Neurons are sensitive to the adverse effects of ultrasound. Cerebral tissue has a relatively low absorption coefficient, but the temperature of the cranium increases during ultrasound exposure and raises the temperature of the adjacent brain through a conduction mechanism.97This phenomenon is particularly important in the fetus when using a Doppler ultrasound mode, which is a stationary mode with the potential for producing the greatest temperature increases in bone. In addition to these indirect thermal effects, ultrasound also causes direct neural effects. For example, high-intensity focused ultrasound was previously used to produce destructive lesions in the brain. Fry et al. demonstrated that focused ultrasound was capable of causing reversible suppression of neural transmission.98Direct exposure of the brain to high-intensity (150–1,500 W/cm2) ultrasound was also shown to produce thermal and cavitation effects as indicated by neural apoptosis.99,100Ultrasound exposure to the lumbar plexus causes hind limb paralysis in experimental animals.101Hind limb paralysis was observed at room temperature after a 4.3-s ultrasound exposure (35 W/cm2) to the lumbar area, but more prolonged exposure duration (7.3 s) was required to produce similar neurologic damage at cooler temperatures (1–2°C).101Histologic analysis revealed neuronal and myelin destruction in the spinal cord, and axonal degeneration, chromatolysis, pyknosis with intact mesenchymal structures, and clumping of myelin in the peripheral nerves and cauda equina.102These data indicated that ultrasound-induced neural injury was temperature dependent. An increase in the peak rarefactional pressures or the pulse repetition frequency also worsens these adverse effects.103,104The rapid onset of spinal cord injury suggested that cavitation was the most likely mechanism because thermal damage requires adequate time for temperature rise and most often occurs at an ultrasound focal point at which maximum temperature increase is known to occur.99,103,105Nevertheless, there is some experimental evidence suggesting that myelin is especially sensitive to ultrasound. Such effects impair neural conduction through disruption of contact processes, periaxonal enlargement, and direct alterations in myelination.106Studies examining the effects of ultrasound on myelin and nerve conduction velocity in conscious animals may be difficult to interpret because animal restraint also changes myelin formation.107Reversible changes in conduction velocity and compound action potential have been reported during the use of ultrasound. Smaller unmyelinated fibers are most susceptible to these effects. The compound action potential decreases with repeated pulses of ultrasound.108,109A direct relationship between acoustic intensities and conduction velocity has also been demonstrated in vitro . Sodium and potassium channels open with increases in temperature during ultrasound exposure, thereby affecting conduction velocity. An increase in ultrasound intensity (2–3 W) inactivates stretch-sensitive channels and decreases the compound action potential. Mechanical effects (e.g. , radiation pressure) may also play a role in ultrasound-induced changes in ion channel function through stretch-sensitive channels.110,–,112Highly focused ultrasound decreased presynaptic activity and increased dendritic field potentials in hippocampal slices.113Auditory evoked potentials were also transiently suppressed after ultrasound exposure in the diagnostic range.114In contrast to these studies suggesting that high-intensity ultrasound may cause neural dysfunction, exposure to lower intensity may cause beneficial effects. Rat tibial nerves exposed to therapeutic ultrasound intensities between 0.5 and 1 W/cm2demonstrated more rapid recovery of nerve conduction velocity and compound action potential after a crush injury115concomitant with functional improvement.116,117Injured nerves exposed to therapeutic ultrasound also showed histologic evidence of regeneration including increased nerve fiber density, prominent Schwann cell nuclei, and previous myelin formation compared with nerves that had not been exposed to ultrasound.118