Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1 (5-Year IF – 2.0)
Journal Citation Indicator (JCI) (2023) – 0.4
Scopus CiteScore – 3.7 (CiteScore Tracker 3.3)
Index Copernicus  – 161.11; MNiSW – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2024, vol. 33, nr 4, April, p. 321–326

doi: 10.17219/acem/185689

Publication type: editorial

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Cite as:

Di Gregorio F, Battaglia S. The intricate brain–body interaction in psychiatric and neurological diseases. Adv Clin Exp Med. 2024;33(4):321–326. doi:10.17219/acem/185689

The intricate brain–body interaction in psychiatric and neurological diseases

Francesco Di Gregorio1,A,D,E,F, Simone Battaglia1,A,D,E,F

1 Center for Studies and Research in Cognitive Neuroscience, Department of Psychology “Renzo Canestrari”, University of Bologna, Italy

Graphical abstract

Graphical abstracts


A harmonic brain–body communication is fundamental to individual wellbeing and is the basis of human cognition and behavior. In the last 2 decades, the interaction between the brain and body functioning has become a central area of study for neurologists and neuroscientists in clinical and non-clinical contexts. Indeed, brain–body axis dysfunctions occur in many psychiatric, neurological and neurodegenerative diseases. This editorial will focus on recent advances and future therapeutic perspectives for studying brain–body interactions in health and diseases.

Key words: psychiatric disorders, central nervous system, neurodegeneration, autonomic nervous system, neurological disorders

The brain–body balance

Coordinated interactions between the brain and the body are crucial for survival. The human body is a complex system of interconnected structures and functions, each playing a crucial role in maintaining brain–body homeostasis and driving behavior and cognition. However, brain–body balance disruption can lead to neurological or psychological diseases. Indeed, several psychiatric, neurological and neurodegenerative disorders present with dysregulations of brain and body functioning.1, 2, 3 In this context, the combined assessment of brain and body functioning becomes fundamental in clinical practice, as it offers valuable insights into the relationship between brain function and body regulation.4, 5

In this manuscript, we will delve into the profound interplay between the brain and the body, examining how disruptions in this dynamic relationship contribute to the onset and/or progression of debilitating conditions. Despite extensive research on dysfunctional brain–body interactions in neurological and psychiatric disorders, it is not currently possible to establish causative and/or hierarchical links between dysfunctional brain–body interactions and neuropsychiatric disease onset.

The onset and progression of many psychiatric and neurological diseases often involve intricate molecular, cellular and systemic changes that impact the central and autonomic nervous systems.6 Neuronal damage, inflammation and aberrant protein accumulation can disrupt the normal flow of signals within brain networks. Such brain-level dysfunctions are linked to a cascade of symptoms and dysregulation of the autonomic nervous system while concurrently revealing the interplay between neural substrates and neuropsychiatric diseases.6 For instance, dysfunctional cardiac activity was linked to impaired cognitive functioning in healthy and neurological populations,7, 8, 9 and heart rate variability (i.e., a measure of cardiac functioning) was recently used as a biomarker to differentiate Alzheimer’s disease from Lewy body dementia in patients with mild cognitive impairment.10 Moreover, the degeneration of dopaminergic neurons in Parkinson’s disease results in motor fluctuations and dyskinetic movements. However, relevant works have also highlighted the role of the gut microbiome in the maladaptive immune and inflammatory responses that accelerate Parkinson’s pathogenesis.11, 12 Crucially, preclinical and clinical studies indicate that gut microbiome alterations may be susceptibility factors for the progression of several neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease, and major psychiatric disorders.13, 14, 15, 16, 17 For instance, recent findings demonstrate a consistent decrease in microbial richness in bipolar disorder patients, while differences in beta diversity were observed in major depressive disorder, schizophrenia and psychosis, compared with controls.16 Similarly, liver diseases such as cirrhosis and hepatic encephalopathy are closely related to neurological symptoms through the liver–brain axis.18, 19

The immune system plays a crucial role in multiple sclerosis (MS) etiology and progression.20, 21 Specifically, immunological mechanisms acting at the brain and body levels can interact through multiple pathways22, 23, 24 and, in MS, chronic immunological dysregulations may reflect a long-term stress response to homeostatic dysregulation in the central nervous system, ultimately leading to neurodegeneration.25 However, the role of central and peripheral immunological events in the early inflammatory phase of MS is under debate. In particular, it is unclear whether a primary immunological process occurs in the brain and extends to the periphery or vice versa, where the immune activation initiates in the periphery before transferring to the as-yet unaffected central nervous system.26, 27 Importantly, peripheral and central inflammatory processes likely play a crucial role in fatigue during MS.27, 28

Recent advances in neuroscience and physiology have shed light on the dynamic brain–body relationship in psychiatric disorders, emphasizing the bidirectional communication between the brain and various physiological systems. Dysregulations of specific neural circuits and neurotransmitter systems and structural and functional brain changes contribute to the pathophysiology of various psychiatric disorders.2, 29, 30, 31, 32 For instance, dysfunction in the prefrontal–limbic circuitry and alterations in neurotransmitter systems such as dopamine and glutamate are implicated in mood disorders and schizophrenia.33, 34, 35, 36, 37 Moreover, epigenetic and genetic influences shape susceptibility to neuropsychiatric disorders, with genome-wide association studies identifying risk genes associated with conditions such as bipolar disorder.31, 38, 39 Epigenetic modifications, including DNA methylation and histone modification, further regulate gene expression patterns linked to psychiatric phenotypes.40, 41

Dysregulations of the neuroendocrine and immune systems have been reported in depression, anxiety and elevated stress,42, 43 with a key role for the hypothalamus–pituitary–adrenal axis (HPA).44, 45 In particular, post-traumatic stress disorder (PTSD) was related to abnormal dynamics in HPA axis activation,46, 47 which was responsible for increased cortisol levels.48, 49 This abnormal activity may lead to impairments in cognitive functions like attention, memory and cognitive control,50, 51, 52 in PTSD patients. Moreover, dysfunctions in the heart rate, blood pressure and respiratory rate have been observed in several psychiatric disorders, including panic and generalized anxiety disorders.53, 54, 55, 56 The research framework highlighted the significance of heart rate variability (HRV) in the context of psychiatric disorders, adding a new dimension to our understanding of the dynamic brain–body relationship.57 Decreased HRV has been identified as a contributing factor in heart failure patients with psychiatric conditions; furthermore, abnormal HRV has been reported in various mental disorders, emphasizing the role of the autonomic nervous system in these conditions.58, 59, 60 Increased sympathetic activity and reduced parasympathetic tone are common findings in psychiatric disorders, highlighting the role of autonomic dysregulation in the manifestation and progression of mental health conditions, as the autonomic imbalance contributes to the resulting pro-inflammatory state of depression.42, 44, 61, 62, 63, 64 Finally, chronic inflammation, characterized by elevated levels of pro-inflammatory cytokines, has also been linked to conditions like schizophrenia.65, 66, 67

Diagnostic and therapeutic prospective

Integrating different markers from brain and body functioning would enhance diagnostic and prognostic accuracy across various clinical domains. Definitively, an integrative brain–body assessment approach may enable a more comprehensive understanding of the neurobiological mechanisms and help guide treatment strategies, such as selecting appropriate medications or implementing targeted interventions for personalized medical approaches.5, 68, 69 As such, recent studies highlighted how combining electroencephalography (EEG) and cardiac activity may provide detailed information about the interaction between neural activity and the autonomic nervous system during cognitive processes70 and neurological and psychiatric disorders.71 Specifically, EEG biomarkers, such as aberrant oscillatory patterns or reduced connectivity,37, 72, 73 can indicate early signs of cognitive decline, while cardiac measures may reflect autonomic dysfunction associated with neurodegenerative processes.58, 59, 74, 75 By integrating these measures, it is possible to improve diagnostic accuracy and track disease progression, facilitating the development of personalized treatment plans.5, 76, 77, 78, 79, 80

Advancements in neuroscience and technology have opened new frontiers for treating neurological and psychiatric-related symptoms by integrating different approaches.81, 82, 83 Neurostimulation techniques, such as deep brain stimulation, transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial electrical stimulation, and vagus nerve stimulation, are being explored as potential interventions for various neurological disorders.84, 85, 86, 87, 88, 89 These approaches aim to modulate neural activity within large neural networks, but the effects of these treatments on brain–body communication are scarcely investigated.90

Understanding the multifaceted interactions between the brain and the body in neurological and psychiatric diseases is essential for developing effective therapeutic approaches.5 Current treatments often focus on mitigating symptoms, slowing disease progression or modulating specific pathways. In Parkinson’s disease, for example, medications aim to target the dopaminergic system to alleviate motor symptoms.91 However, new therapeutic approaches are becoming available for the wide range of non-motor symptoms, which are often very disabling and include neuropsychiatric, autonomic, sleep, and pain symptoms (for a review, see Foltynie et al. and Tajti et al.).91, 92 In depression, the crosstalk between inflammation, metabolic pathways and neural circuits can ultimately affect neural network activity, which is responsible for regulating behavioral and emotional responses.63 Accordingly, several studies reported the antidepressant effects of anti-inflammatory treatments in patients with depression.93, 94, 95 Furthermore, recent advances in exercise physiology have yielded crucial insights into the interplay between the brain and body concerning the advantageous effects of physical activity on cognition and mood in states of health and disease.77, 78, 96, 97, 98, 99, 100 Finally, neurostimulation techniques, including TMS and tDCS, have shown efficacy in alleviating depressive symptoms when combined with psychosocial intervention.101, 102, 103 Thus, integrated multidisciplinary approaches are generally recommended to holistically address the disease-related symptoms and ensure the best outcomes for individuals at brain and body levels.

Tip the scale

The synergistic utilization of brain and body functioning measures in clinical practice offers a multidimensional perspective on brain function and physiological regulation.5 This integrative approach holds promise for enhancing diagnostic accuracy, treatment selection and monitoring of various neuropsychiatric and neurodegenerative conditions, ultimately improving patient outcomes and advancing the field of clinical neuroscience.71, 104 The brain–body interaction in neurological and psychiatric diseases is a complex and dynamic system that extends beyond the traditional boundaries of the nervous system,105 including disrupted communication pathways, the influence of the immune and endocrine systems, and the role of the gut–brain axis, though our understanding of these intricate connections continues to evolve. In conclusion, unraveling dysfunctional brain–body interactions in neurological and psychiatric diseases would be the basis for innovative therapeutic interventions.5, 104 The proposal of synergistic approaches to investigating and treating brain–body communication remains at the forefront of scientific research and clinical exploration, with the potential to transform the landscape of health care in years to come. Indeed, a holistic and synergistic approach could enhance diagnostic accuracy, treatment selection, and psychological and neurological health monitoring across the lifespan.

References (105)

  1. Candia-Rivera D. Brain–heart interactions in the neurobiology of consciousness. Curr Res Neurobiol. 2022;3:100050. doi:10.1016/j.crneur.2022.100050
  2. Ibanez A, Northoff G. Intrinsic timescales and predictive allostatic interoception in brain health and disease. Neurosci Biobehav Rev. 2024;157:105510. doi:10.1016/j.neubiorev.2023.105510
  3. Silvani A, Calandra-Buonaura G, Dampney RAL, Cortelli P. Brain–heart interactions: Physiology and clinical implications. Phil Trans R Soc A. 2016;374(2067):20150181. doi:10.1098/rsta.2015.0181
  4. Di Gregorio F, Petrone V, Casanova E, et al. Hierarchical psychophysiological pathways subtend perceptual asymmetries in neglect. NeuroImage. 2023;270:119942. doi:10.1016/j.neuroimage.2023.119942
  5. Ibanez A, Kringelbach ML, Deco G. A synergetic turn in cognitive neuroscience of brain diseases [published online as ahead of print on January 20, 2024]. Trends Cogn Sci. 2024:S1364661323003066. doi:10.1016/j.tics.2023.12.006
  6. Forstenpointner J, Elman I, Freeman R, Borsook D. The omnipresence of autonomic modulation in health and disease. Prog Neurobiol. 2022;210:102218. doi:10.1016/j.pneurobio.2022.102218
  7. Molloy C, Choy EH, Arechavala RJ, et al. Resting heart rate (variability) and cognition relationships reveal cognitively healthy individuals with pathological amyloid/tau ratio. Front Epidemiol. 2023;3:1168847. doi:10.3389/fepid.2023.1168847
  8. Skora LI, Livermore JJA, Roelofs K. The functional role of cardiac activity in perception and action. Neurosci Biobehav Rev. 2022;137:104655. doi:10.1016/j.neubiorev.2022.104655
  9. Thayer JF, Hansen AL, Saus-Rose E, Johnsen BH. Heart rate variability, prefrontal neural function, and cognitive performance: The neurovisceral integration perspective on self-regulation, adaptation, and health. Ann Behav Med. 2009;37(2):141–153. doi:10.1007/s12160-009-9101-z
  10. Kim MS, Yoon JH, Hong JM. Early differentiation of dementia with Lewy bodies and Alzheimer’s disease: Heart rate variability at mild cognitive impairment stage. Clin Neurophysiol. 2018;129(8):1570–1578. doi:10.1016/j.clinph.2018.05.004
  11. Morris HR, Spillantini MG, Sue CM, Williams-Gray CH. The pathogenesis of Parkinson’s disease. Lancet. 2024;403(10423):293–304. doi:10.1016/S0140-6736(23)01478-2
  12. Romano S, Savva GM, Bedarf JR, Charles IG, Hildebrand F, Narbad A. Meta-analysis of the Parkinson’s disease gut microbiome suggests alterations linked to intestinal inflammation. NPJ Parkinsons Dis. 2021;7(1):27. doi:10.1038/s41531-021-00156-z
  13. Andrioaie IM, Duhaniuc A, Nastase EV, et al. The role of the gut microbiome in psychiatric disorders. Microorganisms. 2022;10(12):2436. doi:10.3390/microorganisms10122436
  14. Cryan JF, O’Riordan KJ, Sandhu K, Peterson V, Dinan TG. The gut microbiome in neurological disorders. Lancet Neurol. 2020;19(2):179–194. doi:10.1016/S1474-4422(19)30356-4
  15. Góralczyk-Bińkowska A, Szmajda-Krygier D, Kozłowska E. The microbiota–gut–brain axis in psychiatric disorders. Int J Mol Sci. 2022;23(19):11245. doi:10.3390/ijms231911245
  16. Nikolova VL, Smith MRB, Hall LJ, Cleare AJ, Stone JM, Young AH. Perturbations in gut microbiota composition in psychiatric disorders: A review and meta-analysis. JAMA Psychiatry. 2021;78(12):1343. doi:10.1001/jamapsychiatry.2021.2573
  17. Ullah H, Arbab S, Tian Y, et al. The gut microbiota–brain axis in neurological disorder. Front Neurosci. 2023;17:1225875. doi:10.3389/fnins.2023.1225875
  18. Yan M, Man S, Sun B, et al. Gut liver brain axis in diseases: The implications for therapeutic interventions. Signal Transduct Target Ther. 2023;8(1):443. doi:10.1038/s41392-023-01673-4
  19. Loh JS, Mak WQ, Tan LKS, et al. Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases. Signal Transduct Target Ther. 2024;9(1):37. doi:10.1038/s41392-024-01743-1
  20. Reich DS, Lucchinetti CF, Calabresi PA. Multiple sclerosis. N Engl J Med. 2018;378(2):169–180. doi:10.1056/NEJMra1401483
  21. Thompson AJ, Baranzini SE, Geurts J, Hemmer B, Ciccarelli O. Multiple sclerosis. Lancet. 2018;391(10130):1622–1636. doi:10.1016/S0140-6736(18)30481-1
  22. Dantzer R. Neuroimmune interactions: From the brain to the immune system and vice versa. Physiol Rev. 2018;98(1):477–504. doi:10.1152/physrev.00039.2016
  23. Dinet V, Petry KG, Badaut J. Brain–immune interactions and neuroinflammation after traumatic brain injury. Front Neurosci. 2019;13:1178. doi:10.3389/fnins.2019.01178
  24. Savitz J, Harrison NA. Interoception and inflammation in psychiatric disorders. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018;3(6):514–524. doi:10.1016/j.bpsc.2017.12.011
  25. Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Nat Rev Immunol. 2015;15(9):545–558. doi:10.1038/nri3871
  26. Hemmer B, Kerschensteiner M, Korn T. Role of the innate and adaptive immune responses in the course of multiple sclerosis. Lancet Neurol. 2015;14(4):406–419. doi:10.1016/S1474-4422(14)70305-9
  27. Manjaly ZM, Harrison NA, Critchley HD, et al. Pathophysiological and cognitive mechanisms of fatigue in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2019;90(6):642–651. doi:10.1136/jnnp-2018-320050
  28. Rouault M, Pereira I, Galioulline H, Fleming SM, Stephan KE, Manjaly Z. Interoceptive and metacognitive facets of fatigue in multiple sclerosis. Eur J Neurosci. 2023;58(2):2603–2622. doi:10.1111/ejn.16048
  29. Battaglia S, Di Fazio C, Mazzà M, Tamietto M, Avenanti A. Targeting human glucocorticoid receptors in fear learning: A multiscale integrated approach to study functional connectivity. Int J Mol Sci. 2024;25(2):864. doi:10.3390/ijms25020864
  30. Quadt L, Esposito G, Critchley HD, Garfinkel SN. Brain–body interactions underlying the association of loneliness with mental and physical health. Neurosci Biobehav Rev. 2020;116:283–300. doi:10.1016/j.neubiorev.2020.06.015
  31. Tanaka M, Szabó Á, Spekker E, Polyák H, Tóth F, Vécsei L. Mitochondrial impairment: A common motif in neuropsychiatric presentation? The link to the tryptophan–kynurenine metabolic system. Cells. 2022;11(16):2607. doi:10.3390/cells11162607
  32. Tanaka M, Szabó Á, Vécsei L. Integrating armchair, bench, and bedside research for behavioral neurology and neuropsychiatry: Editorial. Biomedicines. 2022;10(12):2999. doi:10.3390/biomedicines10122999
  33. Paul IA, Skolnick P. Glutamate and depression: Clinical and preclinical studies. Ann N Y Acad Sci. 2003;1003(1):250–272. doi:10.1196/annals.1300.016
  34. Polyák H, Galla Z, Nánási N, et al. The tryptophan–kynurenine metabolic system is suppressed in cuprizone-induced model of demyelination simulating progressive multiple sclerosis. Biomedicines. 2023;11(3):945. doi:10.3390/biomedicines11030945
  35. Tanaka M, Szabó Á, Vécsei L, Giménez-Llort L. Emerging translational research in neurological and psychiatric diseases: From in vitro to in vivo models. Int J Mol Sci. 2023;24(21):15739. doi:10.3390/ijms242115739
  36. Tortora F, Hadipour AL, Battaglia S, Falzone A, Avenanti A, Vicario CM. The role of serotonin in fear learning and memory: A systematic review of human studies. Brain Sci. 2023;13(8):1197. doi:10.3390/brainsci13081197
  37. Trajkovic J, Di Gregorio F, Ferri F, Marzi C, Diciotti S, Romei V. Resting state alpha oscillatory activity is a valid and reliable marker of schizotypy. Sci Rep. 2021;11(1):10379. doi:10.1038/s41598-021-89690-7
  38. McEwen BS. Redefining neuroendocrinology: Epigenetics of brain–body communication over the life course. Front Neuroendocrinol. 2018;49:8–30. doi:10.1016/j.yfrne.2017.11.001
  39. Tanaka M, Vécsei L. Editorial of special issue ‘Dissecting Neurological and Neuropsychiatric Diseases: Neurodegeneration and Neuroprotection.’ Int J Mol Sci. 2022;23(13):6991. doi:10.3390/ijms23136991
  40. Tanaka M, Szabó Á, Körtési T, Szok D, Tajti J, Vécsei L. From CGRP to PACAP, VIP, and beyond: Unraveling the next chapters in migraine treatment. Cells. 2023;12(22):2649. doi:10.3390/cells12222649
  41. Tanaka M, Szabó Á, Vécsei L. Preclinical modeling in depression and anxiety: Current challenges and future research directions. Adv Clin Exp Med. 2023;32(5):505–509. doi:10.17219/acem/165944
  42. Miller AH. Neuroendocrine and immune system interactions in stress and depression. Psychiatr Clin North Am. 1998;21(2):443–463. doi:10.1016/S0193-953X(05)70015-0
  43. Ogłodek E, Szota A, Just M, Moś D, Araszkiewicz A. The role of the neuroendocrine and immune systems in the pathogenesis of depression. Pharmacol Rep. 2014;66(5):776–781. doi:10.1016/j.pharep.2014.04.009
  44. Kim YK, Na KS, Myint AM, Leonard BE. The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2016;64:277–284. doi:10.1016/j.pnpbp.2015.06.008
  45. Tanaka M, Bohár Z, Vécsei L. Are kynurenines accomplices or principal villains in dementia? Maintenance of kynurenine metabolism. Molecules. 2020;25(3):564. doi:10.3390/molecules25030564
  46. Pervanidou P. Biology of post‐traumatic stress disorder in childhood and adolescence. J Neuroendocrinol. 2008;20(5):632–638. doi:10.1111/j.1365-2826.2008.01701.x
  47. Pervanidou P, Chrousos GP. Neuroendocrinology of post-traumatic stress disorder. Prog Brain Res. 2010;182:149–160. doi:10.1016/S0079-6123(10)82005-9
  48. Lehrner A, Daskalakis N, Yehuda R. Cortisol and the hypothalamic–pituitary–adrenal axis in PTSD. In: Bremner JD, ed. Posttraumatic Stress Disorder. Hoboken, USA: Wiley & Sons; 2016:265–290. doi:10.1002/9781118356142.ch11
  49. Yehuda R. Current status of cortisol findings in post-traumatic stress disorder. Psychiatr Clin North Am. 2002;25(2):341–368. doi:10.1016/S0193-953X(02)00002-3
  50. Blair KS, Vythilingam M, Crowe SL, et al. Cognitive control of attention is differentially affected in trauma-exposed individuals with and without post-traumatic stress disorder. Psychol Med. 2013;43(1):85–95. doi:10.1017/S0033291712000840
  51. Flaks MK, Malta SM, Almeida PP, et al. Attentional and executive functions are differentially affected by post-traumatic stress disorder and trauma. J Psychiatr Res. 2014;48(1):32–39. doi:10.1016/j.jpsychires.2013.10.009
  52. Neylan TC, Lenoci M, Rothlind J, et al. Attention, learning, and memory in posttraumatic stress disorder. J Trauma Stress. 2004;17(1):41–46. doi:10.1023/
  53. Alvares GA, Quintana DS, Hickie IB, Guastella AJ. Autonomic nervous system dysfunction in psychiatric disorders and the impact of psychotropic medications: A systematic review and meta-analysis. J Psychiatry Neurosci. 2016;41(2):89–104. doi:10.1503/jpn.140217
  54. Bär KJ. Cardiac autonomic dysfunction in patients with schizophrenia and their healthy relatives: A small review. Front Neurol. 2015;6:139. doi:10.3389/fneur.2015.00139
  55. Bassi A, Bozzali M. Potential interactions between the autonomic nervous system and higher level functions in neurological and neuropsychiatric conditions. Front Neurol. 2015;6:182. doi:10.3389/fneur.2015.00182
  56. Bryant RA, Creamer M, O’Donnell M, Silove D, McFarlane AC. A multisite study of initial respiration rate and heart rate as predictors of posttraumatic stress disorder. J Clin Psychiatry. 2008;69(11):1694–1701. doi:10.4088/JCP.v69n1104
  57. Jung W, Jang KI, Lee SH. Heart and brain interaction of psychiatric illness: A review focused on heart rate variability, cognitive function, and quantitative electroencephalography. Clin Psychopharmacol Neurosci. 2019;17(4):459–474. doi:10.9758/cpn.2019.17.4.459
  58. Battaglia S, Nazzi C, Thayer JF. Heart’s tale of trauma: Fear‐conditioned heart rate changes in post‐traumatic stress disorder. Acta Psychiatr Scand. 2023;148(5):463–466. doi:10.1111/acps.13602
  59. Battaglia S, Nazzi C, Thayer JF. Genetic differences associated with dopamine and serotonin release mediate fear-induced bradycardia in the human brain. Transl Psychiatry. 2024;14(1):24. doi:10.1038/s41398-024-02737-x
  60. Glannon W. Biomarkers in psychiatric disorders. Camb Q Healthc Ethics. 2022;31(4):444–452. doi:10.1017/S0963180122000056
  61. Halaris A. Inflammation and depression but where does the inflammation come from? Curr Opin Psychiatry. 2019;32(5):422–428. doi:10.1097/YCO.0000000000000531
  62. Leonard BE. Inflammation and depression: A causal or coincidental link to the pathophysiology? Acta Neuropsychiatr. 2018;30(1):1–16. doi:10.1017/neu.2016.69
  63. Miller AH, Raison CL. The role of inflammation in depression: From evolutionary imperative to modern treatment target. Nat Rev Immunol. 2016;16(1):22–34. doi:10.1038/nri.2015.5
  64. Zunszain PA, Hepgul N, Pariante CM. Inflammation and depression. In: Cowen PJ, Sharp T, Lau JYF, eds. Behavioral Neurobiology of Depression and Its Treatment. Vol. 14. Current Topics in Behavioral Neurosciences. Berlin–Heidelberg, Germany: Springer Berlin Heidelberg; 2012:135–151. doi:10.1007/7854_2012_211
  65. Dawidowski B, Górniak A, Podwalski P, Lebiecka Z, Misiak B, Samochowiec J. The role of cytokines in the pathogenesis of schizophrenia. J Clin Med. 2021;10(17):3849. doi:10.3390/jcm10173849
  66. Na KS, Jung HY, Kim YK. The role of pro-inflammatory cytokines in the neuroinflammation and neurogenesis of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2014;48:277–286. doi:10.1016/j.pnpbp.2012.10.022
  67. Upthegrove R, Khandaker GM. Cytokines, oxidative stress and cellular markers of inflammation in schizophrenia. In: Khandaker GM, Meyer U, Jones PB, eds. Neuroinflammation and Schizophrenia. Vol. 44. Current Topics in Behavioral Neurosciences. Cham, Switzerland: Springer International Publishing; 2019:49–66. doi:10.1007/7854_2018_88
  68. Hardy-Sosa A, León-Arcia K, Llibre-Guerra JJ, et al. Diagnostic accuracy of blood-based biomarker panels: A systematic review. Front Aging Neurosci. 2022;14:683689. doi:10.3389/fnagi.2022.683689
  69. Songsaeng D, Nava-apisak P, Wongsripuemtet J, et al. The diagnostic accuracy of artificial intelligence in radiological markers of normal-pressure hydrocephalus (NPH) on non-contrast CT scans of the brain. Diagnostics. 2023;13(17):2840. doi:10.3390/diagnostics13172840
  70. Di Gregorio F, Steinhauser M, Maier ME, Thayer JF, Battaglia S. Error-related cardiac deceleration: Functional interplay between error-related brain activity and autonomic nervous system in performance monitoring. Neurosci Biobehav Rev. 2024;157:105542. doi:10.1016/j.neubiorev.2024.105542
  71. Suhail TA, Indiradevi KP, Suhara EM, Poovathinal SA, Ayyappan A. Distinguishing cognitive states using electroencephalography local activation and functional connectivity patterns. Biomed Signal Process Control. 2022;77:103742. doi:10.1016/j.bspc.2022.103742
  72. Di Gregorio F, La Porta F, Petrone V, et al. Accuracy of EEG biomarkers in the detection of clinical outcome in disorders of consciousness after severe acquired brain injury: Preliminary results of a pilot study using a machine learning approach. Biomedicines. 2022;10(8):1897. doi:10.3390/biomedicines10081897
  73. Di Gregorio F, Battaglia S. Advances in EEG-based functional connectivity approaches to the study of the central nervous system in health and disease. Adv Clin Exp Med. 2023;32(6):607–612. doi:10.17219/acem/166476
  74. Alba G, Vila J, Rey B, Montoya P, Muñoz MÁ. The relationship between heart rate variability and electroencephalography functional connectivity variability is associated with cognitive flexibility. Front Hum Neurosci. 2019;13:64. doi:10.3389/fnhum.2019.00064
  75. Battaglia S, Nazzi C, Thayer JF. Fear-induced bradycardia in mental disorders: Foundations, current advances, future perspectives. Neurosci Biobehav Rev. 2023;149:105163. doi:10.1016/j.neubiorev.2023.105163
  76. Ashton NJ, Brum WS, Di Molfetta G, et al. Diagnostic accuracy of a plasma phosphorylated Tau 217 immunoassay for Alzheimer disease pathology [published online as ahead of print on January 22, 2024]. JAMA Neurol. 2024:e235319. doi:10.1001/jamaneurol.2023.5319
  77. Chen C, Nakagawa S. Physical activity for cognitive health promotion: An overview of the underlying neurobiological mechanisms. Ageing Res Rev. 2023;86:101868. doi:10.1016/j.arr.2023.101868
  78. Chen C, Nakagawa S. Recent advances in the study of the neurobiological mechanisms behind the effects of physical activity on mood, resilience and emotional disorders. Adv Clin Exp Med. 2023;32(9):937–942. doi:10.17219/acem/171565
  79. Liloia D, Cauda F, Uddin LQ, et al. Revealing the selectivity of neuroanatomical alteration in autism spectrum disorder via reverse inference. Biol Psychiatry Cogn Neurosci Neuroimaging. 2023;8(11):1075–1083. doi:10.1016/j.bpsc.2022.01.007
  80. Rocha RP, Koçillari L, Suweis S, et al. Recovery of neural dynamics criticality in personalized whole-brain models of stroke. Nat Commun. 2022;13(1):3683. doi:10.1038/s41467-022-30892-6
  81. Di Gregorio F, La Porta F, Casanova E, et al. Efficacy of repetitive transcranial magnetic stimulation combined with visual scanning treatment on cognitive and behavioral symptoms of left hemispatial neglect in right hemispheric stroke patients: Study protocol for a randomized controlled trial. Trials. 2021;22(1):24. doi:10.1186/s13063-020-04943-6
  82. Di Gregorio F, La Porta F, Lullini G, et al. Efficacy of repetitive transcranial magnetic stimulation combined with visual scanning treatment on cognitive–behavioral symptoms of unilateral spatial neglect in patients with traumatic brain injury: Study protocol for a randomized controlled trial. Front Neurol. 2021;12:702649. doi:10.3389/fneur.2021.702649
  83. Trajkovic J, Di Gregorio F, Marcantoni E, Thut G, Romei V. A TMS/EEG protocol for the causal assessment of the functions of the oscillatory brain rhythms in perceptual and cognitive processes. STAR Protoc. 2022;3(2):101435. doi:10.1016/j.xpro.2022.101435
  84. Corazzol M, Lio G, Lefevre A, et al. Restoring consciousness with vagus nerve stimulation. Curr Biol. 2017;27(18):R994–R996. doi:10.1016/j.cub.2017.07.060
  85. Demirtas-Tatlidede A, Vahabzadeh-Hagh AM, Bernabeu M, Tormos JM, Pascual-Leone A. Noninvasive brain stimulation in traumatic brain injury. J Head Trauma Rehab. 2012;27(4):274–292. doi:10.1097/HTR.0b013e318217df55
  86. Formica C, De Salvo S, Corallo F, et al. Role of neurorehabilitative treatment using transcranial magnetic stimulation in disorders of consciousness. J Int Med Res. 2021;49(2):030006052097647. doi:10.1177/0300060520976472
  87. Karatzetzou S, Tsiptsios D, Terzoudi A, Aggeloussis N, Vadikolias K. Trans­cranial magnetic stimulation implementation on stroke prognosis. Neurol Sci. 2022;43(2):873–888. doi:10.1007/s10072-021-05791-1
  88. Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009;120(12):2008–2039. doi:10.1016/j.clinph.2009.08.016
  89. Schulz R, Gerloff C, Hummel FC. Non-invasive brain stimulation in neurological diseases. Neuropharmacology. 2013;64:579–587. doi:10.1016/j.neuropharm.2012.05.016
  90. Chaves AR, Snow NJ, Alcock LR, Ploughman M. Probing the brain–body connection using transcranial magnetic stimulation (TMS): Validating a promising tool to provide biomarkers of neuroplasticity and central nervous system function. Brain Sci. 2021;11(3):384. doi:10.3390/brainsci11030384
  91. Foltynie T, Bruno V, Fox S, Kühn AA, Lindop F, Lees AJ. Medical, surgical, and physical treatments for Parkinson’s disease. Lancet. 2024;403(10423):305–324. doi:10.1016/S0140-6736(23)01429-0
  92. Tajti J, Szok D, Csáti A, Szabó Á, Tanaka M, Vécsei L. Exploring novel therapeutic targets in the common pathogenic factors in migraine and neuropathic pain. Int J Mol Sci. 2023;24(4):4114. doi:10.3390/ijms24044114
  93. Bai S, Guo W, Feng Y, et al. Efficacy and safety of anti-inflammatory agents for the treatment of major depressive disorder: A systematic review and meta-analysis of randomised controlled trials. J Neurol Neurosurg Psychiatry. 2020;91(1):21–32. doi:10.1136/jnnp-2019-320912
  94. Köhler O, Benros ME, Nordentoft M, et al. 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(12):1381. doi:10.1001/jamapsychiatry.2014.1611
  95. Köhler‐Forsberg O, Lydholm CN, Hjorthøj C, Nordentoft M, Mors O, Benros ME. Efficacy of anti‐inflammatory treatment on major depressive disorder or depressive symptoms: Meta‐analysis of clinical trials. Acta Psychiatr Scand. 2019;139(5):404–419. doi:10.1111/acps.13016
  96. Ellis TD, Colón-Semenza C, DeAngelis TR, et al. Evidence for early and regular physical therapy and exercise in Parkinson’s disease. Semin Neurol. 2021;41(2):189–205. doi:10.1055/s-0041-1725133
  97. Ernst M, Folkerts AK, Gollan R, et al. Physical exercise for people with Parkinson’s disease: A systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023;2023(5):CD013856. doi:10.1002/14651858.CD013856.pub2
  98. Motl RW, Sandroff BM, Kwakkel G, et al. Exercise in patients with multiple sclerosis. Lancet Neurol. 2017;16(10):848–856. doi:10.1016/S1474-4422(17)30281-8
  99. Schuch FB, Vancampfort D. Physical activity, exercise, and mental disorders: It is time to move on. Trends Psychiatry Psychother. 2021;43(3):177–184. doi:10.47626/2237-6089-2021-0237
  100. Sun W, Yu M, Zhou X. Effects of physical exercise on attention deficit and other major symptoms in children with ADHD: A meta-analysis. Psychiatry Res. 2022;311:114509. doi:10.1016/j.psychres.2022.114509
  101. Battaglia S, Schmidt A, Hassel S, Tanaka M. Editorial: Case reports in neuroimaging and stimulation. Front Psychiatry. 2023;14:1264669. doi:10.3389/fpsyt.2023.1264669
  102. Liu S, Sheng J, Li B, Zhang X. Recent advances in non-invasive brain stimulation for major depressive disorder. Front Hum Neurosci. 2017;11:526. doi:10.3389/fnhum.2017.00526
  103. Tanaka M, Diano M, Battaglia S. Editorial: Insights into structural and functional organization of the brain: Evidence from neuroimaging and non-invasive brain stimulation techniques. Front Psychiatry. 2023;14:1225755. doi:10.3389/fpsyt.2023.1225755
  104. Owolabi MO, Leonardi M, Bassetti C, et al. Global synergistic actions to improve brain health for human development. Nat Rev Neurol. 2023;19(6):371–383. doi:10.1038/s41582-023-00808-z
  105. Signorelli CM, Boils JD, Tagliazucchi E, Jarraya B, Deco G. From brain–body function to conscious interactions. Neurosci Biobehav Rev. 2022;141:104833. doi:10.1016/j.neubiorev.2022.104833