Local Prefrontal Cortex TMS-Induced Reactivity Is Related to Working Memory and Reasoning in Middle-Aged Adults

María Redondo-Camós; Gabriele Cattaneo; Ruben Perellón-Alfonso; Vanessa Alviarez-Schulze; Timothy P Morris; Javier Solana-Sanchez; Goretti España-Irla; Selma Delgado-Gallén; Catherine Pachón-García; Sergiu Albu; Henrik Zetterberg; Josep M Tormos; Alvaro Pascual-Leone; David Bartres-Faz

doi:10.3389/fpsyg.2022.813444

Local Prefrontal Cortex TMS-Induced Reactivity Is Related to Working Memory and Reasoning in Middle-Aged Adults

Front Psychol. 2022 Feb 10:13:813444. doi: 10.3389/fpsyg.2022.813444. eCollection 2022.

Authors

María Redondo-Camós^{1

2

3}, Gabriele Cattaneo^{1

2

3}, Ruben Perellón-Alfonso^{4

5}, Vanessa Alviarez-Schulze^{1

2

3

6}, Timothy P Morris⁷, Javier Solana-Sanchez^{1

2

3}, Goretti España-Irla^{1

2

3}, Selma Delgado-Gallén^{1

2

3}, Catherine Pachón-García^{1

2

3}, Sergiu Albu^{1

2

3}, Henrik Zetterberg^{8

9

10

11

12}, Josep M Tormos^{1

2

3}, Alvaro Pascual-Leone^{1

13

14}, David Bartres-Faz^{1

4

5}

Affiliations

¹ Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la Universitat Autónoma de Barcelona, Barcelona, Spain.
² Departament de Medicina, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
³ Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Barcelona, Spain.
⁴ Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
⁵ Departament de Medicina, Facultat de Medicina i Ciències de la Salut, i Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain.
⁶ Departamento de Ciencias del Comportamiento, Escuela de Psicología, Universidad Metropolitana, Caracas, Venezuela.
⁷ Center for Cognitive and Brain Health, Department of Psychology, Northeastern University, Boston, MA, United States.
⁸ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁹ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹⁰ Department of Neurodegenerative Disease, University College London Institute of Neurology, London, United Kingdom.
¹¹ UK Dementia Research Institute, University College London, London, United Kingdom.
¹² Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.
¹³ Hinda and Arthur Marcus Institute for Aging Research and Deanna and Sidney Wolk Center for Memory Health, Hebrew SeniorLife, Boston, MA, United States.
¹⁴ Department of Neurology, Harvard Medical School, Boston, MA, United States.

Abstract

Introduction: The prefrontal cortex (PFC) plays a crucial role in cognition, particularly in executive functions. Cortical reactivity measured with Transcranial Magnetic Stimulation combined with Electroencephalography (TMS-EEG) is altered in pathological conditions, and it may also be a marker of cognitive status in middle-aged adults. In this study, we investigated the associations between cognitive measures and TMS evoked EEG reactivity and explored whether the effects of this relationship were related to neurofilament light chain levels (NfL), a marker of neuroaxonal damage.

Methods: Fifty two healthy middle-aged adults (41-65 years) from the Barcelona Brain Health Initiative cohort underwent TMS-EEG, a comprehensive neuropsychological assessment, and a blood test for NfL levels. Global and Local Mean-Field Power (GMFP/LMFP), two measures of cortical reactivity, were quantified after left prefrontal cortex (L-PFC) stimulation, and cognition was set as the outcome of the regression analysis. The left inferior parietal lobe (L-IPL) was used as a control stimulation condition.

Results: Local reactivity was significantly associated with working memory and reasoning only after L-PFC stimulation. No associations were found between NfL and cognition. These specific associations were independent of the status of neuroaxonal damage indexed by the NfL biomarker and remained after adjusting for age, biological sex, and education.

Conclusion: Our results demonstrate that TMS evoked EEG reactivity at the L-PFC, but not the L-IPL, is related to the cognitive status of middle-aged individuals and independent of NfL levels, and may become a valuable biomarker of frontal lobe-associated cognitive function.

Keywords: Electroencephalography; TMS-EEG; cognition; cortical reactivity; prefrontal cortex (PFC); transcranial magnetic stimulation (TMS).

Copyright © 2022 Redondo-Camós, Cattaneo, Perellón-Alfonso, Alviarez-Schulze, Morris, Solana-Sanchez, España-Irla, Delgado-Gallén, Pachón-García, Albu, Zetterberg, Tormos, Pascual-Leone and Bartres-Faz.