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Biomedical subjects

Ivanka Savic

Publications and source records attributed to Ivanka Savic.

12 recordsLinked to original sources
PubMed2007

Odor processing in multiple chemical sensitivity.

Multiple chemical sensitivity (MCS) is characterized by somatic distress upon exposure to odors. As in other idiopathic environmental intolerances, the mechanisms behind the reported hypersensitivity are unknown. Using the advantage of the well-defined trigger (odor), we investigated whether subjects with MCS could have an increased odor-signal response in the odor-processing neuronal circuits. Positron emission tomography (PET) activation studies with several different odorants were carried out in 12 MCS females and 12 female controls. Activation was defined as a significant increase in regional cerebral blood flow (rCBF) during smelling of the respective odorant compared to smelling of odorless air. The study also included online measurements of respiratory frequency and amplitude and heart rate variations by recording of R wave intervals (RR) on the surface electrocardiogram. The MCS subjects activated odor-processing brain regions less than controls, despite the reported, and physiologically indicated (decreased RR interval) distress. In parallel, they showed an odorant-related increase in activation of the anterior cingulate cortex and cuneus-precuneus. Notably, the baseline rCBF was normal. Thus, the abnormal patterns were observed only in response to odor signals. Subjects with MCS process odors differently from controls, however, without signs of neuronal sensitization. One possible explanation for the observed pattern of activation in MCS is a top-down regulation of odor-response via cingulate cortex.

Adult↗
PubMed2006

Structural changes in patients with primary generalized tonic and clonic seizures.

We conducted MR volumetry and voxel-based morphometry in 19 patients who had idiopathic generalized epilepsy (IGE) with tonic clonic seizures as the only seizure type and 52 control subjects. Patients exhibited elevated frontal lobe fraction of CSF and reduced fraction of gray matter in the frontal, parietal, temporal cortex, thalamus, and cerebellum. The thalamus and cerebellum also showed reduced volumes, as did the caudate and putamen. Contrary to current diagnostic criteria, regional tissue abnormalities may be present in IGE.

Adult↗
PubMed2006

Brain response to putative pheromones in lesbian women.

The progesterone derivative 4,16-androstadien-3-one (AND) and the estrogen-like steroid estra-1,3,5(10),16-tetraen-3-ol (EST) are candidate compounds for human pheromones. In previous positron emission tomography studies, we found that smelling AND and EST activated regions primarily incorporating the sexually dimorphic nuclei of the anterior hypothalamus, that this activation was differentiated with respect to sex and compound, and that homosexual men processed AND congruently with heterosexual women rather than heterosexual men. These observations indicate involvement of the anterior hypothalamus in physiological processes related to sexual orientation in humans. We expand the information on this issue in the present study by performing identical positron emission tomography experiments on 12 lesbian women. In contrast to heterosexual women, lesbian women processed AND stimuli by the olfactory networks and not the anterior hypothalamus. Furthermore, when smelling EST, they partly shared activation of the anterior hypothalamus with heterosexual men. These data support our previous results about differentiated processing of pheromone-like stimuli in humans and further strengthen the notion of a coupling between hypothalamic neuronal circuits and sexual preferences.

Adult↗
PubMed2005

Brain response to putative pheromones in homosexual men.

The testosterone derivative 4,16-androstadien-3-one (AND) and the estrogen-like steroid estra-1,3,5(10),16-tetraen-3-ol (EST) are candidate compounds for human pheromones. AND is detected primarily in male sweat, whereas EST has been found in female urine. In a previous positron emission tomography study, we found that smelling AND and EST activated regions covering sexually dimorphic nuclei of the anterior hypothalamus, and that this activation was differentiated with respect to sex and compound. In the present study, the pattern of activation induced by AND and EST was compared among homosexual men, heterosexual men, and heterosexual women. In contrast to heterosexual men, and in congruence with heterosexual women, homosexual men displayed hypothalamic activation in response to AND. Maximal activation was observed in the medial preoptic area/anterior hypothalamus, which, according to animal studies, is highly involved in sexual behavior. As opposed to putative pheromones, common odors were processed similarly in all three groups of subjects and engaged only the olfactory brain (amygdala, piriform, orbitofrontal, and insular cortex). These findings show that our brain reacts differently to the two putative pheromones compared with common odors, and suggest a link between sexual orientation and hypothalamic neuronal processes.

Adult↗
PubMed2005

Regional reductions in serotonin 1A receptor binding in juvenile myoclonic epilepsy.

BACKGROUND: Juvenile myoclonic epilepsy (JME) is classified as primarily generalized epilepsy and as such is assumed to lack an anatomic substrate. Although neurochemical abnormalities are probable, few studies have investigated whether they exist in JME. Animal data and the high incidence of myoclonic seizures in serotonin-intoxicated patients suggest that the serotonin system may be disturbed in JME. OBJECTIVE: To test the hypothesis that JME is associated with a disturbed serotonin system and that this disturbance could be reflected in altered serotonin 1A receptor binding. DESIGN: The serotonin 1A receptor binding potential (BP) was measured with positron emission tomography and serotonin 1A receptor antagonist carbonyl-carbon 11-WAY-100635. The BP was calculated using a reference tissue model in several limbic and neocortical regions and the raphe nuclei. SETTING: Epilepsy clinics of the Karolinska University Hospital, Stockholm, Sweden. PATIENTS: Eleven patients with JME and 11 controls were studied. MAIN OUTCOME MEASURE: Serotonin 1A receptor BP calculated in a set of volumes of interest. RESULTS: The patients with JME showed a reduced BP in the dorsolateral prefrontal cortex, raphe nuclei, and hippocampus. CONCLUSIONS: The observed reductions in serotonin 1A receptor BP suggest that the serotonin system is affected in JME. Although the data give no definitive information about underlying mechanisms, they provide a strong argument for the view that not all brain regions are homogeneously involved in this condition, further questioning the current classification of primarily generalized epilepsy.

Adult↗
PubMed2005

Preparation of highly specific radioactivity [18F]flumazenil and its evaluation in cynomolgus monkey by positron emission tomography.

A straightforward method for the preparation of no-carrier-added (n.c.a.) [18F]flumazenil via standard nucleophilic radiofluorination of the corresponding nitro-analog Ro 15-2344 has been developed. The labeling was performed by employing the K18F/kryptofix complex in DMF at 160 degrees C for 30 min and equimolar ratio [K/K2.2.2]+18F-/precursor. Under these conditions, an 18F incorporation rate into flumazenil was in the range of 55-60%. The final product was isolated by HPLC purification within a total synthesis time of 75 min and a radiochemical yield of about 30% (EOB). Human post-mortem whole-hemisphere autoradiography of brain sections demonstrated selective uptake of the radioligand in the areas of high density of the central benzodiazepine receptors (BZR). PET studies in a cynomolgus monkey and metabolite studies by HPLC demonstrated similar results by [18F]flumazenil as for [11C]flumazenil. In blocking experiments, almost all radioactivity was inhibited by the addition of unlabeled flumazenil. [18F]Flumazenil is a suitable radioligand for PET assessment of the BZR.

Animals↗
PubMed2004

Smelling human sex hormone-like compounds affects face gender judgment of men.

Although strong cross-sensory interactions between visual, tactile and auditory modalities have already been shown, we know little about how chemosensory information affects processing in other sensory modalities. We studied whether smelling gender-specific odorous sex hormone-like steroids: 5-alpha-androgenst-16-en-3-one (androgen) or oestra-1, 3, 5 (10), 16-tetraen-3-ol (estrogen) can bias face gender discrimination. We found that, as a result of inhalation of androgen, men perceive faces to be more masculine as compared to when they are exposed to estrogen. Our results provide evidence for specific cross-sensory effects of the gender-specific chemosensory cues on the categorization of visual face gender.

Adult↗
PubMed2004

Passive perception of odors and semantic circuits.

The sense of smell has been traditionally assumed to be different from other sensory modalities in that odors are encoded perceptually, without a semantic component. Recent findings of improved odor memory upon encoding with verbal cues question this view. Furthermore, familiar odors are easier to remember and discriminate than are unfamiliar ones, and odor familiarity is reported to predict odor naming. To investigate whether familiar odors are processed by different cerebral structures than those that process unfamiliar odors, (15)O H(2)O-positron emission tomography (PET) measurements of cerebral blood flow were carried out in 14 healthy men. The task was passive, birhinal, smelling of familiar odors (FAM), unfamiliar odors (uFAM), and odorless air (AIR). Significant activations (P < 0.05) were calculated using the contrasts FAM-AIR, uFAM-AIR, and FAM-uFAM, and deactivations running these contrasts in the opposite direction. In relation to AIR, both FAM and uFAM activated amygdala, piriform cortex, and parts of anterior cingulate cortex. FAM activated, in addition, left frontal cortex (Brodmann's areas 44,45,47), left parietal cortex incorporating precuneus, and right parahippocampus. Clusters covering parahippocampus and precuneus were observed also in FAM-uFAM. The activation of left frontal cortex and right parahippocampus was positively correlated with familiarity ratings. Smelling of familiar but not unfamiliar odorants seems to engage cerebral circuits mediating memory and language functions, in addition to the engagement of olfactory cortex. Already the most elemental form of odor processing, passive perception thus seems to engage semantic circuits. This is achieved by the ability of odorants to immediately elicit associations and judgments of odor characteristics.

Adult↗
PubMed2002

Odorant differentiated pattern of cerebral activation: comparison of acetone and vanillin.

Whether different odorous compounds (odorants) are processed by different cerebral circuits is presently unknown. A first step to address this complicated issue is to investigate how the cerebral regions mediating signals from olfactory (i.e., unimodal) odorants, differ from those mediating the olfactory + trigeminal (i.e., bimodal) odorants. [15O]-H2O-PET scans were conducted in 12 healthy females during three separate conditions: birhinal, passive smelling of: 1) the unimodal odorant vanillin; 2) the bimodal odorant acetone; and 3) odorless air. Significant activations were calculated contrasting vanillin to air, acetone to air, and deactivations, running these contrasts in the opposite direction. Smelling of vanillin activated bilaterally the amygdala and piriform cortex. These regions were only engaged slightly by acetone. Instead, strong activations were found in the anterior and central insula and claustrum, the posterior portion of anterior cingulate, the somatosensory cortex (SI for face), cerebellum, ventral medial (VMPo) and dorsal medial (MDvc) thalamus, the lateral hypothalamus, and pons/medulla. In parallel, the somatosensory (SI, below central representation of face), secondary visual and auditory cortices, as well as the supplementary motor area and the parahippocampal gyri were deactivated. No deactivations were observed with vanillin, although the odor components of acetone and vanillin were rated similarly intense (75 +/- 17 mm vs. 61 +/- 22 mm, NS). The differentiated pattern of cerebral activation during odorant perception seems to be dependent on the signal transducing cranial nerves involved. In contrast to vanillin, which solely activates the olfactory cortex, acetone engages predominantly trigeminal projections from the nasal mucosa. Acetone's limited activation of the olfactory cortex may result from a cross-modal interaction, with inhibition of acetone's odor component by its trigeminal component.

Acetone↗
PubMed2002

Imaging of brain activation by odorants in humans.

Application of positron emission tomography and magnetic resonance imaging has provided several new insights into various olfactory functions. One is that sniffing and smelling engage separate subsystems in the human olfactory cortex. Another is that perception of odorous compounds (odorants) is mediated by a set of core regions, which are partly different for pure olfactory than for olfactory plus trigeminal odorants. Depending on the task associated with odor perception, the core regions are recruited together with other circuits, in a parallel and hierarchical manner. The sense of smell seems, therefore, to be organized similarly to other sensory modalities, and the specific psychophysical characteristics of olfaction should be attributed to an early involvement of the limbic system rather than to a conceptually different mode of processing.

Brain↗
PubMed2002

Brain imaging studies of the functional organization of human olfaction.

It is believed that sensory functions are organized in a hierarchical and parallel manner. The sense of smell differs in several aspects from other senses: odors can immediately elicit emotional evocations, they are remembered after a long time, and they are difficult to label. This raises the question of whether odorous stimuli may be processed differently from the other sensory stimuli. New data from brain imaging studies suggest that this is not the case and that the specific characteristics of the sense of smell can be attributed to the engagement of limbic structures at an early stage in the signal processing.

Animals↗