Theta-phase Gamma-amplitude Coupling Research Articles

Cognitive function based on theta-gamma coupling vs. clinical diagnosis in older adults with mild cognitive impairment with or without major depressive disorder

Whether individuals with mild cognitive impairment (MCI) and a history of major depressive disorder (MDD) are at a higher risk for cognitive decline than those with MCI alone is still not clear. Previous work suggests that a reduction in prefrontal cortical theta phase-gamma amplitude coupling (TGC) is an early marker of cognitive impairment. This study aimed to determine whether using a TGC cutoff is better at separating individuals with MCI or MCI with remitted MDD (MCI+rMDD) on cognitive performance than their clinical diagnosis. Our hypothesis was that global cognition would differ more between TGC-based groups than diagnostic groups. We analyzed data from 128 MCI (mean age: 71.8, SD: 7.3) and 85 MCI+rMDD (mean age: 70.9, SD: 4.7) participants. Participants completed a comprehensive neuropsychological battery; TGC was measured during the N-back task. An optimal TGC cutoff was determined during the performance of the 2-back. This TGC cutoff was used to classify participants into low vs. high-TGC groups. We then compared Cohen’s d of the difference in global cognition between the high and low TGC groups to Cohen’s d between the MCI and MCI+rMDD groups. We used bootstrapping to determine 95% confidence intervals for Cohen’s d values using the whole sample. As hypothesized, Cohen’s d for the difference in global cognition between the TGC groups was larger (0.64 [0.32, 0.88]) than between the diagnostic groups (0.10 [0.004, 0.37]) with a difference between these two Cohen’s d’s of 0.54 [0.10, 0.80]. Our findings suggest that TGC is a useful marker to identify individuals at high risk for cognitive decline, beyond clinical diagnosis. This could be due to TGC being a sensitive marker of prefrontal cortical dysfunction that would lead to an accelerated cognitive decline.

Aberrant hyperfocusing in schizophrenia indicated by elevated theta phase-gamma amplitude coupling

ObjectiveWe aimed to investigate electroencephalographic (EEG) markers of aberrant hyperfocusing, a novel framework of impaired selective attention, in schizophrenia patients by using theta phase-gamma amplitude coupling (TGC). MethodsFifty-four schizophrenia patients and 73 healthy controls (HCs) underwent EEG recording during an auditory oddball paradigm. For the standard and target conditions, TGC was calculated using the source signals from 25 brain regions of interest (ROIs) related to attention networks and sensory processing; TGC values were then compared across groups and conditions using two-way analysis of covariance. Correlations of altered TGC with performance on the Trail Making Test Parts A and B (TMT-A/B), were explored. ResultsCompared to HCs, schizophrenia patients showed elevated TGC in the left inferior frontal gyrus (IFG) and superior temporal gyrus in the standard condition but not in the target condition. Correlation analyses revealed that the TGC in the left IFG was positively correlated with the TMT-A/B completion times. ConclusionsAberrant hyperfocusing, as reflected by elevated TGC in attention-related brain regions, was related to behavioral performance on the TMT-A/B in schizophrenia patients. SignificanceThis study suggests that TGC is a electrophysiological marker for aberrant hyperfocusing of attentional processes that may result in cognitive impairments in schizophrenia patients.

Altered fronto-central theta-gamma coupling in major depressive disorder during auditory steady-state responses

ObjectiveNeural oscillations during sensory and cognitive events interact at different frequencies. However, such evidence in major depressive disorder (MDD) remains scarce. We explored the possible abnormal neural oscillations in MDD by analyzing theta-phase/gamma-amplitude coupling (TGC). MethodsResting-state and auditory steady-state response (ASSR) electroencephalography recordings were obtained from 35 first-episode MDD and 35 healthy controls (HCs). TGC during rest, ASSR stimulation, and ASSR baseline between and within groups were analyzed to evaluate MDD alterations. Receiver operating characteristic (ROC), TGC comparison between MDD severity subgroups (mild, moderate, major), and correlations were investigated to determine the potential use of altered TGC for identifying MDD. ResultsIn MDD, left fronto-central TGC decreased during stimulation, while right fronto-central TGC increased during baseline. The area under ROC curve for altered TGC was 0.863. Furthermore, during stimulation, moderate and major MDD groups exhibited significantly lower TGC than mild group, and fronto-central TGC was negatively correlated with depression scale scores. ConclusionsOur results provided the first evidence for an abnormal TGC response of fronto-central regions in MDD during an ASSR task. Importantly, altered TGC may be promising biomarkers of MDD. SignificanceOur findings enhance the understanding of physiological mechanisms underlying MDD and aid in its clinical diagnosis.

TREM2 Deficiency Disrupts Network Oscillations Leading to Epileptic Activity and Aggravates Amyloid-β-Related Hippocampal Pathophysiology in Mice.

Genetic mutations in triggering receptor expressed on myeloid cells-2 (TREM2) have been strongly associated with increased risk of developing Alzheimer's disease (AD) and other progressive dementias. In the brain, TREM2 protein is specifically expressed on microglia suggesting their active involvement in driving disease pathology. Using various transgenic AD models to interfere with microglial function through TREM2, several recent studies provided important data indicating a causal link between TREM2 and underlying amyloid-β (Aβ) and tau pathology. However, mechanisms by which TREM2 contributes to increased predisposition to clinical AD and influences its progression still remain largely unknown. Our aim was to elucidate the potential contribution of TREM2 on specific oscillatory dynamic changes associated with AD pathophysiology. Spontaneous and brainstem nucleus pontis oralis stimulation-induced hippocampal oscillation paradigm was used to investigate the impact of TREM2 haploinsufficiency TREM2(Het) or total deficiency TREM2(Hom) on hippocampal network function in wild-type and Aβ overproducing Tg2576 mice under urethane anesthesia. Partial (TREM2(Het)) or total (TREM2(Hom)) deletion of TREM2 led to increased incidence of spontaneous epileptiform seizures in both wild-type and Tg2576 mice. Importantly, deficiency of TREM2 in Tg2576 mice significantly diminished power of theta oscillation in the hippocampus elicited by brainstem-stimulation compared to wild-type mice. However, it did not affect hippocampal theta-phase gamma-amplitude coupling significantly, since over a 60%reduction was found in coupling in Tg2576 mice regardless of TREM2 function. Our findings indicate a role for TREM2-dependent microglial function in the hippocampal neuronal excitability in both wild type and Aβ overproducing mice, whereas deficiency in TREM2 function exacerbates disruptive effects of Aβ on hippocampal network oscillations.

The Functional Interactions between Cortical Regions through Theta-Gamma Coupling during Resting-State and a Visual Working Memory Task.

Theta phase-gamma amplitude coupling (TGC) plays an important role in several different cognitive processes. Although spontaneous brain activity at the resting state is crucial in preparing for cognitive performance, the functional role of resting-state TGC remains unclear. To investigate the role of resting-state TGC, electroencephalogram recordings were obtained for 56 healthy volunteers while they were in the resting state, with their eyes closed, and then when they were engaged in a retention interval period in the visual memory task. The TGCs of the two different conditions were calculated and compared. The results indicated that the modulation index of TGC during the retention interval of the visual working memory (VWM) task was not higher than that during the resting state; however, the topographical distribution of TGC during the resting state was negatively correlated with TGC during VWM task at the local level. The topographical distribution of TGC during the resting state was negatively correlated with TGC coordinates’ engagement of brain areas in local and large-scale networks and during task performance at the local level. These findings support the view that TGC reflects information-processing and signal interaction across distant brain areas. These results demonstrate that TGC could explain the efficiency of competing brain networks.

Impact of TREM2 on hippocampal network oscillations in Tg2576 mice modeling amyloid-β pathology.

Loss of function mutations in gene encoding triggering receptor expressed on myeloid cells-2 (TREM2) have been strongly associated with the risk of developing Alzheimer's disease (AD) and other progressive dementias. In the brain, TREM2 is specifically expressed on microglia suggesting their active involvement in driving disease pathology. Using various transgenic AD models to interfere with microglial function through TREM2, several recent studies provided important data for indicating a causal link between TREM2 and underlying amyloid-β (Aβ) and tau pathology in AD. However, mechanisms by which TREM2 contributes to increased predisposition to AD and influences its progression still remain ill-defined. We investigated the impact of TREM2 haploinsufficiency TREM2(Het) or total deficiency TREM2(Hom) on hippocampal neuronal network oscillations in wild-type and Aβ overproducing Tg2576 mice by in vivo monitoring spontaneous and brainstem stimulation-induced local field potentials from CA1 region under urethane anesthesia. Functional impairment of TREM2, either in TREM2(Het) or TREM2(Hom), resulted in increased incidence of spontaneous epileptiform seizures in both wild-type and Tg2576 mice. Furthermore, deficiency of TREM2 significantly reduced the power of stimulation-induced hippocampal theta oscillation in Tg2576 mice compared to wild-type mice. However, dysfunction of TREM2 did not influence hippocampal theta-phase gamma-amplitude coupling per se, given that both TREM2 intact and TREM2 total deficient Tg2576 mice had a comparable decrease in the phase-amplitude coupling between theta and gamma oscillations when compared to wild-type counterparts. Our findings indicate a TREM2-dependent microglial function in the hippocampal neuronal network oscillations in both physiological conditions and the setting of Aβ overproduction.

Thalamocortical dysrhythmia in patients with schizophrenia spectrum disorder and individuals at clinical high risk for psychosis.

Thalamocortical dysrhythmia (TCD) is a model characterized by abnormal resting-state thalamic oscillatory patterns where the alpha rhythm is replaced by cross-frequency coupling of low- and high-frequency rhythms. Although disrupted thalamic function is a suggested important pathophysiological mechanism underlying schizophrenia, knowledge regarding the TCD model in schizophrenia spectrum disorder (SSD) patients and individuals at clinical high risk (CHR) for psychosis is limited. A total of 169 SSD patients, 106 individuals at CHR for psychosis, and 105 healthy controls (HCs) underwent resting-state electroencephalography recordings. We performed mean global field power (MGFP) spectral analysis between 1 and 49 Hz as well as source-level theta phase-gamma amplitude coupling (TGC) analysis and compared resting-state oscillatory patterns across groups. Correlations between altered TGC values and psychotic symptom severity in the patient group were investigated. Spectral MGFP of low- and high-frequencies was larger in the SSD and CHR groups than in the HC group. The TGC of SSD patients was greater than that of HCs in the right frontal, right parietal, and left and right limbic lobes. Greater TGC in the right frontal and limbic lobes was associated with positive symptom severity in SSD patients. However, TGC in the CHR group was comparable to that in the HCs and was smaller than that in the SSD group in widespread cortical regions. The TCD pattern may be apparent after frank psychotic disorder onset in tandem with overt positive symptoms. A psychosis-risk state without overt psychotic symptoms could be characterized by abnormally increased low- and high-frequency activities with relatively preserved TGC.

The Role of Quantitative Electroencephalogram in the Diagnosis and Subgrouping of Attention-Deficit/Hyperactivity Disorder

Attention-deficit/hyperactivity disorder (ADHD) leads to functional decline in academic performance, interpersonal relationships, and development in school-aged children. Early diagnosis and appropriate intervention can significantly reduce the functional decline caused by ADHD. Currently, there is no established biological marker for ADHD. Some studies have suggested that various indicators from the quantitative electroencephalogram (QEEG) may be useful biological markers for the diagnosis of ADHD. Until the 2010s, theta/beta ratio (TBR) was a biomarker candidate for ADHD that consistently showed high diagnostic value. However, limitations of TBR have recently been reported. Studies have demonstrated that phase-amplitude coupling, especially theta phase-gamma amplitude coupling, are related to cognitive dysfunction and may assist in the diagnosis of ADHD. As yet, the underlying mechanism is not clearly established, and the clinical efficacy of these biomarkers needs to be proven through well-controlled studies. Based on the heterogeneous characteristics of ADHD, subgrouping through QEEG plays a key role in diagnosis and treatment planning. Sophisticated, well-designed studies and meta-analyses are necessary to confirm these findings.

Theta Phase-Gamma Amplitude Coupling During Working Memory and its Relationships With Demographic, Clinical, Genetic, Neurochemical, and Neurostructural Measures in Older Adults at Risk for Dementia

Theta phase-gamma amplitude coupling (TGC) is a neurophysiological mechanism that underlies working memory (WM). WM is also associated with demographic, clinical, genetic and neuroimaging measures. However, the relative contributions of TGC and these measures to WM, and the relationship between TGC and these measures, remains unclear. We examined the relative contributions of TGC and these measures to WM performance in a group of participants at-risk for Alzheimer’s dementia.

Relationship between resting-state theta phase-gamma amplitude coupling and neurocognitive functioning in patients with first-episode psychosis

BackgroundAlthough cognitive dysfunction is a core element of schizophrenia, the neurobiological underpinnings of the pathophysiology are not yet sufficiently understood. Because the resting state is crucial for cognitive functioning and electroencephalography (EEG) can reflect instantaneous neural activity, we investigated theta phase-gamma amplitude coupling (TGC) of resting-state EEG and its relationship with cognitive function in patients with first-episode psychosis (FEP) to reveal the neural correlates of cognitive dysfunction. MethodsA total of 59 FEP patients and 50 healthy controls (HCs) underwent resting-state, eyes-closed EEG recordings and performed the Trail Making Test Part A (TMT-A) and Part B (TMT-B) and California Verbal Learning Test (CVLT). TGC from the source signal of the resting-state EEG in default mode network (DMN)-related brain regions was compared between groups. Correlation analyses were performed between TGC and cognitive function test performance in FEP patients. ResultsMean resting-state TGC was larger for the FEP patients than for the HCs. Patients with FEP showed increased TGC in the left posterior cingulate cortex, which was correlated with better performance on the TMT-A and TMT-B and on immediate and delayed recall in the CVLT. ConclusionsThese results suggest that patients with FEP show compensatory hyperactivation of resting-state TGC in DMN-related brain regions, which may be related to the reallocation of cognitive resources to prepare for successful cognitive execution. This study not only highlights the neural underpinnings of cognitive dysfunction in FEP patients but also provides useful background to support the development of treatments for cognitive dysfunction in schizophrenia.

Altered Cortical and Hippocampal Excitability in TgF344-AD Rats Modeling Alzheimer's Disease Pathology.

Current findings suggest that accumulation of amyloid-β (Aβ) and hyperphosphorylated tau in the brain disrupt synaptic function in hippocampal-cortical neuronal networks leading to impairment in cognitive and affective functions in Alzheimer's disease (AD). Development of new disease-modifying AD drugs are challenging due to the lack of predictive animal models and efficacy assays. In the present study we recorded neural activity in TgF344-AD rats, a transgenic model with a full array of AD pathological features, including age-dependent Aβ accumulation, tauopathy, neuronal loss, and cognitive impairments. Under urethane anesthesia, TgF344-AD rats showed significant age-dependent decline in brainstem-elicited hippocampal theta oscillation and decreased theta-phase gamma-amplitude coupling comparing to their age-matched wild-type counterparts. In freely-behaving condition, the power of hippocampal theta oscillation and gamma power during sharp-wave ripples were significantly lower in TgF344-AD rats. Additionally, these rats showed impaired coherence in both intercortical and hippocampal-cortical network dynamics, and increased incidence of paroxysmal high-voltage spindles, which occur during awake, behaviorally quiescent state. TgF344-AD rats demonstrated impairments in sensory processing, having diminished auditory gating and 40-Hz auditory evoked steady-state response. The observed differences in neurophysiological activities in TgF344-AD rats, which mirror several abnormalities described in AD patients, may be used as promising markers to monitor disease-modifying therapies.

Theta-phase gamma-amplitude coupling as a neurophysiological marker in neuroleptic-naïve schizophrenia

Theta-phase gamma-amplitude coupling (TGC) was used as an evidence-based tool to reflect the dysfunctional cortico-thalamic interaction in patients with schizophrenia. The aim of the present study was to evaluate the diagnostic utility of TGC. The subjects included 90 patients with schizophrenia and 90 healthy controls. We compared the TGC results between the groups using an analysis of covariance (ANCOVA) to adjust for age and sex and receiver operator characteristic (ROC) curve analyses to examine the discrimination ability of delta to gamma frequency bands and TGC. Patients with schizophrenia showed a significant increase in the resting-state TGC at all 19 electrodes. The analysis of the ROC curves for each frequency band exhibited relatively low classification accuracies for the delta, theta, slow alpha, fast alpha, and beta power. The TGC generated the most accurate results among the electroencephalography (EEG) measures, with an overall classification accuracy of 92.5%. The resting-state TGC value was increased in patients with schizophrenia compared to that in healthy controls and had a higher discriminating ability than the other parameters. These findings may be related to the compensatory hyper-arousal patterns of the dysfunctional default-mode network (DMN) in schizophrenia. Therefore, resting-state TGC is a promising neurophysiological marker of schizophrenia.

Selective activation of α7 nicotinic acetylcholine receptors augments hippocampal oscillations

Neural α7 nicotinic acetylcholine receptors (α7 nAChRs) emerged as a potential pharmacologic target for treating cognitive deficits in schizophrenia and Alzheimer’s disease. Experiments modeling these dysfunctions, as well as clinical evidence, demonstrate the relatively consistent procognitive effects of α7 nAChR agonists. One preclinical observation supporting the procognitive role of α7 nAChRs is their ability to modulate neuronal network oscillations closely associated with learning and memory, especially hippocampal oscillations. Due to the high degree of structural similarity between α7 nACh and 5-HT receptors, the majority of α7 nAChR agonists to date also act as 5-HT3 antagonists. To address this confounding property and determine the relevance of α7 nAChR agonist binding to 5-HT3 receptors in modulating hippocampal activity, we tested two well-described α7 nAChR agonists, PNU-282987 and FRM-17874, in mice lacking α7 nAChRs (α7 knock-out, α7KO) using the brainstem simulation-elicited hippocampal theta oscillation assay. Under urethane anesthesia both agonists at equivalent doses demonstrated efficacy in wild-type (WT) mice, significantly enhancing theta power and theta phase-gamma amplitude coupling as compared to saline treated control mice. These effects are comparable to those seen with drugs clinically used to treat Alzheimer’s disease. Although α7KO mice showed no alterations in elicited hippocampal oscillations, both α7 nAChR agonists failed to enhance theta power or theta phase – gamma amplitude coupling in these mice. Our findings demonstrate that selective activation of α7 nAChRs can modulate hippocampal oscillation, and these receptors are the primary targets of the tested agonists, PNU-282987 and FRM-17874 and likely underlies their observed procognitive activity.

Hippocampal network dynamics in response to α7 nACh receptors activation in amyloid-β overproducing transgenic mice

Amyloid-β (Aβ) peptide overproduction is one of the pathomechanisms contributing to Alzheimer's disease (AD). Agonists of α7 nicotinic acetylcholine receptors (α7 nAChRs) are under development as symptomatic treatments for AD, and clinical findings suggest that α7 nAChR agonists may improve cognitive functions in AD patients. However, interactions between Aβ and α7 nAChRs have been observed, implying that high levels of Aβ may modify the effects of α7 nAChR agonists. Therefore, we tested the α7 nAChR agonist FRM-17874, an analogue of encenicline, in 8-month-old Aβ overproducing 5xFAD mice in an in vivo neurophysiological assay with a high construct and predictive validity for testing procognitive drugs. By recording changes in brainstem-stimulation–elicited hippocampal oscillations, we identified previously undescribed neurophysiological impairments in 5xFAD mice, including significantly decreased power of theta and gamma oscillations and theta-phase–gamma-amplitude coupling. Compared with their saline controls, systemically administered FRM-17874 significantly increased stimulation-induced theta power by 30% in both 5xFAD and wild-type mice. However, FRM-17874 did not impact gamma oscillation or theta-phase–gamma-amplitude coupling in either wild type or 5xFAD mice, and it did not eliminate the significant differences in these parameters between the 2 groups.

PM349. Desynchronization of theta-phase gamma-amplitude coupling appeared during the mental arithmetic task in children with attention deficit/hyperactivity disorder

PM349. Desynchronization of theta-phase gamma-amplitude coupling appeared during the mental arithmetic task in children with attention deficit/hyperactivity disorder

Desynchronization of Theta-Phase Gamma-Amplitude Coupling during a Mental Arithmetic Task in Children with Attention Deficit/Hyperactivity Disorder.

IntroductionTheta-phase gamma-amplitude coupling (TGC) measurement has recently received attention as a feasible method of assessing brain functions such as neuronal interactions. The purpose of this electroencephalographic (EEG) study is to understand the mechanisms underlying the deficits in attentional control in children with attention deficit/hyperactivity disorder (ADHD) by comparing the power spectra and TGC at rest and during a mental arithmetic task.MethodsNineteen-channel EEGs were recorded from 97 volunteers (including 53 subjects with ADHD) from a camp for hyperactive children under two conditions (rest and task performance). The EEG power spectra and the TGC data were analyzed. Correlation analyses between the Intermediate Visual and Auditory (IVA) continuous performance test (CPT) scores and EEG parameters were performed.ResultsNo significant difference in the power spectra was detected between the groups at rest and during task performance. However, TGC was reduced during the arithmetic task in the ADHD group compared with the normal group (F = 16.70, p < 0.001). The TGC values positively correlated with the IVA CPT scores but negatively correlated with theta power.ConclusionsOur findings suggest that desynchronization of TGC occurred during the arithmetic task in ADHD children. TGC in ADHD children is expected to serve as a promising neurophysiological marker of network deactivation during attention-demanding tasks.

Ordering Information in Working Memory and Modulation of Gamma by Theta Oscillations in Humans.

Ordering information is a critical process underlying several cognitive functions, especially working memory. Theta phase-gamma amplitude coupling is regarded as a neurophysiological representation of ordering information during working memory performance. However, direct evidence has been lacking in humans. Seventy healthy subjects performed the N-back task, a working memory task that tests ordering information at 3 different levels of difficulties and with 3 different types of trials. Using electroencephalography (EEG) during N-back performance, theta-gamma coupling was assessed during response trials. Multivariate general linear model (GLM) and discriminant analysis were used to assess coupling and theta and gamma power across the N-back conditions and the trial types. During the N-back trials that required ordering of information, N-back condition had independent effects on coupling and on theta and gamma power, with equal contributions among these 3 variables. Theta-gamma coupling contribution declined significantly on the trials that did not require ordering and was intermediate on trials that favored but not necessarily required ordering. Our findings demonstrate for the first time the role of theta-gamma coupling as a mechanism that supports ordering information. They also highlight the potential of using theta-gamma coupling as a neurophysiological marker of brain function in health or disease states.

Nicotinic receptor excitation of descending pain modulatory pathways

Synchronization of neuronal network oscillations within the cortex and hippocampus has been closely linked to various cognitive domains, including attention, learning, and memory. The frequency, power, and connectivity of hippocampal oscillations provide quantitative measures for examining the modulation of network activity, which influences mnemonic functions and memory formation. The wide distribution of α7 nicotinic acetylcholine receptors (α7 nAChRs) throughout the hippocampus makes them well positioned to modulate neuronal network activity. Elicitation of hippocampal theta through high frequency stimulation of the brainstem nucleus pontis oralis (nPO) is shown to be sensitive to several agents exhibiting pharmacological effects on cognition, thus representing a suitable preclinical screening assay for such drugs, including α7 nAChR agonists. We hypothesize that increases in theta power and theta-phase gamma-amplitude coupling due to α7 nAChR agonists during elicited hippocampal oscillations could reflect changes in synchronous activity of pyramidal neurons which is a critical factor for hippocampal-dependent cognitive function. In this review, four major topics are discussed: neuronal network oscillations in the hippocampus, the characteristics and distribution of α7 nAChRs therein, the modulation of elicited hippocampal theta and gamma oscillations by α7 nAChR agonists, as well as potential intrinsic roles of α7 nAChRs in hippocampal oscillations using α7 nAChR knock-out mice.

Theta-phase gamma-amplitude coupling as a neurophysiological marker of attention deficit/hyperactivity disorder in children

Theta-phase gamma-amplitude coupling (TGC) between slow and fast oscillations is considered to represent cortico-subcortical interactions. The purpose of this electroencephalographic (EEG) study was to evaluate the diagnostic utility of TGC by comparing the power spectra and TGC at rest between ADHD and control children. Nineteen-channel EEGs were recorded from 97 volunteers (including 53 subjects with ADHD attending a camp for hyperactive children). The EEG power spectra and TGC data were analyzed. Analysis of covariance (ANCOVA) was conducted on the quantitative EEG results between the groups to adjust for sex. Receiver operator characteristic (ROC) analysis was conducted to examine the discriminating ability of each parameter for ADHD diagnosis. The ADHD group exhibited significantly decreased TGC in multiple areas, including frontal (Fp1, F3, F7, F6), temporal (T3), and occipital (O2) areas, compared with the control group. The ROC analysis performed on the TGC data generated the most accurate result among the EEG measures, with an overall classification accuracy of 71.7%. TGC, which reflects the degree of neuronal interactions between functional systems, provides information about an individual's attentional network. Therefore, resting-state TGC is a promising neurophysiological marker of ADHD in children.

Relationship between theta-phase gamma-amplitude coupling and attention-deficit/hyperactivity behavior in children

The Continuous Performance Test (CPT) is a valuable tool for assessing behavior in attention-deficit/hyperactivity disorder (ADHD). Quantitative electroencephalography (QEEG) is a promising tool for the diagnosis of ADHD. Recently, theta-phase gamma-amplitude coupling (TGC) measurement has received attention because it is a feasible method of assessing brain function. We investigated the relationship between CPT performance and EEG measures such as TGC and theta and gamma activity. EEGs were recorded from 68 volunteers from a camp for hyperactive children using a 19-electrode system. Their TGC, theta and 40Hz gamma activity were estimated and compared with results obtained on the Korean ADHD Rating Scale (KARS) and the Intermediate Visual and Auditory (IVA) CPT. The results demonstrated significant negative partial correlations between TGC and the IVA CPT, such as the Response Control Quotient (RCQ) and Attention Quotient (AQ). TGC successfully identified the level of dysfunctional interaction of the attention/arousal system at a multi-scale large network level. It is thought that as the TGC increases, the efficacy of the system is very low or dysfunctional. Compensatory hyper-arousal patterns of the dysfunctional attention/arousal system may account for this effect. TGC is a promising neurophysiological marker for ADHD behavior in children.