Abstract
Although deep brain stimulation of the entorhinal cortex has recently shown promise in the treatment of early forms of cognitive decline, the underlying neurophysiological processes remain elusive. Therefore, the lateral entorhinal cortex (LEC) was stimulated with trains of continuous 5 Hz and 20 Hz pulses or with bursts of 100 Hz pulses to visualize activated neuronal networks, i.e., neuronal responses in the dentate gyrus and BOLD responses in the entire brain were simultaneously recorded. Electrical stimulation of the LEC caused a wide spread pattern of BOLD responses. Dependent on the stimulation frequency, BOLD responses were only triggered in the amygdala, infralimbic, prelimbic, and dorsal peduncular cortex (5 Hz), or in the nucleus accumbens, piriform cortex, dorsal medial prefrontal cortex, hippocampus (20 Hz), and contralateral entorhinal cortex (100 Hz). In general, LEC stimulation caused stronger BOLD responses in frontal cortex regions than in the hippocampus. Identical stimulation of the perforant pathway, a fiber bundle projecting from the entorhinal cortex to the dentate gyrus, hippocampus proper, and subiculum, mainly elicited significant BOLD responses in the hippocampus but rarely in frontal cortex regions. Consequently, BOLD responses in frontal cortex regions are mediated by direct projections from the LEC rather than via signal propagation through the hippocampus. Thus, the beneficial effects of deep brain stimulation of the entorhinal cortex on cognitive skills might depend more on an altered prefrontal cortex than hippocampal function.
Highlights
Deep brain stimulation has become an emerging tool for the treatment of cognitive decline during the progression of neurodegenerative diseases
To compare putative frequency-dependent specific BOLD activation patterns, the same animals were used for all four different stimulation conditions, so differences in the BOLD activation pattern were not caused by different locations of the stimulation electrode
All electrophysiological recordings were simultaneously performed during the Functional MRI (fMRI) measurements, so the electrophysiological responses reflect neuronal activities in the dentate gyrus during formation of the corresponding BOLD responses
Summary
Deep brain stimulation has become an emerging tool for the treatment of cognitive decline during the progression of neurodegenerative diseases. LEC Stimulation and BOLD fMRI Responses plaque load in the hippocampus (Xia et al, 2017); entorhinal cortex stimulation might act by improving hippocampal signal processing. We employed electrical perforant pathway stimulation to activate the hippocampal formation, i.e., orthodromic neurons in the dentate gyrus, hippocampus proper (CA1-CA3), subiculum, and antidromic neurons in the entorhinal cortex. Under certain stimulation conditions, significant fMRI responses were triggered in several cortical and subcortical structures outside the hippocampal formation, in particular in the septal area and in the nucleus accumbens, medial prefrontal cortex/anterior cingulate, basolateral amygdala, and VTA/substantia nigra (Helbing et al, 2013; Riemann et al, 2017). Co-activation of the medial prefrontal cortex (mPFC) and other cortical areas critically depends on the applied stimulation frequency
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