PMID- 29277405 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20181211 IS - 1095-9572 (Electronic) IS - 1053-8119 (Linking) VI - 169 DP - 2018 Apr 1 TI - Transcranial magnetic stimulation of the precuneus enhances memory and neural activity in prodromal Alzheimer's disease. PG - 302-311 LID - S1053-8119(17)31072-8 [pii] LID - 10.1016/j.neuroimage.2017.12.048 [doi] AB - Memory loss is one of the first symptoms of typical Alzheimer's disease (AD), for which there are no effective therapies available. The precuneus (PC) has been recently emphasized as a key area for the memory impairment observed in early AD, likely due to disconnection mechanisms within large-scale networks such as the default mode network (DMN). Using a multimodal approach we investigated in a two-week, randomized, sham-controlled, double-blinded trial the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the PC on cognition, as measured by the Alzheimer Disease Cooperative Study Preclinical Alzheimer Cognitive Composite in 14 patients with early AD (7 females). TMS combined with electroencephalography (TMS-EEG) was used to detect changes in brain connectivity. We found that rTMS of the PC induced a selective improvement in episodic memory, but not in other cognitive domains. Analysis of TMS-EEG signal revealed an increase of neural activity in patients' PC, an enhancement of brain oscillations in the beta band and a modification of functional connections between the PC and medial frontal areas within the DMN. Our findings show that high-frequency rTMS of the PC is a promising, non-invasive treatment for memory dysfunction in patients at early stages of AD. This clinical improvement is accompanied by modulation of brain connectivity, consistently with the pathophysiological model of brain disconnection in AD. CI - Copyright (c) 2017. Published by Elsevier Inc. FAU - Koch, Giacomo AU - Koch G AD - Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Via Ardeatina 354, 00179, Rome, Italy; Stroke Unit, Tor Vergata Policlinic, Viale Oxford 81, 00133, Rome, Italy. Electronic address: g.koch@hsantalucia.it. FAU - Bonni, Sonia AU - Bonni S AD - Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Via Ardeatina 354, 00179, Rome, Italy. FAU - Pellicciari, Maria Concetta AU - Pellicciari MC AD - Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Via Ardeatina 354, 00179, Rome, Italy. FAU - Casula, Elias P AU - Casula EP AD - Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Via Ardeatina 354, 00179, Rome, Italy. FAU - Mancini, Matteo AU - Mancini M AD - Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, 00179, Italy. FAU - Esposito, Romina AU - Esposito R AD - Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Via Ardeatina 354, 00179, Rome, Italy. FAU - Ponzo, Viviana AU - Ponzo V AD - Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Via Ardeatina 354, 00179, Rome, Italy. FAU - Picazio, Silvia AU - Picazio S AD - Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Via Ardeatina 354, 00179, Rome, Italy. FAU - Di Lorenzo, Francesco AU - Di Lorenzo F AD - Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Via Ardeatina 354, 00179, Rome, Italy; Department of Systems Medicine, University of Rome Tor Vergata, Viale Oxford 81, 00133, Rome, Italy. FAU - Serra, Laura AU - Serra L AD - Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, 00179, Italy. FAU - Motta, Caterina AU - Motta C AD - Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Via Ardeatina 354, 00179, Rome, Italy. FAU - Maiella, Michele AU - Maiella M AD - Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Via Ardeatina 354, 00179, Rome, Italy. FAU - Marra, Camillo AU - Marra C AD - Memory Clinic, Neurology Department, Catholic University of Rome, Italy. FAU - Cercignani, Mara AU - Cercignani M AD - Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex, Brighton BN1 9RR, East Sussex, UK. FAU - Martorana, Alessandro AU - Martorana A AD - Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Via Ardeatina 354, 00179, Rome, Italy; Department of Systems Medicine, University of Rome Tor Vergata, Viale Oxford 81, 00133, Rome, Italy. FAU - Caltagirone, Carlo AU - Caltagirone C AD - Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Via Ardeatina 354, 00179, Rome, Italy; Department of Systems Medicine, University of Rome Tor Vergata, Viale Oxford 81, 00133, Rome, Italy. FAU - Bozzali, Marco AU - Bozzali M AD - Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, 00179, Italy; Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex, Brighton BN1 9RR, East Sussex, UK. Electronic address: m.bozzali@bsms.ac.uk. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171219 PL - United States TA - Neuroimage JT - NeuroImage JID - 9215515 SB - IM MH - Aged MH - Alzheimer Disease/*physiopathology MH - Beta Rhythm/*physiology MH - Female MH - Functional Neuroimaging/*methods MH - Humans MH - Male MH - Memory Disorders/*physiopathology MH - *Memory, Episodic MH - Parietal Lobe/*physiopathology MH - *Prodromal Symptoms MH - Transcranial Magnetic Stimulation/*methods OTO - NOTNLM OT - AD OT - Memory OT - Precuneus OT - Transcranial magnetic stimulation EDAT- 2017/12/27 06:00 MHDA- 2018/12/12 06:00 CRDT- 2017/12/27 06:00 PHST- 2017/08/22 00:00 [received] PHST- 2017/12/11 00:00 [revised] PHST- 2017/12/14 00:00 [accepted] PHST- 2017/12/27 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2017/12/27 06:00 [entrez] AID - S1053-8119(17)31072-8 [pii] AID - 10.1016/j.neuroimage.2017.12.048 [doi] PST - ppublish SO - Neuroimage. 2018 Apr 1;169:302-311. doi: 10.1016/j.neuroimage.2017.12.048. Epub 2017 Dec 19.