Clinical use of Electroencephalography in the Assessment of Acute Thermal Pain: A Narrative Review Based on Articles From 2009 to 2019.

Nowadays, no practical system has successfully been able to decode and predict pain in clinical settings. The inability of some patients to verbally express their pain creates the need for a tool that could objectively assess pain in these individuals. Neuroimaging techniques combined with machine learning are seen as possible candidates for the identification of pain biomarkers. This review aimed to address the potential use of electroencephalographic features as predictors of acute experimental pain. Twenty-six studies using only thermal stimulations were identified using a PubMed and Scopus search. Combinations of the following terms were used: "EEG," "Electroencephalography," "Acute," "Pain," "Tonic," "Noxious," "Thermal," "Stimulation," "Brain," "Activity," "Cold," "Subjective," and "Perception." Results revealed that contact-heat-evoked potentials have been widely recorded over central areas during noxious heat stimulations. Furthermore, a decrease in alpha power over central regions was revealed, as well as increased theta and gamma powers over frontal areas. Gamma and theta rhythms were associated with connectivity between sensory and affective regions involved in pain processing. A machine learning analysis revealed that the gamma band is a predominant predictor of acute thermal pain. This review also addressed the need of supplementing current spectral features with techniques that allow the investigation of network dynamics.

Frequency modulation of entorhinal cortex neuronal activity drives distinct frequency-dependent states of brain-wide dynamics.

Human neuroimaging studies have shown that, during cognitive processing, the brain undergoes dynamic transitions between multiple, frequency-tuned states of activity. Although different states may emerge from distinct sources of neural activity, it remains unclear whether single-area neuronal spiking can also drive multiple dynamic states. In mice, we ask whether frequency modulation of the entorhinal cortex activity causes dynamic states to emerge and whether these states respond to distinct stimulation frequencies. Using hidden Markov modeling, we perform unsupervised detection of transient states in mouse brain-wide fMRI fluctuations induced via optogenetic frequency modulation of excitatory neurons. We unveil the existence of multiple, frequency-dependent dynamic states, invisible through standard static fMRI analyses. These states are linked to different anatomical circuits and disrupted in a frequency-dependent fashion in a transgenic model of cognitive disease directly related to entorhinal cortex dysfunction. These findings provide cross-scale insight into basic neuronal mechanisms that may underpin flexibility in brain-wide dynamics.

Dissociable theta networks underlie the switch and mixing costs during task switching.

During task-switching paradigms, both event-related potentials and time-frequency analyses show switch and mixing effects at frontal and parietal sites. Switch and mixing effects are associated with increased power in broad frontoparietal networks, typically stronger in the theta band (~4-8 Hz). However, it is not yet known whether mixing and switch costs rely upon common or distinct networks. In this study, we examine proactive and reactive control networks linked to task switching and mixing effects, and whether strength of connectivity in these networks is associated with behavioural outcomes. Participants (n = 197) completed a cued-trials task-switching paradigm with concurrent electroencephalography, after substantial task practice to establish strong cue-stimulus-response representations. We used inter-site phase clustering, a measure of functional connectivity across electrode sites, to establish cross-site connectivity from a frontal and a parietal seed. Distinct theta networks were activated during proactive and reactive control periods. During the preparation interval, mixing effects were associated with connectivity from the frontal seed to parietal sites, and switch effects with connectivity from the parietal seed to occipital sites. Lateralised occipital connectivity was common to both switch and mixing effects. After target onset, frontal and parietal seeds showed a similar pattern of connectivity across trial types. These findings are consistent with distinct and common proactive control networks and common reactive networks in highly practised task-switching performers.

[Measurement of the theta / beta ratio with the quantified electroencephalogram in attention-deficit hyperactivity disorders]. / Valoración del cociente theta/beta en el electroencefalograma cuantificado de los trastornos por déficit de atención e hiperactividad.

Theta-Beta (T / B) ratio of the quantified electroencephalogram (EEGQ) in patients with attention deficit hyperactivity disorder (ADHD) constitutes a characteristic EEG variable of the primary disorder with an overall accuracy of 89%. The objective of this study was to measure the T/B ratio in a sample of patients with ADHD and the effects of the treatment with psychostimulants and non-psychostimulants on the T/B ratio. The sample consisted of 85 children between 6 and 18 years (68 males and 17 females) with the diagnosis of the inattentive and combined subtype of ADHD, according to the criteria of the DSM-V. An EEGQ was performed with measurement of the T/B ratio before and after 6 months of treatment with psychostimulant and non-psychostimulant drugs. Both groups were compared using the Wilcoxon signed range test for related samples. The results showed that 86% of the cases had a T/B ratio above the normal values for the age of them. The reduction in the T/B ratio was statistically significant in the group of patients treated with psychostimulants. The reduction of non-psychostimulants was not significant. In conclusion, we confirmed the high T/B ratio in patients with ADHD. Psychostimulant drugs decrease the elevated T/B ratio in patients with ADHD after 6 months of treatment.

El cociente Theta-Beta (T/B) del electroencefalograma cuantificado (EEGQ) de los pacientes con trastorno por déficit de atención e hiperactividad (TDAH) constituye una variable del EEG característica del trastorno primario con una precisión global del 89%. El objetivo de este estudio es medir el cociente T/B de una población de con TDAH y los efectos del tratamiento farmacológico con psicoestimulantes y no psicoestimulantes sobre el cociente T/B. La muestra estaba formada por 85 sujetos de entre 6 y los 18 años (68 niños y 17 niñas) con el diagnóstico de TDAH de subtipo inatento y combinado, según los criterios del DSM-V. Se les realizó un EEGQ con medición del cociente T/B antes y después de 6 meses de tratamiento con fármacos psicoestimulantes y no psicoestimulantes. Se compararon ambos grupos mediante la prueba de rangos con signo de Wilcoxon para muestras relacionadas. En el 86% de los casos el cociente T/B fue elevado respecto de los valores normales para la edad. La reducción en el cociente T/B fue significativa en el grupo tratado con psicoestimulantes aunque la reducción con los no psicoestimulantes no fue significativa. En conclusión, se confirma la elevación del cociente T/B en los pacientes con TDAH. Los fármacos psicoestimulantes disminuyen de forma significativa el cociente T/B elevado en los pacientes con TDAH tras 6 meses de tratamiento.

Valoración del cociente Theta/Beta en el electroencefalograma cuantificado de los trastornos por déficit de atención e hiperactividad / Measurement of the theta / beta ratio with the quantified electroencephalogram in attention-deficit hyperactivity disorders

El cociente Theta-Beta (T/B) del electroencefalograma cuantificado (EEGQ) de los pacientes con trastorno por déficit de atención e hiperactividad (TDAH) constituye una variable del EEG característica del trastorno primario con una precisión global del 89%. El objetivo de este estudio es medir el cociente T/B de una población de con TDAH y los efectos del tratamiento farmacológico con psicoestimulantes y no psicoestimulantes sobre el cociente T/B. La muestra estaba formada por 85 sujetos de entre 6 y los 18 años (68 niños y 17 niñas) con el diagnóstico de TDAH de subtipo inatento y combinado, según los criterios del DSM-V. Se les realizó un EEGQ con medición del cociente T/B antes y después de 6 meses de tratamiento con fármacos psicoestimulantes y no psicoestimulantes. Se compararon ambos grupos mediante la prueba de rangos con signo de Wilcoxon para muestras relacionadas. En el 86% de los casos el cociente T/B fue elevado respecto de los valores normales para la edad. La reducción en el cociente T/B fue significativa en el grupo tratado con psicoestimulantes aunque la reducción con los no psicoestimulantes no fue significativa. En conclusión, se confirma la elevación del cociente T/B en los pacientes con TDAH. Los fármacos psicoestimulantes disminuyen de forma significativa el cociente T/B elevado en los pacientes con TDAH tras 6 meses de tratamiento.

Theta-Beta (T / B) ratio of the quantified electroencephalogram (EEGQ) in patients with attention deficit hyperactivity disorder (ADHD) constitutes a characteristic EEG variable of the primary disorder with an overall accuracy of 89%. The objective of this study was to measure the T/B ratio in a sample of patients with ADHD and the effects of the treatment with psychostimulants and non-psychostimulants on the T/B ratio. The sample consisted of 85 children between 6 and 18 years (68 males and 17 females) with the diagnosis of the inattentive and combined subtype of ADHD, according to the criteria of the DSM-V. An EEGQ was performed with measurement of the T/B ratio before and after 6 months of treatment with psychostimulant and non-psychostimulant drugs. Both groups were compared using the Wilcoxon signed range test for related samples. The results showed that 86% of the cases had a T/B ratio above the normal values for the age of them. The reduction in the T/B ratio was statistically significant in the group of patients treated with psychostimulants. The reduction of non-psychostimulants was not significant. In conclusion, we confirmed the high T/B ratio in patients with ADHD. Psychostimulant drugs decrease the elevated T/B ratio in patients with ADHD after 6 months of treatment.

It's costly punishment, not altruistic: Low midfrontal theta and state anger predict punishment.

Punishment in economic games has been interpreted as "altruistic." However, it was shown that punishment is related to trait anger instead of trait altruism in a third-party dictator game if compensation is also available. Here, we investigated the influence of state anger on punishment and compensation in the third-party dictator game. Therefore, we used movie sequences for emotional priming, including the target states anger, happy, and neutral. We measured the Feedback-Related Negativity (FRN) and midfrontal theta band activation, to investigate an electro-cortical correlate of the processing of fair and unfair offers. Also, we assessed single-trial FRN and midfrontal theta band activation as a predictor for punishment and compensation. We found that punishment was linked to state anger. Midfrontal theta band activation, which has previously been linked to altruistic acts and cognitive control, predicted less punishment. Additionally, trait anger led to enhanced FRN for unfair offers. This led to the interpretation that the FRN depicts the evaluation of fairness, while midfrontal theta band activation captures an aspect of cognitive control and altruistic motivation. We conclude that we need to redefine "altruistic punishment" into "costly punishment," as no direct link of altruism and punishment is given. Additionally, midfrontal theta band activation complements the FRN and offers additional insights into complex responses and decision processes, especially as a single trial predictor.

EEG Theta/Beta Ratio Calculations Differ Between Various EEG Neurofeedback and Assessment Software Packages: Clinical Interpretation.

The quantitative electroencephalographic (QEEG) theta/beta power ratio (TBR) has been shown to have an association with attention-deficit hyperactivity disorder (ADHD), with a previous tacit assumption of equivalence across hardware and software systems. Therefore, the International Collaborative ADHD Neurofeedback (ICAN) randomized clinical trial used a fixed TBR ≥ 4.5 cutoff as measured by the Thought Technology Monastra-Lubar Assessment Suite as an inclusion criterion, 1.5 SD above norms collected with that system. However, a difference was noted between the TBR calculated by that assessment suite and the TBR computed by EEGer, the neurofeedback software used for treatment, leading us to investigate the discrepancy. The difference may arise from different calculation methods. This article explains and compares various computational methods used to calculate and display EEG values, including TBR, elucidating why the values are not equivalent across equipment and software programs. Two major sources of variance are (1) how "spectral leakage" at the ends of bands is handled and (2) whether voltages of bins within a band are first averaged and then squared to get bandwidth power or are first squared to get power (turning negative voltages into positive power) and then averaged to get the bandwidth power; the latter method results in higher band power. This article compares methods of computing the TBR. Biofeedback practitioners and investigators should be aware of the algorithms their systems use when interpreting TBRs and require normative comparison data collected with the same system.

Inhibition of the right dlPFC by theta burst stimulation does not alter sustainable decision-making.

Intergenerational sustainability is probably humankind's most pressing challenge, exacerbated by the fact that the present generation has to incur costs in order to benefit future generations. However, people often fail to restrict their consumption, despite reporting strong pro-environmental attitudes. Recent theorising sees self-control processes as key component of sustainable decision-making and correlational studies support this view, yet causal evidence is lacking. Using TMS, we here disrupted an area known to be involved in self-control processes, the right dorsolateral prefrontal cortex (dlPFC), to provide causal evidence as to whether diminished self-control leads to less intergenerational sustainability. Participants then engaged in a behavioural economic paradigm to measure sustainable decision-making towards the next generation. This adequately powered study could not find an effect of inhibiting the right dlPFC on intergenerational sustainability. This result holds when controlling for a number of relevant covariates like gender, trait self-control, pro-environmental attitudes, or cortical thickness at the stimulation site. We seek to explain this result methodologically and theoretically, and speculate about other brain areas that could be more strongly related to intergenerational sustainability, e.g. the mentalising network.

Implementation of intermittent theta burst stimulation compared to conventional repetitive transcranial magnetic stimulation in patients with treatment resistant depression: A cost analysis.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an evidence-based treatment for depression that is increasingly implemented in healthcare systems across the world. A new form of rTMS called intermittent theta burst stimulation (iTBS) can be delivered in 3 min and has demonstrated comparable effectiveness to the conventional 37.5 min 10Hz rTMS protocol in patients with depression. OBJECTIVES: To compare the direct treatment costs per course and per remission for iTBS compared to 10Hz rTMS treatment in depression. METHODS: We conducted a cost analysis from a healthcare system perspective using patient-level data from a large randomized non-inferiority trial (THREE-D). Depressed adults 18 to 65 received either 10Hz rTMS or iTBS treatment. Treatment costs were calculated using direct healthcare costs associated with equipment, coils, physician assessments and technician time over the course of treatment. Cost per remission was estimated using the proportion of patients achieving remission following treatment. Deterministic sensitivity analyses and non-parametric bootstrapping was used to estimate uncertainty. RESULTS: From a healthcare system perspective, the average cost per patient was USD$1,108 (SD 166) for a course of iTBS and $1,844 (SD 304) for 10Hz rTMS, with an incremental net savings of $735 (95% CI 688 to 783). The average cost per remission was $3,695 (SD 552) for iTBS and $6,146 (SD 1,015) for 10Hz rTMS, with an average incremental net savings of $2,451 (95% CI 2,293 to 2,610). CONCLUSIONS: The shorter session durations and treatment capacity increase associated with 3 min iTBS translate into significant cost-savings per patient and per remission when compared to 10Hz rTMS.

Assessment of the effect of continuous theta burst stimulation of the motor cortex on manual dexterity in non-human primates in a direct comparison with invasive intracortical pharmacological inactivation.

Non-invasive reversible perturbation techniques of brain output such as continuous theta burst stimulation (cTBS), commonly used to modulate cortical excitability in humans, allow investigation of possible roles in functional recovery played by distinct intact cortical areas following stroke. To evaluate the potential of cTBS, the behavioural effects of this non-invasive transient perturbation of the hand representation of the primary motor cortex (M1) in non-human primates (two adult macaques) were compared with an invasive focal transient inactivation based on intracortical microinfusion of GABA-A agonist muscimol. The effects on the contralateral arm produced by cTBS or muscimol were directly compared based on a manual dexterity task performed by the monkeys, the "reach and grasp" drawer task, allowing quantitative assessment of the grip force produced between the thumb and index finger and exerted on the drawer's knob. cTBS only induced modest to moderate behavioural effects, with substantial variability on manual dexterity whereas the intracortical muscimol microinfusion completely impaired manual dexterity, producing a strong and clear cortical inhibition of the M1 hand area. In contrast, cTBS induced mixed inhibitory and facilitatory/excitatory perturbations of M1, though with predominant inhibition. Although cTBS impacted on manual dexterity, its effects appear too limited and variable in order to use it as a reliable proof of cortical vicariation mechanism (cortical area replacing another one) underlying functional recovery following a cortical lesion in the motor control domain, in contrast to potent pharmacological block generated by muscimol infusion, whose application is though limited to an animal model such as non-human primate.

Altered transient brain dynamics in multiple sclerosis: Treatment or pathology?

Multiple sclerosis (MS) is a demyelinating, neuroinflammatory, and -degenerative disease that affects the brain's neurophysiological functioning through brain atrophy, a reduced conduction velocity and decreased connectivity. Currently, little is known on how MS affects the fast temporal dynamics of activation and deactivation of the different large-scale, ongoing brain networks. In this study, we investigated whether these temporal dynamics are affected in MS patients and whether these changes are induced by the pathology or by the use of benzodiazepines (BZDs), an important symptomatic treatment that aims at reducing insomnia, spasticity and anxiety and reinforces the inhibitory effect of GABA. To this aim, we employed a novel method capable of detecting these fast dynamics in 90 MS patients and 46 healthy controls. We demonstrated a less dynamic frontal default mode network in male MS patients and a reduced activation of the same network in female MS patients, regardless of BZD usage. Additionally, BZDs strongly altered the brain's dynamics by increasing the time spent in the deactivating sensorimotor network and the activating occipital network. Furthermore, BZDs induced a decreased power in the theta band and an increased power in the beta band. The latter was strongly expressed in those states without activation of the sensorimotor network. In summary, we demonstrate gender-dependent changes to the brain dynamics in the frontal DMN and strong effects from BZDs. This study is the first to characterise the effect of multiple sclerosis and BZDs in vivo in a spatially, temporally and spectrally defined way.

Cerebral cortical networking for mental workload assessment under various demands during dual-task walking.

While several studies have examined attentional reserve (via event-related potentials) and mental effort (via EEG spectral content) from various cortical regions during dual-task walking, none have assessed changes in the magnitude of interregional (cortico-cortical) communication as a measure of mental workload. Therefore, by deploying a traditional montage of electrode sites centered over the motor planning region as well as a more comprehensive graph theory-based approach encompassing the entire scalp, this study aimed to systematically examine changes in the magnitude of functional connectivity underlying cortico-cortical communication to assess changes in mental workload under various levels of challenge. Specifically, the Weighted Phase Lag Index (WPLI) was computed to assess the changes in magnitude of functional connectivity as participants performed a cognitive task under two demands (low and high) and two conditions (seated and walking). The results revealed enhanced fronto-centro-temporo-parietal theta connectivity during dual-task walking relative to being seated as well as a reduced inhibition of fronto-centro-temporo-parieto-occipital alpha networking as the demand on the secondary cognitive task increased. Collectively, these findings may reflect greater recruitment of task relevant processes to respond to increased cognitive-motor demands and thus an elevation of mental workload in an effort to maintain performance under varying levels of challenge. This work has the potential to inform future mental workload assessment applications in patient populations, including those who employ prostheses during cognitive-motor performance under various task demands.

The High Energy Cost of Theta-Gamma Activity during REM Sleep.

The occurrence of wake-like electroencephalography (EEG) traces during rapid-eye movement sleep (REM) has intrigued scientists for decades. A recent study by Bergel et al. (Nat. Commun. 2018;9;5364) imaged brain-wide hemodynamics in rats during wakefulness and sleep. The findings suggest that brain energy expenditure is highest during REM because of heightened theta and gamma activity.

Between-Frequency Topographical and Dynamic High-Order Functional Connectivity for Driving Drowsiness Assessment.

Previous studies exploring driving drowsiness utilized spectral power and functional connectivity without considering between-frequency and more complex synchronizations. To complement such lacks, we explored inter-regional synchronizations based on the topographical and dynamic properties between frequency bands using high-order functional connectivity (HOFC) and envelope correlation. We proposed the dynamic interactions of HOFC, associated-HOFC, and a global metric measuring the aggregated effect of the functional connectivity. The EEG dataset was collected from 30 healthy subjects, undergoing two driving sessions. The two-session setting was employed for evaluating the metric reliability across sessions. Based on the results, we observed reliably significant metric changes, mainly involving the alpha band. In HOFCθα , HOFCαß , associated- HOFCθα , and associated- HOFCαß , the connection-level metrics in frontal-central, central-central, and central-parietal/occipital areas were significantly increased, indicating a dominance in the central region. Similar results were also obtained in the HOFCθαß and aHOFCθαß . For dynamic-low-order-FC and dynamic-HOFC, the global metrics revealed a reliably significant increment in the alpha, theta-alpha, and alpha-beta bands. Modularity indexes of associated- HOFCα and associated- HOFCθα also exhibited reliably significant differences. This paper demonstrated that within-band and between-frequency topographical and dynamic FC can provide complementary information to the traditional individual-band LOFC for assessing driving drowsiness.

Frontal theta activation associated with error detection in toddlers: influence of familial socioeconomic status.

Error detection is one of the functions of the executive attention network, a brain system involved in executive control that includes the anterior cingulate cortex and other prefrontal regions. Despite the key role of this function in a wide range of life outcomes, very limited research has examined the early development of the network and whether its functional efficacy is related to environmental factors. Electrophysiological studies with adults have shown oscillatory activity in theta (4-7 Hz) range arising from medial frontal cortex that follows the detection of self-committed or observed errors. In the current study, we designed a novel experimental procedure that involved a familiarization phase with simple three-pieces puzzles followed by an experimental phase in which toddlers observed the puzzles being formed either correctly or incorrectly. Observation of incorrect configurations produced increased potentials in midline channels and greater power theta activity for both toddlers (n = 56) and adults (n = 14). In addition, socioeconomic status of the family in general, and parental education in particular, contributed to individual differences in the amplitude of the error-related signal and associated theta power in toddlers, indicating that children raised in lower SES families show poorer activation of the executive attention network. These data demonstrate the influence of environmental factors at the earliest stages of development of the executive attention network. Importantly, the results show that error-detection EEG signals can be used as neural markers of the initial development of executive attention, which can be of great help for the early detection of risk for developmental disorders involving deficits in this function.

Frontal theta accounts for individual differences in the cost of conflict on decision making.

Cognitive conflict is often experienced as a difficult, frustrating, and aversive state. Recent studies have indicated that conflict acts as an implicit cost during learning, valuation, and the instantiation of cognitive control. Here we investigated if an implicit manipulation of conflict also influences explicit decision making to risk. Participants were required to perform a Balloon Analogue Risk Task wherein the virtual balloon was inflated by performing a flankers task. By varying the percent of incongruent flanker trials between balloons, we hypothesized that participants would pump the balloon fewer times in conditions of higher conflict and that frontal midline theta would account for significant variance in this relationship. Across two studies, we demonstrate that conflict did not elicit reliable behavioral changes in this task across participants. However, individual differences in frontal theta power accounted for significant variance by predicting diminished balloon pumps. Thus, while conflict costs may act as investments to some individuals (invigorating behavior), it is aversive to others (diminishing behavior), and frontal midline theta power accounts for these varying behavioral tendencies between individuals. These findings demonstrate how frontal midline theta is not only a candidate mechanism for implementing cognitive control, but it is sensitive to the inherent costs therein.

Increasing generosity by disrupting prefrontal cortex.

Recent research suggests that prosocial outcomes in sharing games arise from prefrontal control of self-maximizing impulses. We used continuous theta burst stimulation (cTBS) to disrupt the functioning of two prefrontal areas, the right dorsolateral prefrontal cortex (DLPFC) and the dorsomedial prefrontal cortex (DMPFC). We used cTBS in the right MT/V5, as a control area. We then tested subjects' prosocial inclinations with an unsupervised Dictator Game in which they allocated real money anonymously between themselves and low and high socioeconomic status (SES) players. cTBS over the two prefrontal sites made subjects more generous compared to MT/V5. More specifically, cTBS over DLPFC increased offers to high-SES players, while cTBS over DMPFC caused increased offers to low-SES players. These data, the first to demonstrate an effect of disruptive neuromodulation on costly sharing, suggest that DLPFC and MPFC exert inhibitory control over prosocial inclinations during costly sharing, though they may do so in different ways. DLPFC may implement contextual control, while DMPFC may implement a tonic form of control. This study demonstrates that humans' prepotent inclination is toward prosocial outcomes when cognitive control is reduced, even when prosocial decisions carry no strategic benefit and concerns for reputation are minimized.

Theta/beta neurofeedback in children with ADHD: Feasibility of a short-term setting and plasticity effects.

Neurofeedback (NF) is increasingly used as a therapy for attention-deficit/hyperactivity disorder (ADHD), however behavioral improvements require 20 plus training sessions. More economic evaluation strategies are needed to test methodological optimizations and mechanisms of action. In healthy adults, neuroplastic effects have been demonstrated directly after a single session of NF training. The aim of our study was to test the feasibility of short-term theta/beta NF in children with ADHD and to learn more about the mechanisms underlying this protocol. Children with ADHD conducted two theta/beta NF sessions. In the first half of the sessions, three NF trials (puzzles as feedback animations) were run with pre- and post-reading and picture search tasks. A significant decrease of the theta/beta ratio (TBR), driven by a decrease of theta activity, was found in the NF trials of the second session demonstrating rapid and successful neuroregulation by children with ADHD. For pre-post comparisons, children were split into good vs. poor regulator groups based on the slope of their TBR over the NF trials. For the reading task, significant EEG changes were seen for the theta band from pre- to post-NF depending on individual neuroregulation ability. This neuroplastic effect was not restricted to the feedback electrode Cz, but appeared as a generalized pattern, maximal over midline and right-hemisphere electrodes. Our findings indicate that short-term NF may be a valuable and economical tool to study the neuroplastic mechanisms of targeted NF protocols in clinical disorders, such as theta/beta training in children with ADHD.

(No) time for control: Frontal theta dynamics reveal the cost of temporally guided conflict anticipation.

During situations of response conflict, cognitive control is characterized by prefrontal theta-band (3- to 8-Hz) activity. It has been shown that cognitive control can be triggered proactively by contextual cues that predict conflict. Here, we investigated whether a pretrial preparation interval could serve as such a cue. This would show that the temporal contingencies embedded in the task can be used to anticipate upcoming conflict. To this end, we recorded electroencephalography (EEG) from 30 human subjects while they performed a version of a Simon task in which the duration of a fixation cross between trials predicted whether the next trial would contain response conflict. Both their behavior and EEG activity showed a consistent but unexpected pattern of results: The conflict effect (increased reaction times and decreased accuracy on conflict as compared to nonconflict trials) was stronger when conflict was cued, and this was associated with stronger conflict-related midfrontal theta activity and functional connectivity. Interestingly, intervals that predicted conflict did show a pretarget increase in midfrontal theta power. These findings suggest that temporally guided expectations of conflict do heighten conflict anticipation, but also lead to less efficiently applied reactive control. We further explored this post-hoc interpretation by means of three behavioral follow-up experiments, in which we used nontemporal cues, semantically informative cues, and neutral cues. Together, this body of results suggests that the counterintuitive cost of conflict cueing may not be uniquely related to the temporal domain, but may instead be related to the implicitness and validity of the cue.