporal lobe and bilateral inferior parietal cortex within the DMN. Although patients with PD were cognitively unimpaired, the decreased DMN connectivity significantly correlated with cognitive parameters but not with disease duration, motor impairment, or levodopa therapy. The analysis of regional volume differences did not reveal any differences in local gray matter between patients and controls. Conclusions: Our findings revealed a functional disruption of the DMN in cognitively unimpaired patients with PD, in the absence of significant structural differences between patients and controls. We hypothesize that a dysfunction of the DMN connectivity may have a role in the development of cognitive decline in PD.