What constitutes normal cortical dynamics in healthy human subjects is a major question in systems neuroscience. Numerous in vitro and in vivo animal studies have shown that ongoing or resting cortical dynamics are characterized by cascades of activity across many spatial scales, termed neuronal avalanches. In experiment and theory, avalanche dynamics are identified by two measures: (1) a power law in the size distribution of activity cascades with an exponent of −3/2 and (2) a branching parameter of the critical value of 1, reflecting balanced propagation of activity at the border of premature termination and potential blowup. Here we analyzed resting-state brain activity recorded using noninvasive magnetoencephalography (MEG) from 124 healthy human subjects and two different MEG facilities using different sensor technologies. We identified large deflections at single MEG sensors and combined them into spatiotemporal cascades on the sensor array using multiple timescales. Cascade size distributions obeyed power laws. For the timescale at which the branching parameter was close to 1, the power law exponent was −3/2. This relationship was robust to scaling and coarse graining of the sensor array. It was absent in phase-shuffled controls with the same power spectrum or empty scanner data. Our results demonstrate that normal cortical activity in healthy human subjects at rest organizes as neuronal avalanches and is well described by a critical branching process. Theory and experiment have shown that such critical, scale-free dynamics optimize information processing. Therefore, our findings imply that the human brain attains an optimal dynamical regime for information processing.

The hippocampus and parahippocampal cortices exhibit theta oscillations during spatial navigation in animals and humans, and in the former are thought to mediate spatial memory formation. Functional specificity of human hippocampal theta, however, is unclear. Neuromagnetic activity was recorded with a whole-head 275-channel magnetoencephalographic (MEG) system as healthy participants navigated to a hidden platform in a virtual reality Morris water maze. MEG data were analyzed for underlying oscillatory sources in the 4 -8 Hz band using a spatial filtering technique (i.e., synthetic aperture magnetometry). Source analyses revealed greater theta activity in the left anterior hippocampus and parahippocampal cortices during goal-directed navigation relative to aimless movements in a sensorimotor control condition. Additional analyses showed that left anterior hippocampal activity was predominantly observed during the first one-half of training, pointing to a role for this region in early learning. Moreover, posterior hippocampal theta was highly correlated with navigation performance, with the former accounting for 76% of the variance of the latter. Our findings suggest human spatial learning is dependent on hippocampal and parahippocampal theta oscillations, extending to humans a significant body of research demonstrating such a pivotal role for hippocampal theta in animal navigation.

Facial threat conveys important information about imminent environmental danger. The rapid detection of this information is critical for survival and social interaction. However, due to technical and methodological difficulties, the spatiotemporal profile for facial threat processing is unknown. By utilizing Magnetoencephalography (MEG), a brain-imaging technique with superb temporal resolution and fairly good spatial resolution, Synthetic Aperture Magnetometry (SAM), a recently developed source analysis technique, and a sliding window analysis, we identified the spatiotemporal development of facial threat processing in the gamma frequency band. We also tested the dual-route hypothesis by LeDoux who proposed, based on animal research, that there are two routes to the amygdala: a quick subcortical routeand a slower and cortical route. Direct evidence with humans supporting this model has been lacking. Moreover, it has been unclear whether the subcortical route responds specifically to fearful expressions or to threatening expressions in general. We found early event-related synchronizations (ERS) in response to fearful faces in the hypothalamus/thalamus area (10-20 ms) and then the amygdala (20-30 ms). This was even earlier than the ERS response seen to fearful faces in visual cortex (40-50 ms). These data support LeDoux's suggestion of a quick, subcortical thamaloamygdala route. Moreover, this route was specific for fear expressions; the ERS response in the amygdala to angry expressions had a late onset (150-160 ms). The ERS onset in prefrontal cortex followed that seen within the amygdala (around 160-210 ms). This is consistent with its role in higher-level emotional/cognitive processing.

Pregenual anterior cingulate (pgACC) hyperactivity differentiates treatment responders from non-responders to various pharmacological antidepressant interventions, including ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist. Evidence of pgACC hyperactivition during non-emotional working memory tasks in patients with major depressive disorder (MDD) highlights the importance of this region for processing both emotionally-salient and cognitive stimuli. However, it is unclear whether pgACC activity might serve as a potential biomarker of antidepressant response during working memory tasks as well, in line with previous research with emotionally-arousing tasks. The present study tested the hypothesis that during the N-back task, a widely-used working memory paradigm, low pre-treatment pgACC activity, as well as coherence between the pgACC and the amygdala, would be correlated with the clinical improvement following ketamine. Magnetoencephalography (MEG) recordings were obtained from 15 drug-free patients with MDD during working memory performance one to three days before receiving a single ketamine infusion. Functional activation patterns were analyzed using advanced MEG source analysis. Source coherence analyses were conducted to quantify the degree of long-range functional connectivity between the pgACC and the amygdala. Patients who showed the least engagement of the pgACC in response to increased working memory load showed the greatest symptomatic improvement within four hours of ketamine administration (r = 0.82, p = 0.0002, FDR < 0.05). Pre-treatment functional connectivity between the pgACC and the left amygdala was negatively correlated with antidepressant symptom change (r = −0.73, p = 0.0021, FDR <0.05). These data implicate the pgACC and its putative interaction with the amygdala in predicting antidepressant response to ketamine in a working memory task context.