PURPOSE: Our clinical treatments for peripheral nerve injuries are limited in their ability to understand the cortical changes that occur in response to injury and their subsequent repair.  The purpose of the study is to develop an fMRI version of the ‘ratunculus’ to build an animal model that can be used to study cortical plasticity that occurs with peripheral nerve injuries and repair.

METHOD: The first part of the study uses BOLD fMRI to measure the cortical activity in response to direct electrical stimulation of the median, ulnar, radial and musculocutaneous nerves of the rat upper extremity.  The second study measures the BOLD fMRI signals in response to direct cutaneous stimulation of individual digits.  Twenty-one Spague-Dawley rats were used for the first part of this study.  Each rat underwent surgery to cannulate the femoral artery and vein under isoflurane anesthesia as well as a tracheotomy for mechanical ventilation.  The terminal branches of the brachial plexus were exposed surgically and a 150μm diameter stainless-steel bipolar electrodes was attached to the ulnar (in 6 rats), median (5 rats), radial (5 rats) and musculocutaneous (5 rats) nerves.  For the digital stimulation, 150μm diameter stainless-steel bipolar electrodes were attached to the each of the 4 individual digits of the left and right forepaw (8 digits total) in 6 rats.  Medetomidine (Domitor) anesthesia (Infusion 0.1mg/kg/hr) was used during the fMRI portion of the procedure.  In addition, pancuronium bromide (1.0mg/kg/hr) was used during the direct nerve stimulation procedure.  The data were acquired with a Bruker AVANCE 9.4T MRI animal scanner. The nerves and digits were electrically stimulated with a 20 seconds ON / 40 seconds OFF (3 blocks) boxcar sequence with an initial 40 seconds off. A p-value of 0.005 was the activation threshold.  Two different frequencies (5 Hz and 10 Hz) and two different currents (0.5 mA and 1.0 mA) were used for the ON period of the direct nerve stimulation protocol.  A current of 1.0 mA was used during the ON periods for the digital stimulation protocol. 

RESULTS: A distinct pattern of cortical activation was found for each nerve. The higher stimulation current resulted in a dramatic increase in the level of cortical activation. The higher stimulation frequency resulted in both increases and attenuation of cortical activation in different regions of the brain, depending on which nerve was stimulated. For digital stimulation, higher resolution fMRI enabled the discrimination between the individual digits in the sensory region of the rat cortex.

CONCLUSION: This study describes a novel approach for mapping the motor and sensory pathways in the rat brain by directly stimulating the nerves or individual digits of the rat upper extremity. The goal of developing a rodent fMRI model for brachial plexus and peripheral nerve injuries appears within reach.