Theta-modulated oscillatory transcranial direct current stimulation over posterior parietal cortex improves associative memory.

Associative memory (AM) reflects the ability to remember and retrieve multiple pieces of information bound together thus enabling complex episodic experiences. Despite growing interest in the use of transcranial direct current stimulation (tDCS) for the modulation of AM, there are inconsistent evidence regarding its benefits. An alternative to standard constant tDCS could be the application of frequency-modulated tDCS protocols, that mimic natural function-relevant brain rhythms. Here, we show the effects of anodal tDCS oscillating in theta rhythm (5 Hz; 1.5 ± 0.1 mA) versus constant anodal tDCS and sham over left posterior parietal cortex on cued recall of face-word associations. In a crossover design, each participant completed AM assessment immediately following 20-min theta-oscillatory, constant, and sham tDCS, as well as 1 and 5 days after. Theta oscillatory tDCS increased initial AM performance in comparison to sham, and so did constant tDCS. On the group level, no differences between oscillatory and constant tDCS were observed, but individual-level analysis revealed that some participants responded to theta-oscillatory but not to constant tDCS, and vice versa, which could be attributed to their different physiological modes of action. This study shows the potential of oscillatory tDCS protocols for memory enhancement to produce strong and reliable memory-modulating effects which deserve to be investigated further.

Optogenetic activation of septal cholinergic neurons suppresses sharp wave ripples and enhances theta oscillations in the hippocampus.

Theta oscillations in the limbic system depend on the integrity of the medial septum. The different populations of medial septal neurons (cholinergic and GABAergic) are assumed to affect different aspects of theta oscillations. Using optogenetic stimulation of cholinergic neurons in ChAT-Cre mice, we investigated their effects on hippocampal local field potentials in both anesthetized and behaving mice. Cholinergic stimulation completely blocked sharp wave ripples and strongly suppressed the power of both slow oscillations (0.5-2 Hz in anesthetized, 0.5-4 Hz in behaving animals) and supratheta (6-10 Hz in anesthetized, 10-25 Hz in behaving animals) bands. The same stimulation robustly increased both the power and coherence of theta oscillations (2-6 Hz) in urethane-anesthetized mice. In behaving mice, cholinergic stimulation was less effective in the theta (4-10 Hz) band yet it also increased the ratio of theta/slow oscillation and theta coherence. The effects on gamma oscillations largely mirrored those of theta. These findings show that medial septal cholinergic activation can both enhance theta rhythm and suppress peri-theta frequency bands, allowing theta oscillations to dominate.

Intermittent θ burst stimulation over primary motor cortex enhances movement-related ß synchronisation.

OBJECTIVE: The objective of this study is to investigate how transcranial magnetic intermittent theta burst stimulation (iTBS) with a prolonged protocol affects human cortical excitability and movement-related oscillations. METHODS: Using motor-evoked potentials (MEPs) and movement-related magnetoencephalography (MEG), we assessed the changes of corticospinal excitability and cortical oscillations after iTBS with double the conventional stimulation time (1200 pulses, iTBS1200) over the primary motor cortex (M1) in 10 healthy subjects. Continuous TBS (cTBS1200) and sham stimulation served as controls. RESULTS: iTBS1200 facilitated MEPs evoked from the conditioned M1, while inhibiting MEPs from the contralateral M1 for 30 min. By contrast, cTBS1200 inhibited MEPs from the conditioned M1. Importantly, empirical mode decomposition-based MEG analysis showed that the amplitude of post-movement beta synchronisation (16-26 Hz) was significantly increased by iTBS1200 at the conditioned M1, but was suppressed at the nonconditioned M1. Alpha (8-13 Hz) and low gamma-ranged (35-45 Hz) rhythms were not notably affected. Movement kinetics remained consistent throughout. CONCLUSIONS: TBS1200 modulated corticospinal excitability in parallel with the direction of conventional paradigms with modestly prolonged efficacy. Moreover, iTBS1200 increased post-movement beta synchronisation of the stimulated M1, and decreased that of the contralateral M1, probably through interhemispheric interaction. SIGNIFICANCE: Our results provide insight into the underlying mechanism of TBS and reinforce the connection between movement-related beta synchronisation and corticospinal output.

Increased theta activity in quantitative electroencephalographic (QEEG) measurements during exposure to complex weak magnetic fields.

Previous research has shown that exposure to circumcerebral weak magnetic fields with different rates of acceleration applied in a counterclockwise rotation around the head was associated with increased estimations of subjective time and as much as a 30% increase in power within the theta range within quantitative electroencephalographic (QEEG) recordings. The largest effect was associated with magnetic fields applied with 20 ms rates of change through each of the successively stimulated, equally spaced, 8 circumcerebral solenoids. The purpose of the present study was to compare the intracerebral power spectra associated with the rotation of the same patterns in either the clockwise or counterclockwise direction. The results generally replicated previous reports and showed enhanced power over regions of the left hemisphere during clockwise rotations and over the right hemisphere during counterclockwise rotations. These results were considered congruent with the creation of "interference patterns" between the rostral-caudal generation of endogenous cerebral magnetic fields putatively associated with consciousness and the spatial direction of the applied rotating magnetic fields.

Phase-locking of spontaneous and tone-elicited pontine waves to hippocampal theta waves during REM sleep in rats.

Temporal relationships between hippocampal theta waves and pontine waves (P waves) during rapid-eye-movement (REM) sleep were investigated in rats. P waves were phase-locked to the positive theta peak. The phase relationships of P waves elicited by a tone stimulus (P(E) waves) to hippocampal theta waves were also analyzed to qualitatively clarify the mechanism of phase-locking between these two phenomena. P(E) waves occurred at the positive theta peak, as seen for spontaneous P waves. This phase preference of P(E) waves could be understood as that of the response probability to tone stimulus. These data suggest that the P-wave generator receives inputs that mimic theta waves. As hippocampal theta waves and P waves are known to be involved in learning and memory processes during REM sleep, the present studies could help to clarify these functions.

Restoring theta-like rhythmicity in rats restores initial learning in the Morris water maze.

Neural activity often becomes rhythmic during mental processing. But there has been no direct proof that rhythmicity, per se, is important for mental function. We assessed this issue in relation to the contribution of hippocampal theta-frequency rhythmicity to learning in the Morris water maze by blocking theta (and other septal inputs to the hippocampus) and then using electrical stimulation to restore rhythmicity. We injected tetracaine into the medial septal area, and so blocked septal input to the hippocampus in rats throughout 16 consecutive trials in a Morris water maze. Rats with no hippocampal theta also showed no initial learning in the maze. Theta rhythmicity in the supramammillary area remained after septal blockade, and we used this to trigger electrical stimulation of the fornix superior. This substantially restored hippocampal theta-like rhythmicity throughout training at a normal frequency but with abnormal wave forms. This treatment applied throughout training substantially restored initial learning. Fixed frequency (7.7 Hz) stimulation produced rhythmic activity and a brief improvement in learning. Irregular stimulation with an average frequency of 7.7 Hz produced little rhythmicity and little improvement in learning. These results demonstrate that brain rhythmicity, per se, can be important for mental processing even when the detailed information originally carried by neurons is lost and when the reinstated pattern of population firing is not normal. The results suggest that the precise frequency of rhythmicity may be important for hippocampal function. Functional rhythmicity needs, therefore, to be included in neural models of cognitive processing. The success of our procedure also suggests that simple alterations of rhythmicity could be used to ameliorate deficits in learning and memory. (c) 2006 Wiley-Liss, Inc.

Activation of alpha7 acetylcholine receptors augments stimulation-induced hippocampal theta oscillation.

In the septohippocampal formation alpha7 nicotinic receptors (alpha7 nAChRs) are predominantly expressed by neurons well positioned to modulate hippocampal theta oscillation, such as GABAergic interneurons in the hippocampus, and by both GABAergic and cholinergic septal neurons. In the present experiments, we evaluated the efficacy of the recently developed selective alpha7 nAChR agonist PNU-282987 on hippocampal theta oscillation in anaesthetized rats. This compound shows high affinity for the rat alpha7 nAChRs (Ki = 26 nM) but a negligible activity at other nAChRs. Systemic administration of PNU-282987 significantly enhanced the power (by 40%) of hippocampal theta oscillation induced by electrical stimulation of the brainstem reticular formation. In contrast, the amnesic and muscarinic receptor antagonist scopolamine significantly decreased the power (by 68%) of the stimulation-induced theta oscillation. Given the connection between hippocampal theta oscillation and cognitive processes, it is proposed that precognitive actions of alpha7 nAChR agonists could be mediated, at least in part, by modulation of hippocampal oscillatory activity.

Dopamine D1-like receptor modulates layer- and frequency-specific short-term synaptic plasticity in rat prefrontal cortical neurons.

The mesocortical dopamine (DA) input to the prefrontal cortex (PFC) is crucial for processing short-term working memory (STWM) to guide forthcoming behavior. Short-term plasticity-like post-tetanic potentiation (PTP, < 3 min) and short-term potentiation (STP, < 10 min) may underlie STWM. Using whole-cell voltage-clamp recordings, mixed glutamatergic excitatory postsynaptic currents (EPSCs) evoked by layer III or layer V stimulation (0.5 or 0.067 Hz) were recorded from layer V pyramidal neurons. With 0.5 Hz basal stimulation of layer III, brief tetani (2 x 50 Hz) induced a homosynaptic PTP (decayed: approximately 1 min). The D1-like antagonist SCH23390 (1 microm) increased the PTP amplitude and decay time without inducing changes to the tetanic response. The tetani may evoke endogenous DA release, which activates a presynaptic D1-like receptor to inhibit glutamate release to modulate PTP. With a slower (0.067 Hz) basal stimulation, the same tetani induced STP (lasting approximately 4 min, but only at 2x intensity only) that was insignificantly suppressed by SCH23390. With stimulation of layer-V-->V inputs at 0.5 Hz, layer V tetani yielded inconsisitent responses. However, at 0.067 Hz, tetani at double the intensity resulted in an STP (lasting approximately 6 min), but a long-term depression after SCH23390 application. Endogenous DA released by tetanic stimulation can interact with a D1-like receptor to induce STP in layer V-->V synapses that receive slower (0.067 Hz) frequency inputs, but suppresses PTP at layer III-->V synapses that receive higher (0.5 Hz) frequency inputs. This D1-like modulation of layer- and frequency-specific synaptic responses in the PFC may contribute to STWM processing.

Weak ELF magnetic field effects on hippocampal rhythmic slow activity.

Several investigations have revealed that electrical activity within the central nervous system (CNS) can be affected by exposure to weak extremely-low-frequency (ELF) magnetic fields. Many of these studies have implicated CNS structures exhibiting endogenous oscillation and synchrony as optimal sites for field coupling. A particularly well characterized structure in this regard is the rat hippocampus. Under urethane anesthesia, synchronous bursting among hippocampal pyramidal neurons produces a large-amplitude quasi-sinusoidal field potential oscillation, termed "rhythmic slow activity" (RSA) or "theta." Using this in vivo model, we investigated the effect of exposure to an externally applied sinusoidal magnetic field (16.0 Hz; 28.9 microT(rms)) on RSA. During a 60-min exposure interval, the probability of RSA decaying to a less coherent mode of oscillation, termed "large irregular-amplitude activity" (LIA), was increased significantly. Moreover, this instability persisted for up to 90 min postexposure. These results are consistent with the hypothesis that endogenous CNS oscillators are uniquely susceptible to field-mediated perturbation and suggest that the sensitivity of these networks to such fields may be far greater than had previously been assumed. This sensitivity may reflect nonlinearities inherent to these networks which permit amplification of endogenous fields mediating the initiation and propagation of neuronal synchrony.