1. Critical brain dynamics are increasingly recognized to be important in cortex function. We have expanded on our previous finding of neuronal avalanches maintained during the resting state. We now have demonstrated the first study on linking deviations in avalanche dynamics with basal ganglia dysfunction in an animal model of Tourettes syndrome. See, A low-correlation resting state of the striatum that suppresses involuntary movements during cortical avalanches, by Klaus and Plenz (2016), PloS Biology: Author Summary Even in the absence of apparent motor output, the brain produces a rich repertoire of neuronal activity patterns known as resting state activity. In the outer layer of the cortex, resting state patterns emerge as neuronal avalanches, precisely scale-invariant spatiotemporal bursts that often engage large populations of neurons. Little is known about how the brain suppresses involuntary movements during such activity. Here, we show that the striatum, which is part of the cortex-basal ganglia loop, maintains a low-correlation state during resting activity. By using a combination of in vivo and in vitro approaches with pharmacological manipulations, we demonstrate that the precise configuration of this low-correlation state effectively contributes to involuntary movements. Nonselective blockade of intra-striatal inhibition abolished the low-correlation striatal resting state, barely affected cortical avalanches, and led to involuntary movements at low rate. In contrast, selectively reducing striatal interneuron inhibition strongly affected cortical avalanches and triggered involuntary movements at high rate while maintaining a relatively decorrelated striatal resting state. Our results demonstrate the importance of different inhibitory striatal circuits in the suppression of involuntary movements and suggest that the precise spatiotemporal configuration of striatal activity plays an active role in the regulation of cortical resting state activity and motor control. 2. We published a new approach to predict the size of future neuronal avalanches with wide implications including earthquake forecasting. See Temporal correlations in neuronal avalanche occurrence, by Lombardi, F., Herrmann, H. J., Plenz,D., and L. de Arcangelis (2016): Abstract Ongoing cortical activity consists of sequences of synchronized bursts, named neuronal avalanches, whose size and duration are power law distributed. These features have been observed in a variety of systems and conditions, at all spatial scales, supporting scale invariance, universality and therefore criticality. However, the mechanisms leading to burst triggering, as well as the relationship between bursts and quiescence, are still unclear. The analysis of temporal correlations constitutes a major step towards a deeper understanding of burst dynamics. Here, we investigate the relation between avalanche sizes and quiet times, as well as between sizes of consecutive avalanches recorded in cortex slice cultures. We show that quiet times depend on the size of preceding avalanches and, at the same time, influence the size of the following one. Moreover we evidence that sizes of consecutive avalanches are correlated. In particular, we show that an avalanche tends to be larger or smaller than the following one for short or long time separation, respectively. Our analysis represents the first attempt to provide a quantitative estimate of correlations between activity and quiescence in the framework of neuronal avalanches and will help to enlighten the mechanisms underlying spontaneous activity. 3. We published the first quantitative assessment of anti-epileptic drug action using the framework of critical brain dynamics in humans suffering from intractable epilepsy. Data were obtained from a data repository and consisted of multi-day recordings from 10 patients undergoing presurgical monitoring at the Epilepsy Center of the University Hospital of Freiburg. See, Quantifying antiepileptic drug effects using intrinsic excitability measures, by Meisel et al. (2016), Epilepsia: Abstract Pathologic increases in excitability levels of cortical tissue commonly underlie the initiation and spread of seizure activity in patients with epilepsy. By reducing the excitability levels in neural tissue, antiepileptic drug (AED) pharmacotherapy aims to reduce seizure severity and frequency. However, AEDs may also bring about adverse effects, which have been reported to increase with higher AED load. Measures that monitor the dose-dependent effects of AEDs on cortical tissue and quantify its excitability level are therefore of prime importance for efficient clinical care and treatment but have been difficult to identify. Here, we systematically analyze continuous multiday electrocorticography (ECoG) data from 10 patients under different levels of AED load and derive the recently proposed intrinsic excitability measures (IEMs) from different brain regions and across different frequency bands. We find that IEMs are significantly negatively correlated with AED load (prescribed daily dose/defined daily dose). Furthermore, we demonstrate that IEMs derived from different brain regions can robustly capture global changes in the degree of excitability. These results provide a step toward the ultimate goal of developing a reliable quantitative measure of central physiologic effects of AEDs in patients with epilepsy. 4. In collaboration with Dr. Peter Basser's group (NICHD), we provided the first experimental proof of functional diffusion MRI to reliably identify hyper-excitable, abnormal brain activities. See Assessing the sensitivity of diffusion MRI to detect neuronal activity directly, Bai et al. (2016) Proc Natl Acad Sci USA: Abstract Functional MRI (fMRI) is widely used to study brain function in the neurosciences. Unfortunately, conventional fMRI only indirectly assesses neuronal activity via hemodynamic coupling. Diffusion fMRI was proposed as a more direct and accurate fMRI method to detect neuronal activity, yet confirmative findings have proven difficult to obtain. Given that the underlying relation between tissue water diffusion changes and neuronal activity remains unclear, the rationale for using diffusion MRI to monitor neuronal activity has yet to be clearly established. Here, we studied the correlation between water diffusion and neuronal activity in vitro by simultaneous calcium fluorescence imaging and diffusion MR acquisition. We used organotypic cortical cultures from rat brains as a biological model system, in which spontaneous neuronal activity robustly emerges free of hemodynamic and other artifacts. Simultaneous fluorescent calcium images of neuronal activity are then directly correlated with diffusion MR signals now free of confounds typically encountered in vivo. Although a simultaneous increase of diffusion-weighted MR signals was observed together with the prolonged depolarization of neurons induced by pharmacological manipulations (in which cell swelling was demonstrated to play an important role), no evidence was found that diffusion MR signals directly correlate with normal spontaneous neuronal activity. These results suggest that, whereas current diffusion MR methods could monitor pathological conditions such as hyperexcitability, e.g., those seen in epilepsy, they do not appear to be sensitive or specific enough to detect or follow normal neuronal activity.
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