Kay Jann

Ryouhei Ishii

Shun Takahashi

Sunichiro Ikeda

Frontiers in Human Neuroscience

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TYPE EditorialPUBLISHED 19 May 2023DOI 10.3389/fnhum.2023.1212625OPEN ACCESSEDITED AND REVIEWED BYMingzhou Ding,University of Florida, United States*CORRESPONDENCERyouhei Ishiiishii@psy.med.osaka-u.ac.jpRECEIVED 26 April 2023ACCEPTED 03 May 2023PUBLISHED 19 May 2023CITATIONJann K, Ishii R, Takahashi S and Ikeda S (2023)Editorial: Neuromodulation in basic,translational and clinical research in psychiatry,volume II. Front. Hum. Neurosci. 17:1212625.doi: 10.3389/fnhum.2023.1212625COPYRIGHT© 2023 Jann, Ishii, Takahashi and Ikeda. This isan open-access article distributed under theterms of the Creative Commons AttributionLicense (CC BY). The use, distribution orreproduction in other forums is permitted,provided the original author(s) and thecopyright owner(s) are credited and that theoriginal publication in this journal is cited, inaccordance with accepted academic practice.No use, distribution or reproduction ispermitted which does not comply with theseterms.Editorial: Neuromodulation inbasic, translational and clinicalresearch in psychiatry, volume IIKay Jann1, Ryouhei Ishii2,3*, Shun Takahashi3 and Sunichiro Ikeda41USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, University ofSouthern California, Los Angeles, CA, United States, 2Department of Occupational Therapy, GraduateSchool of Rehabilitation Science, Osaka Metropolitan University, Habikino, Japan, 3Department ofPsychiatry, Graduate School of Medicine, Osaka University, Suita, Japan, 4Department ofNeuropsychiatry, Kansai Medical University, Osaka, JapanKEYWORDSmagnetoencephalography (MEG), transcranial magnetic stimulation (TMS),electroconvulsive therapy (ECT), major depression (MD), anesthesia, epigenetics,neuromodulationEditorial on the Research TopicNeuromodulation in basic, translational and clinical research inpsychiatry, volume IIThe term “neuromodulation” is a wide-ranging concept that could be technically appliedto any medical, surgical or physiological therapy designed to modulate the nervous system’sfunction. In clinical neuroscience, however, the concept of neuromodulation is specificallyused to refer to therapies that employ the targeted administration of an electric currentor magnetic field. These techniques include electroconvulsive therapy (ECT), vagus nervestimulation (VNS) and repetitive transcranial magnetic stimulation (rTMS). More recently,research has been conducted using transcranial direct current stimulation (tDCS), trigeminalnerve stimulation (TNS) and deep brain stimulation (DBS). In order to develop morepromising therapies for psychiatric disorders, translational research bridging basic andclinical sciences should be pursued.The aim of this Research Topic is to provide a forum for researchers interested inbasic, translational and clinical research on neuromodulation in psychiatric disorders, toprovide an inclusive perspective on neuromodulation, and to encourage discussion andcollaboration across research areas. Four manuscripts (three original papers, one mini-review) have been accepted for this theme, all presenting significant new findings andresearch methods, such as the effect of inhalational anesthesia on ECT, a systematicreview of epigenetic mechanisms associated with ECT, prediction of treatment responseto rTMS in depression, and magnetoencephalography (MEG) analysis during automaticlexical processing of Japanese kanji compound words. The objective of each investigator is toelucidate the mechanisms underlying the pathogenesis of psychiatric disorders using basicresearch techniques and to apply the discoveries to the care of actual patients.Electroconvulsive therapy (ECT), which delivers a short burst of electrical impulsesto the brain under anesthesia, is the most effective therapeutic intervention available forthe treatment of medication-refractory major depressive disorder (MDD), bipolar disorder(BD), suicidal behavior, severe agitation, catatonia, and clozapine-refractory schizophrenia.The effectiveness of ECT is three times greater on average than that of drug therapy,providing up to 60% improvement in symptoms in patients with MDD, and response totherapeutic intervention is usually more rapid than with current medications, however, themechanism of therapeutic action has not been clearly understood.Frontiers inHumanNeuroscience 01 frontiersin.orgJann et al. 10.3389/fnhum.2023.1212625While anesthetics, such as sevoflurane and thiopental, playan important role in ECT, the seizure adequacy and clinicalefficacy of anesthetics on ECT are still unclear. Yatomi et al.tried to examine the seizure tolerance and clinical effectiveness ofsevoflurane compared with thiopental during ECT in people withmood disorders (MD). They conducted a single-center study witha retrospective chart review. People with MD who had receivedECT and administered sevoflurane (n = 26) or thiopental (n= 26) were enrolled. ECT outcomes and factors were assessedand compared between the two groups using propensity score(PS) matching. They found that people with MD who receivedsevoflurane required significantly more stimulations and moresessions and had more ineffective seizures than those who receivedthiopental. Both groups had similar remission and response rates.They therefore suggested that sevoflurane should be used withmore caution in ECT and only when the clinical indications arewell established.Although themechanism of ECT is not well understood and thenumber of studies is relatively poor, the development of biomarkersfor response to ECT is a very attractive area in epigenetics. Castroet al. performed a review of previous studies published in themedical and scientific literatures that investigated the epigenetics ofECT in samples obtained from peripheral blood of people sufferingfrom MDD. A systematic review was conducted according to thePRISMA guidelines. They enrolled nine studies and found thatseven studies investigated DNA methylation and three studiesassessed microRNAs (miR). Overall, most studies were explorative,with small sample sizes and high variability in study design,especially about ECT protocols, molecular biology methods, andepigenetic results. The candidate genes investigated with someevidence of an associated effect on treatment response to ECTwere,TNKS, S100A10, FKBP5, RNF213M, miR-106a, miR-24, miR-126and BDNF. They concluded that these findings supported previousstudies, suggesting that epigenetic pathways may be important inthe molecular mechanisms underlying the mechanism of ECT.TMS is a non-invasive brain stimulation technique thatgenerates a high- or low-intensity magnetic field that is supposedto regulate brain cortical excitability. rTMS applies repetitive TMSpulses to a targeted area of the brain. rTMS has been investigatedas a potential therapeutic modality for several neurological andpsychiatric disorders. The neuromodulation effects are dependenton various parameters of rTMS, such as stimulation frequency,stimulation intensity, stimulation duration, cortical target, numberof trials, and individual patient characteristics, such as age, diseaseseverity, medical history, and symptoms. Generally, rTMS hasbeen categorized as high frequency (>1Hz), which enhancescortical excitability, and low frequency (<1Hz), which suppressescortical excitability.Cognitive impairment is common in people with both unipolarand bipolar depressive disorders (UDD and BDD, respectively). Asassessment of cognitive function becomes more widely availableto both researchers and practitioners, it may be useful to targetthese symptoms in treatment and to use them at treatment entryas potential markers of treatment response. In a retrospectiveobservational and naturalistic study, Rostomi et al. evaluated theirown data from 120 people with UDD (n = 56) and BDD (n= 64) who were treated with 20 sessions of bilateral rTMS,consisted of 10Hz over the LDLPFC and 1Hz over the RDLPFC.They evaluated depressive symptoms, sustained attention, workingmemory and executive function at baseline and at the completionof the rTMS treatment course. They found that more than half ofall these subjects (n = 64), especially 53.1% of UDD subjects (n= 34) and 46.9% of BDD subjects (n = 30), showed treatmentresponse. They also reported that bilateral rTMS significantlyimproved several cognitive functions (attention, working memoryand executive function) excluding visual memory and led to morechanges in working memory in UDD subjects compared to BDDsubjects. More marked improvements in working memory werefound in patients who responded, and visual memory, age and sexwere determined to be predictors of treatment response. Workingmemory, visual memory and age were identified as predictors ofresponse to treatment in BDD and UDD subjects, respectively.They concluded that bilateral rTMS significantly improved severalcognitive functions and depressive symptoms in UDD and BDDpatients, probably by modifying top-down cognitive controlmechanisms and by processing negative emotional biases.When the semantic dimension of a word is processedautomatically during lexical processing, the response to apreattentive presentation of a semantically incorrect wordvariant may show greater brain activity than the response tothe semantically accurate word presented. The Japanese kanjicompound, which consists of two or more characters, is suitablefor examining this problem. The written Japanese language iscomposed of kana sounds, which are similar to the alphabet, andideograms, known as kanji, which are more typically processed bywhole-word reading. These ideograms often show up in the formof a kanji compound. A kanji compound consists of a specific kanjicombination, and an invalid combination is considered non-lexicalas a kanji compound, even though the single kanji character couldbe lexical. Kanji compounds, however, generally express not onlyconcepts but also their associated meanings. Therefore, this featureof kanji compounds can be used as an experimental setting forsemantically incorrect variation. It is important to note that sinceKanji reveals reading and/or writing impairments in Japanese,understanding the visual recognition of Kanji helps to understandthe underlying mechanisms of fluent reading capability. Forthese reasons, they focused on the semantic processing of visualkanji compounds.To investigate this phenomenon for Japanese kanji compounds,where lexicality is associated with semantic connotations, Egashiraet al. used three types of deviants: font differences, lexicallycorrect or incorrect Japanese kanji compound words, and pseudo-kanji characters that were modified from correct and incorrectcompounds. They applied MEG to elucidate the spatio-temporalpatterns of the relevant brain areas. The three types of stimulilisted above, with 20% deviations, were displayed during the MEGrecordings. They found clear occipital pole activity during therecognition of font type variations within 250ms of stimulus onset.The reported that no significant activity was observed duringthe detection of lexically correct or incorrect Kanji compoundsor pseudo-Kanji character deviations, although activity in theposterior transverse region of the collateral sulcus (pCoS)—a fusiform adjacent area—was larger for the recognition oflexically correct Kanji compounds than for the recognition ofFrontiers inHumanNeuroscience 02 frontiersin.orgJann et al. 10.3389/fnhum.2023.1212625pseudo-Kanji characters. They concluded that the automaticrecognition of deviance in kanji compounds may be restrictedto a lower-level characteristic, such as the thickness of thestimulus line.The Research Theme, in summary, provided a broadoverview of the clinical applicability of the most recentresearch discoveries to psychiatric disorders and cognitivefunction, and offered an insight into the translation of basicresearch into current psychiatric clinical practice. As a result,these papers illuminated the pathogenesis of psychiatricdisorders by using basic research techniques and by applyingthe novel findings to the treatment of real patients, andsuggested new directions for exploring the new frontiersof basic and clinical neuroscience for clinical applicationin psychiatry.Author contributionsKJ and RI discussed about this Research Topic and wrote themanuscript. ST and SI gave significant advice and helped the editingthe manuscript.FundingThis study was supported in part by a Grant-in-Aid forScientific Research (C) 22K11453 from the Ministry of Education,Culture, Sports, Science and Technology in Japan.Conflict of interestThe authors declare that the research was conducted in theabsence of any commercial or financial relationships that could beconstrued as a potential conflict of interest.Publisher’s noteAll claims expressed in this article are solely those of theauthors and do not necessarily represent those of their affiliatedorganizations, or those of the publisher, the editors and thereviewers. Any product that may be evaluated in this article, orclaim that may be made by its manufacturer, is not guaranteed orendorsed by the publisher.Frontiers inHumanNeuroscience 03 frontiersin.org

Editorial: Neuromodulation in basic, translational and clinical research in psychiatry, volume II

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Editorial: Neuromodulation in basic, translational and clinical research in psychiatry, volume II

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