Brain imaging correlates of peripheral nerve stimulation

Abstract

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.

Effects of chronic abdominal vagal stimulation of small-diameter neurons on brain metabolism and food intake

“…Furthermore, we also observed an activation of the cingular cortex irrespective of the stimulation pattern, which is compatible with DVC projection (20,22). Finally, the activation of the prefrontal cortex could reflect its connectivity with the thalamo-insular pathway, which is altered during VNS-dependent alterations in synaptic plasticity (30).…”

“…Since the number of axons involved in the generation of action potentials during S1 stimulation represents only a small fraction of the nerve, the activation of the primary brain integrator, i.e., the DVC, may not be strong enough to be detected with PET imaging (35). Such phenomena have already been noticed during vagal stimulation performed at the cervical vagus level (20).…”

“…The extend of activated DVC neurons might be so small that it impossible to identify a DVC activation (versus background noise) because of the intrinsic limitations of our present imaging methods (18). Hence the reported absence of activation of the DVC in individuals with vagal stimulation irrespective of the brain imaging method used (15,(19)(20)(21)(22). Conversely, using pulsons, large intensity currents could be applied to the nerve trunk, allowing effective triggering of a neuronal response through a larger amount of small diameter neurons being recruited.…”

Trigeminal nerve stimulation modulates brainstem more than cortical excitability in healthy humans

“…The similarity of clinical effects induced by VNS and TNS has given rise to the hypothesis that these neuromodulatory interventions may share not only crucial anatomical structures but also neurobiological mechanisms (Fanselow 2012;Bari and Pouratian 2012). The effects of VNS on hand cortical excitability, namely on SICI were explored by only one study (Di Lazzaro et al 2004).…”

Trigeminal branch stimulation for the treatment of intractable craniofacial pain

“…Indeed, the mechanism by which peripheral neurostimulation works is unclear and probably involves a complex interplay between the central and peripheral nervous system. 2,3 Only a few practitioners at specialized centers routinely implant peripheral neurostimulatory devices, so it comes as no surprise that case studies in its use for craniofacial pain have been limited. Thus, we have shared our extensive experience with the use of trigeminal branch stimulation in the treatment of intractable craniofacial pain.…”