Non-Invasive Brain Stimulation Effects on Biomarkers of Tryptophan Metabolism: A Scoping Review and Meta-Analysis

Cristian G Giron, Tim T Z Lin, Rebecca L D Kan, Bella B B Zhang, Suk Yu Yau, Georg S Kranz, Cristian G Giron, Tim T Z Lin, Rebecca L D Kan, Bella B B Zhang, Suk Yu Yau, Georg S Kranz

Abstract

Abnormal activation of the kynurenine and serotonin pathways of tryptophan metabolism is linked to a host of neuropsychiatric disorders. Concurrently, noninvasive brain stimulation (NIBS) techniques demonstrate high therapeutic efficacy across neuropsychiatric disorders, with indications for modulated neuroplasticity underlying such effects. We therefore conducted a scoping review with meta-analysis of eligible studies, conforming with the PRISMA statement, by searching the PubMed and Web of Science databases for clinical and preclinical studies that report the effects of NIBS on biomarkers of tryptophan metabolism. NIBS techniques reviewed were electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS). Of the 564 search results, 65 studies were included with publications dating back to 1971 until 2022. The Robust Bayesian Meta-Analysis on clinical studies and qualitative analysis identified general null effects by NIBS on biomarkers of tryptophan metabolism, but moderate evidence for TMS effects on elevating serum serotonin levels. We cannot interpret this as evidence for or against the effects of NIBS on these biomarkers, as there exists several confounding methodological differences in this literature. Future controlled studies are needed to elucidate the effects of NIBS on biomarkers of tryptophan metabolism, an under-investigated question with substantial implications to clinical research and practice.

Keywords: biomarker; electroconvulsive therapy; kynurenine; repetitive transcranial magnetic stimulation; serotonin; transcranial direct current stimulation; tryptophan.

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Products of tryptophan metabolism via serotonin (red) and kynurenine (blue) pathways. Arrows point toward the direction of metabolism as mediated by different enzymes or other catalysts, with fields showing metabolites produced along these pathways. Double arrows indicate multiple metabolic steps (catalysts not shown). Abbreviations: TPH2: tryptophan hydroxylase, isoenzyme 2; AAAD: aromatic acid decarboxylase; MAO-A: monoamine oxidase A; HIOMT: hydroxyindole O-methyl transferase; SNAT: serotonin-N-acetyltransferase; IDO: indoleamine 2,3-dioxyenase; KAT: kynurenine aminotransferase; KMO: kynurenine 3-monooxygenase; KYNU: kynurinase; ACMS: 2-amino-3-carboxymuconic-6-semialdehyde decarboxylase.
Figure 2
Figure 2
PRISMA flowchart. *: for each database in our search; **: no automation tools were used.
Figure 3
Figure 3
Publication year of included studies. Abbreviations: ECT: electroconvulsive therapy; TMS: transcranial magnetic stimulation; tDCS: transcranial direct current stimulation.
Figure 4
Figure 4
Summary of (a) clinical and (b) preclinical trials findings, including direction of effects by NIBS and by biomarker. Colors indicate statistical effects on biomarkers by NIBS: red = significant increase; blue = significant decrease; yellow = no significant changes to biomarker levels following NIBS. ↑: Significantly increased or the experimental group levels were significantly larger than the control group; ↓: significantly decreased or the experimental group levels significantly smaller than the control group, *: biomarkers in the serotonin pathway; #: biomarkers in the kynurenine pathway. TRP refers to total TRP when not specified, and for brain tissue and microdialysis the regions are collapsed. Abbreviations: TRP: tryptophan; 5-HT: serotonin; 5-HIAA: 5-hydroxyindoleacetic acid; KYN: kynurenine; KA: kynurenic acid; 3-HK: 3-hydroxykynurenine; QA: quinolinic acid; XA: xanthurenic acid; AA: anthranilic acid; PA: picolinic acid; ECT: electroconvulsive therapy; TMS: transcranial magnetic stimulation; ns: not significant.
Figure 5
Figure 5
Count of experimental groups reporting significant increases, decreases, or non-significant changes in the metabolites by NIBS. (a–c) From CSF, plasma, and serum in clinical studies respectively. (d–f) from brain tissue, microdialysis, and plasma in preclinical studies respectively. Colors indicate statistical effects on biomarkers by NIBS: red = significant increase; blue = significant decrease; yellow = no significant changes to biomarker levels following NIBS. *: biomarkers in the serotonin pathway; #: biomarkers in the kynurenine pathway. TRP refers to total TRP when not specified, and for brain tissue and microdialysis the regions are collapsed. Abbreviations: TRP: tryptophan; 5-HT: serotonin; 5-HIAA: 5-hydroxyindoleacetic acid; KYN: kynurenine; KA: kynurenic acid; 3-HK: 3-hydroxykynurenine; QA: quinolinic acid; XA: xanthurenic acid; AA: anthranilic acid; PA: picolinic acid; ECT: electroconvulsive therapy; TMS: transcranial magnetic stimulation; ns: not significant.
Figure 5
Figure 5
Count of experimental groups reporting significant increases, decreases, or non-significant changes in the metabolites by NIBS. (a–c) From CSF, plasma, and serum in clinical studies respectively. (d–f) from brain tissue, microdialysis, and plasma in preclinical studies respectively. Colors indicate statistical effects on biomarkers by NIBS: red = significant increase; blue = significant decrease; yellow = no significant changes to biomarker levels following NIBS. *: biomarkers in the serotonin pathway; #: biomarkers in the kynurenine pathway. TRP refers to total TRP when not specified, and for brain tissue and microdialysis the regions are collapsed. Abbreviations: TRP: tryptophan; 5-HT: serotonin; 5-HIAA: 5-hydroxyindoleacetic acid; KYN: kynurenine; KA: kynurenic acid; 3-HK: 3-hydroxykynurenine; QA: quinolinic acid; XA: xanthurenic acid; AA: anthranilic acid; PA: picolinic acid; ECT: electroconvulsive therapy; TMS: transcranial magnetic stimulation; ns: not significant.

References

    1. Melhem N.J., Taleb S. Tryptophan: From Diet to Cardiovascular Diseases. Int. J. Mol. Sci. 2021;22:9904. doi: 10.3390/ijms22189904.
    1. Roth W., Zadeh K., Vekariya R., Ge Y., Mohamadzadeh M. Tryptophan Metabolism and Gut-Brain Homeostasis. Int. J. Mol. Sci. 2021;22:2973. doi: 10.3390/ijms22062973.
    1. Bacqué-Cazenave J., Bharatiya R., Barrière G., Delbecque J.-P., Bouguiyoud N., Di Giovanni G., Cattaert D., De Deurwaerdère P. Serotonin in Animal Cognition and Behavior. Int. J. Mol. Sci. 2020;21:1649. doi: 10.3390/ijms21051649.
    1. Cowen P.J., Browning M. What has serotonin to do with depression? World Psychiatry. 2015;14:158–160. doi: 10.1002/wps.20229.
    1. Kanova M., Kohout P. Tryptophan: A Unique Role in the Critically III. Int. J. Mol. Sci. 2021;22:11714. doi: 10.3390/ijms222111714.
    1. James G.M., Gryglewski G., Vanicek T., Berroterán-Infante N., Philippe C., Kautzky A., Nics L., Vraka C., Godbersen G.M., Unterholzner J., et al. Parcellation of the Human Cerebral Cortex Based on Molecular Targets in the Serotonin System Quantified by Positron Emission Tomography In vivo. Cereb. Cortex. 2019;29:372–382. doi: 10.1093/cercor/bhy249.
    1. Savitz J. The kynurenine pathway: A finger in every pie. Mol. Psychiatry. 2020;25:131–147. doi: 10.1038/s41380-019-0414-4.
    1. Carvalho A.F., Solmi M., Sanches M., Machado M.O., Stubbs B., Ajnakina O., Sherman C., Sun Y.R., Liu C.S., Brunoni A.R., et al. Evidence-based umbrella review of 162 peripheral biomarkers for major mental disorders. Transl. Psychiatry. 2020;10:152. doi: 10.1038/s41398-020-0835-5.
    1. Marx W., McGuinness A.J., Rocks T., Ruusunen A., Cleminson J., Walker A.J., Gomes-da-Costa S., Lane M., Sanches M., Diaz A.P., et al. The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: A meta-analysis of 101 studies. Mol. Psychiatry. 2021;26:4158–4178. doi: 10.1038/s41380-020-00951-9.
    1. Ogyu K., Kubo K., Noda Y., Iwata Y., Tsugawa S., Omura Y., Wada M., Tarumi R., Plitman E., Moriguchi S., et al. Kynurenine pathway in depression: A systematic review and meta-analysis. Neurosci. Biobehav. Rev. 2018;90:16–25. doi: 10.1016/j.neubiorev.2018.03.023.
    1. Kappelmann N., Lewis G., Dantzer R., Jones P.B., Khandaker G.M. Antidepressant activity of anti-cytokine treatment: A systematic review and meta-analysis of clinical trials of chronic inflammatory conditions. Mol. Psychiatry. 2018;23:335–343. doi: 10.1038/mp.2016.167.
    1. Köhler-Forsberg O., Benros M.E., Nordentoft M., Farkouh M.E., Iyengar R.L., Mors O., Krogh J. Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: A systematic review and meta-analysis of randomized clinical trials. JAMA Psychiatry. 2014;71:1381–1391. doi: 10.1001/jamapsychiatry.2014.1611.
    1. Erabi H., Okada G., Shibasaki C., Setoyama D., Kang D., Takamura M., Yoshino A., Fuchikami M., Kurata A., Kato T.A., et al. Kynurenic acid is a potential overlapped biomarker between diagnosis and treatment response for depression from metabolome analysis. Sci. Rep. 2020;10:16822. doi: 10.1038/s41598-020-73918-z.
    1. Haroon E., Welle J.R., Woolwine B.J., Goldsmith D.R., Baer W., Patel T., Felger J.C., Miller A.H. Associations among peripheral and central kynurenine pathway metabolites and inflammation in depression. Neuropsychopharmacology. 2020;45:998–1007. doi: 10.1038/s41386-020-0607-1.
    1. Kraus C., Castrén E., Kasper S., Lanzenberger R. Serotonin and neuroplasticity—Links between molecular, functional and structural pathophysiology in depression. Neurosci. Biobehav. Rev. 2017;77:317–326. doi: 10.1016/j.neubiorev.2017.03.007.
    1. Westfall S., Caracci F., Estill M., Frolinger T., Shen L., Pasinetti G.M. Chronic Stress-Induced Depression and Anxiety Priming Modulated by Gut-Brain-Axis Immunity. Front. Immunol. 2021;12:670500. doi: 10.3389/fimmu.2021.670500.
    1. Rosson S., de Filippis R., Croatto G., Collantoni E., Pallottino S., Guinart D., Brunoni A.R., Dell’Osso B., Pigato G., Hyde J., et al. Brain stimulation and other biological non-pharmacological interventions in mental disorders: An umbrella review. Neurosci. Biobehav. Rev. 2022;139:104743. doi: 10.1016/j.neubiorev.2022.104743.
    1. Hyde J., Carr H., Kelley N., Seneviratne R., Reed C., Parlatini V., Garner M., Solmi M., Rosson S., Cortese S., et al. Efficacy of neurostimulation across mental disorders: Systematic review and meta-analysis of 208 randomized controlled trials. Mol. Psychiatry. 2022;27:2709–2719. doi: 10.1038/s41380-022-01524-8.
    1. Lefaucheur J.-P., Aleman A., Baeken C., Benninger D.H., Brunelin J., Di Lazzaro V., Filipović S.R., Grefkes C., Hasan A., Hummel F.C., et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014–2018) Clin. Neurophysiol. 2020;131:474–528. doi: 10.1016/j.clinph.2019.11.002.
    1. Kan R.L.D., Zhang B.B.B., Zhang J.J.Q., Kranz G.S. Non-invasive brain stimulation for posttraumatic stress disorder: A systematic review and meta-analysis. Transl. Psychiatry. 2020;10:168. doi: 10.1038/s41398-020-0851-5.
    1. Kellner C.H., Greenberg R.M., Petrides G., Ahle G.M., Adams D.A., Liebman L.S. Electroconvulsive Therapy Is a Noninvasive Brain Stimulation Technique. J. ECT. 2016;32:70. doi: 10.1097/YCT.0000000000000255.
    1. Padberg F., Bulubas L., Mizutani-Tiebel Y., Burkhardt G., Kranz G.S., Koutsouleris N., Kambeitz J., Hasan A., Takahashi S., Keeser D., et al. The intervention, the patient and the illness—Personalizing non-invasive brain stimulation in psychiatry. Exp. Neurol. 2021;341:113713. doi: 10.1016/j.expneurol.2021.113713.
    1. Cirillo G., Di Pino G., Capone F., Ranieri F., Florio L., Todisco V., Tedeschi G., Funke K., Di Lazzaro V. Neurobiological after-effects of non-invasive brain stimulation. Brain Stimul. 2017;10:1–18. doi: 10.1016/j.brs.2016.11.009.
    1. Tateishi H., Mizoguchi Y., Monji A. Is the Therapeutic Mechanism of Repetitive Transcranial Magnetic Stimulation in Cognitive Dysfunctions of Depression Related to the Neuroinflammatory Processes in Depression? Front. Psychiatry. 2022;13:834425. doi: 10.3389/fpsyt.2022.834425.
    1. Baldinger-Melich P., Gryglewski G., Philippe C., James G.M., Vraka C., Silberbauer L., Balber T., Vanicek T., Pichler V., Unterholzner J., et al. The effect of electroconvulsive therapy on cerebral monoamine oxidase A expression in treatment-resistant depression investigated using positron emission tomography. Brain Stimul. 2019;12:714–723. doi: 10.1016/j.brs.2018.12.976.
    1. Yrondi A., Sporer M., Péran P., Schmitt L., Arbus C., Sauvaget A. Electroconvulsive therapy, depression, the immune system and inflammation: A systematic review. Brain Stimul. 2018;11:29–51. doi: 10.1016/j.brs.2017.10.013.
    1. Tricco A.C., Lillie E., Zarin W., O’Brien K.K., Colquhoun H., Levac D., Moher D., Peters M.D.J., Horsley T., Weeks L., et al. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann. Intern. Med. 2018;169:467–473. doi: 10.7326/M18-0850.
    1. Maier M., Bartoš F., Wagenmakers E.-J. Robust Bayesian meta-analysis: Addressing publication bias with model-averaging. Psychol. Methods. 2022 doi: 10.1037/met0000405.
    1. Lee M.D., Wagenmakers E.-J. Bayesian Cognitive Modeling. Cambridge University Press; Cambridge, UK: 2014.
    1. Rosenthal R. Meta-Analytic Procedures for Social Research. SAGE Publications, Inc.; New York, NY, USA: 1991.
    1. Higgins J.P.T., Li T., Deeks J.J. Cochrane Handbook for Systematic Reviews of Interventions. John Wiley & Sons, Inc.; Hoboken, NJ, USA: 2019. Choosing effect measures and computing estimates of effect; pp. 143–176.
    1. McGrath S., Zhao X., Steele R., Thombs B.D., Benedetti A., Levis B., Riehm K.E., Saadat N., Levis A.W., Azar M., et al. Estimating the sample mean and standard deviation from commonly reported quantiles in meta-analysis. Stat. Methods Med. Res. 2020 doi: 10.1177/0962280219889080.
    1. Aarsland T.I., Leskauskaite I., Midttun O., Ulvik A., Ueland P.M., Oltedal L., Erchinger V.J., Oedegaard K.J., Haavik J., Kessler U. The effect of electroconvulsive therapy (ECT) on serum tryptophan metabolites. Brain Stimul. 2019;12:1135–1142. doi: 10.1016/j.brs.2019.05.018.
    1. Aberg-Wistedt A., Mårtensson B., Bertilsson L., Malmgren R. Electroconvulsive Therapy Effects on Cerebrospinal Fluid Monoamine Metabolites and Platelet Serotonin Uptake In Melancholia. Convuls. Ther. 1986;2:91–98.
    1. Allen A.P., Naughton M., Dowling J., Walsh A., O’Shea R., Shorten G., Scott L., McLoughlin D.M., Cryan J.F., Clarke G., et al. Kynurenine pathway metabolism and the neurobiology of treatment-resistant depression: Comparison of multiple ketamine infusions and electroconvulsive therapy. J. Psychiatr. Res. 2018;100:24–32. doi: 10.1016/j.jpsychires.2018.02.011.
    1. D’Elia G., Lehmann J., Raotma H. Evaluation of the combination of tryptophan and ECT in the treatment of depression. Acta Psychiatr. Scand. 1977;56:319–334. doi: 10.1111/j.1600-0447.1977.tb00232.x.
    1. Guloksuz S., Arts B., Walter S., Drukker M., Rodriguez L., Myint A.M., Schwarz M.J., Ponds R., van Os J., Kenis G., et al. The impact of electroconvulsive therapy on the tryptophan-kynurenine metabolic pathway. Brain Behav. Immun. 2015;48:48–52. doi: 10.1016/j.bbi.2015.02.029.
    1. Hasani P.A.M., Moghadam F.M., Mokhtaree M., Nazer M. Effect of Electroconvulsive Therapy on Serum Serotonin Level in Patients with Treatment- Resistant Major Depressive Disorder. J. Evol. Med. Dent. Sci. 2019;8:1283–1286. doi: 10.14260/jemds/2019/286.
    1. Hoekstra R., van den Broek W.W., Fekkes D., Bruijn J.A., Mulder P.G., Pepplinkhuizen L. Effect of electroconvulsive therapy on biopterin and large neutral amino acids in severe, medication-resistant depression. Psychiatry Res. 2001;103:115–123. doi: 10.1016/S0165-1781(01)00282-7.
    1. Hoffmann G., Linkowski P., Kerkhofs M., Desmedt D., Mendlewicz J. Effects of ECT on sleep and CSF biogenic amines in affective illness. Psychiatry Res. 1985;16:199–206. doi: 10.1016/0165-1781(85)90107-6.
    1. Hofmann P., Loimer N., Chaudhry H.R., Pfersmann D., Schmid R., Wieselmann G. 5-Hydroxy-indolacetic-acid (5-HIAA) serum levels in depressive patients and ECT. J. Psychiatr. Res. 1996;30:209–216. doi: 10.1016/0022-3956(96)00015-5.
    1. Jori A., Dolfini E., Casati C., Argenta G. Effect of ECT and imipramine treatment on the concentration of 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) in the cerebrospinal fluid of depressed patients. Psychopharmacologia. 1975;44:87–90. doi: 10.1007/BF00421189.
    1. Kirkegaard C., Mosller S.E., Bjosrum N. Addition of L-tryptophan to electroconvulsive treatment in endogenous depression. A double-blind study. Acta Psychiatr. Scand. 1978;58:457–462. doi: 10.1111/j.1600-0447.1978.tb03576.x.
    1. Lestra C., d’Amato T., Ghaemmaghami C., Perret-Liaudet A., Broyer M., Renaud B., Dalery J., Chamba G. Biological parameters in major depression: Effects of paroxetine, viloxazine, moclobemide, and electroconvulsive therapy. Relation to early clinical outcome. Biol. Psychiatry. 1998;44:274–280. doi: 10.1016/S0006-3223(97)00389-2.
    1. Mokhtar A.S.E., Morgan C.J., Bradley D.M., Badawy A.A.B. No early effects of electroconvulsive therapy on tryptophan metabolism and disposition in endogenous depression. Biol. Psychiatry. 1997;42:201–205. doi: 10.1016/S0006-3223(96)00336-8.
    1. Nikisch G., Mathé A.A. CSF monoamine metabolites and neuropeptides in depressed patients before and after electroconvulsive therapy. Eur. Psychiatry. 2008;23:356–359. doi: 10.1016/j.eurpsy.2008.03.003.
    1. Olajossy M., Olajossy B., Wnuk S., Potembska E., Urbańska E. Blood serum concentrations of kynurenic acid in patients diagnosed with recurrent depressive disorder, depression in bipolar disorder, and schizoaffective disorder treated with electroconvulsive therapy. Psychiatr. Pol. 2017;51:455–468. doi: 10.12740/PP/61584.
    1. Palmio J., Huuhka M., Saransaari P., Oja S.S., Peltola J., Leinonen E., Suhonen J., Keränen T. Changes in plasma amino acids after electroconvulsive therapy of depressed patients. Psychiatry Res. 2005;137:183–190. doi: 10.1016/j.psychres.2005.07.010.
    1. Rudorfer M.V., Risby E.D., Hsiao J.K., Linnoila M., Potter W.Z. Disparate Biochemical Actions of Electroconvulsive Therapy and Antidepressant Drugs. Convuls. Ther. 1988;4:133–140.
    1. Rudorfer M.V., Risby E.D., Osman O.T., Gold P.W., Potter W.Z. Hypothalamic-pituitary-adrenal axis and monoamine transmitter activity in depression: A pilot study of central and peripheral effects of electroconvulsive therapy. Biol. Psychiatry. 1991;29:253–264. doi: 10.1016/0006-3223(91)91287-2.
    1. Ryan K.M., Allers K.A., Harkin A., McLoughlin D.M. Blood plasma B vitamins in depression and the therapeutic response to electroconvulsive therapy. Brain Behav. Immun. Health. 2020;4:100063. doi: 10.1016/j.bbih.2020.100063.
    1. Ryan K.M., Allers K.A., McLoughlin D.M., Harkin A. Tryptophan metabolite concentrations in depressed patients before and after electroconvulsive therapy. Brain Behav. Immun. 2020;83:153–162. doi: 10.1016/j.bbi.2019.10.005.
    1. Sawa Y. The effect of electroconvulsive therapy on plasma cyclic-AMP, non-esterified fatty acid, tryptophan and tyrosine in depression. Keio J. Med. 1981;30:193–204. doi: 10.2302/kjm.30.193.
    1. Schwieler L., Samuelsson M., Frye M.A., Bhat M., Schuppe-Koistinen I., Jungholm O., Johansson A.G., Landén M., Sellgren C.M., Erhardt S. Electroconvulsive therapy suppresses the neurotoxic branch of the kynurenine pathway in treatment-resistant depressed patients. J. Neuroinflamm. 2016;13:51. doi: 10.1186/s12974-016-0517-7.
    1. Smith D.F., Strömgren L.S. Influence of unilateral ECT on tryptophan metabolism in endogenous depression. Pharmacopsychiatria. 1981;14:135–138. doi: 10.1055/s-2007-1019584.
    1. Stelmasiak Z., Curzon G. Effect of electroconvulsive therapy on plasma unesterified fatty acid and free tryptophan concentrations in man. J. Neurochem. 1974;22:603–604. doi: 10.1111/j.1471-4159.1974.tb06901.x.
    1. Udayakumar M.A., Subrahmanyam T.S., Ramanamurthy P.S.V., Haranath P.S. Influence of single ECT on dopamine, noradrenaline and 5-hydroxytryptamine concentrations in CSF of schizophenics. Indian J. Med. Res. 1981;74:757–762.
    1. Whalley L.J., Yates C.M., Christie J.E. Effect of electroconvulsive therapy (ECT) on plasma tryptophan. Psychol. Med. 1980;10:377–380. doi: 10.1017/S0033291700044159.
    1. Leblhuber F., Geisler S., Ehrlich D., Steiner K., Reibnegger G., Fuchs D., Kurz K. Repetitive transcranial magnetic stimulation in the treatment of resistant depression: Changes of specific neurotransmitter precursor amino acids. J. Neural Transm. 2021;128:1225–1231. doi: 10.1007/s00702-021-02363-7.
    1. Leblhuber F., Steiner K., Fuchs D. Treatment of patients with geriatric depression with repetitive transcranial magnetic stimulation. J. Neural Transm. 2019;126:1105–1110. doi: 10.1007/s00702-019-02037-5.
    1. Leblhuber F., Steiner K., Gostner J., Fuchs D. Repetitive transcranial magnetic stimulation in patients with late life depression influences phenylalanine metabolism. Pteridines. 2018;29:87–90. doi: 10.1515/pteridines-2018-0008.
    1. Liu S., Wang X., Yu R., Sun Y. Effect of transcranial magnetic stimulation on treatment effect and immune function. Saudi J. Biol. Sci. 2022;29:379–384. doi: 10.1016/j.sjbs.2021.08.104.
    1. Lu R., Zhang C., Liu Y., Wang L., Chen X., Zhou X. The effect of bilateral low-frequency rTMS over dorsolateral prefrontal cortex on serum brain-derived neurotropic factor and serotonin in patients with generalized anxiety disorder. Neurosci. Lett. 2018;684:67–71. doi: 10.1016/j.neulet.2018.07.008.
    1. Maestú C., Blanco M., Nevado A., Romero J., Rodriguez-Rubio P., Galindo J., Bautista Lorite J., de las Morenas F., Fernández-Argüelles P. Reduction of pain thresholds in fibromyalgia after very low-intensity magnetic stimulation: A double-blinded, randomized placebo-controlled clinical trial. Pain Res. Manag. 2013;18:e101–e106. doi: 10.1155/2013/270183.
    1. Miniussi C., Bonato C., Bignotti S., Gazzoli A., Gennarelli M., Pasqualetti P., Tura G.B., Ventriglia M., Rossini P.M. Repetitive transcranial magnetic stimulation (rTMS) at high and low frequency: An efficacious therapy for major drug-resistant depression? Clin. Neurophysiol. 2005;116:1062–1071. doi: 10.1016/j.clinph.2005.01.002.
    1. Niimi M., Ishima T., Hashimoto K., Hara T., Yamada N., Abo M. Effect of repetitive transcranial magnetic stimulation on the kynurenine pathway in stroke patients. Neuroreport. 2020;31:629–636. doi: 10.1097/WNR.0000000000001438.
    1. Sibon I., Strafella A.P., Gravel P., Ko J.H., Booij L., Soucy J.P., Leyton M., Diksic M., Benkelfat C. Acute prefrontal cortex TMS in healthy volunteers: Effects on brain 11C-alphaMtrp trapping. Neuroimage. 2007;34:1658–1664. doi: 10.1016/j.neuroimage.2006.08.059.
    1. Tateishi H., Setoyama D., Kang D., Matsushima J., Kojima R., Fujii Y., Mawatari S., Kikuchi J., Sakemura Y., Fukuchi J., et al. The changes in kynurenine metabolites induced by rTMS in treatment-resistant depression: A pilot study. J. Psychiatr. Res. 2021;138:194–199. doi: 10.1016/j.jpsychires.2021.04.009.
    1. Tateishi H., Setoyama D., Kato T.A., Kang D., Matsushima J., Nogami K., Mawatari S., Kojima R., Fujii Y., Sakemura Y., et al. Changes in the metabolites of cerebrospinal fluid induced by rTMS in treatment-resistant depression: A pilot study. Psychiatry Res. 2022;313:114636. doi: 10.1016/j.psychres.2022.114636.
    1. Hadoush H., Alqudah A., Banihani S.A., Al-Jarrah M., Amro A., Aldajah S. Melatonin serum level, sleep functions, and depression level after bilateral anodal transcranial direct current stimulation in patients with Parkinson’s disease: A feasibility study. Sleep Sci. 2021;14:25–30. doi: 10.5935/1984-0063.20200083.
    1. Evans J.P., Grahame-Smith D.G., Green A.R., Tordoff A.F. Electroconvulsive shock increases the behavioural responses of rats to brain 5-hydroxytryptamine accumulation and central nervous system stimulant drugs. Br. J. Pharmacol. 1976;56:193–199. doi: 10.1111/j.1476-5381.1976.tb07442.x.
    1. Gur E., Dremencov E., Garcia F., Van de Kar L.D., Lerer B., Newman M.E. Functional effects of chronic electroconvulsive shock on serotonergic 5-HT(1A) and 5-HT(1B) receptor activity in rat hippocampus and hypothalamus. Brain Res. 2002;952:52–60. doi: 10.1016/S0006-8993(02)03193-1.
    1. Juckel G., Mendlin A., Jacobs B.L. Electrical stimulation of rat medial prefrontal cortex enhances forebrain serotonin output: Implications for electroconvulsive therapy and transcranial magnetic stimulation in depression. Neuropsychopharmacology. 1999;21:391–398. doi: 10.1016/S0893-133X(98)00097-9.
    1. Karoum F., Korpi E.R., Chuang L.W., Linnoila M., Wyatt R.J. The effects of desipramine, zimelidine, electroconvulsive treatment and lithium on rat brain biogenic amines: A comparison with peripheral changes. Eur. J. Pharmacol. 1986;121:377–385. doi: 10.1016/0014-2999(86)90258-X.
    1. Khanna N.K., Lauria P., Sharma V.N. 5-hydroxytryptamine content of the dog myocardium after chronic electroconvulsive therapy. Indian J. Physiol. Pharmacol. 1971;15:187–188.
    1. Madhav T.R., Pei Q., Grahame-Smith D.G., Zetterström T.S. Repeated electroconvulsive shock promotes the sprouting of serotonergic axons in the lesioned rat hippocampus. Neuroscience. 2000;97:677–683. doi: 10.1016/S0306-4522(00)00083-X.
    1. McIntyre I.M., Oxenkrug G.F. Electroconvulsive shock: Effect on pineal and hypothalamic indoles. J. Pineal Res. 1984;1:273–279. doi: 10.1111/j.1600-079X.1984.tb00218.x.
    1. Shields P.J. Effects of electroconvulsive shock on the metabolism of 5-hydroxytryptamine in the rat brain. J. Pharm. Pharmacol. 1972;24:919–920. doi: 10.1111/j.2042-7158.1972.tb08920.x.
    1. Sugrue M.F. Some effects of chronic antidepressant treatments on rat brain monoaminergic systems. J. Neural Transm. 1983;57:281–295. doi: 10.1007/BF01248999.
    1. Tagliamonte A., Tagliamonte P., Di Chiara G., Gessa R., Gessa G.L. Increase of brain tryptophan by electroconvulsive shock in rats. J. Neurochem. 1972;19:1509–1512. doi: 10.1111/j.1471-4159.1972.tb05094.x.
    1. Yoshida K., Higuchi H., Kamata M., Yoshimoto M., Shimizu T., Hishikawa Y. Dopamine releasing response in rat striatum to single and repeated electroconvulsive shock treatment. Prog. Neuropsychopharmacol. Biol. Psychiatry. 1997;21:707–715. doi: 10.1016/S0278-5846(97)00043-2.
    1. Yoshida K., Higuchi H., Kamata M., Yoshimoto M., Shimizu T., Hishikawa Y. Single and repeated electroconvulsive shocks activate dopaminergic and 5-hydroxytryptaminergic neurotransmission in the frontal cortex of rats. Prog. Neuropsychopharmacol. Biol. Psychiatry. 1998;22:435–444. doi: 10.1016/S0278-5846(98)00015-3.
    1. Ben-Shachar D., Belmaker R.H., Grisaru N., Klein E. Transcranial magnetic stimulation induces alterations in brain monoamines. J. Neural Transm. 1997;104:191–197. doi: 10.1007/BF01273180.
    1. Ben-Shachar D., Gazawi H., Riboyad-Levin J., Klein E. Chronic repetitive transcranial magnetic stimulation alters beta-adrenergic and 5-HT2 receptor characteristics in rat brain. Brain Res. 1999;816:78–83. doi: 10.1016/S0006-8993(98)01119-6.
    1. El Arfani A., Parthoens J., Demuyser T., Servaes S., De Coninck M., De Deyn P.P., Van Dam D., Wyckhuys T., Baeken C., Smolders I., et al. Accelerated high-frequency repetitive transcranial magnetic stimulation enhances motor activity in rats. Neuroscience. 2017;347:103–110. doi: 10.1016/j.neuroscience.2017.01.045.
    1. Gur E., Lerer B., Dremencov E., Newman M.E. Chronic repetitive transcranial magnetic stimulation induces subsensitivity of presynaptic serotonergic autoreceptor activity in rat brain. Neuroreport. 2000;11:2925–2929. doi: 10.1097/00001756-200009110-00019.
    1. Heath A., Lindberg D.R., Makowiecki K., Gray A., Asp A.J., Rodger J., Choi D.S., Croarkin P.E. Medium- and high-intensity rTMS reduces psychomotor agitation with distinct neurobiologic mechanisms. Transl. Psychiatry. 2018;8:126. doi: 10.1038/s41398-018-0129-3.
    1. Kanno M., Matsumoto M., Togashi H., Yoshioka M., Mano Y. Effects of repetitive transcranial magnetic stimulation on behavioral and neurochemical changes in rats during an elevated plus-maze test. J. Neurol. Sci. 2003;211:5–14. doi: 10.1016/S0022-510X(03)00030-3.
    1. Kanno M., Matsumoto M., Togashi H., Yoshioka M., Mano Y. Effects of acute repetitive transcranial magnetic stimulation on extracellular serotonin concentration in the rat prefrontal cortex. J. Pharmacol. Sci. 2003;93:451–457. doi: 10.1254/jphs.93.451.
    1. Kanno M., Matsumoto M., Togashi H., Yoshioka M., Mano Y. Effects of acute repetitive transcranial magnetic stimulation on dopamine release in the rat dorsolateral striatum. J. Neurol. Sci. 2004;217:73–81. doi: 10.1016/j.jns.2003.08.013.
    1. Keck M.E., Sillaber I., Ebner K., Welt T., Toschi N., Kaehler S.T., Singewald N., Philippu A., Elbel G.K., Wotjak C.T., et al. Acute transcranial magnetic stimulation of frontal brain regions selectively modulates the release of vasopressin, biogenic amines and amino acids in the rat brain. Eur. J. Neurosci. 2000;12:3713–3720. doi: 10.1046/j.1460-9568.2000.00243.x.
    1. Kim J., Park H., Yu S.L., Jee S., Cheon K.A., Song D.H., Kim S.J., Im W.Y., Kang J. Effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) on spontaneously hypertensive rats, an animal model of attention-deficit/hyperactivity disorder. Int. J. Dev. Neurosci. 2016;53:83–89. doi: 10.1016/j.ijdevneu.2016.07.006.
    1. Löffler S., Gasca F., Richter L., Leipscher U., Trillenberg P., Moser A. The effect of repetitive transcranial magnetic stimulation on monoamine outflow in the nucleus accumbens shell in freely moving rats. Neuropharmacology. 2012;63:898–904. doi: 10.1016/j.neuropharm.2012.06.045.
    1. Peng Z.W., Xue F., Zhou C.H., Zhang R.G., Wang Y., Liu L., Sang H.F., Wang H.N., Tan Q.R. Repetitive transcranial magnetic stimulation inhibits Sirt1/MAO-A signaling in the prefrontal cortex in a rat model of depression and cortex-derived astrocytes. Mol. Cell. Biochem. 2018;442:59–72. doi: 10.1007/s11010-017-3193-8.
    1. Poh E.Z., Hahne D., Moretti J., Harvey A.R., Clarke M.W., Rodger J. Simultaneous quantification of dopamine, serotonin, their metabolites and amino acids by LC-MS/MS in mouse brain following repetitive transcranial magnetic stimulation. Neurochem. Int. 2019;131:104546. doi: 10.1016/j.neuint.2019.104546.
    1. Wang S., Wang P., Yin R., Xiao M., Zhang Y., Reinhardt J.D., Wang H., Xu G. Combination of repetitive transcranial magnetic stimulation and treadmill training reduces hyperreflexia by rebalancing motoneuron excitability in rats after spinal cord contusion. Neurosci. Lett. 2022;775:136536. doi: 10.1016/j.neulet.2022.136536.
    1. Tanaka T., Takano Y., Tanaka S., Hironaka N., Kobayashi K., Hanakawa T., Watanabe K., Honda M. Transcranial direct-current stimulation increases extracellular dopamine levels in the rat striatum. Front. Syst. Neurosci. 2013;7:6. doi: 10.3389/fnsys.2013.00006.
    1. Cassidy F., Murry E., Weiner R.D., Carroll B.J. Lack of relapse with tryptophan depletion following successful treatment with ECT. Am. J. Psychiatry. 1997;154:1151–1152. doi: 10.1176/ajp.154.8.1151.
    1. Cassidy F., Weiner R.D., Cooper T.B., Carroll B.J. Combined catecholamine and indoleamine depletion following response to ECT. Br. J. Psychiatry. 2010;196:493–494. doi: 10.1192/bjp.bp.109.070573.
    1. Chang T.G., Wang C.H., Chiu N.Y., Hsu W.Y. Application of electroconvulsive therapy in treatment of retinitis pigmentosa comorbid with major depressive disorder and panic disorder. J. ECT. 2011;27:e57–e58. doi: 10.1097/YCT.0b013e3182189455.
    1. Costain D.W., Grahame-Smith D.G., Green A.R. Relevance of the enhanced 5-hydroxytryptamine behavioural responses in rats to electroconvulsive therapy [proceedings] Br. J. Pharmacol. 1978;62:394P.
    1. D’Elia G., Lehmann J., Raotma H. Influence of tryptophan on memory functions in depressive patients treated with unilateral ECT. Acta Psychiatr. Scand. 1978;57:259–268. doi: 10.1111/j.1600-0447.1978.tb06892.x.
    1. Green A.R. Repeated exposure of rats to the convulsant agent flurothyl enhances 5-hydroxytryptamine- and dopamine-mediated behavioural responses. Br. J. Pharmacol. 1978;62:325–331. doi: 10.1111/j.1476-5381.1978.tb08464.x.
    1. Ikeda T., Kurosawa M., Uchikawa C., Kitayama S., Nukina N. Modulation of monoamine transporter expression and function by repetitive transcranial magnetic stimulation. Biochem. Biophys. Res. Commun. 2005;327:218–224. doi: 10.1016/j.bbrc.2004.12.009.
    1. Krahn L.E., Gleber E., Rummans T.A., Pileggi T.S., Lucas D.L., Li H. The effects of electroconvulsive therapy on melatonin. J. ECT. 2000;16:391–398. doi: 10.1097/00124509-200012000-00009.
    1. Kranaster L., Hoyer C., Mindt S., Neumaier M., Müller N., Zill P., Schwarz M.J., Moll N., Lutz B., Bindila L., et al. The novel seizure quality index for the antidepressant outcome prediction in electroconvulsive therapy: Association with biomarkers in the cerebrospinal fluid. Eur. Arch. Psychiatry Clin. Neurosci. 2020;270:911–919. doi: 10.1007/s00406-019-01086-x.
    1. Liu H., Xiong D., Pang R., Deng Q., Sun N., Zheng J., Liu J., Xiang W., Chen Z., Lu J., et al. Effects of repetitive magnetic stimulation on motor function and GAP43 and 5-HT expression in rats with spinal cord injury. J. Int. Med. Res. 2020;48 doi: 10.1177/0300060520970765.
    1. Nordin G., Ottosson J.O., Roos B.E. Influence of convulsive therapy on 5-hydroxyindoleacetic acid and homovanillic acid in cerebrospinal fluid in endogenous depression. Psychopharmacologia. 1971;20:315–320. doi: 10.1007/BF00403563.
    1. Olajossy M., Olajossy B., Potembska E., Skoczen N., Wnuk S., Urbanska E. Differences in the dynamics of changes in the concentration of kynurenic acid in the blood serum of depressed patients treated with electroconvulsive therapy. Psychiatr. Danub. 2018;30:331–339. doi: 10.24869/psyd.2018.331.
    1. Papakostas Y.G., Markianos M., Zervas I.M., Theodoropoulou M., Vaidakis N., Daras M. Administration of Citalopram Before ECT: Seizure Duration and Hormone Responses. J. ECT. 2000;16:356–360. doi: 10.1097/00124509-200012000-00005.
    1. Peng Y., Lin Y., Yu N.W., Liao X.L., Shi L. The Clinical Efficacy and Possible Mechanism of Combination Treatment of Cerebral Ischemic Stroke with Ginkgo Biloba Extract and Low-Frequency Repetitive Transcranial Magnetic Stimulation. Sichuan Da Xue Xue Bao Yi Xue Ban. 2021;52:883–889. doi: 10.12182/20210960202.
    1. Potter W.Z., Rudorfer M.V., Pickar D., Linnoila M. Effects of psychotropic drugs on neurotransmitters in man. Life Sci. 1987;41:817–820. doi: 10.1016/0024-3205(87)90170-6.
    1. Price W.A., Zimmer B. Effects of L-Tryptophan on Electroconvulsive Therapy Seizure Time. J. Nerv. Ment. Dis. 1985;175:636–638. doi: 10.1097/00005053-198510000-00011.
    1. Rausch J.L., Rich C.L., Risch S.C. Platelet serotonin transport after a single ECT. Psychopharmacology. 1988;95:139–141. doi: 10.1007/BF00212783.
    1. Shiiba S.J., Yamamoto S., Sasaki H., Nishi M., Ishikawa K., Yasuda S., Tokuda N., Nakanishi O., Ishikawa T. Cutaneous magnetic stimulation reduces rat chronic pain via activation of the supra-spinal descending pathway. Cell. Mol. Neurobiol. 2012;32:245–253. doi: 10.1007/s10571-011-9756-4.
    1. Wägner A., Aberg-Wistedt A., Åsberg M., Bertilsson L., Mårtensson B., Montero D. Effects of antidepressant treatments on platelet tritiated imipramine binding in major depressive disorder. Arch. Gen. Psychiatry. 1987;44:870–877. doi: 10.1001/archpsyc.1987.01800220032006.
    1. Abrams R., Essman W.B., Taylor M.A., Fink M. Concentration of 5-hydroxyindoleacetic acid, homovanillic acid, and tryptophan in the cerebrospinal fluid of depressed patients before and after ECT. Biol. Psychiatry. 1976;11:85–90.
    1. Belmaker R.H., Grisaru N. Magnetic stimulation of the brain in animal depression models responsive to ECS. J. ECT. 1998;14:194–205. doi: 10.1097/00124509-199809000-00005.
    1. Mano Y., Funakawa I., Nakamuro T., Takayanagi T., Matsui K. The kinesiological, chemical and pathological analysis in pulsed magnetic stimulation to the brain. Rinsho Shinkeigaku. 1989;29:982–988.
    1. Molnár L., Degrell I., Rochlitz S. Effect of bilateral and unilateral electroconvulsive therapy (ECT) on the composition of the cerebrospinal fluid (CSF). A possibility to calculate the intracellular redox changes of the brain in humans (author’s transl) Arch. Psychiatr. Nervenkr. 1979;227:159–169. doi: 10.1007/BF00347163.
    1. Mohamad Safiai N.I., Amir N.A., Basri H., Inche Mat L.N., Hoo F.K., Yusof Khan A.H.K., Loh W.C., Chia P.K., Ramachandran V., Mat Din H., et al. Effectiveness and tolerability of repetitive transcranial magnetic stimulation for preventive treatment of episodic migraine: A single-centre, randomised, double-blind, sham-controlled phase 2 trial (Magnet-EM) Trials. 2020;21:923. doi: 10.1186/s13063-020-04832-y.
    1. Papakostas Y., Markianos M., Papadimitriou G., Stefanis C. Thyrotropin and Prolactin Secretion During ECT: Implications for the Mechanism of ECT Action. Convuls. Ther. 1990;6:214–220.
    1. Wang M., Li Y., Wang X., Guo M. Study on the influence of simulative EEG modulation magnetic field on the discharge of median raphe nuclei. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2004;21:219–224.
    1. Dalal P.K., Lal N., Trivedi J.K., Seth P.K., Agarwal A.K., Khalid A. Ect and platelet 5ht uptake in major depression. Indian J. Psychiatry. 1997;39:272–277.
    1. D’Elia G., Lehmann J., Raotma H. Bimodal distribution of serum trypotphan level. Acta Psychiatr. Scand. 1979;60:10–16. doi: 10.1111/j.1600-0447.1979.tb00260.x.
    1. Tateishi H., Mizoguchi Y., Kawaguchi A., Imamura Y., Matsushima J., Kunitake H., Murakawa T., Haraguchi Y., Kunitake Y., Maekawa T., et al. Changes in interleukin-1 beta induced by rTMS are significantly correlated with partial improvement of cognitive dysfunction in treatment-resistant depression: A pilot study. Psychiatry Res. 2020;289:112995. doi: 10.1016/j.psychres.2020.112995.
    1. Iseger T.A., van Bueren N.E.R., Kenemans J.L., Gevirtz R., Arns M. A frontal-vagal network theory for Major Depressive Disorder: Implications for optimizing neuromodulation techniques. Brain Stimul. 2020;13:1–9. doi: 10.1016/j.brs.2019.10.006.
    1. Michael J.A., Kaur M. The Heart-Brain Connection in Depression: Can it inform a personalised approach for repetitive transcranial magnetic stimulation (rTMS) treatment? Neurosci. Biobehav. Rev. 2021;127:136–143. doi: 10.1016/j.neubiorev.2021.04.016.
    1. Iseger T.A., Arns M., Downar J., Blumberger D.M., Daskalakis Z.J., Vila-Rodriguez F. Cardiovascular differences between sham and active iTBS related to treatment response in MDD. Brain Stimul. 2020;13:167–174. doi: 10.1016/j.brs.2019.09.016.
    1. Fukui S., Schwarcz R., Rapoport S.I., Takada Y., Smith Q.R. Blood-brain barrier transport of kynurenines: Implications for brain synthesis and metabolism. J. Neurochem. 1991;56:2007–2017. doi: 10.1111/j.1471-4159.1991.tb03460.x.
    1. Meier T.B., Drevets W.C., Wurfel B.E., Ford B.N., Morris H.M., Victor T.A., Bodurka J., Teague T.K., Dantzer R., Savitz J. Relationship between neurotoxic kynurenine metabolites and reductions in right medial prefrontal cortical thickness in major depressive disorder. Brain Behav. Immun. 2016;53:39–48. doi: 10.1016/j.bbi.2015.11.003.
    1. Savitz J., Dantzer R., Wurfel B.E., Victor T.A., Ford B.N., Bodurka J., Bellgowan P.S., Teague T.K., Drevets W.C. Neuroprotective kynurenine metabolite indices are abnormally reduced and positively associated with hippocampal and amygdalar volume in bipolar disorder. Psychoneuroendocrinology. 2015;52:200–211. doi: 10.1016/j.psyneuen.2014.11.015.
    1. Baeken C., De Raedt R., Bossuyt A., Van Hove C., Mertens J., Dobbeleir A., Blanckaert P., Goethals I. The impact of HF-rTMS treatment on serotonin(2A) receptors in unipolar melancholic depression. Brain Stimul. 2011;4:104–111. doi: 10.1016/j.brs.2010.09.002.
    1. Vaidya V.A., Marek G.J., Aghajanian G.K., Duman R.S. 5-HT2A receptor-mediated regulation of brain-derived neurotrophic factor mRNA in the hippocampus and the neocortex. J. Neurosci. 1997;17:2785–2795. doi: 10.1523/JNEUROSCI.17-08-02785.1997.
    1. Baldinger P., Lotan A., Frey R., Kasper S., Lerer B., Lanzenberger R. Neurotransmitters and electroconvulsive therapy. J. ECT. 2014;30:116–121. doi: 10.1097/YCT.0000000000000138.
    1. Saijo T., Takano A., Suhara T., Arakawa R., Okumura M., Ichimiya T., Ito H., Okubo Y. Effect of electroconvulsive therapy on 5-HT1A receptor binding in patients with depression: A PET study with [11C]WAY 100635. Int. J. Neuropsychopharmacol. 2010;13:785–791. doi: 10.1017/S1461145709991209.
    1. Lanzenberger R., Baldinger P., Hahn A., Ungersboeck J., Mitterhauser M., Winkler D., Micskei Z., Stein P., Karanikas G., Wadsak W., et al. Global decrease of serotonin-1A receptor binding after electroconvulsive therapy in major depression measured by PET. Mol. Psychiatry. 2013;18:93–100. doi: 10.1038/mp.2012.93.
    1. Yatham L.N., Liddle P.F., Lam R.W., Zis A.P., Stoessl A.J., Sossi V., Adam M.J., Ruth T.J. Effect of electroconvulsive therapy on brain 5-HT(2) receptors in major depression. Br. J. Psychiatry. 2010;196:474–479. doi: 10.1192/bjp.bp.109.069567.
    1. Wilkinson S.T., Holtzheimer P.E., Gao S., Kirwin D.S., Price R.B. Leveraging Neuroplasticity to Enhance Adaptive Learning: The Potential for Synergistic Somatic-Behavioral Treatment Combinations to Improve Clinical Outcomes in Depression. Biol. Psychiatry. 2019;85:454–465. doi: 10.1016/j.biopsych.2018.09.004.
    1. Winter N.R., Leenings R., Ernsting J., Sarink K., Fisch L., Emden D., Blanke J., Goltermann J., Opel N., Barkhau C., et al. Quantifying Deviations of Brain Structure and Function in Major Depressive Disorder Across Neuroimaging Modalities. JAMA Psychiatry. 2022 doi: 10.1001/jamapsychiatry.2022.1780.
    1. Bucolo M., Buscarino A., Fortuna L., Gagliano S. Can Noise in the Feedback Improve the Performance of a Control System? J. Phys. Soc. Jpn. 2021;90:075002. doi: 10.7566/JPSJ.90.075002.
    1. Corradino C., Bucolo M. Automatic preprocessing of EEG signals in long time scale; Proceedings of the 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society; Milan, Italy. 25–29 August 2015; pp. 4110–4113.
    1. Fortuna L., Bucolo M., Frasca M., La Rosa M., Shannahoff-Khalsa D.S., Schult R.L., Wright J.A. Independent component analysis of magnetoencephalography data; Proceedings of the 23rd Annual International Conference of the IEEE; Istanbul, Turkey. 25–28 October 2001; pp. 1981–1984.

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