Induced Theta Activity Research Articles

Nucleus incertus projections to rat medial septum and entorhinal cortex: rare collateralization and septal-gating of temporal lobe theta rhythm activity

Nucleus incertus (NI) neurons in the pontine tegmentum give rise to ascending forebrain projections and express the neuropeptide relaxin-3 (RLN3) which acts via the relaxin-family peptide 3 receptor (RXFP3). Activity in the hippocampus and entorhinal cortex can be driven from the medial septum (MS), and the NI projects to all these centers, where a prominent pattern of activity is theta rhythm, which is related to spatial memory processing. Therefore, we examined the degree of collateralization of NI projections to the MS and the medial temporal lobe (MTL), comprising medial and lateral entorhinal cortex (MEnt, LEnt) and dentate gyrus (DG), and the ability of the MS to drive entorhinal theta in the adult rat. We injected fluorogold and cholera toxin-B into the MS septum and either MEnt, LEnt or DG, to determine the percentage of retrogradely labeled neurons in the NI projecting to both or single targets, and the relative proportion of these neurons that were RLN3-positive ( +). The projection to the MS was threefold stronger than that to the MTL. Moreover, a majority of NI neurons projected independently to either MS or the MTL. However, RLN3 + neurons collateralize significantly more than RLN3-negative (–) neurons. In in vivo studies, electrical stimulation of the NI induced theta activity in the MS and the entorhinal cortex, which was impaired by intraseptal infusion of an RXFP3 antagonist, R3(BΔ23-27)R/I5, particularly at ~ 20 min post-injection. These findings suggest that the MS plays an important relay function in the NI-induced generation of theta within the entorhinal cortex.

Frontal theta reveals further information about neural valence-dependent processing of augmented feedback in extensive motor practice-A secondary analysis.

Supplementing an earlier analysis of event-related potentials in extensive motor learning (Margraf et al.,2022a, 2022b), frontal theta-band activity (4-8Hz) was scrutinized. Thirty-seven participants learned a sequential arm movement with 192 trials in each of five practice sessions. Feedback, based on a performance adaptive bandwidth, was given after every trial. Electroencephalogram (EEG) was recorded in the first and last practice sessions. The degree of motor automatization was tested under dual-task conditions in a pre-test-post-test design. Quantitative error information was transported in both feedback conditions (positive and negative). Frontal theta activity was discussed as a general signal that cognitive control is needed and, therefore, was expected to be higher after negative feedback. Extensive motor practice promotes automatization, and therefore, decreased frontal theta activity was expected in the later practice. Further, it was expected that frontal theta was predictive for subsequent behavioural adaptations and the amount of motor automatization. As the results show, induced frontal theta power was higher after negative feedback and decreased after five sessions of practice. Moreover, induced theta activity was predictive for error correction and, therefore, an indicator of whether the recruited cognitive resources successfully induced behavioural adaptations. It remains to be solved why these effects, which fit well with the theoretical assumptions, were only revealed by the induced part of frontal theta activity. Further, the amount of theta activity during practice was not predictive for the degree of motor automatization. It seems that there might be a dissociation between attentional resources associated with feedback processing and attentional resources associated with motor control.

Significance of Non-phase Locked Oscillatory Brain Activity in Response to Noxious Stimuli.

Although current pain-evoked electroencephalographic (EEG) studies provide valuable information regarding human brain regions involved in pain, they have mostly considered neuronal responses which oscillate in phase following a painful event. In many instances, cortical neurons respond by generating bursts of activity that are slightly out of phase from trial-to-trial. These types of activity bursts are known as induced brain responses. The significance of induced brain responses to pain is still unknown. In this study, 23 healthy subjects were given both non-painful and painful transcutaneous electrical stimulations in separate testing blocks (stimulation strength was kept constant within blocks). Subjective intensity was rated using a numerical rating scale, while cerebral activity tied to each stimulation was measured using EEG recordings. Induced brain responses were identified using a time frequency wavelet transform applied to average-removed single trials. Results showed a pain-specific burst of induced theta activity occurring between 180 and 500 ms post-shock onset. Source current density estimations located this activity within the dorsolateral prefrontal cortex (DLPFC, bilaterally), however, only right DLPFC activity predicted a decrease in subjective pain as testing progressed. This finding suggests that non-phase locked neuronal responses in the right DLPFC contribute to the endogenous attenuation of pain through time. This article presents neuroimaging findings demonstrating that, in response to pain, non-phase locked bursts of theta activity located in the right dorsolateral prefrontal cortex are associated with a progressive decrease in subjective pain intensity, which has potentially important implications regarding how humans endogenously control their experiences of pain.

Induced Theta Activity as a Biomarker for a Morbid Effect of Alcoholism on the Brain in Long-Term Abstinent Alcoholics

Event-related, target stimulus-phase-locked (evoked) brain activity in both the time and time-frequency (TF) domains (the P3b ERP; evoked theta oscillations) has been shown to be reduced in alcoholics. Recently, studies have suggested that there is alcohol-related information in the non-stimulus-phase-locked (induced) theta TF activity. We applied TF analysis to target stimulus event-related EEG recorded during an oddball task from 41 long-term abstinent alcoholics (LTAA) and 74 nonalcoholic controls (NAC) to investigate the relationship between P3b, evoked theta, and induced theta activity. Results showed that an event-related synchronization (ERS) of induced theta (1) was larger in LTAA compared to NAC, and (2) was sensitive to differences between LTAA and NAC groups that was independent of the differences accounted for by P3b amplitude or evoked theta. These findings suggest that increased induced theta ERS may likely be a biomarker for a morbid effect of alcohol abuse on brain function.

The generation of theta rhythm in hippocampal formation maintainedin vitro

The most spectacular example of oscillations and synchrony which appear in the brain is the rhythmic slow activity (theta) of the limbic cortex. Theta rhythm is the best synchronized electroencephalographic activity that can be recorded from the mammalian brain. Hippocampal formation is considered to be the main structure involved in the generation of this activity. Although detailed studies of the physiology and pharmacology of theta-band oscillations have been carried out since the early 1950s, the first demonstration of atropine-sensitive theta rhythm, recorded in completely deafferented hippocampal slices of a rat, was performed in the second half of the 1980s. Since the discovery of cholinergically induced in vitro theta rhythm recorded from hippocampal formation slices, the central mechanisms underlying theta generation have been successfully studied in in vitro conditions. Most of these experiments were focused on the basic question regarding the similarities between the cholinergically induced theta activity and theta rhythm examined in vivo. The results of numerous in vitro experiments strongly suggest that cholinergically induced theta rhythm recorded in hippocampal slices is a useful analogue of theta observed in intact animals, and could be helpful in searching for the mechanisms of oscillations and synchrony in the central nervous system neuronal networks. The objective of the present review is to discuss the main results of experiments concerning theta oscillations recorded in in vitro conditions. It is our intent to provide, on the basis of these results, the characteristics of essential mechanisms underlying the generation of atropine-sensitive in vitro theta.

Theta event‐related synchronization is a biomarker for a morbid effect of alcoholism on the brain that may partially resolve with extended abstinence

Analyzing the induced (non-stimulus-phase-locked) EEG activity elicited by targets in a three-condition visual oddball task, Fein and colleagues have shown increased theta band event-related synchronization (ERS) in two different samples of long-term abstinent alcoholics (LTAA) compared with age- and gender-comparable controls. The theta ERS effect in alcoholics was also shown to be independent of, and opposite in direction to, the reduced amplitude evoked (stimulus-phase-locked) activity typically found in alcoholics and those at genetic risk of developing alcoholism. This study extends these findings by applying time-frequency analysis to target stimulus event-related EEG to compare evoked and induced theta activity in 43 LTAA and 72 nonalcoholic controls with a group of 31 alcoholics who just recently initiated abstinence from alcohol (between 6- and 15-week abstinent; referred to as short-term abstinent alcoholics, STAA). Results demonstrated that (1) evoked theta power was reduced to the same degree in STAA and LTAA compared with nonalcoholic control participants, while (2) induced theta activity, measured by theta ERS, was increased in both STAA and LTAA relative to controls, but was also increased in STAA relative to LTAA. The STAA and LTAA groups did not differ on measures of alcohol use severity or family history of alcohol problems. These results, coupled with previous findings that show a relationship between stronger theta ERS and increased memory load and attention allocation, suggest that increased theta ERS may be a biomarker for a detrimental effect of chronic alcohol abuse on the brain – a detriment that may recover, at least partially, with extended abstinence.

Effects of the muscarinic agonist pilocarpine on vigilance states and locomotor activity in ring doves

Cholinergic systems play a significant role in regulating a variety of behavioral functions in mammals and birds. The aim of this work is to study the effects of the muscarinic agonist pilocarpine on behavioral states by visual inspection and electroencephalographic recording; also, locomotor activity was continuously recorded by infrared interruption system in ring doves. The current results in birds demonstrated that the muscarinic agonist pilocarpine (1 and 3mg/kg, i.p.) primarily induced theta activity in addition to promote passive waking, while diminished active waking, the EEG slow wave rhythm and REM sleep in ring doves. The locomotor activity recorded continuously in ring doves diminished after pilocarpine treatment, which was in good agreement with the observed reduction of active waking derived of the EEG study. Altogether, the current results are similar to the effects of pilocarpine previously reported in mammals. In conclusion, hippocampal theta rhythm in birds suggests that this rhythm is an ancestral property of hippocampal function and similar cholinergic mechanisms regulate vigilance states and theta generation in mammals and birds.

Abnormal-induced theta activity supports early directed-attention network deficits in progressive MCI

The electroencephalography (EEG) theta frequency band reacts to memory and selective attention paradigms. Global theta oscillatory activity includes a posterior phase-locked component related to stimulus processing and a frontal-induced component modulated by directed attention. To investigate the presence of early deficits in the directed attention-related network in elderly individuals with mild cognitive impairment (MCI), time–frequency analysis at baseline was used to assess global and induced theta oscillatory activity (4–6 Hz) during n-back working memory tasks in 29 individuals with MCI and 24 elderly controls (EC). At 1-year follow-up, 13 MCI patients were still stable and 16 had progressed. Baseline task performance was similar in stable and progressive MCI cases. Induced theta activity at baseline was significantly reduced in progressive MCI as compared to EC and stable MCI in all n-back tasks, which were similar in terms of directed attention requirements. While performance is maintained, the decrease of induced theta activity suggests early deficits in the directed-attention network in progressive MCI, whereas this network is functionally preserved in stable MCI.

Distinction between Perceptual and Attentional Processing in Working Memory Tasks: A Study of Phase-locked and Induced Oscillatory Brain Dynamics

Working memory involves the short-term storage and manipulation of information necessary for cognitive performance, including comprehension, learning, reasoning and planning. Although electroencephalogram (EEG) rhythms are modulated during working memory, the temporal relationship of EEG oscillations with the eliciting event has not been well studied. In particular, the dynamics of the neural network supporting memory processes may be best captured in induced oscillations, characterized by a loose temporal link with the stimulus. In order to differentiate induced from evoked functional processes, the present study proposes a time-frequency analysis of the 3 to 30 Hz EEG oscillatory activity in a verbal n-back working memory paradigm. Control tasks were designed to identify oscillatory activity related to stimulus presentation (passive task) and focused attention to the stimulus (detection task). Evoked theta activity (4-8 Hz) phase-locked to the visual stimulus was evidenced in the parieto-occipital region for all tasks. In parallel, induced theta activity was recorded in the frontal region for detection and n-back memory tasks, but not for the passive task, suggesting its dependency on focused attention to the stimulus. Sustained induced oscillatory activity was identified in relation to working memory in the theta and beta (15-25 Hz) frequency bands, larger for the highest memory load. Its late occurrence limited to nonmatched items suggests that it could be related to item retention and active maintenance for further task requirements. Induced theta and beta activities displayed respectively a frontal and parietal topographical distribution, providing further functional information on the fronto-posterior network supporting working memory.

Septohippocampal properties of N‐methyl‐D‐aspartate‐induced theta‐band oscillation and synchrony

Microinfusion of N-methyl-D-aspartate (NMDA) into apical dendrites of hippocampal CA1 pyramidal cells of urethane-anesthetized rats resulted in long lasting (20-30 min) induction of hippocampal synchrony at the field and cellular level. Power but not frequency of NMDA-induced theta was significantly greater than tail pinch-induced theta activity. This effect was antagonized by intrahippocampal infusion of AP5, but unaffected by i.v. atropine sulfate. During AP5 blockade tail pinch theta frequency and power were significantly reduced. Microinfusion of NMDA into the medial septum also resulted in long lasting induction of hippocampal theta field activity. Contrary to the results of hippocampal NMDA microinfusions, frequency but not power of NMDA-induced theta was significantly greater than tail pinch- induced theta activity. Microinfusion of AP5 into the medial septum significantly lowered power of tail pinch-induced theta but did not affect frequency. Wheel running behavior of rats induced by low levels of electrical stimulation of the posterior hypothalamic nucleus (PH) was completely abolished by microinfusion of AP5 into the medial septum, accompanied by a significant reduction in theta power and frequency. Wheel running and theta were maintained at control levels with high intensity PH stimulation. We propose that: (1) the glutamatergic septohippocampal projection represents a third pathway capable of generating hippocampal field and cellular synchrony, independent of that generated by the septohippocampal cholinergic and GABAergic projections, and (2) the septohippocampal glutamatergic projection serves to function as an interface between cholinergic and GABAergic modulated sensory processing Type 2 theta and movement related Type 1 theta.

Automated analysis of rhythmicity of physiologically identified hippocampal formation neurons

The participation of physiologically identified hippocampal neurons in spontaneous and hypothalamically induced theta activity was studied in rabbits lightly anaesthetized with urethane. Dentate granule cells were identified by their orthodromic response to perforant path stimulation, CA1 and CA3 pyramids by antidromic activation from the alveus and Schaffer collaterals, respectively, and basket cells by their response to increasing orthodromic activation. The discharges of many hippocampal cells were grossly correlated to the pattern of slow wave activity. Few cells were spontaneously active during irregular slow wave activity. With the appearance of rhythmical slow wave activity of 4–6 Hz, the unit discharges also increased in frequency. Dentate granule cells had the lowest threshold for activation and also a longer duration of the increased discharge frequency, compared to other cell types. There was a characteristic pattern of transition for dentate granule cells and CA1 pyramidal cells from a silent to an active state. The cell discharges paralleled the changes in amplitude, regularity, and frequency of theta slow waves. Large-amplitude, high-frequency theta was correlated with rhythmic burst discharges of up to 2–3 spikes per burst. As theta amplitude and frequency decreased, the number of spikes per burst reduced until only regular single spikes occurred. When theta activity was replaced by irregular slow wave activity, the cell discharges became irregular and sometimes ceased entirely. At high levels of activation, CA1 pyramids often showed clusters of high-frequency discharges with declining amplitude (complex spikes). For each cell a cycle histogram was constructed, placing the discharges in one of 20 bins according to their time relation to the simultaneously recorded slow theta waves. In addition, by Fourier transformation of the cycle histograms, the technique allowed a quantitative description of the degree and type of rhythmicity. The analysis indicated that virtually all dentate granule cells and CA1 pyramidal cells were phaselocked to the negative portion of the theta waves recorded from the corresponding region. The cells differed in their degree of coupling, as expressed by the modulation index of their cyclic histograms. Dentate granule cells had higher modulation indices than the CA1 pyramids. There was a suggestion that basket cells and CA3 cells had smaller modulation indices, but the low number of cells recorded mitigate against any strong conclusions. The results are interpreted as corroborating earlier findings that the dentate granule region and the CA1 pyramidal region are the main generators of hippocampal theta activity. A “size principle” was proposed to explain the role of synaptic depolarizing pressure in the rhythmic activation of hippocampal neurons and the fact that small neurons (dentate granules and CA1 pyramids) were better driven than larger neurons.

Changes in excitability of the theta activity generating substrate by ACTH 4–10 in the rat

The present experiments tested the sensitivity of theta activity to ACTH 4-10 a peptide known to facilitate the maintenance of conditioned behaviors. Hippocampal theta activity was induced by electrical stimulation of the reticular formation in freely moving rats. The administration of ACTH 4-10 produced a typical 0.5 c/s shift indominant frequency and an increase in 7.5-9.0 c/s components of induced theta activity. The effects were maximal between 60-120 min after subcutaneous injection and lasted several hours. The fact, that a similar effect could be obtained by an increase in stimulus intensity suggests an elevated excitability in the theta generating system in the presence of the peptide. The possible significance of this finding for the maintenance of learned behavior is discussed.

Two generators of hippocampal theta activity in rabbits

Spontaneous and hypothalamically induced theta activity was studied in rabbits lightly anaesthetized with urethane or urethane-chloralose. Well-developed theta activity was found over a large area of the dorsal part of the hippocampal formation, roughly corresponding to the CA1 field. Cross-correlation analysis between a stationary and a moving electrode showed that a large sheet of tissue oscillated in remarkable synchrony. This region was at least 8 mm along the longitudinal axis of the hippocampus and 6 mm in a plane transverse to this axis, thus comprising the whole of the rostro-caudal extension of the CA1 region. For technical reasons the temporal half was not explored. Depth recordings showed two foci of theta activity, one in the basal part of CA1 (stratum oriens) and a second, separate region with considerably larger amplitudes in the dentate region, having its maximum in the molecular layer. Due to the folded nature of the dentate fascia, an electrode often recorded two maxima corresponding to its upper and lower blades. Wave form analysis showed that the dentate and CA1 rhythmic activity was roughly 180° out of phase. The dentate theta activity remained in conditions where the CA1 theta activity was absent, either spontaneously or due to experimental interference. Systematic micro-electrode tracking showed absence of theta activity in the CA3 region. Nor was convincing theta activity found in the subiculum, parasubiculum, presubiculum or entorhinal areas.

Differential projections of septal nuclei to ventral and dorsal hippocampus in rabbits

Different data suggest the existence of a septum-hippocampus system topographically organized, the dorsomedial septal nuclei projecting mainly to the dorsal hippocampus, and the ventrolateral to the ventral hippocampus. Experiments were performed in two groups of rabbits, in which theta activity produced by intravenous eserine injection and evoked potentials elicited by septal electrical stimulation were recorded in both dorsal and ventral hippocampus. Theta activity was also recorded in the thalamus and mesencephalon. During some of these recordings procaine solution (10%) was microinjected into the septum. The dorsomedial part of the septum drives the spontaneous activity, evokes the potentials with the lowest stimulus intensity and when injected with procaine blocks eserine induced theta activity in the dorsal hippocampus. The same effects, but in the ventral hippocampus, were obtained from the ventrolateral part of the septum. The activity recorded in the thalamic nuclei seems to follow the changes exhibited by the dorsal hippocampus while the electrical activity recorded in the mesencephalon follows that of the ventral hippocampus. The experiments showed functional differential septal projections to the dorsal or ventral hippocampus, thus giving further support to the idea that the septum-hippocampal system consists of at least two parts with a specific anatomic organization presumably involved in different functions.