Hypothalamic deep brain stimulation in positron emission tomography

Abstract

Recently, functional imaging data have underscored the crucial role the hypothalamus plays in cluster headache, one of the most severe forms of primary headache. This prompted the application of hypothalamic deep brain stimulation. Yet, it is not apparent how stimulation of an area that is thought to act as a pace-maker for acute headache attacks is able to prevent these attacks from occurring. We addressed this issue by examining 10 operated chronic cluster headache patients, using H2(15O)-positron emission tomography and alternately switching the hypothalamic stimulator on and off. The stimulation induced activation in the ipsilateral hypothalamic gray (the site of the stimulator tip), the ipsilateral thalamus, somatosensory cortex and praecuneus, the anterior cingulate cortex, and the ipsilateral trigeminal nucleus and ganglion. We additionally observed deactivation in the middle temporal gyrus, posterior cingulate cortex, and contralateral anterior insula. Both activation and deactivation are situated in cerebral structures belonging to neuronal circuits usually activated in pain transmission and notably in acute cluster headache attacks. Our data argue against an unspecific antinociceptive effect or pure inhibition of hypothalamic activity. Instead, the data suggest a hitherto unrecognized functional modulation of the pain processing network as the mode of action of hypothalamic deep brain stimulation in cluster headache.

Figure 1.

A, Design of the PET study in 10 cluster headache patients. Using a block design and alternately switching the hypothalamic stimulator on and off, each patient had 12 consecutive H₂¹⁵O-water PET scans during two conditions: (1) baseline (stimulator off) and (2) during DBS (stimulator on). To allow for comparable conditions, the stimulator was turned on or off exactly 60 s before the start of each scan and was kept in this position until 60 s before the consecutive scan. stim, Stimulation. B–E, Comparison of hypothalamic stimulator on and off condition in 10 patients with chronic cluster headache. The activations during the condition stimulator on are displayed as statistical parametric maps that show the areas of significant rCBF increases (p < 0.05) in yellow superimposed on a normalized T1-weighted image of a healthy control subject. Significant activation was detected in the ipsilateral posterior inferior hypothalamic gray (the site of the stimulator tip) and the ipsilateral insula (B) and the ipsilateral trigeminal nucleus and ganglion (C). Additionally significant deactivations during the condition stimulator on are displayed as statistical parametric maps that show the areas of significant rCBF decreases (p < 0.05) in blue superimposed on a normalized T1-weighted image of a healthy control subject. Deactivations occurred in the contralateral insula and the primary somatosensory cortex (B) and in the inferior temporal cortex bilaterally (D). Both activations and deactivations are situated in cerebral structures belonging to neuronal circuits usually activated in pain transmission. E magnifies the same axial view as C, to better visualize the finding. The right side of the picture is the right side of the brain.