Mapping cross-modal functional connectivity of major neurotransmitter systems in the human brain
Por:
Saiz-Masvidal, C, De la Peña-Arteaga, V, Bertolín, S, Diez, I, Juaneda-Seguí, A, Martínez-Zalacaín, I, Chavarría-Elizondo, P, Subirà, M, Menchón, JM, Sepulcre, J, Fullana, MA, Soriano-Mas, C
Publicada:
19 ago 2025
Resumen:
Monoaminergic systems, including serotonin, dopamine, and norepinephrine, are essential for regulating brain activity and facilitating behavioral flexibility. These systems originate from brainstem nuclei and project widely to modulate functions such as mood, attention, memory, and adaptability. Using resting-state functional MRI (rs-fMRI), this study aimed to investigate the connectivity networks of key monoaminergic nuclei in 193 healthy adults and explore their correspondence with molecular imaging maps of neurotransmitter-specific biochemical markers. Functional connectivity (FC) was assessed using seed-based rs-fMRI analyses with seeds placed in the dorsal raphe nucleus (DRN), nucleus centralis superior (NCS), ventral tegmental area (VTA), substantia nigra pars compacta (SNc), and locus coeruleus (LC). Cross-modal analyses using molecular imaging data were performed to correlate these rs-FC maps with the distribution of neurotransmitter-related receptors, transporters, and synthesis enzymes, providing insights into the molecular architecture underlying the FC of monoaminergic systems. Whole-brain FC maps revealed distinct patterns for each nucleus. DRN projections were extensive, connecting to subcortical regions such as the hippocampus and amygdala and cortical areas including the precuneus, cingulate, and medial frontal cortex. NCS projections overlapped partially but uniquely targeted the orbitofrontal and insular cortices. Dopaminergic pathways exhibited connectivity with the striatum, thalamus, and prefrontal cortex, while noradrenergic LC projections displayed lateralized connectivity to occipital, temporal, and frontal regions. Cross-modal correlations with molecular imaging demonstrated significant spatial associations between rs-FC maps and neurotransmitter-specific markers, including 5HTT, DAT, and FDOPA. This study enhances our understanding of neurotransmitter networks, highlighting their relevance in brain function and potential as biomarkers for neuropsychiatric conditions.
Filiaciones:
Saiz-Masvidal, C:
Bellvitge Biomed Res Inst IDIBEL, Neurosci Program, Psychiat & Mental Hlth Grp, Lhosp De Llobregat, Spain
Univ Barcelona, Sch Med, Dept Clin Sci, Lhosp De Llobregat, Spain
Bertolín, S:
Bellvitge Biomed Res Inst IDIBEL, Neurosci Program, Psychiat & Mental Hlth Grp, Lhosp De Llobregat, Spain
Univ Barcelona, Sch Med, Dept Clin Sci, Lhosp De Llobregat, Spain
Bellvitge Univ Hosp, Dept Psychiat, Lhosp De Llobregat, Barcelona, Spain
Carlos III Hlth Inst ISCIII, Network Ctr Biomed Res Mental Hlth CIBERSAM, Madrid, Spain
Diez, I:
Harvard Med Sch, Massachusetts Gen Hosp, Gordon Ctr Med Imaging, Dept Radiol, Boston, MA USA
Harvard Med Sch, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Boston, MA USA
Juaneda-Seguí, A:
Bellvitge Biomed Res Inst IDIBEL, Neurosci Program, Psychiat & Mental Hlth Grp, Lhosp De Llobregat, Spain
Martínez-Zalacaín, I:
Bellvitge Biomed Res Inst IDIBEL, Neurosci Program, Psychiat & Mental Hlth Grp, Lhosp De Llobregat, Spain
Hosp Univ Bellvitge, Radiol Dept, Carrer Feixa Llarga SN, LHosp De Llobregat 08907, Barcelona, Spain
Chavarría-Elizondo, P:
Bellvitge Biomed Res Inst IDIBEL, Neurosci Program, Psychiat & Mental Hlth Grp, Lhosp De Llobregat, Spain
Univ Barcelona, Sch Med, Dept Clin Sci, Lhosp De Llobregat, Spain
Carlos III Hlth Inst ISCIII, Network Ctr Biomed Res Mental Hlth CIBERSAM, Madrid, Spain
Subirà, M:
Bellvitge Biomed Res Inst IDIBEL, Neurosci Program, Psychiat & Mental Hlth Grp, Lhosp De Llobregat, Spain
Univ Barcelona, Sch Med, Dept Clin Sci, Lhosp De Llobregat, Spain
Bellvitge Univ Hosp, Dept Psychiat, Lhosp De Llobregat, Barcelona, Spain
Carlos III Hlth Inst ISCIII, Network Ctr Biomed Res Mental Hlth CIBERSAM, Madrid, Spain
Menchón, JM:
Bellvitge Biomed Res Inst IDIBEL, Neurosci Program, Psychiat & Mental Hlth Grp, Lhosp De Llobregat, Spain
Univ Barcelona, Sch Med, Dept Clin Sci, Lhosp De Llobregat, Spain
Bellvitge Univ Hosp, Dept Psychiat, Lhosp De Llobregat, Barcelona, Spain
Carlos III Hlth Inst ISCIII, Network Ctr Biomed Res Mental Hlth CIBERSAM, Madrid, Spain
Sepulcre, J:
Harvard Med Sch, Massachusetts Gen Hosp, Gordon Ctr Med Imaging, Dept Radiol, Boston, MA USA
Harvard Med Sch, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Boston, MA USA
Yale Univ, Yale PET Ctr, Yale Med Sch, Dept Radiol, New Haven, CT USA
Fullana, MA:
Carlos III Hlth Inst ISCIII, Network Ctr Biomed Res Mental Hlth CIBERSAM, Madrid, Spain
Inst Invest Biomed August Pi i Sunyer, Barcelona, Spain
Hosp Clin Barcelona, Clin Inst Neurosci, Psychiat & Psychol Serv, Barcelona, Spain
Soriano-Mas, C:
Univ Barcelona, Inst Neurosci, Bellvitge Biomed Res Inst IDIBELL, Dept Social Psychol & Quantitat Psychol, Barcelona, Spain
CIBERSAM, Barcelona, Spain
Inst Rec St Pau IR St Pau, St Pau Mental Hlth Res Grp, Barcelona, Spain
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