24 research outputs found

    Feed-Forward Propagation of Temporal and Rate Information between Cortical Populations during Coherent Activation in Engineered In Vitro Networks.

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    Transient propagation of information across neuronal assembles is thought to underlie many cognitive processes. However, the nature of the neural code that is embedded within these transmissions remains uncertain. Much of our understanding of how information is transmitted among these assemblies has been derived from computational models. While these models have been instrumental in understanding these processes they often make simplifying assumptions about the biophysical properties of neurons that may influence the nature and properties expressed. To address this issue we created an in vitro analog of a feed-forward network composed of two small populations (also referred to as assemblies or layers) of living dissociated rat cortical neurons. The populations were separated by, and communicated through, a microelectromechanical systems (MEMS) device containing a strip of microscale tunnels. Delayed culturing of one population in the first layer followed by the second a few days later induced the unidirectional growth of axons through the microtunnels resulting in a primarily feed-forward communication between these two small neural populations. In this study we systematically manipulated the number of tunnels that connected each layer and hence, the number of axons providing communication between those populations. We then assess the effect of reducing the number of tunnels has upon the properties of between-layer communication capacity and fidelity of neural transmission among spike trains transmitted across and within layers. We show evidence based on Victor-Purpura's and van Rossum's spike train similarity metrics supporting the presence of both rate and temporal information embedded within these transmissions whose fidelity increased during communication both between and within layers when the number of tunnels are increased. We also provide evidence reinforcing the role of synchronized activity upon transmission fidelity during the spontaneous synchronized network burst events that propagated between layers and highlight the potential applications of these MEMs devices as a tool for further investigation of structure and functional dynamics among neural populations

    Feedback-Controlled Transcranial Alternating Current Stimulation Reveals a Functional Role of Sleep Spindles in Motor Memory Consolidation

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    Transient episodes of brain oscillations are a common feature of both the waking and sleeping brain. Sleep spindles represent a prominent example of a poorly understood transient brain oscillation that is impaired in disorders such as Alzheimer’s disease and schizophrenia. Yet, the causal role of these bouts of thalamo-cortical oscillations remains unknown. Demonstrating a functional role of sleep spindles in cognitive processes has so far been hindered by the lack of a tool to target transient brain oscillations in real-time. Here, we show for the first time selective enhancement of sleep spindles with non-invasive brain stimulation in humans. We developed a system that detects sleep spindles in real-time and applies oscillatory stimulation. Our stimulation selectively enhanced spindle activity as determined by increased sigma activity after tACS application. This targeted modulation caused significant enhancement of motor memory consolidation that correlated with the stimulation-induced change in fast spindle activity. Strikingly, we found a similar correlation between motor memory and spindle characteristics during the sham night for the same spindle frequencies and electrode locations. Therefore, our results directly demonstrate a functional relationship between oscillatory spindle activity and cognition

    Modulation of Cortical Oscillations by Low-Frequency Direct Cortical Stimulation Is State-Dependent

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    Cortical oscillations play a fundamental role in organizing large-scale functional brain networks. Noninvasive brain stimulation with temporally patterned waveforms such as repetitive transcranial magnetic stimulation (rTMS) and transcranial alternating current stimulation (tACS) have been proposed to modulate these oscillations. Thus, these stimulation modalities represent promising new approaches for the treatment of psychiatric illnesses in which these oscillations are impaired. However, the mechanism by which periodic brain stimulation alters endogenous oscillation dynamics is debated and appears to depend on brain state. Here, we demonstrate with a static model and a neural oscillator model that recurrent excitation in the thalamo-cortical circuit, together with recruitment of cortico-cortical connections, can explain the enhancement of oscillations by brain stimulation as a function of brain state. We then performed concurrent invasive recording and stimulation of the human cortical surface to elucidate the response of cortical oscillations to periodic stimulation and support the findings from the computational models. We found that (1) stimulation enhanced the targeted oscillation power, (2) this enhancement outlasted stimulation, and (3) the effect of stimulation depended on behavioral state. Together, our results show successful target engagement of oscillations by periodic brain stimulation and highlight the role of nonlinear interaction between endogenous network oscillations and stimulation. These mechanistic insights will contribute to the design of adaptive, more targeted stimulation paradigms

    Dataset accompanying: Network-targeted, multi-site direct cortical stimulation enhances working memory by modulating phase lag of low frequency oscillations

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    Working memory is supported by the coordinated activation of frontal and parietal cortices mediated through oscillations in theta and alpha frequency. We tested whether targeting multiple nodes of the network with brain stimulation at the frequency of interaction is effective in modulating working memory. We identified working memory nodes that are functionally connected in theta and alpha frequency bands and intracranially stimulated both nodes simultaneously in participants performing working memory task. We found that in-phase stimulation resulted in improvement in performance compared to sham stimulation. Additionally, in-phase stimulation resulted in decreased phase lag between regions within working memory network while anti-phase stimulation resulted in increased phase lag suggesting that shorter phase lag in oscillatory connectivity may lead to better performance. The results support the idea that phase lag may play a key role in information transmission across brain regions. Thus, brain stimulation strategies that aim to improve cognition may be better served targeting multiple nodes of brain networks

    Double-blind, randomized pilot clinical trial targeting alpha oscillations with transcranial alternating current stimulation (tACS) for the treatment of major depressive disorder (MDD)

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    Major depressive disorder (MDD) is one of the most common psychiatric disorders, but pharmacological treatments are ineffective in a substantial fraction of patients and are accompanied by unwanted side effects. Here we evaluated the feasibility and efficacy of transcranial alternating current stimulation (tACS) at 10 Hz, which we hypothesized would improve clinical symptoms by renormalizing alpha oscillations in the left dorsolateral prefrontal cortex (dlPFC). To this end, 32 participants with MDD were randomized to 1 of 3 arms and received daily 40 min sessions of either 10 Hz-tACS, 40 Hz-tACS, or active sham stimulation for 5 consecutive days. Symptom improvement was assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS) as the primary outcome. High-density electroencephalograms (hdEEGs) were recorded to measure changes in alpha oscillations as the secondary outcome. For the primary outcome, we did not observe a significant interaction between treatment condition (10 Hz-tACS, 40 Hz-tACS, sham) and session (baseline to 4 weeks after completion of treatment); however, exploratory analyses show that 2 weeks after completion of the intervention, the 10 Hz-tACS group had more responders (MADRS and HDRS) compared with 40 Hz-tACS and sham groups (n = 30, p = 0.026). Concurrently, we found a significant reduction in alpha power over the left frontal regions in EEG after completion of the intervention for the group that received per-protocol 10 Hz-tACS (n = 26, p < 0.05). Our data suggest that targeting oscillations with tACS has potential as a therapeutic intervention for treatment of MDD.ISSN:2158-318

    Oscillatory Dynamics in the Frontoparietal Attention Network during Sustained Attention in the Ferret

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    Sustained attention requires the coordination of neural activity across multiple cortical areas in the frontoparietal network, in particular the prefrontal cortex (PFC) and posterior parietal cortex (PPC). Previous work has demonstrated that activity in these brain regions is coordinated by neuronal oscillations of the local field potential (LFP). However, the underlying coordination of activity in terms of organization of single unit (SU) spiking activity has remained poorly understood, particularly in the freely moving animal. We found that long-range functional connectivity between anatomically connected PFC and PPC was mediated by oscillations in the theta frequency band. SU activity in PFC was phase locked to theta oscillations in PPC, and spiking activity in PFC and PPC was locked to local high-gamma activity. Together, our results support a model in which frequency-specific synchronization mediates functional connectivity between and within PFC and PPC of the frontoparietal attention network in the freely moving animal
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