The interplay of resting and inhibitory control‐related theta‐band activity depends on age

Resting‐state neural activity plays an important role for cognitive control processes. Regarding response inhibition processes, an important facet of cognitive control, especially theta‐band activity has been the focus of research. Theoretical considerations suggest that the interrelation of resting and task‐related theta activity is subject to maturational effects. To investigate whether the relationship between resting theta activity and task‐related theta activity during a response inhibition task changes even in young age, we tested N = 166 healthy participants between 8 and 30 years of age. We found significant correlations between resting and inhibitory control‐related theta activity as well as behavioral inhibition performance. Importantly, these correlations were moderated by age. The moderation analysis revealed that higher resting theta activity was associated with stronger inhibition‐related theta activity in individuals above the age of ~10.7 years. The EEG beamforming analysis showed that this activity is associated with superior frontal region function (BA6). The correlation between resting and superior frontal response inhibition‐related theta activity became stronger with increasing age. A similar pattern was found for response inhibition performance, albeit only evident from the age of ~19.5 years. The results suggest that with increasing age, resting theta activity becomes increasingly important for processing the alarm/surprise signals in superior frontal brain regions during inhibitory control. Possible causes for these developmental changes are discussed.     

Hippocampal theta‐driving cells revealed by Granger causality

The two‐dipole model of theta generation in hippocampal CA1 suggests that the inhibitory perisomatic theta dipole is generated by local GABAergic interneurons. Various CA1 interneurons fire preferentially at different theta phases, raising the question of how these theta‐locked interneurons contribute to the generation of theta oscillations. We here recorded interneurons in the hippocampal CA1 area of freely behaving mice, and identified a unique subset of theta‐locked interneurons by using the Granger causality approach. These cells fired in an extremely reliable theta‐burst pattern at high firing rates (～90 Hz) during exploration and always locked to ascending phases of the theta waves. Among theta‐locked interneurons we recorded, only these cells generated strong Granger causal influences on local field potential (LFP) signals within the theta band (4–12 Hz), and the influences were persistent across behavioral states. Our results suggest that this unique type of theta‐locked interneurons serve as the local inhibitory theta dipole control cells in shaping hippocampal theta oscillations. © 2012 Wiley Periodicals, Inc.     

Recognition memory and theta–gamma interactions in the hippocampus

Neuronal oscillations and cross‐frequency interactions in the rat hippocampus relate in important ways to memory processes and serve as a model for studying oscillatory activity in cognition more broadly. We report here that hippocampal synchrony (CA3–CA1 coherence) increased markedly in the low gamma range as rats were exploring novel objects, particularly those for which the rat subsequently showed good memory. The gamma synchrony varied across phases of the theta rhythm such that coherence was highest at the falling slope and trough of the theta wave. Further, the shape of the theta wave was more asymmetric and elongated at the falling slope during exploration of objects for which the rat subsequently showed good memory as compared with objects for which the rat subsequently showed poor memory. The results showed a strong association between event‐related gamma synchrony in rat hippocampus and memory encoding for novel objects. In addition, a novel potential mechanism of cross‐frequency interactions was observed whereby dynamic alterations in the shape of theta wave related to memory in correspondence with the strength of gamma synchrony. These findings add to our understanding of how theta and gamma oscillations interact in the hippocampus in the service of memory. © 2013 Wiley Periodicals, Inc.     

Supramodal neural networks support top‐down processing of social signals

The perception of facial and vocal stimuli is driven by sensory input and cognitive top‐down influences. Important top‐down influences are attentional focus and supramodal social memory representations. The present study investigated the neural networks underlying these top‐down processes and their role in social stimulus classification. In a neuroimaging study with 45 healthy participants, we employed a social adaptation of the Implicit Association Test. Attentional focus was modified via the classification task, which compared two domains of social perception (emotion and gender), using the exactly same stimulus set. Supramodal memory representations were addressed via congruency of the target categories for the classification of auditory and visual social stimuli (voices and faces). Functional magnetic resonance imaging identified attention‐specific and supramodal networks. Emotion classification networks included bilateral anterior insula, pre‐supplementary motor area, and right inferior frontal gyrus. They were pure attention‐driven and independent from stimulus modality or congruency of the target concepts. No neural contribution of supramodal memory representations could be revealed for emotion classification. In contrast, gender classification relied on supramodal memory representations in rostral anterior cingulate and ventromedial prefrontal cortices. In summary, different domains of social perception involve different top‐down processes which take place in clearly distinguishable neural networks.     

The phase of pre‐stimulus brain oscillations correlates with cross‐modal synchrony perception

In everyday life multisensory events, such as a glass crashing on the floor, the different sensory inputs are often experienced as simultaneous, despite the sensory processing of sound and sight within the brain are temporally misaligned. This lack of cross‐modal synchrony is the unavoidable consequence of different light and sound speeds, and their different neural transmission times in the corresponding sensory pathways. Hence, cross‐modal synchrony must be reconstructed during perception. It has been suggested that spontaneous fluctuations in neural excitability might be involved in the temporal organisation of sensory events during perception and account for variability in behavioural performance. Here, we addressed the relationship between ongoing brain oscillations and the perception of cross‐modal simultaneity. Participants performed an audio‐visual simultaneity judgement task while their EEG was recorded. We focused on pre‐stimulu activity, and found that the phase of neural oscillations at 13 ± 2 Hz 200 ms prior to the stimulus correlated with subjective simultaneity of otherwise identical sound‐flash events. Remarkably, the correlation between EEG phase and behavioural report occurred in the absence of concomitant changes in EEG amplitude. The probability of simultaneity perception fluctuated significantly as a function of pre‐stimulus phase, with the largest perceptual variation being accounted for phase angles nearly 180º apart. This pattern was strongly reliable for sound‐flash pairs but not for flash‐sound pairs. Overall, these findings suggest that the phase of ongoing brain activity might underlie internal states of the observer that influence cross‐modal temporal organisation between the senses and, in turn, subjective synchrony.     

Decrease in early right alpha band phase synchronization and late gamma band oscillations in processing syntax in music

The present study investigated the neural correlates associated with the processing of music-syntactical irregularities as compared with regular syntactic structures in music. Previous studies reported an early ( approximately 200 ms) right anterior negative component (ERAN) by traditional event-related-potential analysis during music-syntactical irregularities, yet little is known about the underlying oscillatory and synchronization properties of brain responses which are supposed to play a crucial role in general cognition including music perception. First we showed that the ERAN was primarily represented by low frequency (<8 Hz) brain oscillations. Further, we found that music-syntactical irregularities as compared with music-syntactical regularities, were associated with (i) an early decrease in the alpha band (9-10 Hz) phase synchronization between right fronto-central and left temporal brain regions, and (ii) a late ( approximately 500 ms) decrease in gamma band (38-50 Hz) oscillations over fronto-central brain regions. These results indicate a weaker degree of long-range integration when the musical expectancy is violated. In summary, our results reveal neural mechanisms of music-syntactic processing that operate at different levels of cortical integration, ranging from early decrease in long-range alpha phase synchronization to late local gamma oscillations.     

Someone has to give in: theta oscillations correlate with adaptive behavior in social bargaining

During social bargain, one has to both figure out the others’ intentions and behave strategically in such a way that the others’ behaviors will be consistent with one’s expectations. To understand the neurobiological mechanisms underlying these behaviors, we used electroencephalography while subjects played as proposers in a repeated ultimatum game. We found that subjects adapted their offers to obtain more acceptances in the last round and that this adaptation correlated negatively with prefrontal theta oscillations. People with higher prefrontal theta activity related to a rejection did not adapt their offers along the game to maximize their earning. Moreover, between-subject variation in posterior theta oscillations correlated positively with how individual theta activity influenced the change of offer after a rejection, reflecting a process of behavioral adaptation to the others’ demands. Interestingly, people adapted better their offers when they knew that they where playing against a computer, although the behavioral adaptation did not correlate with prefrontal theta oscillation. Behavioral changes between human and computer games correlated with prefrontal theta activity, suggesting that low adaptation in human games could be a strategy. Taken together, these results provide evidence for specific roles of prefrontal and posterior theta oscillations in social bargaining.     

A bias‐free two‐alternative forced choice procedure to examine intersensory illusions applied to the ventriloquist effect by flashes and averted eye‐gazes

We compared with a new psychophysical method whether flashes and averted eye‐gazes of a cartoon face induce a ventriloquist illusion (an illusory shift of the apparent location of a sound by a visual distracter). With standard psychophysical procedures that measure a direct ventriloquist effect and a ventriloquist aftereffect, we found in human subjects that both types of stimuli induced an illusory shift of sound location. These traditional methods, though, are probably contaminated by response strategies. We therefore developed a new two‐alternative forced choice procedure that allows measuring the strength of an intersensory illusion in a bias‐free way. With this new procedure we found that only flashes, but not averted eye‐gazes, induced an illusory shift in sound location. This difference between flashes and eye‐gazes was validated in an EEG study in which again only flashes illusorily shifted the apparent location of a sound thereby evoking a mismatch negativity response. These results are important because they highlight that commonly used measures of multisensory illusions are contaminated while there is an easy yet stringent way to measure the strength of an illusion in a bias‐free way.     

Transfreq: A Python package for computing the theta‐to‐alpha transition frequency from resting state electroencephalographic data

A classic approach to estimate individual theta‐to‐alpha transition frequency (TF) requires two electroencephalographic (EEG) recordings, one acquired in a resting state condition and one showing alpha desynchronisation due, for example, to task execution. This translates into long recording sessions that may be cumbersome in studies involving patients. Moreover, an incomplete desynchronisation of the alpha rhythm may compromise TF estimates. Here we present transfreq, a publicly available Python library that allows TF computation from resting state data by clustering the spectral profiles associated to the EEG channels based on their content in alpha and theta bands. A detailed overview of transfreq core algorithm and software architecture is provided. Its effectiveness and robustness across different experimental setups are demonstrated on a publicly available EEG data set and on in‐house recordings, including scenarios where the classic approach fails to estimate TF. We conclude with a proof of concept of the predictive power of transfreq TF as a clinical marker. Specifically, we present a scenario where transfreq TF shows a stronger correlation with the mini mental state examination score than other widely used EEG features, including individual alpha peak and median/mean frequency. The documentation of transfreq and the codes for reproducing the analysis of the article with the open‐source data set are available online at https://elisabettavallarino.github.io/transfreq/. Motivated by the results showed in this article, we believe our method will provide a robust tool for discovering markers of neurodegenerative diseases.     

Gamma band oscillations reveal neural network cortical coherence dysfunction in schizophrenia patients.

BACKGROUND: Gamma band activity has been associated with many sensory and cognitive functions, and is important for cortico-cortical transmission and the integration of information across neural networks. The aims of the present study were to determine if schizophrenia patients have deficits in the generation and maintenance of coherent, synchronized oscillations in response to steady-state stimulation, and to examine the clinical and cognitive correlates of the electroencephalography (EEG) oscillatory dynamics. METHODS: Schizophrenia patients (n = 100) and nonpsychiatric subjects (n = 80) underwent auditory steady-state event-related potential testing. Click trains varying in rate of stimulation (20, 30, and 40 Hz) were presented; EEG-evoked power and intertrial phase synchronization were obtained in response to each stimulation frequency. Subjects also underwent clinical and neurocognitive assessments. RESULTS: Patients had reductions in both evoked power and phase synchronization in response to 30- and 40-Hz stimulation but normal responsivity to 20-Hz stimulation. Maximal deficits were detected in response to 40-Hz stimulation. A modest association of reduced working memory performance and 40-Hz intertrial phase synchronization was present in schizophrenia patients (r = .32, p <.01). CONCLUSIONS: Schizophrenia patients have frequency-specific deficits in the generation and maintenance of coherent gamma-range oscillations, reflecting a fundamental degradation of basic integrated neural network activity.     

The CAN‐In network: A biologically inspired model for self‐sustained theta oscillations and memory maintenance in the hippocampus

During working memory tasks, the hippocampus exhibits synchronous theta‐band activity, which is thought to be correlated with the short‐term memory maintenance of salient stimuli. Recent studies indicate that the hippocampus contains the necessary circuitry allowing it to generate and sustain theta oscillations without the need of extrinsic drive. However, the cellular and network mechanisms supporting synchronous rhythmic activity are far from being fully understood. Based on electrophysiological recordings from hippocampal pyramidal CA1 cells, we present a possible mechanism for the maintenance of such rhythmic theta‐band activity in the isolated hippocampus. Our model network, based on the Hodgkin‐Huxley formalism, comprising pyramidal neurons equipped with calcium‐activated nonspecific cationic (CAN) ion channels, is able to generate and sustain synchronized theta oscillations (4–12 Hz), following a transient stimulation. The synchronous network activity is maintained by an intrinsic CAN current (I_CAN), in the absence of constant external input. When connecting the pyramidal‐CAN network to fast‐spiking inhibitory interneurons, the dynamics of the model reveal that feedback inhibition improves the robustness of fast theta oscillations, by tightening the synchronization of the pyramidal CAN neurons. The frequency and power of the theta oscillations are both modulated by the intensity of the I_CAN, which allows for a wide range of oscillation rates within the theta band. This biologically plausible mechanism for the maintenance of synchronous theta oscillations in the hippocampus aims at extending the traditional models of septum‐driven hippocampal rhythmic activity. © 2017 Wiley Periodicals, Inc.     

Dynamic changes of ictal high-frequency oscillations in neocortical epilepsy: using multiple band frequency analysis

PURPOSE: To characterize the spatial and temporal course of ictal high-frequency oscillations (HFOs) recorded by subdural EEG in children with intractable neocortical epilepsy. METHODS: We retrospectively studied nine children (four girls, five boys; 4-17 yr) who presented with intractable extrahippocampal localization-related epilepsy and who underwent extraoperative video subdural EEG (1000 Hz sampling rate) and cortical resection. We performed multiple band frequency analysis (MBFA) to evaluate the frequency, time course, and distribution of ictal HFOs. We compared ictal HFO changes before and after clinical onset and postsurgical seizure outcomes. RESULTS: Seventy-eight of 79 seizures showed HFOs. We observed wide-band HFOs ( approximately 250 Hz, approximately 120 electrodes) in six patients either with partial seizures alone (three patients) or with epileptic spasms (three patients). Three patients with partial seizures that secondarily generalized had wide-band HFOs ( approximately 170 Hz) before clinical onset and sustained narrow-band HFOs (60-164 Hz) with electrodecremental events after clinical onset ( approximately 28 electrodes). In four postoperatively seizure-free patients, more electrodes recorded higher-frequency HFOs inside the resection area than outside before and after clinical seizure onset. In five patients with residual seizures, electrodes recorded more HFOs that were of higher or equal frequency outside the surgical area than inside after clinical onset. CONCLUSION: For partial seizures alone and epileptic spasms, more electrodes recorded only wide-band HFOs; for partial seizures that secondarily generalized, fewer electrodes recorded wide-band HFOs, but in these seizures electrodes also recorded subsequent sustained narrow-band ictal HFOs. Resection of those brain regions having electrodes with ictal, higher HFOs resulted in postsurgical seizure-free outcomes.     

Role of amygdala oscillations in the consolidation of emotional memories.

Much evidence indicates that emotional arousal generally improves memory and that the amygdala is responsible for this effect. The available data suggest that stress hormones and neuromodulators released in emotionally arousing conditions alter the activity of basolateral amygdala (BLA) neurons in the hours after the learning episode. In turn, these changes would facilitate synaptic plasticity elsewhere in the brain; however, the biological mechanisms underlying the facilitation of memory consolidation by the BLA remain unknown. This article focuses on data suggesting that synchronized oscillatory BLA activity promotes synaptic plasticity by facilitating interactions between neocortical and temporal lobe areas involved in declarative memory.     

Enhanced resting‐state oscillations in schizophrenia are associated with decreased synchronization during inattentional blindness

Patients suffering from schizophrenia have been characterized by an apparent lack of theta (around 6 Hz) and gamma (>40 Hz) brain oscillatory activity during task execution. The neurocognitive reasons for these abnormal synchronization patterns, however, remain elusive. Recording the electroencephalogramm (EEG) during a selective visual attention task, the current study investigates whether abnormal brain oscillatory resting‐state activity in the theta band might account for a lack of task‐related brain oscillatory activity in schizophrenia. EEGs were recorded from 26 patients with schizophrenia and 26 healthy matched controls during rest and during the execution of a selective visual attention task, in which an unexpected object (monkey) appeared on the screen. On a behavioral level, patients were less likely to report perceiving the unexpected event than controls. Controls showed a stronger increase in task‐related theta power than patients in prefrontal, parietal, and occipital brain regions. Task‐related theta power change differed between patients who perceived, and patients who did not perceive the unexpected event. Moreover, patients showed higher levels of theta power during rest than controls, whereas the absolute theta power values during the selective attention task did not differ between groups. These results suggest that the failure to increase oscillatory activity during a cognitive task can be accounted for by abnormally high oscillatory activity in a resting state. This finding has important implications for future studies examining abnormal brain oscillatory activity in schizophrenia, which usually treat resting‐state activity as a baseline for task‐related activity. Hum Brain Mapp 34:2266–2275, 2013. © 2012 Wiley Periodicals, Inc.     

Regular theta‐firing neurons in the nucleus incertus during sustained hippocampal activation

This paper describes the existence of theta‐coupled neuronal activity in the nucleus incertus (NI). Theta rhythm is relevant for cognitive processes such as spatial navigation and memory processing, and can be recorded in a number of structures related to the hippocampal activation including the NI. Strong evidence supports the role of this tegmental nucleus in neural circuits integrating behavioural activation with the hippocampal theta rhythm. Theta oscillations have been recorded in the local field potential of the NI, highly coupled to the hippocampal waves, although no rhythmical activity has been reported in neurons of this nucleus. The present work analyses the neuronal activity in the NI in conditions leading to sustained hippocampal theta in the urethane‐anaesthetised rat, in order to test whether such activation elicits a differential firing pattern. Wavelet analysis has been used to better define the neuronal activity already described in the nucleus, i.e., non‐rhythmical neurons firing at theta frequency (type I neurons) and fast‐firing rhythmical neurons (type II). However, the most remarkable finding was that sustained stimulation activated regular‐theta neurons (type III), which were almost silent in baseline conditions and have not previously been reported. Thus, we describe the electrophysiological properties of type III neurons, focusing on their coupling to the hippocampal theta. Their spike rate, regularity and phase locking to the oscillations increased at the beginning of the stimulation, suggesting a role in the activation or reset of the oscillation. Further research is needed to address the specific contribution of these neurons to the entire circuit.     

Selective tuning of hippocampal oscillations by phasic locus coeruleus activation in awake male rats

Theta and gamma oscillations are thought to provide signal sets that promote neural coding of cognitive processes. Over 40 yrs ago, Jeffrey Gray reported event‐related changes in a narrow band of hippocampal theta (7.5–8.5 Hz) which appeared to involve norepinephrine (NE) release from, the noradrenergic nucleus, the locus coeruleus (LC). These event‐related alterations in EEG were elicited by novelty, attentional changes, the use of preparatory signals, and signal‐mismatch events. Gray et al. have since provided indirect evidence that supports the role of NE in the modulation of 7.5‐ to 8.5‐Hz oscillations in the hippocampus, but studies investigating the effects of direct LC activation in awake rats have been lacking. In the present study, dentate gyrus EEG was examined during glutamatergic activation of the LC in awake male rats in relation to plasticity effects on simultaneously recorded perforant path‐evoked field potentials. Glutamate‐injected animals were divided into three groups based on histological and plasticity outcomes; perforant path stimulated controls were also included. The three injected groups were: (1) rats with positive LC placements, demonstrating NE‐LTP of the dentate gyrus evoked potential, (2) rats with positive LC placements, without NE‐LTP, and (3) Non‐LC injected controls. Activation of the LC in awake rats demonstrating NE‐LTP increased the relative power of 7‐ to 9‐Hz theta, a result masked in broader 4‐ to 12‐Hz analysis. Comparatively, urethane‐anesthetized rats showed an increase in 5–7 Hz, but not 7‐ to 9‐Hz theta with LC activation. Discriminative analysis in the approximate theta band predicted by Gray (7.4–8.5 Hz) revealed that awake rats demonstrating NE‐LTP had increased relative power in this narrow frequency compared to rats receiving perforant path only (noninjected) and Non‐LC injected rats. Transiently reduced gamma (20–40 Hz) relative power was most commonly observed in rats with verified LC placements failing to express NE‐LTP. Given current theories of LC function, these results suggest oscillatory tuning within the theta and gamma range may facilitate shifts in cognitive set. © 2010 Wiley Periodicals, Inc.     

The top‐down regulation from the prefrontal cortex to insula via hypnotic aversion suggestions reduces smoking craving

Hypnosis has been shown to have treatment effects on nicotine addiction. However, the neural basis of these effects is poorly understood. This preliminary study investigated the neural mechanisms of hypnosis‐based treatment on cigarette smoking, specifically, whether the hypnosis involves a top‐down or bottom‐up mechanism. Two groups of 45 smokers underwent a smoking aversion suggestion and viewed smoking‐related pictures and neutral pictures. One group underwent functional magnetic resonance imaging scanning twice (control and hypnotic states), whereas the other group underwent two electroencephalograph sessions. Our study found that self‐reported smoking craving decreased in both groups following hypnosis. Smoking cue‐elicited activations in the right dorsal lateral prefrontal cortex (rDLPFC) and left insula (lI) and the functional connectivity between the rDLPFC and lI were increased in the hypnotic state compared with the control state. The delta band source waveforms indicated the activation from 390 to 862 ms at the rDLPFC and from 490 to 900 ms at the lI was significantly different between the smoking and neutral conditions in the hypnotic state, suggesting the activation in the rDLPFC preceded that in the lI. These results suggest that the decreased smoking craving via hypnotic aversion suggestions may arise from the top‐down regulation of the rDLPFC to the lI. Our findings provide novel neurobiological evidence for understanding the therapeutic effects of hypnosis on nicotine addiction, and the prefrontal–insula circuit may serve as an imaging biomarker to monitor the treatment efficacy noninvasively.     

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.     

EEG alpha oscillations in the preparation for global and local processing predict behavioral performance

Visual attention can be directed either to the global features of a display or to the local elements that make up the display. We investigated whether oscillatory brain responses to globally or locally directed cue stimuli predict behavioral performance in subsequent target processing. Induced alpha band (8-12 Hz) amplitudes in the pre-stimulus interval were measured separately for the global and the local level, where individual trials were assigned to one of three groups according to the response speed towards incongruent stimuli. Fast responses to local features were associated with high alpha amplitudes in the right centro-parietal cortex, whereas fast responses to global forms were associated with high alpha in left centro-parietal cortex. For trials with slower responses, the pattern of hemispheric differences was diminished or even reversed. It is interpreted that the left and the right parietal cortex exert top-down control over hierarchical processing by inhibiting stimulus representations in one hemisphere.