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.

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.

Stimulus novelty or deviance may be especially salient in anxiety-related states due to sensitization to environmental change, a key symptom of anxiety disorders such as posttraumatic stress disorder (PTSD). We aimed to identify human brain regions that show potentiated responses to stimulus deviance during anticipatory anxiety. Twenty participants (14 men) were presented a passive oddball auditory task in which they were exposed to uniform auditory stimulation of tones with occasional deviations in tone frequency, a procedure that elicits the mismatch negativity (MMN) and its magnetic counterpart (MMNm). These stimuli were presented during threat periods when participants anticipated unpleasant electric shocks, and safe periods when no shocks were anticipated. Neuromagnetic data were collected with a 275-channel whole-head MEG system and event-related beamformer analyses were conducted to estimate source power across the brain in response to stimulus deviance. Source analyses revealed greater right auditory and inferior parietal activity to stimulus deviance under threat relative to safe conditions, consistent with locations of MMN and MMNm sources identified in other studies. Structures related to evaluation of threat, left amygdala and right insula, also showed increased activity to stimulus deviance under threat. As anxiety level increased across participants, right and left auditory cortical as well as right amygdala activity increased to stimulus deviance. These findings fit with evidence of a potentiated MMN in PTSD relative to healthy controls, and warrant closer evaluation of how these structures might form a functional network mediating sensitization to stimulus deviance during anticipatory anxiety.During a state of behavioral inhibition, stimulus novelty or deviance may be especially salient, driving an organism into an extremely cautious stance and poised to activate fight-flight mechanisms based on further evaluation of the perceived danger (Blanchard et al., 2001;Gray, 1982;Gray and McNaughton, 2000). Heightened responses to stimulus novelty may be governed by mechanisms related to sensitization processes in clinical anxiety disorders such as post-traumatic stress disorder (PTSD, American Psychiatric Association, 2000;Siegmund and Wotjak, 2006). This study aimed to identify human brain regions that show enhanced responses to stimulus deviance during a state of anticipatory anxiety. We studied this contextspecific, increased salience of stimulus deviance in humans by using an instructed threat paradigm in which periods of potential threat (i.e., unpredictable electric shocks) and periods (Grillon, 2002;Grillon et al., 2004). To characterize the neural structures involved in sensitization to stimulus deviance, we used spatially-filtered magnetoencephalography (MEG) or adaptive beamformer analyses to estimate the volumetric distribution of source power across the brain (Hillebrand et al., 2005;Robinson and Vrba, 1999).Our procedure consisted of a passive oddball auditory task in which partici...