Application of magnetic or electrical stimulation to the motor cortex can result in a period of electromyography (EMG) silence in a tonically active peripheral muscle. This period of EMG silence is ...referred to as the silent period (SP). The duration of SP shows intersubject variability and reflects the integrity of cortical and corticospinal pathways. A non-invasive technique for assessing the duration of SP is the combination of Transcranial Magnetic Stimulation (TMS) with EMG. Utilizing TMS–EMG, several studies have reported on the shortening or lengthening of SP in neuropsychiatric disorders such as schizophrenia, bipolar disorder, depression, obsessive compulsive disorder, epilepsy, Parkinson's disease, and stroke. However, cortical, corticospinal and peripheral components are difficult to disentangle from EMG alone. Here, we use the multimodal neuroimaging technique of TMS–EMG combined with concurrent electroencephalography (EEG) recording to further examine the cortical origin of SP and the cortical oscillatory activity that underlies SP genesis. We demonstrate that the duration of SP is related to the temporal characteristics of the cortical reactivity and the power of delta to alpha oscillations in both local and remote areas ipsilateral and contralateral to the stimulation site, and beta oscillations locally. We illustrate that, compared to EMG, the EEG indices of the SP provide additional information about the brain dynamics and propose that the EEG measures of SP may be used in future clinical and research investigations to more precisely delineate the mechanisms underlying inhibitory impairments.
•We examined the EEG characteristics during the TMS-induced EMG silent period.•Silent period is related to EEG duration, peaks, and amplitude of N100 component.•Silent period may be mediated by local and distributed slow oscillations (1-12Hz).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Gamma (γ) oscillations (30-50 Hz) have been shown to be excessive in patients with schizophrenia (SCZ) during working memory (WM). WM is a cognitive process that involves the online maintenance and ...manipulation of information that is mediated largely by the dorsolateral prefrontal cortex (DLPFC). Repetitive transcranial magnetic stimulation (rTMS) represents a non-invasive method to stimulate the cortex that has been shown to enhance cognition and γ oscillatory activity during WM.
We examined the effect of 20 Hz rTMS over the DLPFC on γ oscillatory activity elicited during the N-back task in 24 patients with SCZ compared to 22 healthy subjects. Prior to rTMS, patients with SCZ elicited excessive γ oscillatory activity compared to healthy subjects across WM load. Active rTMS resulted in the reduction of frontal γ oscillatory activity in patients with SCZ, while potentiating activity in healthy subjects in the 3-back, the most difficult condition. Further, these effects on γ oscillatory activity were found to be specific to the frontal brain region and were absent in the parieto-occipital brain region.
We suggest that this opposing effect of rTMS on γ oscillatory activity in patients with SCZ versus healthy subjects may be related to homeostatic plasticity leading to differential effects of rTMS on γ oscillatory activity depending on baseline differences. These findings provide important insights into the neurophysiological mechanisms underlying WM deficits in SCZ and demonstrated that rTMS can modulate γ oscillatory activity that may be a possible avenue for cognitive potentiation in this disorder.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Working memory represents a core cognitive domain that is impaired in schizophrenia for which there are currently no satisfactory treatments. Repetitive transcranial magnetic stimulation ...(rTMS) targeted over the dorsolateral prefrontal cortex has been shown to modulate neurophysiological mechanisms linked to working memory in schizophrenia and improves working memory performance in healthy subjects and might therefore represent a treatment modality for schizophrenia patients. The objectives were to evaluate the effects of rTMS on working memory performance in schizophrenia patients and evaluate whether rTMS normalizes performance to healthy subject levels. Methods In a 4-week randomized double-blind sham-controlled pilot study design, 27 medicated schizophrenia patients were tested at the Centre for Addiction and Mental Health (a university teaching hospital that provides psychiatric care to a large urban catchment area and serves as a tertiary referral center for the province of Ontario). Patients performed the verbal working memory n-back task before and after rTMS magnetic resonance image targeted bilaterally sequentially to left and right dorsolateral prefrontal cortex 750 pulses/side at 20 Hz for 20 treatments. The main outcome measure was mean magnitude of change in the n-back accuracy for target responses with active ( n =13) or sham ( n =12) rTMS treatment course. Results The rTMS significantly improved 3-back accuracy for targets compared with placebo sham (Cohen’s d =.92). The improvement in 3-back accuracy was also found to be at a level comparable to healthy subjects. Conclusions These pilot data suggest that bilateral rTMS might be a novel, efficacious, and safe treatment for working memory deficits in patients with schizophrenia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Delay discounting (DD) represents decreased subjective value for delayed reward relative to the same reward at present. The concept of DD has been applied for pathophysiology of addiction and ...psychiatric disorders. However, the detailed neuroimaging correlates of DD underlying pathophysiology still remain unclear. Thus, we conducted a systematic review to investigate neural correlates of DD on magnetic resonance imaging studies among addiction and psychiatric disorders. Specific search terms were set on PubMed to identify relevant articles. Initial search identified 551 records and 31 studies met the inclusion criteria. The present review revealed that greater DD was correlated with increased activity in areas related to reward evaluation and prediction as well as decreased activity in areas related to cognitive control. Healthy controls showed smaller changes in activities of these areas associated with DD when compared to patient groups. As the neural basis related to DD, three neural networks have been proposed that are associated with the actions of short-term interests and long-term benefits. Among the three potential neural networks on DD, the first one included the ventromedial prefrontal cortex and ventral striatum and implicated in evaluating reward values, the second network included the anterior cingulate cortex and linked to cognitive control, and the third network included the middle temporal gyrus and was involved in predictions and affection. This review generated consistent findings on the neural basis of DD among patients with addiction and psychiatric disorders, which may represent the pathophysiology related to DD and impulsivity of mental illness.
•In general, patients with addiction and psychiatric disorders have greater DD.•Greater DD correlates with increased activity in the reward evaluation system.•Greater DD is associated with decreased activity in the cognitive control.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background Working memory deficits represent a core feature of schizophrenia. These deficits have been associated with dysfunctional dorsolateral prefrontal cortex (DLPFC) cortical ...oscillations. Theta-gamma coupling describes the modulation of gamma oscillations by theta phasic activity that has been directly associated with the ordering of information during working memory performance. Evaluating theta-gamma coupling may provide greater insight into the neural mechanisms mediating working memory deficits in this disorder. Methods Thirty-eight patients diagnosed with schizophrenia or schizoaffective disorder and 38 healthy controls performed the verbal N-Back task administered at 4 levels, while EEG was recorded. Theta (4–7 Hz)-gamma (30–50 Hz) coupling was calculated for target and non-target correct trials for each working memory load. The relationship between theta-gamma coupling and accuracy was determined. Results Theta-gamma coupling was significantly and selectively impaired during correct responses to target letters among schizophrenia patients compared to healthy controls. A significant and positive relationship was found between theta-gamma coupling and 3-Back accuracy in controls, while this relationship was not observed in patients. Conclusions These findings suggest that impaired theta-gamma coupling contribute to working memory dysfunction in schizophrenia. Future work is needed to evaluate the predictive utility of theta-gamma coupling as a neurophysiological marker for functional outcomes in this disorder.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Working memory deficits are common among individuals with Alzheimer's dementia (AD) or mild cognitive impairment (MCI). Yet, little is known about the mechanisms underlying these deficits. ...Theta-gamma coupling-the modulation of high-frequency gamma oscillations by low-frequency theta oscillations-is a neurophysiologic process underlying working memory. We assessed the relationship between theta-gamma coupling and working memory deficits in AD and MCI. We hypothesized that: (1) individuals with AD would display the most significant working memory impairments followed by MCI and finally healthy control (HC) participants; and (2) there would be a significant association between working memory performance and theta-gamma coupling across all participants. Ninety-eight participants completed the N-back working memory task during an electroencephalography (EEG) recording: 33 with AD (mean ± SD age: 76.5 ± 6.2), 34 with MCI (mean ± SD age: 74.8 ± 5.9) and 31 HCs (mean ± SD age: 73.5 ± 5.2). AD participants performed significantly worse than control and MCI participants on the 1- and 2-back conditions. Regarding theta-gamma coupling, AD participants demonstrated the lowest level of coupling followed by the MCI and finally control participants on the 2-back condition. Finally, a linear regression analysis demonstrated that theta-gamma coupling (
= 0.69,
< 0.001) was the most significant predictor of 2-back performance. Our results provide evidence for a relationship between altered theta-gamma coupling and working memory deficits in individuals with AD and MCI. They also provide insight into a potential mechanism underlying working memory impairments in these individuals.
Several studies have demonstrated that cortical inhibition (CI) can be recorded by paired transcranial magnetic stimulation (TMS) of the motor cortex and recorded by surface electromyography (EMG). ...However, recording CI from other cortical regions that are more closely associated with the pathophysiology of some neurological and psychiatric disorders (eg, dorsolateral prefrontal cortex (DLPFC) in schizophrenia) was previously unattainable. This study, therefore, was designed to investigate whether CI could be measured directly from the motor cortex and DLPFC by combining TMS with electroencephalography (EEG). Long-interval CI (LICI) is a TMS paradigm that was used to index CI in the motor cortex and DLPFC in healthy subjects. In the motor cortex, LICI resulted in significant suppression (32.8+/-30.5%) of mean cortical evoked activity on EEG, which was strongly correlated with LICI recorded by EMG. In the DLPFC, LICI resulted in significant suppression (30.1+/-26.9%) of mean cortical evoked activity and also correlated with LICI in the motor cortex. These data suggest that CI can be recorded by combining TMS with EEG and may facilitate future research attempting to ascertain the role of CI in the pathophysiology of several neurological and psychiatric disorders.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Brain oscillations are increasingly used for understanding complex psychiatric disorders. Gamma (30–50 Hz) oscillations have warranted special attention due to their omnipresence in ...cognitive tasks. For patients with schizophrenia (SCZ), a disease associated with poor cognition, abnormal gamma oscillations have been reported in many experimental paradigms. The goal of this paper is to review the literature on gamma oscillations in SCZ. The review is structured into four sections. First, the functional role, neurobiology, and analysis of brain oscillations, especially gamma oscillations will be outlined. Second, the neurobiological abnormalities of SCZ in relation to gamma oscillations will be reviewed. Third, selected paradigms for investigating irregular gamma oscillations in SCZ will be discussed in detail. Finally, a discussion on the limitations of current findings and potential future research directions will be provided. The reviewed evidence suggests that gamma oscillations are disrupted in SCZ and could account for cognitive disturbances in this disorder. With additional analysis and experimentation, these indices may ultimately serve as endophenotypes that facilitate the development of etiologically based diagnostic methods, foster early identification and treatment, and advance our understanding of the complex genetic mechanisms involved in this disorder.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background The corpus callosum, the main interhemispheric connection in the brain, may serve to preserve functional asymmetry between homologous cortical regions. Methods To test this hypothesis, 30 ...healthy adult subjects underwent combined transcranial magnetic stimulation (TMS)–electroencephalography procedures. Nineteen of these subjects also completed diffusion tensor imaging and tractography procedures. We examined the relationship between microstructural integrity of subdivisions of the corpus callosum with TMS-induced interhemispheric signal propagation. Results We found a significant inverse relationship between microstructural integrity of callosal motor fibers with TMS-induced interhemispheric signal propagation from left to right motor cortex. We also found a significant inverse relationship between microstructural integrity of genu fibers of the corpus callosum and TMS-induced interhemispheric signal propagation from left to right dorsolateral prefrontal cortex (DLPFC). We then demonstrated neuroanatomic specificity of these relationships. Conclusions Taken together, our findings suggest that TMS-induced interhemispheric signal propagation is transcallosally mediated and neuroanatomically specific and support a role for the corpus callosum in preservation of functional asymmetry between homologous cortical regions. Delineation of the relationship between corpus callosum microstructure and interhemispheric signal propagation in neuropsychiatric disorders, such as schizophrenia, may reveal novel mechanisms of pathophysiology.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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