Theta-burst direct electrical stimulation remodels human brain networks.

Theta-burst stimulation (TBS), a patterned brain stimulation technique that mimics rhythmic bursts of 3-8 Hz endogenous brain rhythms, has emerged as a promising therapeutic approach for treating a wide range of brain disorders, though the neural mechanism of TBS action remains poorly understood. We investigated the neural effects of TBS using intracranial EEG (iEEG) in 10 pre-surgical epilepsy participants undergoing intracranial monitoring. Here we show that individual bursts of direct electrical TBS at 29 frontal and temporal sites evoked strong neural responses spanning broad cortical regions. These responses exhibited dynamic local field potential voltage changes over the course of stimulation presentations, including either increasing or decreasing responses, suggestive of short-term plasticity. Stronger stimulation augmented the mean TBS response amplitude and spread with more recording sites demonstrating short-term plasticity. TBS responses were stimulation site-specific with stronger TBS responses observed in regions with strong baseline stimulation effective (cortico-cortical evoked potentials) and functional (low frequency phase locking) connectivity. Further, we could use these measures to predict stable and varying (e.g. short-term plasticity) TBS response locations. Future work may integrate pre-treatment connectivity alongside other biophysical factors to personalize stimulation parameters, thereby optimizing induction of neuroplasticity within disease-relevant brain networks.

Predictive grid coding in the medial entorhinal cortex.

The entorhinal cortex represents allocentric spatial geometry and egocentric speed and heading information required for spatial navigation. However, it remains unclear whether it contributes to the prediction of an animal's future location. We discovered grid cells in the medial entorhinal cortex (MEC) that have grid fields representing future locations during goal-directed behavior. These predictive grid cells represented prospective spatial information by shifting their grid fields against the direction of travel. Predictive grid cells discharged at the trough phases of the hippocampal CA1 theta oscillation and, together with other types of grid cells, organized sequences of the trajectory from the current to future positions across each theta cycle. Our results suggest that the MEC provides a predictive map that supports forward planning in spatial navigation.

A picture is worth a thousand words: Framing of food choice options affects decision conflict and mid-fontal theta in food choice task.

In food choices, conflict arises when choosing between a healthy, but less tasty food item and a tasty, but less healthy food item. The underlying assumption is that people trade-off the health and taste properties of food items to reach a decision. To probe this assumption, we presented food items either as colored images (image condition, e.g. photograph of a granola bar) or as pre-matched percentages of taste and health values (text condition, e.g., 20% healthy and 80% tasty). We recorded choices, response times and electroencephalography activity to calculate mid-frontal theta power as a marker of conflict. At the behavioral level, we found higher response times for healthy compared to unhealthy choices, and for difficult compared to easy decisions in both conditions, indicating the experience of a decision conflict. At the neural level, mid-frontal theta power was higher for healthy choices than unhealthy choices and difficult choices compared to easy choices, but only in the image condition. Those results suggest that either conflict type and/or decision strategies differ between the image and text conditions. The present results can be helpful in understanding how dietary decisions can be influenced towards healthier food choices.

The interplay of cognitive control and feature integration: insights from theta oscillatory dynamics during conflict processing.

Adaptive behavior is fundamental to cognitive control and executive functioning. This study investigates how cognitive control mechanisms and episodic feature retrieval interact to influence adaptiveness, focusing particularly on theta (4 to 8 Hz) oscillatory dynamics. We conducted two variations of the Simon task, incorporating response-incompatible, response-compatible, and neutral trials. Experiment 1 demonstrated that cognitive adjustments-specifically, cognitive shielding following incompatible trials and cognitive relaxation following compatible ones-are reflected in midfrontal theta power modulations associated with the Simon effect. Experiment 2 showed that reducing feature overlap between trials leads to less pronounced sequential modulations in behavior and midfrontal theta activity, supporting the hypothesis that cognitive control and feature integration share a common neural mechanism. These findings highlight the interaction of cognitive control processes and episodic feature integration in modulating behavior. The results advocate for hybrid models that combine top-down and bottom-up processes as a comprehensive framework to understand cognitive control dynamics and adaptive behavior.

Continuous theta burst stimulation to relieve symptoms in patients with moderate obsessive-compulsive disorder: a preliminary study with an external validation.

Obsessive-compulsive disorder (OCD) is a clinically challenging and refractory psychiatric disorder characterized by pathologically hyperactivated brain activity. Continuous theta burst stimulation (cTBS) is considered a potentially non-invasive treatment for inducing inhibitory effects on the underlying cortex. Numerous studies showed an unsatisfactory efficacy of cTBS for OCD. Accordingly, it seems that cTBS is ineffective for OCD. However, the neglect of varying OCD severities, modest sample size, absence of a multicenter design incorporating inpatients and outpatients, and lack of personalized imaging-guided targeting may constrain the conclusive findings of cTBS efficacy for OCD. In the preliminary experiment, 50 inpatients with OCD were enrolled to receive cTBS (10 sessions/day for five continuous days) or sham over the personalized right pre-supplementary motor area determined by the highest functional connectivity with the subthalamic nucleus according to our prior study. In the extension experiment, 32 outpatients with OCD received cTBS to generalize the treatment effects. The Yale-Brown Obsessive-Compulsive Scale (YBOCS) was assessed before and after treatment. In the preliminary experiment, the response rates in the cTBS group were 56.52%, respectively, significantly higher than those in the sham group. Further analysis revealed significant YBOCS improvement in patients with moderate OCD symptoms than those with severe OCD symptoms. In the extension experiment, the response rates were 50.00%. Additionally, a significant decrease in YBOCS scores was only found in patients with moderate OCD symptoms. This is the first study with an external validation design across two centers to identify OCD symptoms as playing an important role in cTBS treatment effects, especially in patients with moderate OCD symptoms.

Accurate Mental Stress Detection Using Sequential Backward Selection and Adaptive Synthetic Methods.

The daily experience of mental stress profoundly influences our health and work performance while concurrently triggering alterations in brain electrical activity. Electroencephalogram (EEG) is a widely adopted method for assessing cognitive and affective states. This study delves into the EEG correlates of stress and the potential use of resting EEG in evaluating stress levels. Over 13 weeks, our longitudinal study focuses on the real-life experiences of college students, collecting data from each of the 18 participants across multiple days in classroom settings. To tackle the complexity arising from the multitude of EEG features and the imbalance in data samples across stress levels, we use the sequential backward selection (SBS) method for feature selection and the adaptive synthetic (ADASYN) sampling algorithm for imbalanced data. Our findings unveil that delta and theta features account for approximately 50% of the selected features through the SBS process. In leave-one-out (LOO) cross-validation, the combination of band power and pair-wise coherence (COH) achieves a maximum balanced accuracy of 94.8% in stress-level detection for the above daily stress dataset. Notably, using ADASYN and borderline synthesized minority over-sampling technique (borderline-SMOTE) methods enhances model accuracy compared to the traditional SMOTE approach. These results provide valuable insights into using EEG signals for assessing stress levels in real-life scenarios, shedding light on potential strategies for managing stress more effectively.

A computational model elucidating mechanisms and variability in theta burst stimulation responses.

Theta burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation (rTMS) with unknown underlying mechanisms and highly variable responses across subjects. To investigate these issues, we developed a simple computational model. Our model consisted of two neurons linked by an excitatory synapse that incorporates two mechanisms: short-term plasticity (STP) and spike-timing-dependent plasticity (STDP). We applied a variable-amplitude current through I-clamp with a TBS time pattern to the pre- and post-synaptic neurons, simulating synaptic plasticity. We analyzed the results and provided an explanation for the effects of TBS, as well as the variability of responses to it. Our findings suggest that the interplay of STP and STDP mechanisms determines the direction of plasticity, which selectively affects synapses in extended neurons and underlies functional effects. Our model describes how the timing, number, and intensity of pulses delivered to neurons during rTMS contribute to induced plasticity. This not only successfully explains the different effects of intermittent TBS (iTBS) and continuous TBS (cTBS), but also predicts the results of other protocols such as 10 Hz rTMS. We propose that the variability in responses to TBS can be attributed to the variable span of neuronal thresholds across individuals and sessions. Our model suggests a biologically plausible mechanism for the diverse responses to TBS protocols and aligns with experimental data on iTBS and cTBS outcomes. This model could potentially aid in improving TBS and rTMS protocols and customizing treatments for patients, brain areas, and brain disorders.

Restoring initial steps by intermittent theta burst stimulation in complete spinal cord injury patient: a case report.

INTRODUCTION: Spinal cord injury (SCI) causes damage to neurons and results in motor and sensory dysfunction. Intermittent theta burst stimulation (iTBS) has been used to induce neuronal and synaptic plasticity by applying a magnetic field in the brain. The plasticity induced in the cortex has an imperative role in the recovery of motor and sensory functioning. However, the effect of iTBS in complete SCI patients is still elusive. CASE PRESENTATION: We report here the case of a 27-year-old female who sustained an L1 complete spinal cord injury (SCI) with an ASIA score of A. The patient lost all the sensory and motor functions below the level of injury. Intermittent theta burst stimulation (iTBS) was administered at 80% of the resting motor threshold over the M1 motor cortex, along with intensive rehabilitation training to promote sensorimotor function. DISCUSSION: There was a partial recovery in functional, electrophysiological, and neurological parameters. The case report also demonstrates the safety and efficacy of iTBS in complete SCI patients. No adverse event has been observed in the patient during intervention sessions.

My choice, my actions: self-determination, not instrumental value of outcomes enhances outcome monitoring during learning.

Freedom of choice enhances our sense of agency. During goal-directed behavior, the freedom to choose between different response options increases the neural processing of positive and negative feedback, indicating enhanced outcome monitoring under conditions of high agency experience. However, it is unclear whether this enhancement is predominantly driven by an increased salience of self- compared to externally determined action outcomes or whether differences in the perceived instrumental value of outcomes contribute to outcome monitoring in goal-directed tasks. To test this, we recorded electroencephalography while participants performed a reinforcement learning task involving free choices, action-relevant forced choices, and action-irrelevant forced choices. We observed larger midfrontal theta power and N100 amplitudes for feedback following free choices compared with action-relevant and action-irrelevant forced choices. In addition, a Reward Positivity was only present for free but not forced choice outcomes. Crucially, our results indicate that enhanced outcome processing is not driven by the relevance of outcomes for future actions but rather stems from the association of outcomes with recent self-determined choice. Our findings highlight the pivotal role of self-determination in tracking the consequences of our actions and contribute to an understanding of the cognitive processes underlying the choice-induced facilitation in outcome monitoring.

Modeling the contribution of theta-gamma coupling to sequential memory, imagination, and dreaming.

Gamma oscillations nested in a theta rhythm are observed in the hippocampus, where are assumed to play a role in sequential episodic memory, i.e., memorization and retrieval of events that unfold in time. In this work, we present an original neurocomputational model based on neural masses, which simulates the encoding of sequences of events in the hippocampus and subsequent retrieval by exploiting the theta-gamma code. The model is based on a three-layer structure in which individual Units oscillate with a gamma rhythm and code for individual features of an episode. The first layer (working memory in the prefrontal cortex) maintains a cue in memory until a new signal is presented. The second layer (CA3 cells) implements an auto-associative memory, exploiting excitatory and inhibitory plastic synapses to recover an entire episode from a single feature. Units in this layer are disinhibited by a theta rhythm from an external source (septum or Papez circuit). The third layer (CA1 cells) implements a hetero-associative net with the previous layer, able to recover a sequence of episodes from the first one. During an encoding phase, simulating high-acetylcholine levels, the network is trained with Hebbian (synchronizing) and anti-Hebbian (desynchronizing) rules. During retrieval (low-acetylcholine), the network can correctly recover sequences from an initial cue using gamma oscillations nested inside the theta rhythm. Moreover, in high noise, the network isolated from the environment simulates a mind-wandering condition, randomly replicating previous sequences. Interestingly, in a state simulating sleep, with increased noise and reduced synapses, the network can "dream" by creatively combining sequences, exploiting features shared by different episodes. Finally, an irrational behavior (erroneous superimposition of features in various episodes, like "delusion") occurs after pathological-like reduction in fast inhibitory synapses. The model can represent a straightforward and innovative tool to help mechanistically understand the theta-gamma code in different mental states.

Homeostatic metaplasticity induced by the combination of two inhibitory brain stimulation techniques: Continuous theta burst and transcranial static magnetic stimulation.

Aftereffects of non-invasive brain stimulation techniques may be brain state-dependent. Either continuous theta-burst stimulation (cTBS) as transcranial static magnetic field stimulation (tSMS) reduce cortical excitability. Our objective was to explore the aftereffects of tSMS on a M1 previously stimulated with cTBS. The interaction effect of two inhibitory protocols on cortical excitability was tested on healthy volunteers (n = 20), in two different sessions. A first application cTBS was followed by real-tSMS in one session, or sham-tSMS in the other session. When intracortical inhibition was tested with paired-pulse transcranial magnetic stimulation, LICI (ie., long intracortical inhibition) increased, although the unconditioned motor-evoked potential (MEP) remained stable. These effects were observed in the whole sample of participants regardless of the type of static magnetic field stimulation (real or sham) applied after cTBS. Subsequently, we defined a group of good-responders to cTBS (n = 9) on whom the unconditioned MEP amplitude reduced after cTBS and found that application of real-tSMS (subsequent to cTBS) increased the unconditioned MEP. This MEP increase was not found when sham-tSMS followed cTBS. The interaction of tSMS with cTBS seems not to take place at inhibitory cortical interneurons tested by LICI, since LICI was not differently affected after real and sham tSMS. Our results indicate the existence of a process of homeostatic plasticity when tSMS is applied after cTBS. This work suggests that tSMS aftereffects arise at the synaptic level and supports further investigation into tSMS as a useful tool to restore pathological conditions with altered cortical excitability.

Obedience to authority reduces cognitive conflict before an action.

How obeying orders impacts moral decision-making remains an open question, despite its significant societal implications. The goal of this study was to determine if cognitive conflict, indexed by mid-frontal theta activity observed before an action, is influenced by the context of obedience. Participants came in pairs and were assigned roles as either agent or victim. Those in the agent role could either decide freely or follow the experimenter's instructions to administer (or refrain from administering) a mildly painful electric shock to the victim in exchange for a small monetary reward. Mid-frontal theta activity was recorded before the agent made their keypress. Results indicated that mid-frontal theta activity was reduced when participants obeyed the experimenter's orders compared to when they acted of their own volition, even though the outcomes of the actions were similar. This finding suggests that obeying orders diminishes cognitive conflict preceding moral decisions that could harm another person. This study sheds light on a potential mechanism explaining how obedience can blurr morality and lessen our natural aversion to harming others.

Oscillatory Neural Correlates of Police Firearms Decision-Making in Virtual Reality.

We investigated the neural signatures of expert decision-making in the context of police training in a virtual reality-based shoot/don't shoot scenario. Police officers can use stopping force against a perpetrator, which may require using a firearm and each decision made by an officer to discharge their firearm or not has substantial implications. Therefore, it is important to understand the cognitive and underlying neurophysiological processes that lead to such a decision. We used virtual reality-based simulations to elicit ecologically valid behavior from authorized firearms officers (AFOs) in the UK and matched novices in a shoot/don't shoot task and recorded electroencephalography concurrently. We found that AFOs had consistently faster response times than novices, suggesting our task was sensitive to their expertise. To investigate differences in decision-making processes under varying levels of threat and expertise, we analyzed electrophysiological signals originating from the anterior cingulate cortex. In line with similar response inhibition tasks, we found greater increases in preresponse theta power when participants inhibited the response to shoot when under no threat as compared with shooting. Most importantly, we showed that when preparing against threat, theta power increase was greater for experts than novices, suggesting that differences in performance between experts and novices are due to their greater orientation toward threat. Additionally, shorter beta rebounds suggest that experts were "ready for action" sooner. More generally, we demonstrate that the investigation of expert decision-making should incorporate naturalistic stimuli and an appropriate control group to enhance validity.

Difference between subjective and objective cognitive decline confirmed by power spectral density.

INTRODUCTION: The study aims to use power spectrum changes in subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI), preclinical stages of Alzheimer's disease (AD), for future biomarker studies in early AD diagnosis. METHODS: We recruited 23 SCD and 32 aMCI subjects and conducted comparative analysis using relative power spectral density (PSD). Automated preprocessing and statistical analysis were performed using iSync Brain® (iMediSync Inc., Republic of Korea) (https://isyncbrain.com/). RESULTS: Theta band power in the temporal region was 14.826 ± 7.2394 for the SCD group and 20.003 ± 10.1768 for the aMCI group. In the parietal region, theta band power was 13.614 ± 7.5689 for SCD and 19.894 ± 11.1387 for aMCI. Beta1 band power in the frontal region was 6.639 ± 2.2904 for SCD and 5.465 ± 1.8907 for aMCI, and in the temporal region it was 7.359 ± 2.5619 for SCD and 5.921 ± 2.1605 for aMCI. CONCLUSION: PSD analysis of resting-state EEG predicted SCD, a preclinical stage of AD. This cross-sectional study observed electrical-physiological characteristics of preclinical AD; however, follow-up studies are needed to evaluate predictive value for future cognitive decline.

Beta and theta oscillations track effort and previous reward in the human basal ganglia and prefrontal cortex during decision making.

Choosing whether to exert effort to obtain rewards is fundamental to human motivated behavior. However, the neural dynamics underlying the evaluation of reward and effort in humans is poorly understood. Here, we report an exploratory investigation into this with chronic intracranial recordings from the prefrontal cortex (PFC) and basal ganglia (BG; subthalamic nuclei and globus pallidus) in people with Parkinson's disease performing a decision-making task with offers that varied in levels of reward and physical effort required. This revealed dissociable neural signatures of reward and effort, with BG beta (12 to 20 Hz) oscillations tracking effort on a single-trial basis and PFC theta (4 to 7 Hz) signaling previous trial reward, with no effects of net subjective value. Stimulation of PFC increased overall acceptance of offers and sensitivity to reward while decreasing the impact of effort on choices. This work uncovers oscillatory mechanisms that guide fundamental decisions to exert effort for reward across BG and PFC, supports a causal role of PFC for such choices, and seeds hypotheses for future studies.

Top-down and bottom-up oscillatory dynamics regulate implicit visuomotor sequence learning.

Implicit visuomotor sequence learning is crucial for acquiring skills that result in automated behaviors. The oscillatory dynamics underpinning this learning process are not well understood. To address this gap, the current study employed electroencephalography with a medium-density array (64 electrodes) to investigate oscillatory activity associated with implicit visuomotor sequence learning in the Serial Reaction Time task. In the task, participants unknowingly learn a series of finger movements. Eighty-five healthy adults participated in the study. Analyses revealed that theta activity at the vertex and alpha/beta activity over the motor areas decreased over the course of learning. No associations between alpha/beta and theta power were observed. These findings are interpreted within a dual-process framework: midline theta activity is posited to regulate top-down attentional processes, whereas beta activity from motor areas underlies the bottom-up encoding of sensory information from movement. From this model, we suggest that during implicit visuomotor sequence learning, top-down processes become disengaged (indicated by a reduction in theta activity), and modality specific bottom-up processes encode the motor sequence (indicated by a reduction in alpha/beta activity).

Investigating the impact of schizophrenia traits on attention: the role of the theta band in a modified Posner cueing paradigm.

Joint attention is an indispensable tool for daily communication. Abnormalities in joint attention may be a key reason underlying social impairment in schizophrenia spectrum disorders. In this study, we aimed to explore the attentional orientation mechanism related to schizotypal traits in a social situation. Here, we employed a Posner cueing paradigm with social attentional cues. Subjects needed to detect the location of a target that is cued by gaze and head orientation. The power in the theta frequency band was used to examine the attentional process in the schizophrenia spectrum. There were four main findings. First, a significant association was found between schizotypal traits and attention orientation in response to invalid gaze cues. Second, individuals with schizotypal traits exhibited significant activation of neural oscillations and synchrony in the theta band, which correlated with their schizotypal tendencies. Third, neural oscillations and synchrony demonstrated a synergistic effect during social tasks, particularly when processing gaze cues. Finally, the relationship between schizotypal traits and attention orientation was mediated by neural oscillations and synchrony in the theta frequency band. These findings deepen our understanding of the impact of theta activity in schizotypal traits on joint attention and offer new insights for future intervention strategies.

Firing rate adaptation affords place cell theta sweeps, phase precession, and procession.

Hippocampal place cells in freely moving rodents display both theta phase precession and procession, which is thought to play important roles in cognition, but the neural mechanism for producing theta phase shift remains largely unknown. Here, we show that firing rate adaptation within a continuous attractor neural network causes the neural activity bump to oscillate around the external input, resembling theta sweeps of decoded position during locomotion. These forward and backward sweeps naturally account for theta phase precession and procession of individual neurons, respectively. By tuning the adaptation strength, our model explains the difference between 'bimodal cells' showing interleaved phase precession and procession, and 'unimodal cells' in which phase precession predominates. Our model also explains the constant cycling of theta sweeps along different arms in a T-maze environment, the speed modulation of place cells' firing frequency, and the continued phase shift after transient silencing of the hippocampus. We hope that this study will aid an understanding of the neural mechanism supporting theta phase coding in the brain.

Using synchronized brain rhythms to bias memory-guided decisions.

Functional interactions between the prefrontal cortex and hippocampus, as revealed by strong oscillatory synchronization in the theta (6-11 Hz) frequency range, correlate with memory-guided decision-making. However, the degree to which this form of long-range synchronization influences memory-guided choice remains unclear. We developed a brain-machine interface that initiated task trials based on the magnitude of prefrontal-hippocampal theta synchronization, then measured choice outcomes. Trials initiated based on strong prefrontal-hippocampal theta synchrony were more likely to be correct compared to control trials on both working memory-dependent and -independent tasks. Prefrontal-thalamic neural interactions increased with prefrontal-hippocampal synchrony and optogenetic activation of the ventral midline thalamus primarily entrained prefrontal theta rhythms, but dynamically modulated synchrony. Together, our results show that prefrontal-hippocampal theta synchronization leads to a higher probability of a correct choice and strengthens prefrontal-thalamic dialogue. Our findings reveal new insights into the neural circuit dynamics underlying memory-guided choices and highlight a promising technique to potentiate cognitive processes or behavior via brain-machine interfacing.

Aperiodic and periodic components of oscillatory brain activity in relation to cognition and symptoms in pediatric ADHD.

Children with attention-deficit/hyperactivity disorder show deficits in processing speed, as well as aberrant neural oscillations, including both periodic (oscillatory) and aperiodic (1/f-like) activity, reflecting the pattern of power across frequencies. Both components were suggested as underlying neural mechanisms of cognitive dysfunctions in attention-deficit/hyperactivity disorder. Here, we examined differences in processing speed and resting-state-Electroencephalogram neural oscillations and their associations between 6- and 12-year-old children with (n = 33) and without (n = 33) attention-deficit/hyperactivity disorder. Spectral analyses of the resting-state EEG signal using fast Fourier transform revealed increased power in fronto-central theta and beta oscillations for the attention-deficit/hyperactivity disorder group, but no differences in the theta/beta ratio. Using the parameterization method, we found a higher aperiodic exponent, which has been suggested to reflect lower neuronal excitation-inhibition, in the attention-deficit/hyperactivity disorder group. While fast Fourier transform-based theta power correlated with clinical symptoms for the attention-deficit/hyperactivity disorder group only, the aperiodic exponent was negatively correlated with processing speed across the entire sample. Finally, the aperiodic exponent was correlated with fast Fourier transform-based beta power. These results highlight the different and complementary contribution of periodic and aperiodic components of the neural spectrum as metrics for evaluation of processing speed in attention-deficit/hyperactivity disorder. Future studies should further clarify the roles of periodic and aperiodic components in additional cognitive functions and in relation to clinical status.