Water diffusion reveals networks that modulate multiregional morphological plasticity after repetitive brain stimulation

Abstract

Repetitive brain stimulation protocols induce plasticity in the stimulated site in brain slice models. Recent evidence from network models has indicated that additional plasticity-related changes occur in nonstimulated remote regions. Despite increasing use of brain stimulation protocols in experimental and clinical settings, the neural substrates underlying the additional effects in remote regions are unknown. Diffusion-weighted MRI (DWI) probes water diffusion and can be used to estimate morphological changes in cortical tissue that occur with the induction of plasticity. Using DWI techniques, we estimated morphological changes induced by application of repetitive transcranial magnetic stimulation (rTMS) over the left primary motor cortex (M1). We found that rTMS altered water diffusion in multiple regions including the left M1. Notably, the change in water diffusion was retained longest in the left M1 and remote regions that had a correlation of baseline fluctuations in water diffusion before rTMS. We conclude that synchronization of water diffusion at rest between stimulated and remote regions ensures retention of rTMS-induced changes in water diffusion in remote regions. Synchronized fluctuations in the morphology of cortical microstructures between stimulated and remote regions might identify networks that allow retention of plasticityrelated morphological changes in multiple regions after brain stimulation protocols. These results increase our understanding of the effects of brain stimulation-induced plasticity on multiregional brain networks. DWI techniques could provide a tool to evaluate treatment effects of brain stimulation protocols in patients with brain disorders.R epetitive electrical brain stimulation induces long-term potentiation (LTP) or depression (LTD) at the stimulated neurons (1-4). In humans, repetitive transcranial magnetic stimulation (rTMS) alters cortical excitability at the stimulated site that outlasts the end of the stimulation, analogous to LTP or LTD in animal models (5, 6), but also affects remote regions, possibly through transsynaptic pathways (7,8). Although rTMS has been proposed as a potential treatment for neurological and psychiatric disorders (9, 10) and as a method to facilitate learning (11), the neural substrates underlying the effects of rTMS on remote regions of the brain remain poorly understood.Diffusion-weighted MRI (DWI) probes water diffusion, a thermal physical phenomena that is characterized by random motion of water molecules (12). Water diffusion is altered by the structures of gray matter (12). DWI can be used to evaluate morphological changes in cortical microstructures (13)(14)(15)(16)(17)(18)(19) and can function as a probe to estimate immediate and transient changes in water diffusion that are associated with ischemia (17) or neuronal firing (13,16,19) and delayed and persistent changes that are associated with long-term plasticity in experimental settings (20) or pathological conditions (15,18,21). Here, using DWI techniques, we examined whether subt...

Mean diffusivity of globus pallidus associated with verbal creativity measured by divergent thinking and creativity‐related temperaments in young healthy adults

“…In other words, MD decreases are likely to reflect an increase in tissue density due to the shape of neurons or glia, enhancement of tissue organization (strengthening of axonal or dendritic backbones and surrounding tissue) [ Assaf and Pasternak , ]. Further, intervention paradigms that caused these tissue density increases, decreases MD [ Sagi et al ., ] and intervention paradigms that caused the synaptic decreases, increases MD [ Abe et al ., ], thus confirming these ideas. In addition, a wide range of clinical studies of neuronal degeneration have shown an increase in MD, which also confirmed this idea [ Andreone et al ., ; Kantarci et al ., ; Nusbaum et al ., ].…”

Working memory training impacts the mean diffusivity in the dopaminergic system

“…Therefore, although there is a wide range of possible mechanisms, these generally considered mechanisms, whether functional (such as activity) or structural (such as synaptic changes), suggest that an increase in MD values in the normal sample represents a certain loss of the components of the tissue system. This interpretation of cognitive intervention-related changes in MD has been proposed in recent studies (Abe et al 2014 ; Johansen-Berg et al 2012 ; Sagi et al 2012 ). However, our previous study, which was performed using a sample that overlapped with the present one, reported WMT-related regional gray matter volume increases in areas that included the left DLFPC, ACC, and left caudate (Takeuchi et al 2013a ).…”

“…Nonetheless, as discussed above, the present result of WMT-related increase in MD is not congruent with our previously reported WMT-related regional gray matter volume increase in a similar area, if we assume the same physiological mechanisms (such as synaptic changes) underlie both changes. Furthermore, recent previous studies reported the sensitivity of MD to detect the neural plasticity that occurs soon after the intervention (Abe et al 2014 ; Johansen-Berg et al 2012 ). Thus, the results of the present study, together with those of previous studies, suggest the applicability of the unique properties of MD to investigate and identify regional neural plasticity.…”

Cognitive and neural correlates of the 5-repeat allele of the dopamine D4 receptor gene in a population lacking the 7-repeat allele

“…Furthermore, a recent investigation elucidated a unique property of MD in the gray matter. This is partly due to its sensitivity toward neural plasticity (Abe et al, 2014;Sagi et al, 2012). More pertinent to the present study's subject is its association with dopamine.…”