Heterogeneity of stimulus-specific response modification—an fMRI study on neuroplasticity

Abstract

Long-term potentiation (LTP) is a key element of synaptic plasticity. At the macroscopic level, similar effects can be induced in the human brain using repetitive stimulation with identical stimuli. High-frequency stimulation (HFS) can increase neuronal responses whereas low-frequency stimulation may produce the opposite effect. Optimal stimulation frequencies and characteristics for inducing stimulus-specific response modification (SRM) differ substantially from those applied to brain tissue slices but have been explored in recent studies. In contrast, the individual manifestation of this effect in terms of its spatial location and extent are unclear. Using functional magnetic resonance imaging (fMRI) in 18 subjects (mean age 25.3 years), we attempted to induce LTP-like effects by HFS with checkerboard flashes at 9 Hz for 120 s. As expected, flashes induced strong activation in primary and secondary visual cortices. Contrary to our expectations, we found clusters of decreased activations induced by pattern flashes after HFS in the primary and secondary visual cortices. On the level of the individual subject, some showed significantly increased activations in the post-HFS session while the majority showed significant decreases. The locations of areas showing altered activations before and after HFS were only partly overlapping. No association between location, extent and direction of the HFS-effect was observed. The findings are unexpected in the light of existing HFS-studies, but mirror the high inter-subject variability, concerning even the directionality of the induced effects shown for other indices of LTP-like plasticity in the human brain. As this variability is not observed in LTP at the cellular level, a better understanding of LTP-like mechanisms on the macroscopic level is essential for establishing tools to quantify individual synaptic plasticity in-vivo.

Glutamatergic metabolites are associated with visual plasticity in humans

“…A modified visual plasticity fMRI task based on a study by Clapp et al (2005) and updated based on more recent studies [5, 18, 19, 47] was created in E-Prime 2.0 (Psychology Software Tools, Inc., Sharpsburg, PA, USA). E-prime was used to display the visual stimulus (a centrally located flashing checkerboard at a visual angle of 10°).…”

“…E-prime was used to display the visual stimulus (a centrally located flashing checkerboard at a visual angle of 10°). The visual checkerboard was presented centrally similar to Cavus et al [18] and Lahr et al [47]. Figure 2 illustrates the fMRI block design.…”

“…For each LFS run, a checkerboard flashed at a rate of 0.9 Hz for one minute “on”, followed by 30 seconds of rest “off.” Each run consisted of 2 “on” and 2 “off” periods, lasting a total of 3 minutes. The choice of LFS used in this study was motivated by the unpredictable neural response observed by Lahr et al with a LFS of 0.05–0.23 Hz [47] and the observation of increased neural response after HFS using a LFS of 0.83 Hz or 1 Hz by Cavus et al [18] and Teyler et al [5]. For HFS, the checkerboard flashed at a rate of 9 Hz for two minutes.…”

“…Clapp et al observed increased BOLD response bilaterally in the extrastriate visual cortex whereas Lahr et al reported decreased activations in primary and secondary visual cortices following HFS [12, 17]. Using EEG, Cavus et al demonstrated sustained potentiation after HFS in the primary visual cortex and visual association cortices in healthy volunteers, but not in adults with schizophrenia [18].…”

Tuning noninvasive brain stimulation with MRI to cope with intersubject variability

“…Accordingly, the existing criteria for the definition of LTP at the synapse, more specifically persistence, input specificity, associativity, and cooperativity, could be employed as a starting point to justify the choice of terminology on the network level while also entailing separate analyses of network stimulation effects. Finding a bridge between local plasticity processes observed at the cellular level and the global network behaviour might provide researchers with crucial hints as to the underlying neurophysiological factors for the observed high interindividual variability [17][18][19], which impedes the efficacy and reliability of common tDCS paradigms [20,21 && ].…”