Event-related theta and gamma band oscillatory dynamics during visuo-spatial sequence memory in younger and older adults.

Visuo-spatial working memory (VSWM) for sequences is thought to be crucial for daily behaviors. Decades of research indicate that oscillations in the gamma and theta bands play important functional roles in the support of visuo-spatial working memory, but the vast majority of that research emphasizes measures of neural activity during memory retention. The primary aims of the present study were (1) to determine whether oscillatory dynamics in the Theta and Gamma ranges would reflect item-level sequence encoding during a computerized spatial span task, (2) to determine whether item-level sequence recall is also related to these neural oscillations, and (3) to determine the nature of potential changes to these processes in healthy cognitive aging. Results indicate that VSWM sequence encoding is related to later (∼700 ms) gamma band oscillatory dynamics and may be preserved in healthy older adults; high gamma power over midline frontal and posterior sites increased monotonically as items were added to the spatial sequence in both age groups. Item-level oscillatory dynamics during the recall of VSWM sequences were related only to theta-gamma phase amplitude coupling (PAC), which increased monotonically with serial position in both age groups. Results suggest that, despite a general decrease in frontal theta power during VSWM sequence recall in older adults, gamma band dynamics during encoding and theta-gamma PAC during retrieval play unique roles in VSWM and that the processes they reflect may be spared in healthy aging.

Increases in pre-stimulus theta and alpha oscillations precede successful encoding of crossmodal associations.

A central aspect of episodic memory is the formation of associations between stimuli from different modalities. Current theoretical approaches assume a functional role of ongoing oscillatory power and phase in the theta band (3-7 Hz) for the encoding of crossmodal associations. Furthermore, ongoing activity in the theta range as well as alpha (8-12 Hz) and low beta activity (13-20 Hz) before the presentation of a stimulus is thought to modulate subsequent cognitive processing, including processes that are related to memory. In this study, we tested the hypothesis that pre-stimulus characteristics of low frequency activity are relevant for the successful formation of crossmodal memory. The experimental design that was used specifically allowed for the investigation of associative memory independent from individual item memory. Participants (n = 51) were required to memorize associations between audiovisual stimulus pairs and distinguish them from newly arranged ones consisting of the same single stimuli in the subsequent recognition task. Our results show significant differences in the state of pre-stimulus theta and alpha power between remembered and not remembered crossmodal associations, clearly relating increased power to successful recognition. These differences were positively correlated with memory performance, suggesting functional relevance for behavioral measures of associative memory. Further analysis revealed similar effects in the low beta frequency ranges, indicating the involvement of different pre-stimulus-related cognitive processes. Phase-based connectivity measures in the theta band did not differ between remembered and not remembered stimulus pairs. The findings support the assumed functional relevance of theta band oscillations for the formation of associative memory and demonstrate that an increase of theta as well as alpha band oscillations in the pre-stimulus period is beneficial for the establishment of crossmodal memory.

Tracking the Immediate and Short-Term Effects of Continuous Theta Burst Stimulation on Dynamic Brain States.

Continuous Theta Burst Stimulation (cTBS) has been shown to modulate cortical oscillations and induce cortical inhibitory effects. Electroencephalography (EEG) studies have shown some immediate effects of cTBS on brain activity. To investigate both immediate effects and short-term effects of cTBS on dynamic brain changes, cTBS was applied to 22 healthy participants over their left motor cortex. We recorded eyes-open, resting-state EEG and performance in the Nine-Hole Peg Test (NHPT) before cTBS, immediately after cTBS, and 80 minutes after cTBS. We identified nine states using a Hidden Markov Model (HMM)-based approach to describe the process of dynamic brain changes. The spatial activation, temporal profiles of HMM states and behavioral performance of NHPT were assessed and compared. cTBS altered the temporal profiles of S1-S5 immediately after cTBS and the temporal profiles of S5, S6 and S7 80 min after cTBS. Moreover, cTBS improved motor function of the left hand. State 1 was characterized as the activation of right occipito-temporal area, and NHPT behavioral performance of the left hand positively correlated with the occurrence of state 1, and negatively correlated with the interval time of state 1 after cTBS. The transitions between S1 or S7 and other states showed dynamic reconfiguration during after-effect sustained time after cTBS. These results suggest that the dynamic characteristics of state 1 are potential biomarkers for characterizing the aftereffect changes of cTBS.

CA3 Circuit Model Compressing Sequential Information in Theta Oscillation and Replay.

The hippocampus plays a critical role in the compression and retrieval of sequential information. During wakefulness, it achieves this through theta phase precession and theta sequences. Subsequently, during periods of sleep or rest, the compressed information reactivates through sharp-wave ripple events, manifesting as memory replay. However, how these sequential neuronal activities are generated and how they store information about the external environment remain unknown. We developed a hippocampal cornu ammonis 3 (CA3) computational model based on anatomical and electrophysiological evidence from the biological CA3 circuit to address these questions. The model comprises theta rhythm inhibition, place input, and CA3-CA3 plastic recurrent connection. The model can compress the sequence of the external inputs, reproduce theta phase precession and replay, learn additional sequences, and reorganize previously learned sequences. A gradual increase in synaptic inputs, controlled by interactions between theta-paced inhibition and place inputs, explained the mechanism of sequence acquisition. This model highlights the crucial role of plasticity in the CA3 recurrent connection and theta oscillational dynamics and hypothesizes how the CA3 circuit acquires, compresses, and replays sequential information.

Acetylcholine Engages Distinct Amygdala Microcircuits to Gate Internal Theta Rhythm.

Acetylcholine (ACh) is released from basal forebrain cholinergic neurons in response to salient stimuli and engages brain states supporting attention and memory. These high ACh states are associated with theta oscillations, which synchronize neuronal ensembles. Theta oscillations in the basolateral amygdala (BLA) in both humans and rodents have been shown to underlie emotional memory, yet their mechanism remains unclear. Here, using brain slice electrophysiology in male and female mice, we show large ACh stimuli evoke prolonged theta oscillations in BLA local field potentials that depend upon M3 muscarinic receptor activation of cholecystokinin (CCK) interneurons (INs) without the need for external glutamate signaling. Somatostatin (SOM) INs inhibit CCK INs and are themselves inhibited by ACh, providing a functional SOM→CCK IN circuit connection gating BLA theta. Parvalbumin (PV) INs, which can drive BLA oscillations in baseline states, are not involved in the generation of ACh-induced theta, highlighting that ACh induces a cellular switch in the control of BLA oscillatory activity and establishes an internally BLA-driven theta oscillation through CCK INs. Theta activity is more readily evoked in BLA over the cortex or hippocampus, suggesting preferential activation of the BLA during high ACh states. These data reveal a SOM→CCK IN circuit in the BLA that gates internal theta oscillations and suggest a mechanism by which salient stimuli acting through ACh switch the BLA into a network state enabling emotional memory.

Motor oscillations reveal new correlates of error processing in the human brain.

It has been demonstrated that during motor responses, the activation of the motor cortical regions emerges in close association with the activation of the medial frontal cortex implicated with performance monitoring and cognitive control. The present study explored the oscillatory neurodynamics of response-related potentials during correct and error responses to test the hypothesis that such continuous communication would modify the characteristics of motor potentials during performance errors. Electroencephalogram (EEG) was recorded at 64 electrodes in a four-choice reaction task and response-related potentials (RRPs) of correct and error responses were analysed. Oscillatory RRP components at extended motor areas were analysed in the theta (3.5-7 Hz) and delta (1-3 Hz) frequency bands with respect to power, temporal synchronization (phase-locking factor, PLF), and spatial synchronization (phase-locking value, PLV). Major results demonstrated that motor oscillations differed between correct and error responses. Error-related changes (1) were frequency-specific, engaging delta and theta frequency bands, (2) emerged already before response production, and (3) had specific regional topographies at posterior sensorimotor and anterior (premotor and medial frontal) areas. Specifically, the connectedness of motor and sensorimotor areas contra-lateral to the response supported by delta networks was substantially reduced during errors. Also, there was an error-related suppression of the phase stability of delta and theta oscillations at these areas. This synchronization reduction was accompanied by increased temporal synchronization of motor theta oscillations at bi-lateral premotor regions and by two distinctive error-related effects at medial frontal regions: (1) a focused fronto-central enhancement of theta power and (2) a separable enhancement of the temporal synchronization of delta oscillations with a localized medial frontal focus. Together, these observations indicate that the electrophysiological signatures of performance errors are not limited to the medial frontal signals, but they also involve the dynamics of oscillatory motor networks at extended cortical regions generating the movement. Also, they provide a more detailed picture of the medial frontal processes activated in relation to error processing.

[The relationship between the functional state of the brain and clinical and constitutional factors in schizophrenia]. / Svyaz' funktsional'nogo sostoyaniya golovnogo mozga s klinicheskimi i konstitutsional'nymi faktorami pri shizofrenii.

OBJECTIVE: To establish the relationships of functional changes of the brain of patients with schizophrenia with clinical manifestations of the disease and their constitutional and morphological features. MATERIAL AND METHODS: One hundred and eighteen patients with schizophrenia (64 men and 54 women), aged 33 [29; 40], years were examined. The following clinical and dynamic parameters were used: age of manifestation of the disease, duration of the disease, severity of clinical and psychopathological symptoms according to the PANSS. The anthropometric examination of patients was carried out according to V.V. Bunak's method in V.P. Chitetsov's modification for adult samples with calculation of Rees-Eysenk and Tanner indices. The EEG was recorded and analyzed in a state of calm, relaxed wakefulness with closed eyes with the calculation of the absolute spectral power for theta (4-7 Hz), alpha (8-13 Hz) and beta (14-30 Hz) rhythms. RESULTS: Significant (p<0.05) direct correlations between the age of the disease manifestation and the spectral power of the beta rhythm in the frontal leads (Fp1, Fp2, F3 and F4) were revealed. Inverse correlations (p<0.05) were found between the duration of the disease in patients with schizophrenia and the spectral power of the alpha rhythm in the left temporal (T3) and right central leads (C4), the spectral power of the beta rhythm in the parietal-occipital (P3, P4, O1,O2) and temporal leads (T3, T4, T5), the spectral power of the theta rhythm in the left occipital (O1) and posterior temporal leads (T5). Significant inverse correlations were also found between the Tanner index and the spectral power of the alpha rhythm in the frontal and temporal leads, between the Rees-Eysenk index and the spectral power of the theta rhythm in the frontal leads. CONCLUSION: The results indicate the presence of the conjugation of functional changes in the brain of patients with schizophrenia with clinical manifestations of the disease and their constitutional and morphological features. Thus, the assessment of the functional state of the central nervous system in patients with schizophrenia is an important component of the diagnostic search.

Multiplexed Levels of Cognitive Control through Delta and Theta Neural Oscillations.

Cognitive control allows behavior to be guided according to environmental contexts and internal goals. During cognitive control tasks, fMRI analyses typically reveal increased activation in frontal and parietal networks, and EEG analyses reveal increased amplitude of neural oscillations in the delta/theta band (2-3, 4-7 Hz) in frontal electrodes. Previous studies proposed that theta-band activity reflects the maintenance of rules associating stimuli to appropriate actions (i.e., the rule set), whereas delta synchrony is specifically associated with the control over the context for when to apply a set of rules (i.e., the rule abstraction). We tested these predictions using EEG and fMRI data collected during the performance of a hierarchical cognitive control task that manipulated the level of abstraction of task rules and their set-size. Our results show a clear separation of delta and theta oscillations in the control of rule abstraction and of stimulus-action associations, respectively, in distinct frontoparietal association networks. These findings support a model by which frontoparietal networks operate through dynamic, multiplexed neural processes.

Cholinergic-Sensitive Theta Oscillations in Memory Encoding in Mice.

Cholinergic regulation of hippocampal theta oscillations has long been proposed to be a potential mechanism underlying hippocampus-dependent memory encoding processes. However, cholinergic transmission has been traditionally associated with type II theta under urethane anesthesia. The mechanisms and behavioral significance of cholinergic regulation of type I theta in freely exploring animals is much less clear. In this study, we examined the potential behavioral significance of cholinergic regulation of theta oscillations in the object location task in male mice that involves training and testing trials and provides an ideal behavioral task to study the underlying memory encoding and retrieval processes, respectively. Cholinergic regulation of hippocampal theta oscillations and the behavioral outcomes was examined by either intrahippocampal infusion of cholinergic receptor antagonists or knocking out cholinergic receptors in excitatory neurons or interneurons. We found that both muscarinic acetylcholine receptors (mAChRs) and α7 nicotinic AChRs (α7 nAChRs) regulated memory encoding by engaging excitatory neurons and interneurons, respectively. There is a transient upregulated theta oscillation at the beginning of individual object exploration events that only occurred in the training trials, but not in the testing trials. This transient upregulated theta is also the only theta component that significantly differed between training and testing trials and was sensitive to mAChR and α7 nAChR antagonists. Thus, our study has revealed a transient cholinergic-sensitive theta component that is specifically associated with memory encoding, but not memory retrieval, in the object location task, providing direct experimental evidence supporting a role for cholinergic-regulated theta oscillations in hippocampus-dependent memory encoding processes.

Mechanistic role of alpha oscillations in a computational model of working memory.

Brain oscillations are believed to be involved in the different operations necessary to manipulate information during working memory tasks. We propose a mechanistic role for the observed inhibition effect of the alpha rhythm based on its interference with the theta rhythm. Using the Lisman-Idiart model for multi-item working memory, we show that the interaction between these two oscillations is capable of creating a long lasting destructive interference that prevents the cyclic reactivation of neuronal ensembles and, as a consequence, memory maintenance. Additionally, to ensure robustness we propose a modular version of the model and implement oscillations as traveling waves. Using this model, we show that the interactions between theta and gamma determine the allocation of multiple memories in distinct modules, while the interference between theta and alpha disrupts the maintenance of the information already stored in them. The effect of alpha in erasing or blocking storage is robust and seems fairly independent of frequency, as long as it stays within the alpha range. This model helps us to understand why the alpha and theta oscillations, which have close frequency bands, could have opposite roles in working memory.

Internal Representations Are Prioritized by Frontoparietal Theta Connectivity and Suppressed by alpha Oscillation Dynamics: Evidence from Concurrent Transcranial Magnetic Stimulation EEG and Invasive EEG.

Control over internal representations requires the prioritization of relevant information and suppression of irrelevant information. The frontoparietal network exhibits prominent neural oscillations during these distinct cognitive processes. Yet, the causal role of this network-scale activity is unclear. Here, we targeted theta-frequency frontoparietal coherence and dynamic alpha oscillations in the posterior parietal cortex using online rhythmic transcranial magnetic stimulation (TMS) in women and men while they prioritized or suppressed internally maintained working memory (WM) representations. Using concurrent high-density EEG, we provided evidence that we acutely drove the targeted neural oscillation and TMS improved WM capacity only when the evoked activity corresponded with the desired cognitive process. To suppress an internal representation, we increased the amplitude of lateralized alpha oscillations in the posterior parietal cortex contralateral to the irrelevant visual field. For prioritization, we found that TMS to the prefrontal cortex increased theta-frequency connectivity in the prefrontoparietal network contralateral to the relevant visual field. To understand the spatial specificity of these effects, we administered the WM task to participants with implanted electrodes. We found that theta connectivity during prioritization was directed from the lateral prefrontal to the superior posterior parietal cortex. Together, these findings provide causal evidence in support of a model where a frontoparietal theta network prioritizes internally maintained representations and alpha oscillations in the posterior parietal cortex suppress irrelevant representations.

Local activation of CA1 pyramidal cells induces theta-phase precession.

Hippocampal theta-phase precession is involved in spatiotemporal coding and in generating multineural spike sequences, but how precession originates remains unresolved. To determine whether precession can be generated directly in hippocampal area CA1 and disambiguate multiple competing mechanisms, we used closed-loop optogenetics to impose artificial place fields in pyramidal cells of mice running on a linear track. More than one-third of the CA1 artificial fields exhibited synthetic precession that persisted for a full theta cycle. By contrast, artificial fields in the parietal cortex did not exhibit synthetic precession. These findings are incompatible with precession models based on inheritance, dual-input, spreading activation, inhibition-excitation summation, or somato-dendritic competition. Thus, a precession generator resides locally within CA1.

Gamma oscillatory complexity conveys behavioral information in hippocampal networks.

The hippocampus and entorhinal cortex exhibit rich oscillatory patterns critical for cognitive functions. In the hippocampal region CA1, specific gamma-frequency oscillations, timed at different phases of the ongoing theta rhythm, are hypothesized to facilitate the integration of information from varied sources and contribute to distinct cognitive processes. Here, we show that gamma elements -a multidimensional characterization of transient gamma oscillatory episodes- occur at any frequency or phase relative to the ongoing theta rhythm across all CA1 layers in male mice. Despite their low power and stochastic-like nature, individual gamma elements still carry behavior-related information and computational modeling suggests that they reflect neuronal firing. Our findings challenge the idea of rigid gamma sub-bands, showing that behavior shapes ensembles of irregular gamma elements that evolve with learning and depend on hippocampal layers. Widespread gamma diversity, beyond randomness, may thus reflect complexity, likely functional but invisible to classic average-based analyses.

Can epilepsy affect normal EEG variants? A comparative study between subjects with and without epilepsy.

OBJECTIVES: To compare the prevalence of benign EEG variants (BEVs) between epileptic and non-epileptic subjects. METHODS: A prospective, observational EEG study of 1,163 consecutive patients, using the 10-20 international system with systematically two additional anterior/inferior temporal electrodes. The video-EEG monitoring duration was between 24 h and eight days. RESULTS: We identified 917 (78.9%) epileptic patients (mean age: 33.42 ± 15.5 years; females: 53.4%) and 246 (21.2%) non-epileptic patients (mean age: 35.6 ± 18.75 years; females: 54.9%). Despite a shorter mean duration of the EEG recordings, the prevalence of BEVs was higher in non-epileptic vs. epileptic patients (73.2% vs. 57.8%, p = 0.000011). This statistical difference was confirmed for lambda waves (23.6% in the non-epilepsy group vs. 14.8% in the epilepsy group, p = 0.001), POSTs (50.8% vs. 32.5%, p < 0.000001), wicket spikes (20.3% vs. 13.6%, p = 0.009) in particular in NREM and REM sleep, and 14- and 6-Hz positive bursts (13% vs. 7.1% p = 0.003). Mu rhythm was observed at the same frequency in both groups (21.1% in the non-epilepsy group vs. 22.7% in the epilepsy group). There was no difference between the two groups for rarer rhythms, such as rhythmic mid-temporal theta burst of drowsiness, small sharp spikes, and midline theta rhythm. CONCLUSIONS: There was no increase in any of the BEVs in the epilepsy group. On the contrary, BEVs were more frequent and diversified in the non-epilepsy group. Epilepsy may negatively affect the occurrence of the most common BEVs, with the exception of the mu rhythm, which is present in about one-fifth of the population with or without epilepsy.

Accelerated Theta Burst Stimulation: Safety, Efficacy, and Future Advancements.

Theta burst stimulation (TBS) is a noninvasive brain stimulation technique that can be used to modulate neural networks underlying psychiatric and neurological disorders. TBS can be delivered intermittently or continuously. The conventional intermittent TBS protocol is approved by the U.S. Food and Drug Administration to treat otherwise treatment-resistant depression, but the 6-week duration limits the applicability of this therapy. Accelerated TBS protocols present an opportunity to deliver higher pulse doses in shorter periods of time, thus resulting in faster and potentially more clinically effective treatment. However, the acceleration of TBS delivery raises questions regarding the relative safety, efficacy, and durability compared with conventional TBS protocols. In this review paper, we present the data from accelerated TBS trials to date that support the safety and effectiveness of accelerated protocols while acknowledging the need for more durability data. We discuss the stimulation parameters that seem to be important for the efficacy of accelerated TBS protocols and possible avenues for further optimization.

Theta-tACS modulates cerebellar-related motor functions and cerebellar-cortical connectivity.

OBJECTIVE: To evaluate the effects of cerebellar transcranial alternating current stimulation (tACS) delivered at cerebellar-resonant frequencies, i.e., theta (θ) and gamma (γ), on upper limb motor performance and cerebellum-primary motor cortex (M1) connectivity, as assessed by cerebellar-brain inhibition (CBI), in healthy subjects. METHODS: Participants underwent cerebellar-tACS while performing three cerebellar-dependent motor tasks: (i) rhythmic finger-tapping, (ii) arm reaching-to-grasp ('grasping') and (iii) arm reaching-to-point ('pointing') an object. Also, we evaluated possible changes in CBI during cerebellar-tACS. RESULTS: θ-tACS decreased movement regularity during the tapping task and increased the duration of the pointing task compared to sham- and γ-tACS. Additionally, θ-tACS increased the CBI effectiveness (greater inhibition). The effect of θ-tACS on movement rhythm correlated with CBI changes and less tapping regularity corresponded to greater CBI. CONCLUSIONS: Cerebellar-tACS delivered at the θ frequency modulates cerebellar-related motor behavior and this effect is, at least in part, mediated by changes in the cerebellar inhibitory output onto M1. The effects of θ-tACS may be due to the modulation of cerebellar neurons that resonate to the θ rhythm. SIGNIFICANCE: These findings contribute to a better understanding of the physiological mechanisms of motor control and provide new evidence on cerebellar non-invasive brain stimulation.

MTL neurons phase-lock to human hippocampal theta.

Memory formation depends on neural activity across a network of regions, including the hippocampus and broader medial temporal lobe (MTL). Interactions between these regions have been studied indirectly using functional MRI, but the bases for interregional communication at a cellular level remain poorly understood. Here, we evaluate the hypothesis that oscillatory currents in the hippocampus synchronize the firing of neurons both within and outside the hippocampus. We recorded extracellular spikes from 1854 single- and multi-units simultaneously with hippocampal local field potentials (LFPs) in 28 neurosurgical patients who completed virtual navigation experiments. A majority of hippocampal neurons phase-locked to oscillations in the slow (2-4 Hz) or fast (6-10 Hz) theta bands, with a significant subset exhibiting nested slow theta × beta frequency (13-20 Hz) phase-locking. Outside of the hippocampus, phase-locking to hippocampal oscillations occurred only at theta frequencies and primarily among neurons in the entorhinal cortex and amygdala. Moreover, extrahippocampal neurons phase-locked to hippocampal theta even when theta did not appear locally. These results indicate that spike-time synchronization with hippocampal theta is a defining feature of neuronal activity in the hippocampus and structurally connected MTL regions. Theta phase-locking could mediate flexible communication with the hippocampus to influence the content and quality of memories.

Behavioral fluctuation reflecting theta-rhythmic activation of sequential working memory.

Sequential working memory, the ability to actively maintain sequential information, is essential for human cognition. The neural representation of each item in sequential working memory is thought to be activated rhythmically within the theta (3-7 Hz) range of human electrophysiology. In the current study, we predicted that if neural representations of sequential working memory items were truly activated rhythmically, periodic fluctuations in behavior would be evident. That is, the ease and speed of recalling each memory item would oscillate depending on the interval between memory encoding and recall, affected by the rhythmic neural representation. We conducted detailed analyses of reaction times for retrieving sequential and non-sequential information in eight experiments (total n = 125). The results revealed that reaction times for recalling sequential information showed fluctuation in the theta range as a function of the interval between memory encoding and recall, which was significantly stronger than that observed when the task did not require participants to remember the sequential order. Taken together, the current findings revealed that participants' behavior exhibited theta-rhythmic fluctuation when recalling sequential information in a relatively large sample, supporting theta phase-dependent coding of sequential working memory.

Ramping dynamics and theta oscillations reflect dissociable signatures during rule-guided human behavior.

Contextual cues and prior evidence guide human goal-directed behavior. The neurophysiological mechanisms that implement contextual priors to guide subsequent actions in the human brain remain unclear. Using intracranial electroencephalography (iEEG), we demonstrate that increasing uncertainty introduces a shift from a purely oscillatory to a mixed processing regime with an additional ramping component. Oscillatory and ramping dynamics reflect dissociable signatures, which likely differentially contribute to the encoding and transfer of different cognitive variables in a cue-guided motor task. The results support the idea that prefrontal activity encodes rules and ensuing actions in distinct coding subspaces, while theta oscillations synchronize the prefrontal-motor network, possibly to guide action execution. Collectively, our results reveal how two key features of large-scale neural population activity, namely continuous ramping dynamics and oscillatory synchrony, jointly support rule-guided human behavior.