Direct peripheral nerve stimulation is an effective treatment for a number of 
disorders including epilepsy, depression, neuropathic pain, cluster headache, 
and urological dysfunction. The efficacy of this stimulation is ultimately due 
to modulation of activity in the central nervous system. However, the exact 
brain regions involved in each disorder and how they are modulated by peripheral 
nerve stimulation is not fully understood. The use of functional neuroimaging 
such as SPECT, PET and fMRI in patients undergoing peripheral nerve stimulation 
can help us to understand these mechanisms. We review the literature for 
functional neuroimaging performed in patients implanted with peripheral nerve 
stimulators for the above-mentioned disorders. These studies suggest that brain 
activity in response to peripheral nerve stimulation is a complex interaction 
between the stimulation parameters, disease type and severity, chronicity of 
stimulation, as well as nonspecific effects. From this information we may be 
able to understand which brain structures are involved in the mechanism of 
peripheral nerve stimulation as well as define the neural substrates underlying 
these disorders.