反復経頭蓋磁気刺激による神経活動変化―サル皮質硬膜下電位と誘発筋電図の同時計測

Tohoku University筒井健一郎課

Left parietal tACS at alpha frequency induces a shift of visuospatial attention

Background Voluntary shifts of visuospatial attention are associated with a lateralization of parieto-occipital alpha power (7-13Hz), i.e. higher power in the hemisphere ipsilateral and lower power contralateral to the locus of attention. Recent noninvasive neuromodulation studies demonstrated that alpha power can be experimentally increased using transcranial alternating current stimulation (tACS). Objective/Hypothesis We hypothesized that tACS at alpha frequency over the left parietal cortex induces shifts of attention to the left hemifield. However, spatial attention shifts not only occur voluntarily (endogenous/ top-down), but also stimulus-driven (exogenous/ bottom-up). To study the task-specificity of the potential effects of tACS on attentional processes, we administered three conceptually different spatial attention tasks. Methods 36 healthy volunteers were recruited from an academic environment. In two separate sessions, we applied either high-density tACS at 10Hz, or sham tACS, for 35–40 minutes to their left parietal cortex. We systematically compared performance on endogenous attention, exogenous attention, and stimulus detection tasks. Results In the endogenous attention task, a greater leftward bias in reaction times was induced during left parietal 10Hz tACS as compared to sham. There were no stimulation effects in either the exogenous attention or the stimulus detection task. Conclusion The study demonstrates that high-density tACS at 10Hz can be used to modulate visuospatial attention performance. The tACS effect is task-specific, indicating that not all forms of attention are equally susceptible to the stimulation

EEG Phase Synchronization in Persons With Depression Subjected to Transcranial Magnetic Stimulation

Aim: The main objective of this work was to study the impact of repetitive Transcranial Magnetic Stimulation (rTMS) treatment on brain activity in 8 patients with major depressive disorder (MDD) and 10 patients with bipolar disorder (BP). Changes due to rTMS stimulation of the left dorsolateral prefrontal cortex (DLPFC) were investigated considering separately responders and non-responders to therapy in each of both groups. The aim of the research is to determine whether non-responders differ from responders suffered from both diseases, as well as if any change occurred due to rTMS across consecutive rTMS sessions.Methods: The graph-theory-based connectivity analysis of non-linearity measure of phase interdependencies—Phase Locking Value (PLV)—was examined from EEG data. The approximately 15-min EEG recordings from each of participants were recorded before and after 1st, 10th, and 20th session, respectively. PLV calculated from data was analyzed using principal graph theory indices (strength and degree) within five physiological frequency bands and in individual channels separately. The impact of rTMS on the EEG connectivity in every group of patients evaluated by PLV was assessed.Results: Each of four groups reacted differently to rTMS treatment. The strength and degree of PLV increased in gamma band in both groups of responders. Moreover, an increase of indices in beta band for BP-responders was observed. While, in MDD-non-responders the indices decreased in gamma band and increased in beta band. Moreover, the index strength was lower in alpha band for BP- non-responders. The rTMS stimulation caused topographically specific changes, i.e., the increase of the activity in the left DLPFC as well as in other brain regions such as right parieto-occipital areas.Conclusions: The analysis of PLV allowed for evaluation of the rTMS impact on the EEG activity in each group of patients. The changes of PLV under stimulation might be a good indicator of response to depression treatment permitting to improve the effectiveness of therapy

Lasting EEG/MEG aftereffects on human brain oscillations after rhythmic transcranial brain stimulation: Level of control over oscillatory network activity

A number of rhythmic protocols have emerged for non-invasive brain stimulation (NIBS) in humans, including transcranial alternating current stimulation (tACS), oscillatory transcranial direct current stimulation (otDCS) and repetitive (also called rhythmic) transcranial magnetic stimulation (rTMS). With these techniques, it is possible to match the frequency of the externally applied electromagnetic fields to the intrinsic frequency of oscillatory neural population activity ("frequency-tuning"). Mounting evidence suggests that by this means tACS, otDCS, and rTMS can entrain brain oscillations and promote associated functions in a frequency-specific manner, in particular during (i.e. online to) stimulation. Here, we focus instead on the changes in oscillatory brain activity that persist after the end of stimulation. Understanding such aftereffects in healthy participants is an important step for developing these techniques into potentially useful clinical tools for the treatment of specific patient groups. Reviewing the electrophysiological evidence in healthy participants, we find aftereffects on brain oscillations to be a common outcome following tACS/otDCS and rTMS. However, we did not find a consistent, predictable pattern of aftereffects across studies, which is in contrast to the relative homogeneity of reported online effects. This indicates that aftereffects are partially dissociated from online, frequency-specific (entrainment) effects during tACS/otDCS and rTMS. We outline possible accounts and future directions for a better understanding of the link between online entrainment and offline aftereffects, which will be key for developing more targeted interventions into oscillatory brain activity

The relationship between cognitive reserve and neuroplasticity in older adults

This item is only available electronically.Background: Cognitive Reserve (CR) is suggested to explain the difference between the expected impact of levels of age-related neuropathology and the real deficits which people experience. Neuroplasticity is speculated to be the neurophysiological mechanism underlying the cognition-protective effects of CR; however, this has not previously been experimentally demonstrated. Aim: To identify whether neuroplasticity mediates the relationship between CR and cognitive ability. Method: 23 healthy older adults participated in this study, which comprised 3 brain stimulation sessions: (1) continuous theta-burst stimulation (cTBS) applied to left dorsolateral prefrontal cortex, (2) cTBS applied to left motor cortex, and (3) a sham session. Resting electroencephalography (EEG) was used to calculate change in the aperiodic slope of neural power spectra (a novel measure of neuroplasticity) following cTBS. Participants were also assessed with measures of CR (lifetime of experiences; crystallised intelligence) and cognitive ability (fluid intelligence; paired associates learning). Results: We induced a neuroplasticity-like effect in both of the active cTBS conditions. This was not observed in the sham condition. We did not observe a significant relationship between neuroplasticity and CR or cognitive ability. This meant mediational analysis was not justified. Conclusions: We successfully demonstrated that analysis of the aperiodic slope is an effective means of identifying neuroplasticity with EEG. While we did not identify a significant relationship between our neuroplasticity measure and CR, we recommend further studies investigate other forms of neuroplasticity. Continued investigation of the neurophysiology underlying CR may facilitate the development of early interventions which could reduce the prevalence of age-related cognitive impairment.Thesis (B.PsychSc(Hons)) -- University of Adelaide, School of Psychology, 202

Neuroplastische Korrelate des chronischen Tinnitus am auditorischen Kortex: Eine kombinierte TMS-EEG-Untersuchung

Chronischem Tinnitus liegt unter anderem eine veränderte neuronale Aktivität im zentralen Nervensystem zu Grunde. Ein Teil der Patienten mit chronischem Tinnitus profitiert von der Anwendung von repetitiver transkranieller Magnetstimulation (rTMS) am temporalen und/oder frontalen Kortex. Man geht davon aus, dass rTMS einen Einfluss auf die kortikale Neuroplastizität hat. Ruhemessungen mit Elektroenzephalographie zeigen bei Patienten im Vergleich zu gesunden Kontrollen eine veränderte Power in verschiedenen Frequenzbändern. Die vorliegende Studie untersucht, ob sich die neuronale Reaktivität auf rTMS bei Patienten mit chronischem Tinnitus von gesunden Kontrollpersonen unterscheidet. Dazu wurde an 20 Patienten mit chronischem Tinnitus und 20 gesunden Kontrollpersonen ein kombiniertes rTMS-EEG-Protokoll durchgeführt. Im Rahmen des Protokolls wurde an zwei Tagen im Abstand von einer Woche jeweils ein Ruhe-EEG aufgezeichnet und im Anschluss daran am rechten und linken temporalen und frontalen Kortex stimuliert. Dem folgte jeweils eine EEG-Aufzeichnung. Zudem beinhaltet das Protokoll an jedem Stimulationstag eine Sham-Bedingung, die um 180° gedrehte Spule am Vertex. Die Versuchsbedingungen waren randomisiert. Die Gruppen wurden hinsichtlich Alter, Geschlecht, Hörverlust und Händigkeit aneinander angeglichen und ein Einfluss der Faktoren Bildungsgrad, Intelligenzquotient und Geräuschüberempfindlichkeit statistisch ausgeschlossen. Ziel der vorliegenden Dissertation ist die Untersuchung der Effekte temporaler Stimulation. Es konnte nach temporaler Stimulation keine signifikante, sham-kontrollierte Lautstärkereduktion in der Gruppe der Patienten mit chronischem Tinnitus erzielt werden. Es wurden jedoch Gruppenunterschiede zwischen der Patienten- und Kontrollgruppe auf oszillatorischer Ebene festgestellt. Nach linkstemporaler rTMS-Stimulation kam es in der Patientengruppe im EEG zu einer signifikanten Reduktion der Power im Delta- und Theta-Frequenzbereich in frontalen Kanälen sowie zu einer Steigerung der Power im Beta2-Frequenzbereich. In der Kontrollgruppe kam es zu keinen signifikanten Veränderungen in diesen Frequenzbereichen. Mögliche Ursachen für den fehlenden therapeutischen Nutzen können die niedrige Stimulationsfrequenz, die kurze Anwendungszeit, der Stimulationsort sowie die Stimulationsintensität sein. Es konnte jedoch gezeigt werden, dass es bei Patienten mit chronischem Tinnitus auf oszillatorischer Ebene durch temporale rTMS-Stimulation in frontalen kortikalen Arealen zu einer Abnahme der Power im Delta- und Thetafrequenzbereich kommt. Dies unterstützt die These, dass an chronischem Tinnitus ein Netzwerk verschiedener Hirnareale beteiligt ist. Es gibt Studien, die darauf hinweisen, dass bei Patienten mit chronischem Tinnitus eine vermehrte Power im niederfrequenten Bereich als Korrelat einer thalamokortikalen Dysrhythmie abzuleiten ist. Möglicherweise lässt sich diese Zunahme der Power im Delta-und Thetafrequenzbereich bei Patienten mit Tinnitus durch die Anwendung von rTMS beeinflussen. Die Zunahme der Power im Beta2-Frequenzband lässt sich auch in das Modell der thalamokortikalen Dysrhythmie einordnen. In dieser Studie erfolgte eine Analyse der Daten auf Sensor-Ebene. Eine Analyse der Konnektivität könnte darüber hinaus einen weiteren Einblick in die Neuroplastizität bei chronischem Tinnitus geben

The role of cognitive control in prosocial behavior – Investigating the neural foundations of retribution and forgiveness

Forgiveness is a highly relevant ability for a satisfied life with long-lasting relationships. It is hypothesized that cognitive control enables forgiveness through the inhibition of baser revenge seeking feelings. For investigating the exact underlying mechanisms, a set of four studies was run. In order to study the ability to forgive, the participants first played an ultimatum game, in which they learned that some opponents are fair and some are unfair. Following this implicit learning experience the roles were changed and in a subsequent dictator game the participants had to split up money between themselves and the opponents of the previous game. Regarding the previously unfair opponents they had to decide if they wanted to forgive (with allocating a fair amount of money) or to take revenge (with allocating an unfair amount of money). This paradigm sequence was combined in a first study with inhibitory theta-burst stimulation of the right dorsolateral prefrontal cortex (DLPFC), resulting in the causal conclusion that cognitive control is needed for forgiveness processes as after the stimulation the participants were significantly more revenge seeking. In another study, participants with high and low cognitive control were compared. Participants with low cognitive control were significantly more revenge seeking, whereas, participants with high cognitive control were less revenge seeking. Concluding from the results of a regression analysis this difference was (partly) caused by different emotional foundations of the behavior, with sympathy as a relevant factor in the high cognitive control group and revenge in the low cognitive control group. In a third study the gaming paradigms (ultimatum game and dictator game) were used in combination with activating theta-burst stimulation of the right DLPFC in a highly impulsive group which is known to be more revenge seeking than the average. With higher activation in the right DLPFC it was not possible to increase the forgiveness behavior towards the unfair opponents. Surprisingly, the activating neuromodulation increased the generosity towards fair opponents. In an additional study with a different paradigm the ability of emotion regulation (which is assumed to be a key player in forgiveness processes) in participants with low vs. high cognitive control was measured. It was shown that participants with low cognitive control failed, especially in implicit emotion regulation which is essential for daily life forgiveness processes. Based on these results a forgiveness model is proposed. According to this model the probability to forgive a wrongdoer is influenced by cultural/cognitive response tendencies and state/trait emotional tendencies. Cognitive control especially, but also the experienced emotions play a crucial role in forgiveness processes according to this model

The role of the hippocampus and dorsolateral prefrontal cortex in implicit learning of contextual information

The intrinsic brain property to automatically detect and encode repeated regularities or contexts present in the environment is essential for organizing information about the environment and guides many aspects of our behavior, including attention. Decades of research into the neurocognitive mechanisms of attention have revealed that visual attention can be controlled by perceptually salient information (bottom-up) or by internal goals and expectations (top-down). However, recent findings have shown that implicit contextual memory (ICM) also plays an important role in guiding attention. Despite the importance of implicit contextual memory in cognition, it is unclear how the brain encodes and retrieves implicit contextual memories, translates them into an attentional control signal, and interacts with the ventral and dorsal frontoparietal attention networks to control deployment of visual attention. In this thesis, I answer a number of questions about the role of the hippocampus and the DLPFC in implicit contextual memory-guided attention. First, I combine automated segmentation of structural MRI with neurobehavioral assessment of implicit contextual memory-guided attention to test the hypothesis that hippocampal volume would predict the magnitude of implicit contextual learning. Forty healthy subjects underwent 3T magnetic resonance imaging brain scanning with subsequent automatic measurement of the total brain and hippocampal (right and left) volumes. Implicit learning of contextual information was measured using the contextual cueing task. It was shown that both, left and right hippocampal volumes positively predict implicit contextual memory performance. This result provides new evidence for hippocampal involvement in implicit contextual memory-guided attention. Next, I used continuous theta burst stimulation (cTBS) combined with electroencephalography (EEG) to test whether transient disruption of the DLPFC would interfere with implicit learning performance and related electrical brain activity. I applied neuronavigation-guided cTBS to the DLPFC or to the vertex as a control region, prior to the performance of an implicit contextual learning task. It was shown that a transient disruption of the function of the left DLPFC leads to significant enhancement of implicit contextual memory performance. This finding provides novel causal evidence for the interfering role of DLPFC-mediated top-down control on implicit memory-guided attention. Additionally, it was shown that cTBS applied over the left DLPFC significantly decreased task-related beta-band oscillatory activity, suggesting that beta-band oscillatory activity is an index of DLPFC-mediated top-down cognitive control. Together, these results shed light on how implicit memory-guided attention is implemented in the brain