Transcranial Electric Stimulation Entrains Cortical Neuronal Populations in Rats

Low intensity electric fields have been suggested to affect the ongoing neuronal activity in vitro and in human studies. However, the physiological mechanism of how weak electrical fields affect and interact with intact brain activity is not well understood. We performed in vivo extracellular and intracellular recordings from the neocortex and hippocampus of anesthetized rats and extracellular recordings in behaving rats. Electric fields were generated by sinusoid patterns at slow frequency (0.8, 1.25 or 1.7 Hz) via electrodes placed on the surface of the skull or the dura. Transcranial electric stimulation (TES) reliably entrained neurons in widespread cortical areas, including the hippocampus. The percentage of TES phase-locked neurons increased with stimulus intensity and depended on the behavioral state of the animal. TES-induced voltage gradient, as low as 1 mV/mm at the recording sites, was sufficient to phase-bias neuronal spiking. Intracellular recordings showed that both spiking and subthreshold activity were under the combined influence of TES forced fields and network activity. We suggest that TES in chronic preparations may be used for experimental and therapeutic control of brain activity

The spectro-contextual encoding and retrieval theory of episodic memory.

The spectral fingerprint hypothesis, which posits that different frequencies of oscillations underlie different cognitive operations, provides one account for how interactions between brain regions support perceptual and attentive processes (Siegel etal., 2012). Here, we explore and extend this idea to the domain of human episodic memory encoding and retrieval. Incorporating findings from the synaptic to cognitive levels of organization, we argue that spectrally precise cross-frequency coupling and phase-synchronization promote the formation of hippocampal-neocortical cell assemblies that form the basis for episodic memory. We suggest that both cell assembly firing patterns as well as the global pattern of brain oscillatory activity within hippocampal-neocortical networks represents the contents of a particular memory. Drawing upon the ideas of context reinstatement and multiple trace theory, we argue that memory retrieval is driven by internal and/or external factors which recreate these frequency-specific oscillatory patterns which occur during episodic encoding. These ideas are synthesized into a novel model of episodic memory (the spectro-contextual encoding and retrieval theory, or "SCERT") that provides several testable predictions for future research

Restoring the encoding properties of a stochastic neuron model by an exogenous noise

Here we evaluate the possibility of improving the encoding properties of an impaired neuronal system by superimposing an exogenous noise to an external electric stimulation signal. The approach is based on the use of mathematical neuron models consisting of stochastic HH-like circuit, where the impairment of the endogenous presynaptic inputs is described as a subthreshold injected current and the exogenous stimulation signal is a sinusoidal voltage perturbation across the membrane. Our results indicate that a correlated Gaussian noise, added to the sinusoidal signal can significantly increase the encoding properties of the impaired system, through the Stochastic Resonance (SR) phenomenon. These results suggest that an exogenous noise, suitably tailored, could improve the efficacy of those stimulation techniques used in neuronal systems, where the presynaptic sensory neurons are impaired and have to be artificially bypassed

Consciousness operates beyond the timescale for discerning time intervals: implications for Q-mind theories and analysis of quantum decoherence in brain

This paper presents in details how the subjective time is constructed by the brain cortex via reading packets of information called "time labels", produced by the right basal ganglia that act as brain timekeeper. Psychophysiological experiments have measured the subjective "time quanta" to be 40 ms and show that consciousness operates beyond that scale - an important result having profound implications for the Q-mind theory. Although in most current mainstream biophysics research on cognitive processes, the brain is modelled as a neural network obeying classical physics, Penrose (1989, 1997) and others have argued that quantum mechanics may play an essential role, and that successful brain simulations can only be performed with a quantum computer. Tegmark (2000) showed that make-or-break issue for the quantum models of mind is whether the relevant degrees of freedom of the brain can be sufficiently isolated to retain their quantum coherence and tried to settle the issue with detailed calculations of the relevant decoherence rates. He concluded that the mind is classical rather than quantum system, however his reasoning is based on biological inconsistency. Here we present detailed exposition of molecular neurobiology and define the dynamical timescale of cognitive processes linked to consciousness to be 10-15 ps showing that macroscopic quantum coherent phenomena in brain are not ruled out, and even may provide insight in understanding life, information and consciousness

Cholinergic modulation of epileptiform activity in the developing rat neocortex

The effects of carbachol on picrotoxin-induced epileptiform activity and membrane properties of neurons in the developing rat neocortex were examined in an in vitro slice preparation. Intracellular recordings were obtained in layer II–III neurons of slices prepared from rats 9–21 days of age. Epileptiform activity in 9- to 14-day-olds consisted of a sharply rising, sustained (10–30 s) membrane depolarization with superimposed action potentials. Bath application of carbachol (5–50 μM) raised the threshold for evoking epileptiform activity but, when such responses were evoked, their underlying depolarizations were increased in amplitude. Orthodromic stimulation in slices from 15- to 21-day-old animals evoked a prolonged epileptiform burst response that triggered an episode of spreading depression (SD). Carbachol reduced epileptiform responses and suppressed the occurrence of SD. It did not significantly affect the resting membrane potential or the height of the action potential but decreased the rheobase current needed to evoke an action potential and increased the input resistance. All effects of carbachol were antagonized by atropine (1 μM). These results indicate that carbachol has both pre- and postsynaptic effects in the developing neocortex and can significantly modulate neuronal excitability in the immature nervous system

Clinically indicated electrical stimulation strategies to treat patients with medically refractory epilepsy.

Focal epilepsies represent approximately half of all diagnoses, and more than one-third of these patients are refractory to pharmacologic treatment. Although resection can result in seizure freedom, many patients do not meet surgical criteria, as seizures may be multifocal in origin or have a focus in an eloquent region of the brain. For these individuals, several U.S. Food and Drug Administration (FDA)-approved electrical stimulation paradigms serve as alternative options, including vagus nerve stimulation, responsive neurostimulation, and stimulation of the anterior nucleus of the thalamus. All of these are safe, flexible, and lead to progressive seizure control over time when used as an adjunctive therapy to antiepileptic drugs. Focal epilepsies frequently involve significant comorbidities such as cognitive decline. Similar to antiepilepsy medications and surgical resection, current stimulation targets and parameters have yet to address cognitive impairments directly, with patients reporting persistent comorbidities associated with focal epilepsy despite a significant reduction in the number of their seizures. Although low-frequency theta oscillations of the septohippocampal network are critical for modulating cellular activity and, in turn, cognitive processing, the coordination of neural excitability is also imperative for preventing seizures. In this review, we summarize current FDA-approved electrical stimulation paradigms and propose that theta oscillations of the medial septal nucleus represent a novel neuromodulation target for concurrent seizure reduction and cognitive improvement in epilepsy. Ultimately, further advancements in clinical neurostimulation strategies will allow for the efficient treatment of both seizures and comorbidities, thereby improving overall quality of life for patients with epilepsy

Optical neural stimulation modeling on degenerative neocortical neural networks

Neurodegenerative diseases usually appear at advanced age. Medical advances make people live longer and as a consequence, the number of neurodegenerative diseases continuously grows. There is still no cure for these diseases, but several brain stimulation techniques have been proposed to improve patients’ condition. One of them is Optical Neural Stimulation (ONS), which is based on the application of optical radiation over specific brain regions. The outer cerebral zones can be noninvasively stimulated, without the common drawbacks associated to surgical procedures. This work focuses on the analysis of ONS effects in stimulated neurons to determine their influence in neuronal activity. For this purpose a neural network model has been employed. The results show the neural network behavior when the stimulation is provided by means of different optical radiation sources and constitute a first approach to adjust the optical light source parameters to stimulate specific neocortical areas.This work has been partially supported by the project MAT2012-38664-C02-01 of the Spanish Ministry of Economy and Competitiveness, and by San Cándido Foundation