Cognitive Improvement via Left Angular Gyrus-Navigated Repetitive Transcranial Magnetic Stimulation Inducing the Neuroplasticity of Thalamic System in Amnesic Mild Cognitive Impairment Patients
Restricted accessResearch articleFirst published online March 22, 2022
Cognitive Improvement via Left Angular Gyrus-Navigated Repetitive Transcranial Magnetic Stimulation Inducing the Neuroplasticity of Thalamic System in Amnesic Mild Cognitive Impairment Patients
Stimulating superficial brain regions highly associated with the hippocampus by repetitive transcranial magnetic stimulation (rTMS) may improve memory of Alzheimer’s disease (AD) spectrum patients.
Objective:
We recruited 16 amnesic mild cognitive impairment (aMCI) and 6 AD patients in the study. All the patients were stimulated to the left angular gyrus, which was confirmed a strong link to the hippocampus through neuroimaging studies, by the neuro-navigated rTMS for four weeks.
Methods:
Automated fiber quantification using diffusion tensor imaging metrics and graph theory analysis on functional network were employed to detect the neuroplasticity of brain networks.
Results:
After neuro-navigated rTMS intervention, the episodic memory of aMCI patients and Montreal Cognitive Assessment score of two groups were significantly improved. Increased FA values of right anterior thalamic radiation among aMCI patients, while decreased functional network properties of thalamus subregions were observed, whereas similar changes not found in AD patients. It is worth noting that the improvement of cognition was associated with the neuroplasticity of thalamic system.
Conclusion:
We speculated that the rTMS intervention targeting left angular gyrus may be served as a strategy to improve cognitive impairment at the early stage of AD patients, supporting by the neuroplasticity of thalamic system.
NicholsE, SzoekeCEI, VollsetSE, AbbasiN, Abd-AllahF, AbdelaJ, AichourMTE, AkinyemiRO, AlahdabF, AsgedomSW, et al. (2019) Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol18, 88–106.
BellevilleS, GilbertB, FontaineF, GagnonL, MenardE, GauthierS (2006) Improvement of episodic memory in persons with mild cognitive impairment and healthy older adults: Evidence from a cognitive intervention program. Dement Geriatr Cogn Disord22, 486–499.
7.
MoroV, CondoleoMT, ValbusaV, BroggioE, MorettoG, GambinaG (2015) Cognitive stimulation of executive functions in mild cognitive impairment: Specific efficacy and impact in memory. Am J Alzheimers Dis Other Demen30, 153–164.
8.
MoroV, CondoleoMT, SalaF, PernigoS, MorettoG, GambinaG (2012) Cognitive stimulation in a-MCI: An experimental study. Am J Alzheimers Dis Other Demen27, 121–130.
9.
FoxMD, HalkoMA, EldaiefMC, Pascual-LeoneA (2012) Measuring and manipulating brain connectivity with resting state functional connectivity magnetic resonance imaging (fcMRI) and transcranial magnetic stimulation (TMS). Neuroimage62, 2232–2243.
10.
WeiduschatN, ThielA, Rubi-FessenI, HartmannA, KesslerJ, MerlP, KrachtL, RommelT, HeissWD (2011) Effects of repetitive transcranial magnetic stimulation in aphasic stroke: A randomized controlled pilot study. Stroke42, 409–415.
11.
ShafiM, WestoverM, FoxM, Pascual-LeoneA (2012) Exploration and modulation of brain network interactions with noninvasive brain stimulation in combination with neuroimaging. Eur J Neurosci35, 805–825.
12.
King-RobsonJ, WilsonH, PolitisM (2021) Associations between amyloid and tau pathology, and connectome alterations, in Alzheimer’s disease and mild cognitive impairment. J Alzheimers Dis82, 541–560.
13.
GuebelD, TorresN, AcebesÁ (2021) Mapping the transcriptomic changes of endothelial compartment in human hippocampus across aging and mild cognitive impairment. Biol Open10, bio057950.
14.
GuidaliG, PisoniA, BologniniN, PapagnoC (2019) Keeping order in the brain: The supramarginal gyrus and serial order in short-term memory. Cortex119, 89–99.
15.
WangJX, RogersLM, GrossEZ, RyalsAJ, DokucuME, BrandstattKL, HermillerMS, VossJL (2014) Targeted enhancement of cortical-hippocampal brain networks and associative memory. Science345, 1054–1057.
16.
SestieriC, ShulmanG, CorbettaM (2017) The contribution of the human posterior parietal cortex to episodic memory. Nat Rev Neurosci18, 183–192.
17.
RubinsteinDY, Camarillo-RodriguezL, SerruyaMD, HerwegNA, WaldmanZJ, WandaPA, SharanAD, WeissSA, SperlingMR (2021) Contribution of left supramarginal and angular gyri to episodic memory encoding: An intracranial EEG study. Neuroimage225, 117514.
18.
YangC, RenJ, LiW, LuM, WuS, ChuT (2021) Individual-level morphological hippocampal networks in patients with Alzheimer’s disease. Brain Cogn151, 105748.
19.
CunninghamS, TomasiD, VolkowN (2017) Structural and functional connectivity of the precuneus and thalamus to the default mode network. Hum Brain Mapp38, 938–956.
20.
SavageL, HallJ, VetrenoR (2011) Anterior thalamic lesions alter both hippocampal-dependent behavior and hippocampal acetylcholine release in the rat. Learn Mem18, 751–758.
21.
HebscherM, KragelJE, KahntT, VossJL (2021) Enhanced reinstatement of naturalistic event memories due to hippocampal-network-targeted stimulation. Curr Biol31, 1428–1437e1425.
22.
HwangK, ShineJ, CellierD, D’EspositoM (2020) The human intraparietal sulcus modulates task-evoked functional connectivity. Cereb Cortex30, 875–887.
23.
FujikiM, YeeKM, StewardO (2020) Non-invasive high frequency repetitive transcranial magnetic stimulation (hfrTMS) robustly activates molecular pathways implicated in neuronal growth and synaptic plasticity in select populations of neurons. Front Neurosci14, 558.
24.
MeeterLH, KaatLD, RohrerJD, van SwietenJC (2017) Imaging and fluid biomarkers in frontotemporal dementia. Nat Rev Neurol13, 406–419.
25.
YeatmanJ, DoughertyR, MyallN, WandellB, FeldmanH (2012) Tract profiles of white matter properties: Automating fiber-tract quantification. PLoS One7, e49790.
26.
LeeW, ParkB, HanK (2013) Classification of diffusion tensor images for the early detection of Alzheimer’s disease. Comput Biol Med43, 1313–1320.
27.
RoseS, McMahonK, JankeA, O’DowdB, de ZubicarayG, StrudwickM, ChalkJ (2006) Diffusion indices on magnetic resonance imaging and neuropsychological performance in amnestic mild cognitive impairment. J Neurol Neurosurg Psychiatry77, 1122–1128.
28.
LatiniF, FahlströmM, MarklundN, FeresiadouA (2021) White matter abnormalities in a patient with visual snow syndrome: New evidence from a diffusion tensor imaging study. Eur J Neurol28, 2789–2793.
29.
TangF, ZhuD, MaW, YaoQ, LiQ, ShiJ (2021) Differences changes in cerebellar functional connectivity between mild cognitive impairment and Alzheimer’s disease: A seed-based approach. Front Neurol12, 645171.
30.
GilliganT, SibiliaF, FarrellD, LyonsD, KennellyS, BokdeA (2019) No relationship between fornix and cingulum degradation and within-network decreases in functional connectivity in prodromal Alzheimer’s disease. PLoS One14, e0222977.
31.
McKhannGM, KnopmanDS, ChertkowH, HymanBT, JackCR, Jr., KawasCH, KlunkWE, KoroshetzWJ, ManlyJJ, MayeuxR, MohsRC, MorrisJC, RossorMN, ScheltensP, CarrilloMC, ThiesB, WeintraubS, PhelpsCH (2011) The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement7, 263–269.
32.
GuoQ, ZhaoQ, ChenM, DingD, HongZ (2009) A comparison study of mild cognitive impairment with 3 memory tests among Chinese individuals. Alzheimer Dis Assoc Disord23, 253–259.
33.
ShuN, LiangY, LiH, ZhangJ, LiX, WangL, HeY, WangY, ZhangZ (2012) Disrupted topological organization in white matter structural networks in amnestic mild cognitive impairment: Relationship to subtype. Radiology265, 518–527.
34.
PalmqvistS, JanelidzeS, QuirozYT, ZetterbergH, LoperaF, StomrudE, SuY, ChenY, SerranoGE, LeuzyA, Mattsson-CarlgrenN, StrandbergO, SmithR, VillegasA, Sepulveda-FallaD, ChaiX, ProctorNK, BeachTG, BlennowK, DageJL, ReimanEM, HanssonO (2020) Discriminative accuracy of plasma phospho-tau217 for Alzheimer disease vs other neurodegenerative disorders. JAMA324, 772–781.
35.
NasrabadySE, RizviB, GoldmanJE, BrickmanAM (2018) White matter changes in Alzheimer’s disease: A focus on myelin and oligodendrocytes. Acta Neuropathol Commun6, 22.
36.
MomiD, OzdemirRA, TadayonE, BoucherP, ShafiMM, Pascual-LeoneA, SantarnecchiE (2021) Network-level macroscale structural connectivity predicts propagation of transcranial magnetic stimulation. Neuroimage229, 117698.
37.
LinW, LinW, ChenG, ZhangH, GaoQ, HuangY, TongT, DuM, Alzheimer’s Disease Neuroimaging I (2021) Bidirectional mapping of brain MRI and PET with 3D reversible GAN for the diagnosis of Alzheimer’s disease. Front Neurosci15, 646013.
38.
PistonoA, SenoussiM, GuerrierL, RafiqM, GiménoM, PéranP, JuclaM, ParienteJ (2021) Language network connectivity increases in early Alzheimer’s disease. J Alzheimers Dis82, 447–460.
39.
LiW, ZhaoH, QingZ, NedelskaZ, WuS, LuJ, WuW, YinZ, HortJ, XuY, ZhangB (2021) Disrupted network topology contributed to spatial navigation impairment in patients with mild cognitive impairment. Front Aging Neurosci13, 630677.
WangJ, WangX, XiaM, LiaoX, EvansA, HeY (2015) GRETNA: A graph theoretical network analysis toolbox for imaging connectomics. Front Hum Neurosci9, 386.
42.
BasserP, PajevicS, PierpaoliC, DudaJ, AldroubiA (2000) In vivo fiber tractography using DT-MRI data. Magn Reson Med44, 625–632.
43.
WakanaS, CaprihanA, PanzenboeckMM, FallonJH, PerryM, GollubRL, HuaK, ZhangJ, JiangH, DubeyP, BlitzA, van ZijlP, MoriS (2007) Reproducibility of quantitative tractography methods applied to cerebral white matter. Neuroimage36, 630–644.
44.
RubinovM, SpornsO (2010) Complex network measures of brain connectivity: Uses and interpretations. Neuroimage52, 1059–1069.
45.
GolobEJ, IrimajiriR, StarrA (2007) Auditory cortical activity in amnestic mild cognitive impairment: Relationship to subtype and conversion to dementia. Brain130, 740–752.
46.
FanL, LiH, ZhuoJ, ZhangY, WangJ, ChenL, YangZ, ChuC, XieS, LairdAR, FoxPT, EickhoffSB, YuC, JiangT (2016) The Human Brainnetome Atlas: A new brain atlas based on connectional architecture. Cereb Cortex26, 3508–3526.
47.
AhmedMA, DarwishES, KhedrEM, El SerogyYM, AliAM (2012) Effects of low versus high frequencies of repetitive transcranial magnetic stimulation on cognitive function and cortical excitability in Alzheimer’s dementia. J Neurol259, 83–92.
48.
Rubi-FessenI, HartmannA, HuberW, FimmB, RommelT, ThielA, HeissW (2015) Add-on effects of repetitive transcranial magnetic stimulation on subacute aphasia therapy: Enhanced improvement of functional communication and basic linguistic skills. A randomized controlled study. Arch Phys Med Rehabil96, 1932–1944.e1932.
49.
ZhaoJ, LiZ, CongY, ZhangJ, TanM, ZhangH, GengN, LiM, YuW, ShanP (2017) Repetitive transcranial magnetic stimulation improves cognitive function of Alzheimer’s disease patients. Oncotarget8, 33864–33871.
50.
BussSS, FriedPJ, Pascual-LeoneA (2019) Therapeutic noninvasive brain stimulation in Alzheimer’s disease and related dementias. Curr Opin Neurol32, 292–304.
51.
KochG, BonniS, PellicciariMC, CasulaEP, ManciniM, EspositoR, PonzoV, PicazioS, Di LorenzoF, SerraL, MottaC, MaiellaM, MarraC, CercignaniM, MartoranaA, CaltagironeC, BozzaliM (2018) Transcranial magnetic stimulation of the precuneus enhances memory and neural activity in prodromal Alzheimer’s disease. Neuroimage169, 302–311.
52.
EliasovaI, AnderkovaL, MarecekR, RektorovaI (2014) Non-invasive brain stimulation of the right inferior frontal gyrus may improve attention in early Alzheimer’s disease: A pilot study. J Neurol Sci346, 318–322.
53.
MenonV (2010) Dissociable connectivity within human angular gyrus and intraparietal sulcus: Evidence from functional and structural connectivity. Cereb Cortex20, 2636.
54.
SandriniM, UmiltàC, RusconiE (2011) The use of transcranial magnetic stimulation in cognitive neuroscience: A new synthesis of methodological issues. Neurosci Biobehav Rev35, 516–536.
55.
BerryhillM (2012) Insights from neuropsychology: Pinpointing the role of the posterior parietal cortex in episodic and working memory. Front Integr Neurosci6, 31.
56.
RamananS, PiguetO, IrishM (2018) Rethinking the role of the angular gyrus in remembering the past and imagining the future: The contextual integration model. Neuroscientist24, 342–352.
SestieriC, CapotostoP, TosoniA, Luca RomaniG, CorbettaM (2013) Interference with episodic memory retrieval following transcranial stimulation of the inferior but not the superior parietal lobule. Neuropsychologia51, 900–906.
59.
ThakralPP, MadoreKP, SchacterDL (2017) A role for the left angular gyrus in episodic simulation and memory. J Neurosci37, 8142–8149.
60.
KoenJD, ThakralPP, RuggMD (2018) Transcranial magnetic stimulation of the left angular gyrus during encoding does not impair associative memory performance. Cogn Neurosci9, 127–138.
ChenH, ShengX, QinR, LuoC, LiM, LiuR, ZhangB, XuY, ZhaoH, BaiF (2020) Aberrant white matter microstructure as a potential diagnostic marker in Alzheimer’s disease by automated fiber quantification. Front Neurosci14, 570123.
65.
ShaoW, LiX, ZhangJ, YangC, TaoW, ZhangS, ZhangZ, PengD (2019) White matter integrity disruption in the pre-dementia stages of Alzheimer’s disease: From subjective memory impairment to amnestic mild cognitive impairment. Eur J Neurol26, 800–807.
66.
SetiadiTM, MartensS, OpmeerEM, MarsmanJC, TumatiS, ReesinkFE, De DeynPP, AlemanA, Curcic-BlakeB (2021) Widespread white matter aberration is associated with the severity of apathy in amnestic mild cognitive impairment: Tract-based spatial statistics analysis. Neuroimage Clin29, 102567.
67.
BarnesA, IsohanniM, BarnettJ, PietiläinenO, VeijolaJ, MiettunenJ, PaunioT, TanskanenP, RidlerK, SucklingJ, BullmoreE, JonesP, MurrayG (2012) Neuregulin-1 genotype is associated with structural differences in the normal human brain. Neuroimage59, 2057–2061.
68.
NgASL, WangJ, NgKK, ChongJSX, QianX, LimJKW, TanYJ, YongACW, ChanderRJ, HameedS, TingSKS, KandiahN, ZhouJH (2021) Distinct network topology in Alzheimer’s disease and behavioral variant frontotemporal dementia. Alzheimers Res Ther13, 13.
69.
ShuN, WangX, BiQ, ZhaoT, HanY (2018) Disrupted topologic efficiency of white matter structural connectome in individuals with subjective cognitive decline. Radiology286, 229–238.
70.
SmithDM, Yu YangY, Laxman SubramanianD, AMPM, BulkinDA, Matthew LawL (2021) The limbic memory circuit and the neural basis of contextual memory. Neurobiol Learn Mem187, 107557.
71.
TsanovM, O’MaraSM (2015) Decoding signal processing in thalamo-hippocampal circuitry: Implications for theories of memory and spatial processing. Brain Res1621, 368–379.
72.
PilatoF, ProficeP, RanieriF, CaponeF, Di IorioR, FlorioL, Di LazzaroV (2012) Synaptic plasticity in neurodegenerative diseases evaluated and modulated by in vivo neurophysiological techniques. Mol Neurobiol46, 563–571.
73.
FroemkeR (2015) Plasticity of cortical excitatory-inhibitory balance. Annu Rev Neurosci38, 195–219.
74.
ZhouY, SongZ, HanX, LiH, TangX (2021) Prediction of Alzheimer’s disease progression based on magnetic resonance imaging. ACS Chem Neurosci12, 4209–4223.
75.
BullmoreE, SpornsO (2009) Complex brain networks: Graph theoretical analysis of structural and functional systems. Nat Rev Neurosci10, 186–198.
76.
CarmeliC, FornariE, JaliliM, MeuliR, KnyazevaMG (2014) Structural covariance of superficial white matter in mild Alzheimer’s disease compared to normal aging. Brain Behav4, 721–737.
77.
FornariE, MaederP, MeuliR, GhikaJ, KnyazevaM (2012) Demyelination of superficial white matter in early Alzheimer’s disease: A magnetization transfer imaging study. Neurobiol Aging33, 428.e427–419.
78.
SabbaghM, SadowskyC, TousiB, AgroninME, AlvaG, ArmonC, BernickC, KeeganAP, KarantzoulisS, BarorE, PloznikM, Pascual-LeoneA (2020) Effects of a combined transcranial magnetic stimulation (TMS) and cognitive training intervention in patients with Alzheimer’s disease. Alzheimers Dement16, 641–650.
79.
LeeJ, ChoiBH, OhE, SohnEH, LeeAY (2016) Treatment of Alzheimer’s disease with repetitive transcranial magnetic stimulation combined with cognitive training: A prospective, randomized, double-blind, placebo-controlled study. J Clin Neurol12, 57–64.
80.
BagattiniC, ZanniM, BaroccoF, CaffarraP, BrignaniD, MiniussiC, DefantiCA (2020) Enhancing cognitive training effects in Alzheimer’s disease: rTMS as an add-on treatment. Brain Stimul13, 1655–1664.
81.
NguyenJP, SuarezA, KemounG, MeignierM, Le SaoutE, DamierP, NizardJ, LefaucheurJP (2017) Repetitive transcranial magnetic stimulation combined with cognitive training for the treatment of Alzheimer’s disease. Neurophysiol Clin47, 47–53.
82.
ScheltensP, De StrooperB, KivipeltoM, HolstegeH, ChételatG, TeunissenC, CummingsJ, van der FlierW (2021) Alzheimer’s disease. Lancet397, 1577–1590.
