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Abstract
The BDNF Val66Met gene polymorphism is a relevant factor explaining inter-individual differences to TMS responses in studies of the motor system. However, whether this variant also contributes to TMS-induced memory effects, as well as their underlying brain mechanisms, remains unexplored. In this investigation, we applied rTMS during encoding of a visual memory task either over the left frontal cortex (LFC; experimental condition) or the cranial vertex (control condition). Subsequently, individuals underwent a recognition memory phase during a functional MRI acquisition. We included 43 young volunteers and classified them as 19 Met allele carriers and 24 as Val/Val individuals. The results revealed that rTMS delivered over LFC compared to vertex stimulation resulted in reduced memory performance only amongst Val/Val allele carriers. This genetic group also exhibited greater fMRI brain activity during memory recognition, mainly over frontal regions, which was positively associated with cognitive performance. We concluded that BDNF Val66Met gene polymorphism, known to exert a significant effect on neuroplasticity, modulates the impact of rTMS both at the cognitive as well as at the associated brain networks expression levels. This data provides new insights on the brain mechanisms explaining cognitive inter-individual differences to TMS, and may inform future, more individually-tailored rTMS interventions.
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1 University of Barcelona, Medical Psychology Unit, Department of Medicine, Faculty of Medicine and Health Sciences, Barcelona, Spain (GRID:grid.5841.8) (ISNI:0000 0004 1937 0247); Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona, Spain (GRID:grid.10403.36) (ISNI:0000000091771775)
2 CHU Timone, AP-HM, CIC CPCET Service de Pharmacologie Clinique et Pharmacovigilance, Marseille, France (GRID:grid.411266.6) (ISNI:0000 0001 0404 1115)
3 Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona, Spain (GRID:grid.10403.36) (ISNI:0000000091771775)
4 Sapienza University of Rome, Department of Physiology and Pharmacology “V. Erspamer”, Rome, Italy (GRID:grid.7841.a); Department of Neuroscience and Neurorehabilitation, IRCCS S. Raffaele, Roma, Italy (GRID:grid.414603.4)
5 Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) SDN, Naples, Italy (GRID:grid.482882.c) (ISNI:0000 0004 1763 1319)
6 University of Barcelona, Neuroradiology Section, Radiology Department, Diagnostic Image Center, Hospital Clinic of Barcelona, Barcelona, Spain (GRID:grid.5841.8) (ISNI:0000 0004 1937 0247); Magnetic Resonance Image Core Facility (IDIBAPS), Barcelona, Spain (GRID:grid.10403.36) (ISNI:0000000091771775)
7 Department of Neuroscience and Neurorehabilitation, IRCCS S. Raffaele, Roma, Italy (GRID:grid.414603.4)
8 CHU Timone, AP-HM, CIC CPCET Service de Pharmacologie Clinique et Pharmacovigilance, Marseille, France (GRID:grid.411266.6) (ISNI:0000 0001 0404 1115); Aix Marseille Université, INSERM, Inst Neurosci Syst, Marseille, France (GRID:grid.5399.6) (ISNI:0000 0001 2176 4817)
9 University of Lille, Inserm, CHU Lille, U1171, Degenerative and Vascular Cognitive Disorders, Lille, France (GRID:grid.503422.2) (ISNI:0000 0001 2242 6780)
10 Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona, Spain (GRID:grid.10403.36) (ISNI:0000000091771775); Hospital Clinic of Barcelona, Sleep Unit, Neurology Department, Barcelona, Spain (GRID:grid.410458.c) (ISNI:0000 0000 9635 9413)
11 University of Siena, Dipartimento di Scienze Mediche, Chirurgiche e Neuroscienze, Brain Investigation & Neuromodulation Laboratory (Si-BIN Lab), Siena, Italy (GRID:grid.9024.f) (ISNI:0000 0004 1757 4641)
12 Hinda and Arthur Marcus Institute for Aging Research and Deanna and Sidney Wolk Center for Memory Health, Hebrew SeniorLife, Boston, USA (GRID:grid.497274.b) (ISNI:0000 0004 0627 5136); Harvard Medical School, Department of Neurology, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Autonomous University of Barcelona, Guttmann Brain Health Institute, Guttmann University Institute of Neurorehabilitation, Badalona, Spain (GRID:grid.7080.f) (ISNI:0000 0001 2296 0625)
13 GlaxoSmithKline R&D, Neurosciences Therapeutic Area, Stevenage, UK (GRID:grid.5399.6)
14 University of Trento, Center for Mind/Brain Sciences (CIMEC), Trento, Italy (GRID:grid.11696.39) (ISNI:0000 0004 1937 0351)
15 University of Barcelona, Medical Psychology Unit, Department of Medicine, Faculty of Medicine and Health Sciences, Barcelona, Spain (GRID:grid.5841.8) (ISNI:0000 0004 1937 0247); Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona, Spain (GRID:grid.10403.36) (ISNI:0000000091771775); Autonomous University of Barcelona, Guttmann Brain Health Institute, Guttmann University Institute of Neurorehabilitation, Badalona, Spain (GRID:grid.7080.f) (ISNI:0000 0001 2296 0625)