Theta Band Activity Research Articles

Co-localization of theta-band activity and hemodynamic responses during face perception: simultaneous electroencephalography and functional near-infrared spectroscopy recordings.

.Face-specific neural processes in the human brain have been localized to multiple anatomical structures and associated with diverse and dynamic social functions. The question of how various face-related systems and functions may be bound together remains an active area of investigation. We hypothesize that face processing may be associated with specific frequency band oscillations that serve to integrate distributed face processing systems. Using a multimodal imaging approach, including electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS), simultaneous signals were acquired during face and object picture viewing. As expected for face processing, hemodynamic activity in the right occipital face area (OFA) increased during face viewing compared to object viewing, and in a subset of participants, the expected N170 EEG response was observed for faces. Based on recently reported associations between the theta band and visual processing, we hypothesized that increased hemodynamic activity in a face processing area would also be associated with greater theta-band activity originating in the same area. Consistent with our hypothesis, theta-band oscillations were also localized to the right OFA for faces, whereas alpha- and beta-band oscillations were not. Together, these findings suggest that theta-band oscillations originating in the OFA may be part of the distributed face-specific processing mechanism.

A Neuroscientific Approach to Explore Consumers’ Intentions Towards Sustainability within the Luxury Fashion Industry

Little is presently known about customers’ expectations and the unspoken relevant factors which lead them to prefer or not sustainable luxury products. This study aimed to deepen the understanding of luxury consumers’ implicit intentions towards sustainability by using, for the first time, a neuroscientific approach applied to the luxury fashion domain. A greater cortical activity related to cognitive and emotional aspects was hypothesized for luxury sustainability-oriented consumers than for non-sustainability-oriented subjects when presented with sustainability-related cues. Sixteen luxury consumers were divided into two groups according to their sensitivity towards sustainability issues. They were asked to observe a set of 10 stimuli depicting sustainability issues and then to interact with a salesperson while their cortical activity was recorded by an electroencephalogram (EEG). Frequency band analysis revealed higher levels of beta, delta, and theta band EEG activity in temporoparietal than frontocentral areas when observing pictures related to sustainability and a specific right temporoparietal theta band activation for the Nonsustainable Group. An increased level of knowledge of sustainability themes was confirmed by the correct detection of stimuli valence and a significant presence of delta power when the salesperson explained the brand’s sustainable policy. The specific brain responses related to sensitivity towards sustainability and the different effect of knowledge on sustainability topics based on group differences are discussed here in light of emotional behavior.

Neural mechanisms of reinforcement learning under mortality threat

ABSTRACTReinforcement learning – to adjust behaviors in response to feedback regarding reward and punishment – is pivotal to our survival. The present work investigated whether and how reinforcement learning is affected by thoughts of mortality that endanger one’s survival. We recorded electroencephalographic while adults performed a probabilistic learning task that required a forced-choice between two visual patterns for monetary reward for different beneficiaries (i.e., self, stranger, or no one) followed by reward or no-reward feedback. We found that verbal reminders of mortality (vs. negative emotion) enlarged an early positive component (P1) at the occipital electrodes but decreased a late positive potential (LPP) at the frontocentral electrodes in response to learning stimuli. While no-reward feedback relative to reward feedback stimuli elicited a feedback-related negativity (FRN) and increased non-phase locked theta band (4–8 Hz) activity at the frontocentral electrodes during reward learning for all beneficiaries, verbal reminders of mortality (vs. negative emotion) significantly reduced the FRN amplitude but failed to modulate the theta band activity. These results suggest that mortality salience enhances early attentional processing but dampens late cognitive evaluation of the learning stimuli during reinforcement learning. Moreover, mortality salience decreases the neural sensitivity to feedback signaling the absence of monetary reward.

Effects of Transpulmonary Administration of Caffeine on Brain Activity in Healthy Men.

The present study aimed to examine the effect of transpulmonary administration of caffeine on working memory and related brain functions by electroencephalography measurement. The participants performed working memory tasks before and after vaporizer-assisted aspiration with inhalation of caffeinated- and non-caffeinated liquids in the caffeine and sham conditions, respectively. Transpulmonary administration of caffeine tended to increase the rate of correct answers. Moreover, our findings suggest that transpulmonary administration of caffeine increases the theta-band activity in the right prefrontal, central, and temporal areas during the task assigned post-aspiration. Our results may indicate an efficient and fast means of eliciting the stimulatory effects of transpulmonary administration of caffeine.

Pre-stimulus Brain Activity Is Associated With State-Anxiety Changes During Single-Session Transcranial Direct Current Stimulation.

Transcranial direct current stimulation is a promising neuromodulation method for treating depression. However, compared with pharmacological treatment, previous studies have reported that a relatively limited proportion of patients respond to tDCS treatment. In addition, the neurophysiological mechanisms underlying tDCS treatment remain unclear, making it difficult to identify response predictors for tDCS treatment based on neurophysiological function. Because treatment effects are achieved by repetitive application of tDCS, studying the immediate effects of tDCS in depressive patients could extend understanding of its treatment mechanisms. However, immediate changes in a single session of tDCS are not well documented. Thus, in the current study, we focused on the immediate impact of tDCS and its association with pre-stimulus brain activity. To address this question, we applied anodal tDCS to the left dorsolateral prefrontal cortex (DLPFC) or dorsomedial prefrontal cortex (DMPFC) in 14 patients with major depressive disorder (MDD) and 19 healthy controls (HCs), at an intensity of 1.0 mA for 20 min in a single session. To evaluate anxiety, the state trait anxiety inventory was completed before and after tDCS. We recorded resting electroencephalography before tDCS, and calculated electrical neuronal activity in the theta and alpha frequency bands using standardized low-resolution electromagnetic tomography. We found that, during application of left DLPFC tDCS to patients with MDD, the anxiety reduction effect of tDCS was related to higher baseline theta-band activity in the rostral anterior cingulate cortex (rACC) and no medication with benzodiazepine used as hypnotic. For DMPFC stimulation in MDD, the anxiety reduction effect was associated with lower baseline alpha-band activity in the left inferior parietal lobule. In contrast, in HCs, the anxiety reduction effect was associated with higher baseline alpha activity in the precuneus during DMPFC stimulation. The current results suggest that the association between pre-tDCS brain activity and the anxiety reduction effect of tDCS depends on psychopathology (depressed or non-depressed) as well as the site of stimulation (DMPFC or left DLPFC) and insomnia. Furthermore, the results suggest that tDCS response might be associated with baseline resting state electrophysiological neural activity.

Evidence for the Rhythmic Perceptual Sampling of Auditory Scenes.

Converging results suggest that perception is controlled by rhythmic processes in the brain. In the auditory domain, neuroimaging studies show that the perception of sounds is shaped by rhythmic activity prior to the stimulus, and electrophysiological recordings have linked delta and theta band activity to the functioning of individual neurons. These results have promoted theories of rhythmic modes of listening and generally suggest that the perceptually relevant encoding of acoustic information is structured by rhythmic processes along auditory pathways. A prediction from this perspective—which so far has not been tested—is that such rhythmic processes also shape how acoustic information is combined over time to judge extended soundscapes. The present study was designed to directly test this prediction. Human participants judged the overall change in perceived frequency content in temporally extended (1.2–1.8 s) soundscapes, while the perceptual use of the available sensory evidence was quantified using psychophysical reverse correlation. Model-based analysis of individual participant’s perceptual weights revealed a rich temporal structure, including linear trends, a U-shaped profile tied to the overall stimulus duration, and importantly, rhythmic components at the time scale of 1–2 Hz. The collective evidence found here across four versions of the experiment supports the notion that rhythmic processes operating on the delta time scale structure how perception samples temporally extended acoustic scenes.

Speech-specific audiovisual integration modulates induced theta-band oscillations.

Speech perception is influenced by vision through a process of audiovisual integration. This is demonstrated by the McGurk illusion where visual speech (for example /ga/) dubbed with incongruent auditory speech (such as /ba/) leads to a modified auditory percept (/da/). Recent studies have indicated that perception of the incongruent speech stimuli used in McGurk paradigms involves mechanisms of both general and audiovisual speech specific mismatch processing and that general mismatch processing modulates induced theta-band (4–8 Hz) oscillations. Here, we investigated whether the theta modulation merely reflects mismatch processing or, alternatively, audiovisual integration of speech. We used electroencephalographic recordings from two previously published studies using audiovisual sine-wave speech (SWS), a spectrally degraded speech signal sounding nonsensical to naïve perceivers but perceived as speech by informed subjects. Earlier studies have shown that informed, but not naïve subjects integrate SWS phonetically with visual speech. In an N1/P2 event-related potential paradigm, we found a significant difference in theta-band activity between informed and naïve perceivers of audiovisual speech, suggesting that audiovisual integration modulates induced theta-band oscillations. In a McGurk mismatch negativity paradigm (MMN) where infrequent McGurk stimuli were embedded in a sequence of frequent audio-visually congruent stimuli we found no difference between congruent and McGurk stimuli. The infrequent stimuli in this paradigm are violating both the general prediction of stimulus content, and that of audiovisual congruence. Hence, we found no support for the hypothesis that audiovisual mismatch modulates induced theta-band oscillations. We also did not find any effects of audiovisual integration in the MMN paradigm, possibly due to the experimental design.

Mental workload of young and older adults gauged with ERPs and spectral power during N-Back task performance

Mental workload has been shown to correlate with alpha and theta band power but only few EEG studies focused on the relation between these bands and Event Related Potentials (ERPs), more specifically the P300 component. We report on an EEG study on mental workload where not only young but also older adults performed an N-Back task. Participants watched a sequence of visual pictures and indicated whether the current picture was the same as the one shown N pictures before. We considered N = 4 difficulty levels and analyzed the relation between these and P300 amplitude and theta and alpha band power, and also examined the effect of age, level of education, work activities, and task accuracy.Our results revealed a decrease in P300 amplitude and alpha band activity for higher difficulty levels for young adults in the parietal region. However, for older adults, fatigue played a more important role than we could anticipate as the alpha band power increased for the highest task difficulty level, and since performance accuracy also decreased, it could even be a sign of task disengagement. Beside alpha band, theta band activity showed a positive correlation with task difficulty level for both young and older adults. Additionally, we found higher P300 amplitudes for young adults compared to older adults, in line with their higher performance accuracies and lower reaction times.In conclusion, we showed that P300 amplitude and alpha and theta bands power provide complementary information for judging mental workload during N-Back performance for young and older subjects and for detecting mental fatigue and task disengagement.

Neural correlates of cue predictiveness during intentional and incidental associative learning: A time-frequency study

Incidental learning allows us to extract statistical relations between events in our daily lives without the intention to learn them. Whereas anticipation during intentional associative learning has been linked to increased and decreased theta band activity, comparatively little research has focused on incidental learning. The study of such a pervasive mechanism of incidental learning faces the challenge of finding an appropriate paradigm. Similarly, while posterior alpha band activity has been shown to facilitate attention to a predictable target location, it is not clear whether alpha power could mediate attention given other predictive information; e.g., when the only available information provided by the cue is the likelihood of the target outcome. Here we used a stimulus-stimulus associative learning task to investigate whether a cue carries information on its contingent relationship with a target outcome, not only when their relationship is learned intentionally but also when it could be learned incidentally. Moreover, by presenting the target outcome in a visual search task, we were also able to study whether anticipatory attention can be modulated by the intentional or the incidental knowledge of the likelihood of a target outcome given a predictive (or non-predictive) cue. Participants were exposed to streams of cue-target outcome trials, where one of two possible cues and one of two possible outcomes were displayed. Intention to learn was manipulated by asking participants to assess whether one of the target outcomes (the intentional one) was more likely to appear following one of the cues (the intentional one). Any learning regarding the other cue-outcome relationship would be incidental. We found that frontal and temporal theta band activity were sensitive to the predictive value of a cue (predictive cues elicited lower theta power). Moreover, left temporal theta was sensitive to the intention to learn associations (theta activity elicited by intentional learning cues was higher). Alpha power, by contrast, was not modulated by cue predictiveness of the target outcome. These findings suggest that theta band activity carries information about the predictive value of a cue. The topographical differences between theta for intentional and incidental learning suggest distinct cortical networks activated depending on whether the relationship between a cue and an outcome has been learned intentionally or incidentally.

On the relevance of EEG resting theta activity for the neurophysiological dynamics underlying motor inhibitory control.

The modulation of theta frequency activity plays a major role in inhibitory control processes. However, the relevance of resting theta band activity and of the ability to spontaneously modulate this resting theta activity for neural mechanisms underlying inhibitory control is elusive. Various theoretical conceptions suggest to take these aspects into consideration. In the current study, we examine whether the strength of resting theta band activity or the ability to modulate the resting state theta activity affects response inhibition. We combined EEG-time frequency decomposition and beamforming in a conflict-modulated Go/Nogo task. A sample of N = 66 healthy subjects was investigated. We show that the strength of resting state theta activity modulates the effects of conflicts during motor inhibitory control. Especially when resting theta activity was low, conflicts strongly affected response inhibition performance and total theta band activity during Nogo trials. These effects were associated with theta-related activity differences in the superior (BA7) and inferior parietal cortex (BA40). The results were very specific for total theta band activity since evoked theta activity and measures of intertrial phase coherency (phase-locking factor) were not affected. The data suggest that the strength of resting state theta activity modulates processing of a theta-related alarm or surprise signal during inhibitory control. The ability to voluntarily modulate theta band activity did not affect conflict-modulated inhibitory control. These findings have important implications for approaches aiming to optimize human cognitive control.

Synchronization of Slow Cortical Rhythms During Motor Imagery-Based Brain-Machine Interface Control.

Modulation of sensorimotor rhythm (SMR) power, a rhythmic brain oscillation physiologically linked to motor imagery, is a popular Brain-Machine Interface (BMI) paradigm, but its interplay with slower cortical rhythms, also involved in movement preparation and cognitive processing, is not entirely understood. In this study, we evaluated the changes in phase and power of slow cortical activity in delta and theta bands, during a motor imagery task controlled by an SMR-based BMI system. In Experiment I, EEG of 20 right-handed healthy volunteers was recorded performing a motor-imagery task using an SMR-based BMI controlling a visual animation, and during task-free intervals. In Experiment II, 10 subjects were evaluated along five daily sessions, while BMI-controlling same visual animation, a buzzer, and a robotic hand exoskeleton. In both experiments, feedback received from the controlled device was proportional to SMR power (11-14 Hz) detected by a real-time EEG-based system. Synchronization of slow EEG frequencies along the trials was evaluated using inter-trial-phase coherence (ITPC). Results: cortical oscillations of EEG in delta and theta frequencies synchronized at the onset and at the end of both active and task-free trials; ITPC was significantly modulated by feedback sensory modality received during the tasks; and ITPC synchronization progressively increased along the training. These findings suggest that phase-locking of slow rhythms and resetting by sensory afferences might be a functionally relevant mechanism in cortical control of motor function. We propose that analysis of phase synchronization of slow cortical rhythms might also improve identification of temporal edges in BMI tasks and might help to develop physiological markers for identification of context task switching and practice-related changes in brain function, with potentially important implications for design and monitoring of motor imagery-based BMI systems, an emerging tool in neurorehabilitation of stroke.

Neurobiological Mechanisms of Metacognitive Therapy - An Experimental Paradigm.

IntroductionThe neurobiological mechanisms underlying the clinical effects of psychotherapy are scarcely understood. In particular, the modifying effects of psychotherapy on neuronal activity are largely unknown. We here present data from an innovative experimental paradigm using the example of a patient with treatment resistant obsessive-compulsive disorder (trOCD) who underwent implantation of bilateral electrodes for deep brain stimulation (DBS). The aim of the paradigm was to examine the short term effect of metacognitive therapy (MCT) on neuronal local field potentials (LFP) before and after 5 MCT sessions.MethodsDBS electrodes were implanted bilaterally with stereotactic guidance in the bed nucleus of the stria terminalis/ internal capsule (BNST/IC). The period between implantation of the electrodes and the pacemaker was used for the experimental paradigm. DBS electrodes were externalized via extension cables, yielding the opportunity to record LFP directly from the BNST/IC. The experimental paradigm was designed as follows: (a) baseline recording of LFP from the BNST/IC, (b) application of 5 MCT sessions over 3 days, (c) post-MCT recording from the BNST/IC. The Obsessive-Compulsive Disorder- scale (OCD-S) was used to evaluate OCD symptoms.ResultsOCD symptoms decreased after MCT. These reductions were accompanied by a decrease of the relative power of theta band activity, while alpha, beta, and gamma band activity was significantly increased after MCT. Further, analysis of BNST/IC LFP and frontal cortex EEG coherence showed that MCT decreased theta frequency band synchronization.DiscussionImplantation of DBS electrodes for treating psychiatric disorders offers the opportunity to gather data from neuronal circuits, and to compare effects of therapeutic interventions. Here, we demonstrate direct effects of MCT on neuronal oscillatory behavior, which may give possible cues for the neurobiological changes associated with psychotherapy.

Objective identification of pain due to uterine contraction during the first stage of labour using continuous EEG signals and SVM

This study aimed to assess the utility of electroencephalography (EEG) as an objective marker of pain during the first stage of labour. EEG and cardiotocography (CTG) data were obtained from 10 parturient women during their first stage of labour. The study subjects reported the extent of their pain experienced due to uterine contractions, which were recorded by the CTG tracing. Simultaneous 16-channel EEG traces were obtained for spectral analysis and a subsequent machine learning classification using Support Vector Machine (SVM) aiming to predict the pain experienced in relation to uterine contractions. It was found that pain due to uterine contraction correlated positively with relative delta and beta band activities and negatively with relative theta and alpha band activities of the EEG signals. SVM using the spectral activities, statistical and non-linear features of the EEG classified the state of pain with 83% accuracy using a classification model generalizable across subjects. Furthermore, dimension reduction using Principal Component Analysis (PCA) successfully reduced the number of features used in the classification while achieving a maximum classification accuracy of 84%. Continuous EEG affords the means to assess objectively maternal pain experienced during the active contraction phase of the first stage of labour. Monitoring of the pain experience using EEG signals may complement the clinical decision-making process behind administration of epidural anaesthesia during labour. We envision future studies to investigate EEG markers of pain in other clinical states, aiming to generalize the use of EEG as an objective method of pain assessment.

Do theta oscillations explain the somatosensory change detection mechanism?

Recent research has indicated that the mismatch negativity (MMN) is elicited in response to a discernible small change of a somatosensory stimulus applied on the hand. However, the neural mechanism for detecting small change of somatosensory stimulus remains unknown. In the present study, we developed a novel pressure stimulation device using air jet applied on the index finger pad, and determined the just noticeable differences (JNDs) of pressure discrimination for each subject. Using the deviant-standard-reversed oddball paradigm, we analyzed the average dynamic changes in MMN amplitude and changes of evoked spectral power. We found a clear MMN component at the frontal and central regions at 100–300 msec after deviant stimulus presentation. Statistical tests showed that theta band activity played pivotal roles in the generation of the MMN elicited by a change in somatosensory pressure stimulation. Our results indicate that the somatosensory discriminatory process reflected on MMN is accompanied by phase-locked oscillation at the theta frequency.

Anodal tDCS affects neuromodulatory effects of the norepinephrine system on superior frontal theta activity during response inhibition.

Medial and superior frontal theta oscillations are important for response inhibition. The norepinephrine (NE) system has been shown to modulate these oscillations possibly via gain control mechanisms, which depend on the modulation of neuron membrane potentials. Because the latter are also modulated by tDCS, the interrelation of tDCS and NE effects on superior frontal theta band activity needs investigation. We test the hypothesis that anodal tDCS affects modulatory effects of the NE system on theta band activity during inhibitory control in superior frontal regions. Using EEG beamforming, theta band activity in the superior frontal gyrus (SFG) was integrated (correlated) with the pupil diameter data as an indirect index of NE activity. In a within-subject design, healthy participants completed a response inhibition task in two sessions in which they received 2mA anodal tDCS over the vertex, or sham stimulation. There were no behavioral effects of anodal tDCS. Yet, tDCS affected correlations between SFG theta band activity time course and the pupil diameter time course. Correlations were evident after sham stimulation (r = .701; p < .004), but absent after anodal tDCS. The observed power of this dissociation was above 95%. The data suggest that anodal tDCS may eliminate neuromodulatory effects, likely of the NE system, on theta band activity during response inhibition in a structure of the response inhibition network. The NE system and tDCS seem to target similar mechanisms important for cognitive control in the prefrontal cortex. The results provide a hint why tDCS often fails to induce overt behavioral effects and shows that neurobiological systems, which may exert similar effects as tDCS on neural processes should closely be monitored in tDCS experiments.

Early sensitivity of evoked potentials to surface and volumetric structure during the visual perception of three-dimensional object shape.

This study used event-related potentials (ERPs) to elucidate how the human visual system processes three-dimensional (3-D) object shape structure. In particular, we examined whether the perceptual mechanisms that support the analysis of 3-D shape are differentially sensitive to higher order surface and volumetric part structure. Observers performed a whole-part novel object matching task in which part stimuli comprised sub-regions of closed edge contour, surfaces or volumetric parts. Behavioural response latency data showed an advantage in matching surfaces and volumetric parts to whole objects over contours, but no difference between surfaces and volumes. ERPs were analysed using a convergence of approaches based on stimulus dependent amplitude modulations of evoked potentials, topographic segmentation, and spatial frequency oscillations. The results showed early differential perceptual processing of contours, surfaces, and volumetric part stimuli. This was first reliably observed over occipitoparietal electrodes during the N1 (140-200ms) with a mean peak latency of 170ms, and continued on subsequent P2 (220-260ms) and N2 (260-320ms) components. The differential sensitivity in perceptual processing during the N1 was accompanied by distinct microstate patterns that distinguished among contours, surfaces and volumes, and predominant theta band activity around 4-7Hz over right occipitoparietal and orbitofrontal sites. These results provide the first evidence of early differential perceptual processing of higher order surface and volumetric shape structure within the first 200ms of stimulus processing. The findings challenge theoretical models of object recognition that do not attribute functional significance to surface and volumetric object structure during visual perception.

Moving developmental social neuroscience toward a second-person approach.

Infants’ cognitive development and learning rely profoundly on their interactions with other people. In the first year, infants become increasingly sensitive to others’ gaze and use it to focus their own attention on relevant visual input. However, infants are not passive observers in early social interactions, and these exchanges are characterized by high levels of contingency and reciprocity. Wass and colleagues offer first insights into the neurobehavioral dynamics of caregiver–infant interactions, demonstrating that caregivers’ scalp-recorded theta band activity responds to their infant’s changes in attention, and parental brain activation is associated with infants’ sustenance of attention. This research opens up entirely new ways of exploring caregiver–infant interactions and to understand early social attention as a reciprocal and dynamic process.

Frequency-specific noninvasive modulation of memory retrieval and its relationship with hippocampal network connectivity.

Episodic memory is thought to rely on interactions of the hippocampus with other regions of the distributed hippocampal-cortical network (HCN) via interregional activity synchrony in the theta frequency band. We sought to causally test this hypothesis using network-targeted transcranial magnetic stimulation. Healthy human participants completed four experimental sessions, each involving a different stimulation pattern delivered to the same individualized parietal cortex location of the HCN for all sessions. There were three active stimulation conditions, including continuous theta-burst stimulation, intermittent theta-burst stimulation, and beta-frequency (20-Hz) repetitive stimulation, and one sham condition. Resting-state fMRI and episodic memory testing were used to assess the impact of stimulation on hippocampal fMRI connectivity related to retrieval success. We hypothesized that theta-burst stimulation conditions would most strongly influence hippocampal-HCN fMRI connectivity and retrieval, given the hypothesized relevance of theta-band activity for HCN memory function. Continuous theta-burst stimulation improved item retrieval success relative to sham and relative to beta-frequency stimulation, whereas intermittent theta-burst stimulation led to numerical but nonsignificant item retrieval improvement. Mean hippocampal fMRI connectivity did not vary for any stimulation conditions, whereas individual differences in retrieval improvements due to continuous theta-burst stimulation were associated with corresponding increases in fMRI connectivity between the hippocampus and other HCN locations. No such memory-related connectivity effects were identified for the other stimulation conditions, indicating that only continuous theta-burst stimulation affected memory-related hippocampal-HCN connectivity. Furthermore, these effects were specific to the targeted HCN, with no significant memory-related fMRI connectivity effects for two distinct control brain networks. These findings support a causal role for fMRI connectivity of the hippocampus with the HCN in episodic memory retrieval and indicate that contributions of this network to retrieval are particularly sensitive to continuous theta-burst noninvasive stimulation.

Prefrontal Theta Oscillations Promote Selective Encoding of Behaviorally Relevant Events.

The ability to capture the most relevant information from everyday experiences without constantly learning unimportant details is vital to survival and mental health. While decreased activity of the medial prefrontal cortex (mPFC) is associated with failed or inflexible encoding of relevant events in the hippocampus, mechanisms used by the mPFC to discern behavioral relevance of events are not clear. To address this question, we chemogenetically activated excitatory neurons in the mPFC of male rats and examined its impact on local network activity and differential associative learning dependent on the hippocampus. Rats were exposed to two neutral stimuli in two environments whose contingency with an aversive stimulus changed systematically across days. Over 2 weeks of differential and reversal learning, theta band activity began to ramp up toward the expected onset of the aversive stimulus, and this ramping activity tracked the subsequent shift of the set (stimulus modality to environment) predictive of the aversive stimulus. With chemogenetic mPFC activation, the ramping activity emerged within a few sessions of differential learning, which paralleled faster learning and stronger correlations between the ramping activity and conditioned responses. Chemogenetic mPFC activity, however, did not affect the adjustment of ramping activity or behavior during reversal learning or set-shifting, suggesting that the faster learning was not because of a general enhancement of attention, sensory, or motor processing. Thus, the dynamics of the mPFC network activation during events provide a relevance-signaling mechanism through which the mPFC exerts executive control over the encoding of those events in the hippocampus.

Modulation of Hyperpolarization-Activated Inward Current and Thalamic Activity Modes by Different Cyclic Nucleotides.

The hyperpolarization-activated inward current, Ih, plays a key role in the generation of rhythmic activities in thalamocortical (TC) relay neurons. Cyclic nucleotides, like 3′,5′-cyclic adenosine monophosphate (cAMP), facilitate voltage-dependent activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels by shifting the activation curve of Ih to more positive values and thereby terminating the rhythmic burst activity. The role of 3′,5′-cyclic guanosine monophosphate (cGMP) in modulation of Ih is not well understood. To determine the possible role of the nitric oxide (NO)-sensitive cGMP-forming guanylyl cyclase 2 (NO-GC2) in controlling the thalamic Ih, the voltage-dependency and cGMP/cAMP-sensitivity of Ih was analyzed in TC neurons of the dorsal part of the lateral geniculate nucleus (dLGN) in wild type (WT) and NO-GC2-deficit (NO-GC2−/−) mice. Whole cell voltage clamp recordings in brain slices revealed a more hyperpolarized half maximal activation (V1/2) of Ih in NO-GC2−/− TC neurons compared to WT. Different concentrations of 8-Br-cAMP/8-Br-cGMP induced dose-dependent positive shifts of V1/2 in both strains. Treatment of WT slices with lyase enzyme (adenylyl and guanylyl cyclases) inhibitors (SQ22536 and ODQ) resulted in further hyperpolarized V1/2. Under current clamp conditions NO-GC2−/− neurons exhibited a reduction in the Ih-dependent voltage sag and reduced action potential firing with hyperpolarizing and depolarizing current steps, respectively. Intrathalamic rhythmic bursting activity in brain slices and in a simplified mathematical model of the thalamic network was reduced in the absence of NO-GC2. In freely behaving NO-GC2−/− mice, delta and theta band activity was enhanced during active wakefulness (AW) as well as rapid eye movement (REM) sleep in cortical local field potential (LFP) in comparison to WT. These findings indicate that cGMP facilitates Ih activation and contributes to a tonic activity in TC neurons. On the network level basal cGMP production supports fast rhythmic activity in the cortex.