Lateral Prefrontal Cortex rTMS May Affect Functional Controllability in Mild Cognitive Impairment
Poster No:
60
Submission Type:
Abstract Submission
Authors:
Simone Papallo1, Fabrizio Esposito2, Federica Di Nardo3, Sabrina Esposito4, Mario Cirillo2, Giovanni Cirillo2, Mattia Siciliano4, Francesca Trojsi4, Ilaria Gigi4
Institutions:
1University of Campania, "Luigi Vanvitelli", Napoli, NA, 2University of Campania "Luigi Vanvitelli", Naples, Italy, 3University of Campania "Luigi Vanvitelli", Napoli, Napoli, 4University of Campania, "Luigi Vanvitelli", Naples, Italy
First Author:
Co-Author(s):
Introduction:
Mild cognitive impairment (MCI) can be viewed as the prodromal stage of Alzheimer's disease [1]. It refers to a condition of cognitive decline greater than expected in relation to a patient's age and education and can affect all brain domains [2]. Non-invasive brain stimulation might play an important role in slowing down or preventing the transition from MCI to dementia as it is relatively free of adverse effects [3]. Particularly, repetitive transcranial magnetic stimulation (rTMS) has provided therapeutic effects, modifying cognitive performances and brain functional connectivity (FC) in many neurological and psychiatric diseases [4]. Varying the frequency of the stimulation protocol, it can induce an excitatory (high frequency, 5–20 Hz) or inhibitory effect (low frequency, ≤1 Hz) on cortical excitability [5] and previous studies have shown FC increases across different brain regions [6]. Here, by leveraging network control theory (NCT) modelling applied to the human connectome, we investigated the effects of high-frequency (10 Hz) rTMS stimulations applied to the dorso-lateral prefrontal cortex on the average (AC) and modal (MC) controllability [7] [8] of functional connectome nodes encompassing the stimulation site.
Methods:
All details about subject and procedures, including MRI data acquisition and pre-processing and rTMS stimulation protocol can be found in [6]. We extracted FC matrices from n=11 (age: 64.82 ± 10.03, 5 males) and n=12 (age: 68.33 ± 8.56, 4 males) MCI patients who underwent respectively active and sham rTMS sessions and MRI scans at baseline, 4 weeks and 6 months. We applied a 200-region parcellation [9] whose cortical nodes are pre-labelled to seven large-scale functional networks. Based on the NCT formulation for time-invariant systems, we estimated the AC and MC and regressed out age and gender covariates, separately for each group and time point. Resulting AC and MC were converted to percentile ranks and statistically analysed by fitting a 2-way mixed-effects ANOVA model with one between-subject factor (active vs. sham) and one within-subject factor (baseline vs. 4 weeks vs. 6 months). One- and two-sample T-tests were performed for pairwise post-hoc comparisons. ANOVA F-maps for the interaction were projected on a brain template to descriptively display nodes with significant effects.
Results:
The group-by-time interaction was statistically significant in the node closest to the stimulation site (RH_Cont_PFCl_2), within the fronto-parietal control network (FPCN), both for AC (p = 0.033, Figure 1) and MC (p = 0.008, Figure 2). The post-hoc t-test showed a significant difference between groups after 4 weeks from the treatment (p=0.047) for MC, while no effects on AC. However, similar effects were observed in other nodes.
·Top: Boxplots of the distribution of percentile ranking values of the AC in RH_Cont_PFCl_2 for sham TMS subject (red) and real TMS subjects (blue) across the three time points (baseline vs. 4 weeks vs
·Top: Boxplots of the distribution of percentile ranking values of the MC in RH_Cont_PFCl_2 for sham TMS subject (red) and real TMS subjects (blue) across the three time points (baseline vs. 4 weeks vs
Conclusions:
Because the DLPFC was the stimulation site, we focused on lateral pre-frontal cortex (PFCl) nodes to investigate whether and how the treatment had affected their estimated levels of functional controllability. Indeed, DLPFC has a crucial role in cognitive functions early impaired in AD, such as attention, executive functions, and working memory [10] and PFCl nodes are part of the FPCN. Particularly, we expected MC alterations within the FPCN as this NCT metric is supposedly related to the ability of the brain (seen as one networked system) to efficiently transit towards more difficult-to-reach FC states, as required by the performance of cognitively demanding tasks [10]. Albeit only initials, the presented results suggest that DLPFC-rTMS might have affected especially MC changes over the first six months from the treatment.
Brain Stimulation:
Non-invasive Magnetic/TMS 1
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s)
Modeling and Analysis Methods:
fMRI Connectivity and Network Modeling 2
Novel Imaging Acquisition Methods:
BOLD fMRI
Keywords:
FUNCTIONAL MRI
Transcranial Magnetic Stimulation (TMS)
Other - Control Theory, Controllability, Mild Cognitive Impairment, FrontoParietal Control Network
1|2Indicates the priority used for review
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