Alexander J. Radnovich

Alcohol‐Related Olfactory Cues Activate the Nucleus Accumbens and Ventral Tegmental Area in High‐Risk Drinkers: Preliminary Findings

BACKGROUND The mesocorticolimbic dopamine system is implicated in motivation and reward and may be involved in the development of alcoholism. METHODS We used functional magnetic resonance imaging to study the blood oxygen level-dependent (BOLD) response to alcohol-related olfactory stimuli (AROS; odors of beer and whiskey) and non-alcohol-related olfactory stimuli (NAROS; odors of grass and leather) in 10 high-risk (HR) drinkers (average drinks per week, 19.99; SD, 6.99; all with > or = 2 first- or second-degree alcoholic relatives) and 5 low-risk (LR) social drinking controls (drinks per week, 2.82; SD, 2.87; 1 subject had 1 second-degree alcoholic relative). Data were analyzed with SPM99 and random effects analysis by using regions of interest and corrected cluster statistics (p < 0.05) to focus on the nucleus accumbens (NAc) and ventral tegmental area (VTA). RESULTS In HR subjects, there was a greater BOLD signal increase in the NAc during AROS than during clean air. BOLD signal increases during AROS were also greater in the NAc than the signal increases induced by NAROS. The AROS signal was significantly greater than the NAROS signal in a small number of voxels in the VTA. Finally, the AROS/NAROS difference signal was larger in HR drinkers in both the NAc and VTA. CONCLUSIONS Alcoholic olfactory cues may invoke the dopaminergic mesocorticolimbic system to a greater degree than nonalcoholic odors and could be effective tools in exploring the role of the dopamine system in susceptibility to alcoholism.

Olfactory system activation from sniffing: effects in piriform and orbitofrontal cortex

Neuroimaging studies suggest that piriform cortex is activated at least in part by sniffing. We used H(2)(15)O positron emission tomography (PET) to study 15 healthy volunteers while they participated in four conditions, two of which were sniffing odorants and odorless air. The remaining two conditions involved a constant, very low flow of either odorized or odorless air during velopharyngeal closure (VPC), a technique that prevents subject-induced airflow through the nasal passages. Contrary to expectation, sniffing under odorless conditions did not induce significant piriform and surrounding cortical (PC+) activity when compared to odorless VPC, even at a liberal statistical threshold. However, a small correlation emerged in PC+ between the difference signal of [odorless sniffing - odorless VPC] and peak rate of nasal pressure change. PC+ activity was, however, strongly evoked by odorant exposure during sniffing and VPC, with neither technique showing greater activation. Activity in orbitofrontal (olfactory association) cortex was absent during odorant stimulation (OS) with VPC, but present during odorant sniffing. Sniffing may therefore play an important role in facilitating the higher-order analysis of odors. A right orbitofrontal region was also activated with odorless sniffing, which suggests a possible orbitofrontal role in guided olfactory exploration.

Involvement of the Left Anterior Insula and Frontopolar Gyrus in Odor Discrimination

Discriminating between successively presented odors requires brief storage of the first odors perceptual trace, which then needs to be subsequently compared to the second odor in the pair. This study explores the cortical areas involved in odor discrimination and compares them with findings from studies of working‐memory, traditionally investigated with n‐back paradigms. Sixteen right‐handed subjects underwent H215O positron emission tomography during counterbalanced conditions of odorless sniffing, repeated single odor detection, multiple odor detection, and conscious successive discrimination between odor pairs. Eight odorants were delivered using a computer‐controlled olfactometer through a birhinal nasal cannula. Conscious successive odor discrimination evoked significantly greater activity in the left anterior insula and frontopolar gyrus when compared to reported sensory detection of the identical odors. Additional activation was found in the left lateral orbital/inferior frontal and middle frontal gyri when discrimination was compared to the odorless condition. The left anterior insula is likely involved in the evaluation of odor properties. Consistent with other studies, frontopolar and middle frontal gyrus activation is more likely related to working memory during odor discrimination. Hum Brain Mapp, 2007.

Affect Recognition, Empathy, and Dysosmia After Traumatic Brain Injury

OBJECTIVE To investigate if olfaction is associated with affect recognition and empathy deficits after traumatic brain injury (TBI). Prior research has shown that TBI often leads to loss of smell. We hypothesized a relationship with emotion perception, because the neural substrates of the olfactory system overlap with the ventral circuitry of the orbital frontal cortex, which play a critical role in affective responses, such as empathy. DESIGN Comparative study investigating differences between participants with TBI who had impaired olfaction (dysosmia) with those with normal olfaction (normosmia). SETTING Postacute rehabilitation facilities in the United States, Canada, and New Zealand. PARTICIPANTS Participants (N=106) in the current study were a convenience sample of adults with moderate to severe TBI who were tested for olfactory function as part of a larger, related study on affect recognition. On average, participants were 11.5 years postinjury. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Olfaction (Brief Smell Identification Test), facial affect recognition (Diagnostic Assessment of Nonverbal Affect 2-Adult Faces [DANVA2-AF]), vocal affect recognition (Diagnostic Assessment of Nonverbal Affect 2-Adult Paralanguage [DANVA2-AP]), emotional inference (Emotional Inference from Stories Test [EIST]), and empathy (Interpersonal Reactivity Index [IRI]). RESULTS Fifty-six percent of participants were dysosmic and only 36% of these participants were aware of their deficit. Participants with dysosmia performed significantly poorer on the DANVA2-AF (P=.003), DANVA2-AP (P=.007), EIST (P=.016), and IRI (P=.013). Medium effect sizes were found for all measures. Dysosmia had a sensitivity value of 86.4% for detecting facial affect recognition impairments and 67.8% for vocal affect recognition impairments. CONCLUSIONS This study shows that olfactory deficits may be indicative of affect recognition impairments and reduced empathy. Early knowledge of affect recognition and empathy deficits would be valuable so that treatment could be implemented predischarge.

Functional neuroanatomical correlates of episodic memory impairment in early phase psychosis

Studies have demonstrated that episodic memory (EM) is often preferentially disrupted in schizophrenia. The neural substrates that mediate EM impairment in this illness are not fully understood. Several functional magnetic resonance imaging (fMRI) studies have employed EM probe tasks to elucidate the neural underpinnings of impairment, though results have been inconsistent. The majority of EM imaging studies have been conducted in chronic forms of schizophrenia with relatively few studies in early phase patients. Early phase schizophrenia studies are important because they may provide information regarding when EM deficits occur and address potential confounds more frequently observed in chronic populations. In this study, we assessed brain activation during the performance of visual scene encoding and recognition fMRI tasks in patients with earlyphase psychosis (n = 35) and age, sex, and race matched healthy control subjects (n = 20). Patients demonstrated significantly lower activation than controls in the right hippocampus and left fusiform gyrus during scene encoding and lower activation in the posterior cingulate, precuneus, and left middle temporal cortex during recognition of target scenes. Symptom levels were not related to the imaging findings, though better cognitive performance in patients was associated with greater right hippocampal activation during encoding. These results provide evidence of altered function in neuroanatomical circuitry subserving EM early in the course of psychotic illness, which may have implications for pathophysiological models of this illness.