Potential Surgical Targets For Deep Brain Stimulation In Treatment-Resistant Depression

Jason S. Hauptman, MD; Antonio A. F. DeSalles, MD, PhD; Randall Espinoza, MD, MPH; Mark Sedrak, MD; Warren Ishida, MD


Neurosurg Focus. 2008;25(1):E3 

In This Article

Inferior Thalamic Peduncle

The ITP has been identified by Velasco et al.[68] as a potential stimulation target for refractory depression (Fig. 4). The ITP is a bundle of fibers that connects the nonspecific thalamic system to the orbitofrontal cortex; this system induces electrocortical synchronization and aids the inhibition of input of irrelevant stimuli (thus providing selective attention).[23,68] According to functional imaging and PET, both the ITP and orbitofrontal cortex have proven to be hyperactive in depression, a phenomenon that reverses with effective pharmacological treatment.[68] When these areas are lesioned, hyperkinesias and increased attentiveness result.[68] Thus, neuromodulation with high-frequency DBS may be effective during depression episodes.

Figure 4.

Diffusion tensor and stereotactic images revealing localization of the ITP. Note the projections throughout the frontal lobe, ventral tegmentum/brainstem, and mesolimbic structures. Fractional anisotropy = 0.2, minimum fiber length 36 mm.

In 2005 Jiménez et al.[23] published their first report of successful DBS electrode implantation in the ITP for refractory depression. In that case a 49-year-old woman with severe TRD and multiple hospitalizations received bilateral tetrapolar electrodes in the ITP, which were continuously stimulated at 130 Hz. Both EEG studies and clinical changes following a period of acute stimulation with temporary electrodes guided permanent electrode placement. Optimal electrode placement was determined to be 5.0 mm lateral to the midline, 4.0 mm behind the AC, and 0.5 mm below the AC-PC line. Postoperatively, while stimulation was on, the patient experienced global improvement in function, neuropsychological scores, and Hamilton depression scores; this effect was reversed when the stimulator was off. Interestingly, there was an initial temporary antidepressant effect after electrode placement even without stimulation, an occurrence similar to that in some patients who experience transient tremor relief after the placement of thalamic electrodes. Overall, the therapeutic effect of stimulation was believed to be attributable to the inhibition of the orbitofrontal cortex, which is typically overactive in depressed patients.[23] Although this initial report indicates promise, large-scale trials of implantation are necessary to determine the efficacy and safety of this target.


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