Impact of acoustic coordinated reset neuromodulation on effective connectivity within a neural tinnitus network
Silchenko A. N.1, Adamchic I.1, Hauptmann C.1, Tass P.A.1, 2
1 Institute of Neuroscience and Medicine – INM-7, Research Center Juelich, Juelich, Germany
2 Department of Stereotactic and Functional Neurosurgery, University of Cologne, Cologne, Germany
Chronic subjective tinnitus is an auditory phantom sensation, which evolves as a consequence of damage to the peripheral auditory system and causes characteristic changes of brain activity in the central auditory system. In a prospective, randomized, single blind, placebo-controlled clinical trial, we used acoustic coordinated reset (CR) neuromodulation to specifically counteract subjective chronic tonal tinnitus by means of desynchronization of tinnitus related neuronal synchrony. CR treatment was safe and well-tolerated and resulted in a significant decrease of symptoms, as measured by clinical scores, as well as in significant changes in the oscillatory brain activity . A mechanism, underlying the perception of a phantom sound, is likely to include the imbalance in communication between auditory and non-auditory brain areas. The objective of the present study was to analyze whether CR neuromodulation caused an alteration of the effective connectivity in a tinnitus related network of localized EEG brain sources.EEG recordings were performed at baseline and after 12 weeks of CR therapy in 28 patients with bilateral chronic tinnitus and in a control group of healthy subjects.
To increase the signal-to-noise ratio, we focused on a subgroup of good responders, which is characterized by the substantial reduction in clinical scores after 12 weeks. To determine which connections matter, we performed a BESA source reconstruction in the following predefined regions of interest: temporal and frontal areas, parietal cortex, and anterior and posterior cingulate cortex. To that network we applied a data-driven approach, combining empirical mode decomposition and partial directed coherence analysis , in patients with bilateral tinnitus before and after 12 weeks of CR therapy as well as in healthy controls. Dynamic causal modeling (DCM) was used to infer about the types of interactions, which were altered by CR neuromodulation. Prior to CR therapy and compared to the healthy controls, the good responders showed a significantly increased connectivity between the left primary auditory cortex and the posterior cingulate cortex in the gamma and delta bands together with a significantly decreased effective connectivity between the right primary auditory cortex and the dorsolateral prefrontal cortex in the alpha band. After 12 weeks of CR therapy most of the pathological interactions were gone, so that the connectivity patterns of good responders and healthy controls became statistically indistinguishable. Our DCM results show that CR therapy specifically counteracted the imbalance of excitation and inhibition. CR therapy significantly weakened the excitatory connection between posterior cingulate cortex and primary auditory cortex and significantly strengthened inhibitory connections between auditory cortices and the dorsolateral prefrontal cortex .
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