Learning to Control the Brain through Adaptive Closed-Loop Patterned Stimulation

AbstractStimulation of neural activity is an important scientific and clinical tool, causally testing hypotheses and treating neurodegenerative and neuropsychiatric diseases. However, current stimulation approaches cannot flexibly control the pattern of activity in populations of neurons. To address this, we developed an adaptive, closed-loop stimulation (ACLS) system that uses patterned, multi-site electrical stimulation to control the pattern of activity in a population of neurons. Importantly, ACLS is a learning system; it monitors the response to stimulation and iteratively updates the stimulation pattern to produce a specific neural response. In silico and in vivo experiments showed ACLS quickly learns to produce specific patterns of neural activity (∼15 minutes) and was robust to noise and drift in neural responses. In visual cortex of awake mice, ACLS learned electrical stimulation patterns that produced responses similar to the natural response evoked by visual stimuli. Similar to how repetition of a visual stimulus causes an adaptation in the neural response, the response to electrical stimulation was adapted when it was preceded by the associated visual stimulus. Altogether, our results show ACLS can learn, in real-time, to generate specific patterns of neural activity, providing a framework for using closed-loop learning to control neural activity.

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Analysis of an open source, closed-loop, realtime system for hippocampal sharp-wave ripple disruption

10.1101/298661 ◽

2018 ◽

Author(s):

Shayok Dutta ◽

Etienne Ackermann ◽

Caleb Kemere

Keyword(s):

Open Source ◽

Neural Activity ◽

Closed Loop ◽

Detection System ◽

Detection Accuracy ◽

Sharp Wave ◽

Trade Offs ◽

Wide Range ◽

Realtime System

AbstractTransient neural activity pervades hippocampal electrophysiological activity. During more quiescent states, brief ≈100 ms periods comprising large ≈150–250 Hz oscillations known as sharp-wave ripples (SWR) which co-occur with ensemble bursts of spiking activity, are regularly found in local field potentials recorded from area CA1. SWRs and their concomitant neural activity are thought to be important for memory consolidation, recall, and memory-guided decision making. Temporally-selective manipulations of hippocampal neural activity upon online hippocampal SWR detection have been used as causal evidence of the importance of SWR for mnemonic process as evinced by behavioral and/or physiological changes. However, though this approach is becoming more wide spread, the performance trade-offs involved in building a SWR detection and disruption system have not been explored, limiting the design and interpretation of SWR detection experiments. We present an open source, plug-and-play, online ripple detection system with a detailed performance characterization. Our system has been constructed to interface with an open source software platform, Trodes, and two hardware acquisition platforms, Open Ephys and SpikeGadgets. We show that our in vivo results — approximately 80% detection latencies falling in between ≈20–66 ms with ≈2 ms closed-loop latencies while maintaining <10 false detections per minute — are dependent upon both algorithmic trade-offs and acquisition hardware. We discuss strategies to improve detection accuracy and potential limitations of online ripple disruptions. By characterizing this system in detail, we present a template for analyzing other closed-loop neural detection and perturbation systems. Thus, we anticipate our modular, open source, realtime system will facilitate a wide range of carefully-designed causal closed-loop neuroscience experiments.

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In Vivo Measurements of Cranial Electrical Stimulation Using Stereotactic-EEG: A Pilot Study

2021 10th International IEEE/EMBS Conference on Neural Engineering (NER) ◽

10.1109/ner49283.2021.9441106 ◽

2021 ◽

Author(s):

Minmin Wang ◽

Shenghua Zhu ◽

Haonan Guan ◽

Hongjie Jiang ◽

Jianmin Zhang ◽

...

Keyword(s):

Electrical Stimulation ◽

Pilot Study ◽

In Vivo Measurements

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Cellular sources of TSPO expression in healthy and diseased brain

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-020-05166-2 ◽

2021 ◽

Author(s):

Erik Nutma ◽

Kelly Ceyzériat ◽

Sandra Amor ◽

Stergios Tsartsalis ◽

Philippe Millet ◽

...

Keyword(s):

Cell Activity ◽

Brain Regions ◽

Cellular Level ◽

Translocator Protein ◽

Disease Stage ◽

Animal Models Of Disease ◽

Positron Emission ◽

Neuropsychiatric Diseases ◽

Tspo Expression

AbstractThe 18 kDa translocator protein (TSPO) is a highly conserved protein located in the outer mitochondrial membrane. TSPO binding, as measured with positron emission tomography (PET), is considered an in vivo marker of neuroinflammation. Indeed, TSPO expression is altered in neurodegenerative, neuroinflammatory, and neuropsychiatric diseases. In PET studies, the TSPO signal is often viewed as a marker of microglial cell activity. However, there is little evidence in support of a microglia-specific TSPO expression. This review describes the cellular sources and functions of TSPO in animal models of disease and human studies, in health, and in central nervous system diseases. A discussion of methods of analysis and of quantification of TSPO is also presented. Overall, it appears that the alterations of TSPO binding, their cellular underpinnings, and the functional significance of such alterations depend on many factors, notably the pathology or the animal model under study, the disease stage, and the involved brain regions. Thus, further studies are needed to fully determine how changes in TSPO binding occur at the cellular level with the ultimate goal of revealing potential therapeutic pathways.

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Somatostatin modulates cholinergic neurotransmission in canine antral muscle

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1988.254.2.g201 ◽

1988 ◽

Vol 254 (2) ◽

pp. G201-G209 ◽

Cited By ~ 1

Author(s):

C. B. Koelbel ◽

G. van Deventer ◽

S. Khawaja ◽

M. Mogard ◽

J. H. Walsh ◽

...

Keyword(s):

Electrical Stimulation ◽

Substance P ◽

Prostaglandin E2 ◽

Positive Inotropic Effect ◽

Mechanical Response ◽

Inhibitory Effect ◽

Inotropic Effect ◽

Inotropic Response ◽

Cholinergic Neurotransmission

Somatostatin has been shown to inhibit antral motility in vivo. To examine the effect of somatostatin on cholinergic neurotransmission in the canine antrum, we studied the mechanical response of and the release of [3H]acetylcholine from canine longitudinal antral muscle in response to substance P, gastrin 17, and electrical stimulation. In unstimulated tissues, somatostatin had a positive inotropic effect on spontaneous phasic contractions. In tissues stimulated with substance P and gastrin 17, but not with electrical stimulation, somatostatin inhibited the phasic inotropic response dose dependently. This inhibitory effect was abolished by indomethacin. Somatostatin stimulated the release of prostaglandin E2 radioimmunoreactivity, and prostaglandin E2 inhibited the release of [3H]acetylcholine induced by substance P and electrical stimulation. Somatostatin increased the release of [3H]acetylcholine from unstimulated tissues by a tetrodotoxin-sensitive mechanism but inhibited the release induced by substance P and electrical stimulation. These results suggest that somatostatin has a dual modulatory effect on cholinergic neurotransmission in canine longitudinal antral muscle. This effect is excitatory in unstimulated tissues and inhibitory in stimulated tissues. The inhibitory effect is partially mediated by prostaglandins.

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Closed-loop control system for well-defined oxygen supply in micro-physiological systems

Current Directions in Biomedical Engineering ◽

10.1515/cdbme-2017-0075 ◽

2017 ◽

Vol 3 (2) ◽

pp. 363-366

Author(s):

Tobias Steege ◽

Mathias Busek ◽

Stefan Grünzner ◽

Andrés Fabían Lasagni ◽

Frank Sonntag

Keyword(s):

Control System ◽

Oxygen Supply ◽

Closed Loop ◽

Microfluidic System ◽

Closed Loop Control ◽

Loop Control ◽

Cell Vitality ◽

Closed Loop Control System ◽

Loop Control System

AbstractTo improve cell vitality, sufficient oxygen supply is an important factor. A deficiency in oxygen is called Hypoxia and can influence for example tumor growth or inflammatory processes. Hypoxia assays are usually performed with the help of animal or static human cell culture models. The main disadvantage of these methods is that the results are hardly transferable to the human physiology. Microfluidic 3D cell cultivation systems for perfused hypoxia assays may overcome this issue since they can mimic the in-vivo situation in the human body much better. Such a Hypoxia-on-a-Chip system was recently developed. The chip system consists of several individually laser-structured layers which are bonded using a hot press or chemical treatment. Oxygen sensing spots are integrated into the system which can be monitored continuously with an optical sensor by means of fluorescence lifetime detection.Hereby presented is the developed hard- and software requiered to control the oxygen content within this microfluidic system. This system forms a closed-loop control system which is parameterized and evaluated.

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Subthreshold electrical stimulation as a low power electrical treatment for stroke rehabilitation

Scientific Reports ◽

10.1038/s41598-021-93354-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kyungsoo Kim ◽

Seung-Jun Yoo ◽

So Yeon Kim ◽

Taeju Lee ◽

Sung-Ho Lim ◽

...

Keyword(s):

Electrical Stimulation ◽

Energy Consumption ◽

Functional Recovery ◽

Stroke Rehabilitation ◽

Brain Regions ◽

Implantable Devices ◽

Rehabilitation Process ◽

Neural Excitability ◽

Spike Firing

AbstractAs a promising future treatment for stroke rehabilitation, researchers have developed direct brain stimulation to manipulate the neural excitability. However, there has been less interest in energy consumption and unexpected side effect caused by electrical stimulation to bring functional recovery for stroke rehabilitation. In this study, we propose an engineering approach with subthreshold electrical stimulation (STES) to bring functional recovery. Here, we show a low level of electrical stimulation boosted causal excitation in connected neurons and strengthened the synaptic weight in a simulation study. We found that STES with motor training enhanced functional recovery after stroke in vivo. STES was shown to induce neural reconstruction, indicated by higher neurite expression in the stimulated regions and correlated changes in behavioral performance and neural spike firing pattern during the rehabilitation process. This will reduce the energy consumption of implantable devices and the side effects caused by stimulating unwanted brain regions.

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