Wang et al. (2014) found that that five daily sessions of repetitive transcranial magnetic stimulation (rTMS) of the posterior parietal cortex (PPC) significantly increased functional connectivity (FC) in a network centered on the hippocampus, and caused a correlated increase in memory performance. However, this finding has not been reproduced independently and the requirement for five sessions has not been validated. We aimed to reproduce the imaging results of this experiment, focusing on hippocampal FC changes and using fewer days of rTMS. We measured resting state FC before and after three (N = 9) or four (N = 6) consecutive daily PPC rTMS sessions, using similar delivery parameter settings as Wang et al. (2014). Eight subjects received 3 d of rTMS delivered to the vertex as a control. We employed whole-brain and hypothesis-based statistical approaches to test for hippocampal FC changes. Additionally, we calculated FC in 17 brain networks to determine whether the topographic pattern of FC change was similar between studies. We did not include behavioral testing in this study. PPC, but not vertex, rTMS caused significant changes in hippocampal FC to the same regions as in the previous study. Brain-wide changes in hippocampal FC significantly exceeded changes in global connectedness, indicating that the effect of PPC rTMS was specific to the hippocampal network. Baseline hippocampal FC, measured before receiving stimulation, predicted the degree of rTMS-induced hippocampal FC as in the previous study. These findings reproduce the imaging findings of Wang et al. (2014) and show that FC enhancement can occur after only three to four sessions of PPC rTMS.
The ability to interpret transcranial magnetic stimulation (TMS)-evoked electroencephalography (EEG) potentials (TEPs) is limited by artifacts, such as auditory evoked responses produced by discharge of the TMS coil. TEPs generated from direct cortical stimulation should vary in their topographical activity pattern according to stimulation site and differ from responses to sham stimulation. Responses that do not show these effects are likely to be artifactual. In 20 healthy volunteers, we delivered active and sham TMS to the right prefrontal, left primary motor, and left posterior parietal cortex and compared the waveform similarity of TEPs between stimulation sites and active and sham TMS using a cosine similaritybased analysis method. We identified epochs after the stimulus when the spatial pattern of TMS-evoked activation showed greater than random similarity between stimulation sites and sham vs. active TMS, indicating the presence of a dominant artifact. To do this, we binarized the derivatives of the TEPs recorded from 30 EEG channels and calculated cosine similarity between conditions at each time point with millisecond resolution. Only TEP components occurring before approximately 80 ms differed across stimulation sites and between active and sham, indicating site and condition-specific responses. We therefore conclude that, in the absence of noise masking or other measures to decrease neural artifact, TEP components before about 80 ms can be safely interpreted as stimulation locationspecific responses to TMS, but components beyond this latency should be interpreted with caution due to high similarity in their topographical activity pattern.
Objective: Repetitive transcranial magnetic stimulation (rTMS) can cause potentially useful changes in brain functional connectivity (FC), but the number of treatment sessions required is unknown. We applied the continual reassessment method (CRM), a Bayesian, adaptive, dose-finding procedure to a rTMS paradigm in an attempt to answer this question. Materials and Methods: The sample size was predetermined at 15 subjects and the cohort size was set with three individuals (i.e., five total cohorts). In a series of consecutive daily sessions, we delivered rTMS to the left posterior parietal cortex and measured resting-state FC with fMRI in a predefined hippocampal network in the left hemisphere. The session number for each successive cohort was determined by the CRM algorithm. We set a response criterion of a 0.028 change in FC between the hippocampus and the parietal cortex, which was equal to the increase seen in 87.5% of participants in a previous study using five sessions. Results: A ≥criterion change was observed in 9 of 15 participants. The CRM indicated that greater than four sessions are required to produce the criterion change reliably in future studies. Conclusions: The CRM can be adapted for rTMS dose finding when a reliable outcome measure, such as FC, is available. The minimum effective dose needed to produce a criterion increase in FC in our hippocampal network of interest at 87.5% efficacy was estimated to be greater than four sessions. This study is the first demonstration of a Bayesian, adaptive method to explore a rTMS parameter.
Classical lesion studies led to a consensus that episodic and procedural memory arises from segregated networks identified with the hippocampus and the caudate nucleus, respectively. Neuroimaging studies, however, show that competitive and cooperative interactions occur between networks during memory tasks. Furthermore, causal experiments to manipulate connectivity between these networks have not been performed in humans. Although nodes common to both networks, such as the precuneus and ventrolateral thalamus, may mediate their interaction, there is no experimental evidence for this. We tested how network-targeted noninvasive brain stimulation affects episodic–procedural network interactions and how these network manipulations affect episodic and procedural memory in healthy young adults. Compared to control (vertex) stimulation, hippocampal network-targeted stimulation increased within-network functional connectivity and hippocampal connectivity with the caudate. It also increased episodic, relative to procedural, memory, and this persisted one week later. The differential effect on episodic versus procedural memory was associated with increased functional connectivity between the caudate, precuneus, and ventrolateral thalamus. These findings provide direct evidence of episodic–procedural network competition, mediated by regions common to both networks. Enhanced hippocampal network connectivity may boost episodic, but decrease procedural, memory by co-opting resources shared between networks.
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