Patients with essential tremor suffer from involuntary and rhythmic movements of heads, hands, and legs. In addition to motor-related symptoms, non-motor features such as mild cognitive deficits have been discovered, implying the alterations in both cerebellar circuits and cerebral functions. As a disorder with a wide spectrum of clinical features, the underlying mechanisms of essential tremor and its alteration to the brain are not well recognized. Investigation to the animal models of essential tremor can provide more insights into its brain circuitry. This study utilized harmaline injection on rat model to mimic tremor features and characterized its brain networks by using resting-state functional MRI. The tremor movements were monitored by a customized platform combined with an accelerometer. The resting-state networks and the functional connectivity among several brain hubs were identified. Aside from regular movement of the rat, excessive movement frequency within 13–15 Hz was detected in the harmaline-injected rats. The fMRI results reveal the alteration of default mode network in the harmaline-induced tremor rat, particularly the lower connectivity in hippocampus and higher connectivity in primary somatosensory cortex. Furthermore, comparing with control rats, the harmaline-induced rats exhibited significantly higher functional connectivity among several region-pairs, including the connectivity between left hippocampus and left striatum, left hippocampus and right motor, left hippocampus and left somatosensory, and bilateral somatosensory cortex. Although the rat models were scanned under anesthesia, the consequences of the harmaline injection can be probed by using the resting-state fMRI, showing that the alteration is not only on the olivocerebellar circuit but also on other cerebral hubs. Besides, a low-price detection module for tremor measurement was developed by combining the accelerometer. The concept has the potential to be implemented to wearable devices for longitudinal recording in the future. In summary, the alteration in the resting-state brain networks of harmaline-induced tremor rat model has been identified in this study, highlighting specific regions that are associated with harmaline-induced tremor. The brain networks in this rat model can be further examined after various therapeutic approaches in the future.

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Brain Network Changes in the Harmaline Induced Tremor Rat Model

  • Sheng-Min Huang,
  • Li-Wei Kuo

摘要

Patients with essential tremor suffer from involuntary and rhythmic movements of heads, hands, and legs. In addition to motor-related symptoms, non-motor features such as mild cognitive deficits have been discovered, implying the alterations in both cerebellar circuits and cerebral functions. As a disorder with a wide spectrum of clinical features, the underlying mechanisms of essential tremor and its alteration to the brain are not well recognized. Investigation to the animal models of essential tremor can provide more insights into its brain circuitry. This study utilized harmaline injection on rat model to mimic tremor features and characterized its brain networks by using resting-state functional MRI. The tremor movements were monitored by a customized platform combined with an accelerometer. The resting-state networks and the functional connectivity among several brain hubs were identified. Aside from regular movement of the rat, excessive movement frequency within 13–15 Hz was detected in the harmaline-injected rats. The fMRI results reveal the alteration of default mode network in the harmaline-induced tremor rat, particularly the lower connectivity in hippocampus and higher connectivity in primary somatosensory cortex. Furthermore, comparing with control rats, the harmaline-induced rats exhibited significantly higher functional connectivity among several region-pairs, including the connectivity between left hippocampus and left striatum, left hippocampus and right motor, left hippocampus and left somatosensory, and bilateral somatosensory cortex. Although the rat models were scanned under anesthesia, the consequences of the harmaline injection can be probed by using the resting-state fMRI, showing that the alteration is not only on the olivocerebellar circuit but also on other cerebral hubs. Besides, a low-price detection module for tremor measurement was developed by combining the accelerometer. The concept has the potential to be implemented to wearable devices for longitudinal recording in the future. In summary, the alteration in the resting-state brain networks of harmaline-induced tremor rat model has been identified in this study, highlighting specific regions that are associated with harmaline-induced tremor. The brain networks in this rat model can be further examined after various therapeutic approaches in the future.