Physiologically initiated and inhibited phantosmia: Cyclic unirhinal, episodic, recurrent phantosmia revealed by brain fMRI

Purpose: Our goal was to use functional magnetic resonance imaging (fMRI) t o demonstrate brain activation in patients with unirhinal, episodic, recurr ent phantosmia who induced their phantosmia by coughing, sneezing, laughing or vigorous nasal inhalation and expiration, and inhibited it by sleep or performance of a Valsalva type maneuver. Methods: Three patients with unirhinal phantosmia without change in taste o r smell acuity were studied by fast low angle shot (FLASH) MRI and by echo planar imaging (EPI). Brain activation was measured following memory of two tastants (salt, sweet), memory of two odorants (banana and peppermint), ac tual smell of three odors (amyl acetate, menthone, pyridine), memory of pha ntosmia(and phantageusia, where applicable), phantosmia initiated spontaneo usly or by vigorous nasal inhalation and exhalation, phantosmia after inhib ition by Valsalva, and these stimuli before and after treatment with the ne uroleptic thioridazine. Activation images were derived using correlation an alysis and ratios of areas of brain activated to total brain areas were cal culated. Total activated pixel cluster counts were also used to quantitativ e total and regional brain activation. Results: Sensory-specific brain activation was present in each section in e ach patient following memory of tastants and odorants, actual smell of each odor and memory, and initiation of and inhibition of phantosmia. Activatio n to odor memory after phantosmia initiation was very robust, whereas after phantosmia inhibition it was similar to that in normal subjects. Brain act ivation to unirhinal phantosmia was bihemispheric, independent of whether i t was left or right sided or patient handedness. While phantosmia memory ti n the absence of initiated phantosmia) produced extremely robust brain acti vation, after initiation and inhibition of phantosmia apparent brain activa tion decreased. These changes need to be related to shifting state of basel ine brain activation and should be interpreted to reflect increased rather than decreased brain activation over that of phantosmia memory alone. Treat ment with thioridazine inhibited brain activation to all stimuli including phantosmia and phantageusia memory, as it did previously in patients with b irhinal phantosmia. Conclusions: 1) Unirhinal phantosmia can be demonstrated by brain fMRI as c an birhinal phantosmia; 2) unirhinal phantosmia can be initiated and inhibi ted by physiological maneuvers reflected by changes in fMRI brain activatio n; 3) fMRI brain activation of unirhinal phantosmia is bihemispheric and in dependent of peripheral side of phantosmia or patient handedness; 4) anteri or frontal brain region plays a significant role in both phantosmia initiat ion and inhibition as, to some extent, do temporal brain regions; 5) activa tion of brain GABAergic systems appears to play a role in inhibition of uni rhinal phantosmia; and 6) unirhinal phantosmia, similar to birhinal phantos mia, may reflect a type of maladaptive brain plasticity similar to that hyp othesized to be responsible for phantom limb pain.