Body Stuff bibliografia sobre desordens olfativas

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Bibliografia sobre desordens olfativas

: Brain gamma-aminobutyric acid levels are decreased in patients with phantageusia and phantosmia demonstrated by magnetic resonance spectroscopy.

Levy LM, Henkin RI.

Neuroimaging Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.

BACKGROUND: Olfactory and gustatory hallucinations (phantosmias and phantageusias, respectively) are sensory distortions that commonly follow losses of olfactory and gustatory acuity (hyposmia and hypogeusia, respectively). The biochemical basis of these hallucinations is unclear. Functional magnetic resonance imaging has been used previously to demonstrate widespread and robust central nervous system (CNS) activation to memories of these sensory distortions in patients with these symptoms. In this study, possible CNS mechanisms responsible for these distortions were evaluated using magnetic resonance spectroscopy, because this technique has been used to measure various CNS metabolites in patients with neurologic disorders. METHODS: Forty-seven subjects were studied: 28 normal volunteers (13 men and 15 women) and 19 patients (8 men and 11 women) with persistent oral global phantageusia and/or birhinal phantosmia studied before any treatment. Four patients (1 man and 3 women) were studied before and after pharmacologic treatment that reduced the severity of their sensory distortions. All subjects were studied in a Signa 1.5-T magnetic resonance scanner with a quadrature head coil using a modified standard 2-dimensional J-point resolved excitation in the steady state (PRESS) sequence by which gamma-aminobutyric acid (GABA), glutamic acid, choline, N-acetylaspartate, and creatine (Cre) were measured in various CNS regions. Results were expressed using Cre as a denominator to determine ratios for each measurement. Differences were defined between normal subjects and patients before treatment and in patients before and after successful pharmacologic treatment. RESULTS: Before treatment, GABA levels in several CNS regions were lower in patients than in normal volunteers and were the only biochemical changes found; significantly lowered GABA levels were found in the cingulate, right and left insula, and left amygdala. No differences between patients and normal volunteers were found in any of the metabolites in the posterior occipital region. After treatment that inhibited sensory distortions, CNS GABA levels increased in the cingulate, insula, and amygdala but significantly only in the left insula and in the right and left amygdala. After this successful treatment, no change in any biochemical parameter was found in the posterior occipital region. CONCLUSIONS: These results indicate that decreased brain GABA levels can serve as biochemical markers of phantageusia and/or phantosmia in patients with these distortions and are the first biochemical changes in the CNS that reflect these sensory changes. After successful treatment of these distortions, CNS GABA levels increased to levels at or near normal, consistent with functional remission of these symptoms. These results substantiate a role for CNS GABA in the generation and inhibition of these sensory hallucinations. Although the underlying biochemical mechanism(s) for the generation of these decreased GABA levels are complex, because similar types of sensory hallucinations occur as auras or prodromata of epileptic seizure and migraine activity, these results suggest that there may be common biochemical changes among these disorders.

PMID: 15538143 [PubMed - indexed for MEDLINE]

: A study on the prognostic significance of qualitative olfactory dysfunction.

Reden J, Maroldt H, Fritz A, Zahnert T, Hummel T.

Smell and Taste Clinic, Department of Otorhinolaryngology, University of Dresden Medical School ("Technische Universität Dresden"), Fetscherstrasse 74, 01307, Dresden, Germany.

We investigated the frequency and prognostic significance of qualitative olfactory dysfunction (parosmia, phantosmia) in a retrospective patient based study. A total of 392 patients with impairment of olfaction were tested at least two times for their olfactory function using the "Sniffin' Sticks". The mean interval between the first and the last test was 11 months. At the first visit 34% of all patients reported parosmia. Parosmia was most frequent in patients with postinfectious olfactory loss (56%), and less frequent in idiopathic, posttraumatic, sinunasal disease with frequencies of 10, 14, and 28%, respectively. In contrast, only 12% of all patients had phantosmias, with no significant differences between the patient groups. Improvement of olfactory function was found in 23% of all patients (n = 90). Pre-existing parosmia or phantosmia had no significant effect on recovery rate. Regarding qualitative olfactory dysfunction, 29% of those patients reporting parosmia reported relief of this symptom after an average of 12 months, whereas 53% of phantosmic patients lost phantosmia during the observation period. Although it has been suggested that olfactory distortion s could be regarded as an indicator of early recovery of decreased olfactory sensitivity, the current data indicate that occurrence of parosmia or phantosmia has little prognostic value. Phantosmia disappears at a faster rate than parosmia. These insights into qualitative olfactory dysfunction are regarded to be significant in the counseling of patients with olfactory loss.

PMID: 17006637 [PubMed - in process]

3: Percept Mot Skills. 2002 Jun;94(3 Pt 1):841-50.

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Phantom smelling.

Grouios G.

Aristotelian University of Thessaloniki, Greece. ggrouios@phed.auth.gr

A case of phantom smelling (phantosmia) is described in a 28-yr.-old man who developed permanent bilateral anosmia after a serious injury to olfaction-related brain structures at the age of 25 years. The findings indicate that, even years after loss of input from olfactory receptors, the neural representation of olfactory perception can still recreate olfactory sensations without any conscious recall of them. This indicates that the neural representation of olfactory sensations remains functional and implies that neuronal activity in the olfactory organ or in other brain structures gives rise to olfactory experiences perceived as originating from the perception of original odor substances. The report suggests the intriguing possibility that the olfactory perception is not a passive process that merely reflects its normal input from the olfactory system but is continuously generated by a neural representation in the olfactory organ or in other olfaction-related brain structures, based on both genetic and sensory determinants. To the author's knowledge this is the first reported case of its kind.

Publication Types:

Case Reports

PMID: 12081289 [PubMed - indexed for MEDLINE]

4: Chem Senses. 2002 Sep;27(7):611-5.

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Distortion of olfactory perception: diagnosis and treatment.

Leopold D.

Department of Otolaryngology-Head and Neck Surgery, University of Nebraska Medical Center, Omaha, NE 68198-1225, USA. dleopold@unmc.edu

Clinically, olfaction can fail in any of three ways: (i) decreased sensitivity (hyposmia, anosmia) and two types of distortion (dysosmia); (ii) distorted quality of an odorant stimulation (troposmia); (iii) perceived odor when no odorant is present (phantosmia, hallucination). The distortions are usually much more upsetting to a person's quality of life than a simple loss. An ipsilatersal loss of olfactory sensitivity is often identified in the nostril with any type of olfactory distortion. The pathophysiology of a stimulated distortion (troposmia) is likely a decreased number of functioning olfactory primary neurons so that an incomplete characterization of the odorant is made. In phantosmia, two possible causations include an abnormal signal or inhibition from the primary olfactory neurons or peripheral olfactory or trigeminal signals that "trigger" a central process. The clinician's goal is to carefully define the problem (e.g. taste versus smell, real versus perceived, one versus two nostrils), to perform the appropriate examination and testing and to provide therapy if possible. Treatment includes assurance with no active therapy (because many of these will naturally resolve), topical medications, systemic medications, anesthesia to parts of the nose and, rarely, referral for surgical excision of olfactory neurons. Endoscopic transnasal operations have the advantage of treating phantosmia and sometimes allowing a return of olfactory ability after the operation.

Publication Types:

Review

PMID: 12200340 [PubMed - indexed for MEDLINE]

: Long-term follow-up of surgically treated phantosmia.

Leopold DA, Loehrl TA, Schwob JE.

Department of Otolaryngology-Head and Neck Surgery, University of Nebraska Medical Center, 981225 Nebraska Medical Center, Omaha, NE 68198-1225, USA. dleopold@unmc.edu

OBJECTIVES: To determine whether transnasal excision of olfactory epithelium is a safe, effective therapy and to learn more of the pathogenesis of phantosmia by studying the histological features of the excised mucosa. DESIGN: A retrospective study consisting of a medical record review and telephone survey. Follow-up ranged from 1 to 11 years (average, 5.4 years). Excised tissues were histologically processed and descriptively compared with normal and other abnormal olfactory tissues. SETTING: Tertiary university medical referral centers. PATIENTS: All patients who presented to the primary author (D.A.L.) from 1988 to 1999 with unremitting phantosmia lasting longer than 4 years. INTERVENTION: Olfactory testing and transnasal endoscopic excision of olfactory mucosa. MAIN OUTCOME MEASURES: Tested olfactory function, patients' perception of phantom odor resolution, and histological findings. RESULTS: Of 8 patients, 7 have complete and permanent resolution of their phantosmia. Postoperatively, the single nostril olfactory ability in the operated-on nostril is decreased in 2 nostrils, remains unchanged in 7, and is improved in 1. The excised olfactory mucosa generally shows a decreased number of neurons, a greater ratio of immature to mature neurons, and disordered growth of axons with some intraepithelial neuromas. CONCLUSIONS: Surgical excision of olfactory epithelium is an effective and safe method to relieve phantosmia while potentially preserving olfactory ability. The abnormal histological features of the excised olfactory tissue suggest at least some pathological condition in the peripheral olfactory system. This nasal surgery requires intensive olfactory evaluation and follow-up. It is also extremely difficult with significant risks, and therefore should be limited to specialized centers.

PMID: 12049557 [PubMed - indexed for MEDLINE]

: Lateralization of brain activation to imagination and smell of odors using functional magnetic resonance imaging (fMRI): left hemispheric localization of pleasant and right hemispheric localization of unpleasant odors.

Henkin RI, Levy LM.

Taste and Smell Clinic, Washington, DC 20016, USA.

PURPOSE: Our goal was to use functional MRI (fMRI) of brain to reveal activation in each cerebral hemisphere in response to imagination and smell of odors. METHOD: FMRI brain scans were obtained in 24 normal subjects using multislice fast low angle shot (FLASH) MRI in response to imagination of banana and peppermint odors and in response to smell of corresponding odors of amyl acetate and menthone, respectively, and of pyridine. Three coronal sections selected from anterior to posterior brain regions were used. Similar studies were obtained in two patients with hyposmia using FLASH MRI and in one patient with hyposmia using echo planar imaging (EPI) both before and after theophylline treatment that returned smell function to or toward normal in each patient and in two patients with birhinal phantosmia (persistent foul odor) and global phantogeusia (persistent foul taste) with FLASH and EPI fMRI before and after treatment with neuroleptic drugs that inhibited their phantosmia and phantogeusia. Activation images were derived using correlation analysis. Ratios of hemispheric areas of brain activation to total hemispheric brain areas were calculated for FLASH fMRI, and numerical counts of pixel clusters in each hemisphere were made for EPI studies. Total pixel cluster counts in localized regions of each hemispheric section were also obtained. RESULTS: In normal subjects, activation generally occurred in left (L) > right (R) brain hemisphere in response to banana and peppermint odor imagination and to smell of corresponding odors of amyl acetate and menthone. Whereas there were no overall hemispheric differences for pyridine odor, activation in men was R > L hemisphere. Although absolute activation in both L and R hemispheres in response to banana odor imagination and amyl acetate smell was men > women, the ratio of L to R activation was women > men. In hyposmic patients studied by FLASH fMRI, activation to banana odor imagination and amyl acetate smell was L > R hemisphere both before and after theophylline treatment. In the hyposmic patient studied with EPI before theophylline treatment, activation to banana and peppermint odor imagination and to amyl acetate, menthone, and pyridine smell was R > L hemisphere; after theophylline treatment restored normal smell function, activation shifted completely with banana and peppermint odor imagination and amyl acetate and menthone smell to L > R hemisphere, consistent with responses in normal subjects. However, this shift also occurred for pyridine smell, which is opposite to responses in normal control subjects. In patients with phantosmia and phantogeusia, activation to phantosmia and phantogeusia before treatment was R > L hemisphere; after treatment inhibited phantosmia and phantogeusia, activation shifted with a slight L > R hemispheric lateralization. Localization of all lateralized responses indicated that anterior frontal and temporal cortices were brain regions most involved with imagination and smell of odors and with phantosmia and phantogeusia presence. CONCLUSION: Imagination and smell of odors perceived as pleasant generally activated the dominant or L > R brain hemisphere. Smell of odors perceived as unpleasant and unpleasant phantosmia and phantogeusia generally activated the contralateral or R > L brain hemisphere. With remission of phantosmia and phantogeusia, hemispheric activation was not only inhibited, but also there was a slight shift to L > R hemispheric predominance. Predominant L > R hemispheric differences in brain activation in normal subjects occurred in the order amyl acetate > menthone > pyridine, consistent with the hypothesis that pleasant odors are more appreciated in L hemisphere and unpleasant odors more in R hemisphere. Anterior frontal and temporal cortex regions previously found activated by imagination and smell of odors and phantosmia and phantogeusia perception accounted for most hemispheric differences.

PMID: 11473178 [PubMed - indexed for MEDLINE]

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

Levy LM, Henkin RI.

Department of Radiology, Georgetown University Medical Center, Washington, DC, USA.

PURPOSE: Our goal was to use functional magnetic resonance imaging (fMRI) to demonstrate brain activation in patients with unirhinal, episodic, recurrent 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 or 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), actual smell of three odors (amyl acetate, menthone, pyridine), memory of phantosmia (and phantageusia, where applicable), phantosmia initiated spontaneously or by vigorous nasal inhalation and exhalation, phantosmia after inhibition by Valsalva, and these stimuli before and after treatment with the neuroleptic thioridazine. Activation images were derived using correlation analysis and ratios of areas of brain activated to total brain areas were calculated. Total activated pixel cluster counts were also used to quantitative total and regional brain activation. RESULTS: Sensory-specific brain activation was present in each section in each patient following memory of tastants and odorants, actual smell of each odor and memory, and initiation of and inhibition of phantosmia. Activation to odor memory after phantosmia initiation was very robust, whereas after phantosmia inhibition it was similar to that in normal subjects. Brain activation to unirhinal phantosmia was bihemispheric, independent of whether it was left or right sided or patient handedness. While phantosmia memory (in the absence of initiated phantosmia) produced extremely robust brain activation, after initiation and inhibition of phantosmia apparent brain activation decreased. These changes need to be related to shifting state of baseline brain activation and should be interpreted to reflect increased rather than decreased brain activation over that of phantosmia memory alone. Treatment with thioridazine inhibited brain activation to all stimuli including phantosmia and phantageusia memory, as it did previously in patients with birhinal phantosmia. CONCLUSIONS: 1) Unirhinal phantosmia can be demonstrated by brain fMRI as can birhinal phantosmia; 2) unirhinal phantosmia can be initiated and inhibited by physiological maneuvers reflected by changes in fMRI brain activation; 3) fMRI brain activation of unirhinal phantosmia is bihemispheric and independent of peripheral side of phantosmia or patient handedness; 4) anterior frontal brain region plays a significant role in both phantosmia initiation and inhibition as, to some extent, do temporal brain regions; 5) activation of brain GABAergic systems appears to play a role in inhibition of unirhinal phantosmia; and 6) unirhinal phantosmia, similar to birhinal phantosmia, may reflect a type of maladaptive brain plasticity similar to that hypothesized to be responsible for phantom limb pain.

PMID: 10966179 [PubMed - indexed for MEDLINE]

8: J Comput Assist Tomogr. 2000 Jan-Feb;24(1):106-23.

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Taste and smell phantoms revealed by brain functional MRI (fMRI).

Henkin RI, Levy LM, Lin CS.

Taste and Smell Clinic, Department of Radiology, Georgetown University Medical Center, Washington, DC 20016, USA.

PURPOSE: Our goal was to demonstrate the appearance of phantom tastes and smells (phantageusia and phantosmia, respectively) by use of functional MRI (fMRI) of the brain and to demonstrate the efficacy of drug treatment that inhibited both the subjective presence of these phantoms and the fMRI brain activation initiated by these phantoms. METHOD: Multislice FLASH MR or echo planar MR brain scans were obtained in two patients with phantageusia and phantosmia in response to memory of two tastants (salt and sweet); memory of two odors (banana and peppermint); actual smell of amyl acetate, menthone, and pyridine; and memory of phantom tastes and smells before and after treatment with thioridazine and haloperidol. Activation images were derived using correlation analysis, and ratios of brain area activated to total brain area were obtained. RESULTS: Prior to treatment, both patients experienced persistent birhinal and global oral obnoxious tastes and smells in the absence of any external stimulus. The fMRI response to memory of phantoms was activation in sensory-specific brain regions for taste and smell, respectively. fMRI activation was greater than for memory of any tastant or odorant or for actual smell of any odor. After treatment with thioridazine or haloperidol, which successfully inhibited each phantom in each patient, fMRI response to phantom memory was significantly inhibited and was significantly lower than for memory of any tastant or odorant or actual smell of any odorant. CONCLUSION: These results demonstrate that (a) phantom taste and smell can be revealed by fMRI brain activation, (b) brain activation in response to taste and smell phantoms is localized in sensory-specific brain regions for taste and smell, respectively, (c) brain activation in response to memory of each phantom initiated the greatest degree of activation we had previously measured, and (d) treatment with thioridazine or haloperidol inhibited both the presence of each phantom and its associated fMRI brain activation. This is the first study in which phantom tastes and smells have been demonstrated by an objective technique and treatment that inhibited the phantoms was characterized by objective inhibition of fMRI activation. These two patients represent a relatively common group that may be classified as having primary phantageusia and phantosmia distinct from those with phantoms or auras secondary to neurological, migrainous, psychiatric, or other causes.

Publication Types:

PMID: 10667670 [PubMed - indexed for MEDLINE]

1: J Comput Assist Tomogr. 2002 Jan-Feb;26(1):39-61.

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Functional MRI of congenital hyposmia: brain activation to odors and imagination of odors and tastes.

Henkin RI, Levy LM.

Taste and Smell Clinic, Washington, DC 20016, USA. doc@tasteandsmell.com

PURPOSE: Our goal was to use functional MRI (fMRI) to define brain activation in response to odors and imagination ("memory") of odors and tastes in patients who never recognized odors (congenital hyposmia). METHOD: Functional MR brain scans were obtained in nine patients with congenital hyposmia using multislice echo planar imaging (EPI) in response to odors of amyl acetate, menthone, and pyridine and to imagination ("memory") of banana and peppermint odors and to salt and sweet tastes. Functional MR brain scans were compared with those in normal subjects and patients with acquired hyposmia. Activation images were derived using correlation analysis, and ratios of areas of brain activated to total and hemispheric brain areas were calculated. Total and hemispheric activated pixel counts were used to quantitate regional brain activation. RESULTS: Brain activation in response to odors was present in patients with congenital hyposmia. Activation was significantly lower than in normal subjects and patients with acquired hyposmia and did not demonstrate differential vapor pressure-dependent detection responsiveness or odor response lateralization. Regional activation localization was in anterior frontal and temporal cortex similar to that in normal subjects and patients with acquired hyposmia. Activation in response to presented odors was diverse, with a larger group exhibiting little or no activation with localization only in anterior frontal and temporal cortex and a smaller group exhibiting greater activation with localization extending to more complex olfactory integration sites. "Memory" of odors and tastes elicited activation in the same central nervous system (CNS) regions in which activation in response to presented odors occurred, but responses were significantly lower than in normal subjects and patients with acquired hyposmia and did not lateralize. CONCLUSION: Odors induced CNS activation in patients with congenital hyposmia, which distinguishes olfaction from vision and audition since neither light nor acoustic stimuli induce CNS activation. Odor activation localized to anterior frontal and temporal cortex, consistent with the hypothesis that olfactory pathways are hard-wired into the CNS and that further pathways are undeveloped with primary olfactory system CNS connections but lack of secondary connections. However, some patients exhibited greater odor activation with response localization extending to cingulate and opercular cortex, indicating some olfactory signals impinge on and maintain secondary connections consistent with similar functions in vision and audition. Activation localization of taste "memory" to anterior frontal and temporal cortex is consistent with CNS plasticity and cross-modal CNS reorganization as described for vision and audition. Thus, there are differences and similarities between olfaction, vision, and audition, the differences dependent on unique qualities of olfaction, perhaps due to its diffuse, primitive, fundamental role in survival. Response heterogeneity to odors may reflect heterogeneous genetic abnormalities, independent of anatomic or hormonal changes but dependent on molecular abnormalities in growth factor function interfering with growth factor/stem cell interactions. Patients with congenital hyposmia offer an unique model system not previously explored in which congenital smell lack as measured by fMRI is reflective of congenital dysfunction of a major sensory system.

Publication Types:

Review

PMID: 11801904 [PubMed - indexed for MEDLINE]

2: J Hist Neurosci. 1997 Aug;6(2):133-46.

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A memoir of olfaction.

Schiller F.

Department of the History of Health Sciences, University of California, San Francisco 94143-0726, USA.

Osphreiology, though beginning with Aristotle, and the title of a classical monograph from 1819 by Cloquet, has, like the human sense of smell itself, played a relatively modest role, compared to other sensory functions. The anatomical and physiological connections of the nose to the brain proved to be more complex than those of sight, hearing and even touch, and were therefore poorly understood before the second half of the 19th century. Moreover, the close association between smell and taste gave rise to much controversy regarding the respective roles of the first and the fifth cranial nerves. Next, came the unfolding of the evolutionary influence of cerebral structure and function--viz Broca's "limbic" concept, and the "olfactory desert" in the brains of "anosmatic" animals, Jackson's "uncinate" seizures featuring olfactory hallucinations brought the hippocampal formation into focus. Finally, there were the clinical manifestations of hyposmia and hyperosmia, from "coryza", the common cold, to injury or neoplasms causing hyposmia, as well as some endocrine alterations causing hyperosmia. (And let us not forget Charles Huysman's "Against the Grain" and Marcel Proust's evocative fragrant madeleine.).

Publication Types:

Historical Article

PMID: 11619517 [PubMed - indexed for MEDLINE]

3: J Hist Neurosci. 2003 Jun;12(2):175-202.

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The search for a sixth sense: the cases for vestibular, muscle, and temperature senses.

Wade NJ.

Department of Psychology, University of Dundee, Dundee DD1 4HN, Scotland, UK. n.j.wade@dundee.ac.uk

The five senses of sight, hearing, smell, taste, and touch, enumerated by Aristotle, were incremented in the early-nineteenth century by the muscle sense, multiple dimensions of touch, and a movement sense. Aristotle explicitly excluded a sixth sense, and five remains the number of senses in popular imagination. The division of touch into several sensations was entertained and rejected by Aristotle, but it was given anatomical, physiological and psychophysical support in the late-nineteenth century. A separate muscle sense was proposed in the late-eighteenth century, with experimental evidence to support it. However, before these developments, behavioral evidence of the vestibular (movement) sense was available from studies of vertigo, although it was not integrated with the anatomy and physiology of the labyrinth until the nineteenth century. The history of the search for a sixth sense is outlined, and the evidence adduced to support the divisions is assessed. Behavioral evidence generally has been accorded less weight than that from anatomy and physiology.

Publication Types:

Historical Article

PMID: 12953620 [PubMed - indexed for MEDLINE]

: Olfactory and sensory attributes of the nose.

Wrobel BB, Leopold DA.

Department of Otolaryngology-Head and Neck Surgery, University of Southern California, 1520 San Pablo Street, Suite # 4600, Los Angeles, CA 90033, USA.

The human nasal cavity contains multiple sensory and olfactory structures. The nasal mucosa with its complex innervation detects the danger substances in the air and stimulates the protective reflexes. Healthy olfactory mucosa allows for appreciation of pleasant aromas and food flavors.The olfactory nerve, in concert with the trigeminal nerve, serves as a main interpreter and modulator of chemosensory information. The anatomy of the olfactory neuroepithelium, which occupies only a small portion of the nasal mucosa, is generally well understood, while the presence and distribution of the sensory/tactile receptors in the mucosa of the nasal cavity is still a subject of controversy. The nasal vestibule, lined with skin, contains receptors that can sense noxious stimuli and air-flow. The sensitivity of the nasal mucosa to air-flow still needs further research. Understanding the distribution of the air-flow receptors could help to guide nasal surgery for obstruction.

PMID: 16326176 [PubMed - indexed for MEDLINE]

5: Adv Otorhinolaryngol. 2006;63:44-69.

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Smell: central nervous processing.

Gottfried JA.

Northwestern University Feinberg School of Medicine, Cognitive Neurology and Alzheimer's Disease Center, Chicago, IL 60611, USA. j-gottfried@northwestern.edu

This chapter focuses on central olfactory processing in the human brain. As the psychophysiology of human olfactory function is important for appreciating its underlying neurophysiology, the chapter will begin with a brief overview of what the human nose can do, contesting notions that human olfaction is a second-rate system. It will be followed by an anatomical survey of the principal recipients of olfactory bulb input, with some comments on the unique organizing properties that distinguish olfaction from other sensory modalities. The final section will cover the neural correlates of human olfactory function, including aspects of basic chemosensory processing (odor detection, sniffing, intensity, valence) and higher-order olfactory operations (learning, memory, crossmodal integration), with particular emphasis on functional imaging data, though human lesion studies and intracranial recordings will also be discussed.

Publication Types:

Review

PMID: 16733332 [PubMed - indexed for MEDLINE]

6: Physiol Behav. 2004 Oct 30;83(1):3-11.

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Olfactory perception, communication, and the nose-to-brain pathway.

Stockhorst U, Pietrowsky R.

Institute of Medical Psychology, University of Duesseldorf, PO Box 101007, 40001 Duesseldorf, Germany. ursula.stockhorst@uni-duesseldorf.de

The present paper's aim is of to give an overview about the basic knowledge as well as actual topics of olfaction--with a special regard on behavior. We summarize different functions of the nose and the olfactory system in human physiology and psychology. We will first describe the functional anatomy of the olfactory system in man. Afterwards, the function of the olfactory system will be viewed from an evolutionary and phylogenetic perspective. We will further outline the main features of olfactory perception, and will show how olfactory perception is influenced by learning. Olfactory signals are relevant stimuli that affect communication. Consequently, the role of the olfactory system in social interaction and mood will be described and gender differences will be addressed. Finally, the function of the nose as an interface to the brain, including implications for pharmacology, will be discussed.

Publication Types:

Review

PMID: 15501485 [PubMed - indexed for MEDLINE]

7: Percept Mot Skills. 2002 Jun;94(3 Pt 1):841-50.

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Case Reports

PMID: 12081289 [PubMed - indexed for MEDLINE]

8: J Neurophysiol. 2004 Sep;92(3):1892-903. Epub 2004 Apr 21.

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Experience-dependent neural integration of taste and smell in the human brain.

Small DM, Voss J, Mak YE, Simmons KB, Parrish T, Gitelman D.

Cognitive Neurology and Alzheimer's Disease Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611-3008, USA. dsmall@jbpierce.org

Flavor perception arises from the central integration of peripherally distinct sensory inputs (taste, smell, texture, temperature, sight, and even sound of foods). The results from psychophysical and neuroimaging studies in humans are converging with electrophysiological findings in animals and a picture of the neural correlates of flavor processing is beginning to emerge. Here we used event-related fMRI to evaluate brain response during perception of flavors (i.e., taste/odor liquid mixtures not differing in temperature or texture) compared with the sum of the independent presentation of their constituents (taste and/or odor). All stimuli were presented in liquid form so that olfactory stimulation was by the retronasal route. Mode of olfactory delivery is important because neural suppression has been observed in chemosensory regions during congruent taste-odor pairs when the odors are delivered by the orthonasal route and require subjects to sniff. There were 2 flavors. One contained a familiar/congruent taste-odor pair (vanilla/sweet) and the other an unfamiliar/incongruent taste-odor pair (vanilla/salty). Three unimodal stimuli, including 2 tastes (sweet and salty) and one odor (vanilla), as well as a tasteless/odorless liquid (baseline) were presented. Superadditive responses during the perception of the congruent flavor compared with the sum of its constituents were observed in the anterior cingulate cortex (ACC), dorsal insula, anterior ventral insula extending into the caudal orbitofrontal cortex (OFC), frontal operculum, ventral lateral prefrontal cortex, and posterior parietal cortex. These regions were not present in a similar analysis of the incongruent flavor compared with the sum of its constituents. All of these regions except the ventrolateral prefrontal cortex were also isolated in a direct contrast of congruent - incongruent. Additionally, the anterior cingulate, posterior parietal cortex, frontal operculum, and ventral insula/caudal OFC were also more active in vanilla + salty minus incongruent, suggesting that delivery of an unfamiliar taste-odor combination may lead to suppressed neural responses. Taken together with previous findings in the literature, these results suggest that the insula, OFC, and ACC are key components of the network underlying flavor perception and that taste-smell integration within these and other regions is dependent on 1) mode of olfactory delivery and 2) previous experience with taste/smell combinations.

Publication Types:

PMID: 15102894 [PubMed - indexed for MEDLINE]

9: Adv Tech Stand Neurosurg. 2005;30:69-105.

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Basic and clinical aspects of olfaction.

Landis BN, Hummel T, Lacroix JS.

Unité de Rhinologie-Olfactologie, Service d' Oto-Rhinologie-Laryngologie, Hopitaux Universitaires de Genève, Genève, Switzerland.

Disturbances of olfaction are a common occurrence in many neurological and neurosurgical patients and their correct diagnosis might be helpful in management and enhancement of quality of life. However, olfaction is seldom checked in most neurosurgical units and the "smell bottles" are often either absent or out of date. This chapter reviews systematically recent advances in our understanding of the anatomy, physiology (olfactory coding) and measurement of olfactory function in the human. The causes and symptoms of smell disorders, risk of damage to the olfactory system by various surgical procedures and, finally, the natural history of recovery and treatment of smell disorders, for example after trauma, are discussed.

Publication Types:

PMID: 16350453 [PubMed - indexed for MEDLINE]

10: Anat Rec A Discov Mol Cell Evol Biol. 2004 Nov;281(1):1212-25.

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Convergence of sensory systems in the orbitofrontal cortex in primates and brain design for emotion.

Rolls ET.

Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom. edmund.rolls@psy.ox.ac.uk

In primates, stimuli to sensory systems influence motivational and emotional behavior via neural relays to the orbitofrontal cortex. This article reviews studies on the effects of stimuli from multiple sensory modalities on the brain of humans and some other higher primates. The primate orbitofrontal cortex contains the secondary taste cortex, in which the reward value of taste is represented. It also contains the secondary and tertiary olfactory cortical areas, in which information about the identity and also about the reward value of odors is represented. A somatosensory input is revealed by neurons that respond to the viscosity of food in the mouth, to the texture (mouth feel) of fat in the mouth, and to the temperature of liquids placed into the mouth. The orbitofrontal cortex also receives information about the sight of objects from the temporal lobe cortical visual areas. Information about each of these modalities is represented separately by different neurons, but in addition, other neurons show convergence between different types of sensory input. This convergence occurs by associative learning between the visual or olfactory input and the taste. In that emotions can be defined as states elicited by reinforcers, the neurons that respond to primary reinforcers (such as taste and touch), as well as learn associations to visual and olfactory stimuli that become secondary reinforcers, provide a basis for understanding the functions of the orbitofrontal cortex in emotion. In complementary neuroimaging studies in humans, it is being found that areas of the orbitofrontal cortex are activated by pleasant touch, by painful touch, by taste, by smell, and by more abstract reinforcers such as winning or losing money. Damage to the orbitofrontal cortex in humans can impair the learning and reversal of stimulus-reinforcement associations and thus the correction of behavioral responses when these are no longer appropriate because previous reinforcement contingencies change. It is striking that humans and other catarrhines, being visual specialists like other anthropoids, interface the visual system to other sensory systems (e.g., taste and smell) in the orbitofrontal cortex. (c) 2004 Wiley-Liss, Inc.

Publication Types:

PMID: 15470678 [PubMed - indexed for MEDLINE]

11: Cell Mol Life Sci. 2006 Jul;63(13):1465-75.

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The sense of smell: multiple olfactory subsystems.

Breer H, Fleischer J, Strotmann J.

Institute of Physiology, University of Hohenheim, Garbenstrasse 30, 70599, Stuttgart, Germany. breer@uni-hohenheim.de

The mammalian olfactory system is not uniformly organized but consists of several subsystems each of which probably serves distinct functions. Not only are the two major nasal chemosensory systems, the vomeronasal organ and the main olfactory epithelium, structurally and functionally separate entities, but the latter is further subcompartimentalized into overlapping expression zones and projection-related subzones. Moreover, the populations of 'OR37' neurons not only express a unique type of olfactory receptors but also are segregated in a cluster-like manner and generally project to only one receptor-specific glomerulus. The septal organ is an island of sensory epithelium on the nasal septum positioned at the nasoplatine duct; it is considered as a 'mini-nose' with dual function. A specific chemosensory function of the most recently discovered subsystem, the so-called Grueneberg ganglion, is based on the expression of olfactory marker protein and the axonal projections to defined glomeruli within the olfactory bulb. This complexity of distinct olfactory subsystems may be one of the features determining the enormous chemosensory capacity of the sense of smell.

Publication Types:

PMID: 16732429 [PubMed - indexed for MEDLINE]

12: Am J Psychiatry. 2003 Oct;160(10):1740-7.

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The "dreamy state": John Hughlings-Jackson's ideas of epilepsy and consciousness.

Hogan RE, Kaiboriboon K.

Greater Midwest Epilepsy Treatment Center, Deparment of Neurology, Saint Louis University School of Medicine, St Louis, MO 63110, USA. hoganr2@slu.edu

OBJECTIVE: The authors review John Hughlings-Jackson's writings on the "dreamy state" and his subsequent derivation of degrees of consciousness. METHOD: They reviewed the publications of Hughlings-Jackson from his initial description of the "dreamy state" in 1876 until his writing about the "uncinate group of fits" in 1899. They then examined Hughlings-Jackson's use of the associated signs and symptoms of the "dreamy state" to formulate his ideas about human consciousness. RESULTS: Hughlings-Jackson defined the "dreamy state" as "over-consciousness," or a heightened intellectual state. He described associated symptoms of "crude sensations" of smell and taste, an unusual epigastric sensation, chewing and lip smacking, automatisms, postictal symptoms, and at least some degree of alteration of consciousness. Using his observations of the "dreamy state" as a model, Hughlings-Jackson proposed three degrees of consciousness, each with an object and subject component. CONCLUSIONS: Through his description of the "dreamy state," Hughlings-Jackson accurately characterized and localized medial temporal epilepsy. Correlating the ictal semiology of the "dreamy state" with consciousness, he developed a theory of consciousness that remains relevant to current understanding of the mind-brain relationship.

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Personal Name as Subject:

Hughlings-Jackson J

PMID: 14514481 [PubMed - indexed for MEDLINE]

13: PLoS Biol. 2004 May;2(5):E146. Epub 2004 May 11.

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The human sense of smell: are we better than we think?

Shepherd GM.

Department of Neurobiology at the Yale University School of Medicine, New Haven, Connecticut, USA. gordon.shepherd@yale.edu

Publication Types:

PMID: 15138509 [PubMed - indexed for MEDLINE]

14: Chem Senses. 2002 Sep;27(7):611-5.

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Review

PMID: 12200340 [PubMed - indexed for MEDLINE]

15: Conscious Cogn. 2004 Jun;13(2):213-40.

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Comment in:

Consciousness, art, and the brain: lessons from Marcel Proust.

Epstein R.

Department of Psychology and Center for Cognitive Neuroscience, University of Pennsylvania, 3815 Walnut St., Philadelphia, PA 19104-6196, USA. epstein@psych.upenn.edu

In his novel Remembrance of Things Past, Marcel Proust argues that conventional descriptions of the phenomenology of consciousness are incomplete because they focus too much on the highly-salient sensory information that dominates each moment of awareness and ignore the network of associations that lies in the background. In this paper, I explicate Proust's theory of conscious experience and show how it leads him directly to a theory of aesthetic perception. Proust's division of awareness into two components roughly corresponds to William James' division of the stream of thought into a "nucleus" and "fringe." Proust argues that the function of art is to evoke the underlying associative network indirectly in the mind of the observer by using carefully chosen sensory surfaces to control the stream of thought. I propose a possible neural basis for this Proustian/Jamesian phenomenology, and argue that the general principles of Proustian aesthetics can be applied to all forms of art. I conclude that a scientific theory of art should follow in a straightforward manner from a scientific theory of consciousness.

Publication Types:

Personal Name as Subject:

Proust M

PMID: 15134758 [PubMed - indexed for MEDLINE]

16: Microsc Res Tech. 2002 Aug 1;58(3):142-51.

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Cell and molecular biology of human olfaction.

Rawson NE, Gomez G.

Monell Chemical Senses Center, Philadelphia, Pennsylvania 19104, USA. rawson@monell.org

Progress in our understanding of olfactory receptor physiology has progressed greatly over the past 10 years. It has become clear that many anatomical and molecular features of the peripheral aspect of the olfactory system have remained highly conserved across diverse species. Yet, this structure is responsible for conveying a wide variety of information about the environment that is necessary to the successful location of food, mates, and avoidance of danger, and it is thus not surprising that specializations have also evolved to suit the differing needs of different species. While the basic anatomical features reflect those of other mammals, functional studies of human olfactory receptor neurons have revealed physiological features both similar to and differing from those of other mammalian species. This review presents an overview of both the anatomical and physiological data describing the cell and molecular biology of the peripheral human olfactory system and how it functions in health and disease. Copyright 2002 Wiley-Liss, Inc.

Publication Types:

PMID: 12203692 [PubMed - indexed for MEDLINE]

: Hazardous events associated with impaired olfactory function.

Santos DV, Reiter ER, DiNardo LJ, Costanzo RM.

Department of Otolaryngology-Head & Neck Surgery, Virginia Commonwealth University, Richmond, USA.

OBJECTIVE: To evaluate the risk of olfactory-related hazardous events in patients with impaired olfactory function. DESIGN: Retrospective cohort study. SETTING: A university-based clinic for smell and taste disorders. PATIENTS: A total of 445 patients who underwent olfactory testing between 1983 and 2001. INTERVENTIONS: Patient interview, olfactory testing. MAIN OUTCOME MEASURES: (1) Frequency of olfactory-related hazardous events including cooking incidents (ie, burning pots or pans), undetected fires, undetected gas leaks, and ingestion of spoiled foods or toxic substances; (2) level of olfactory function (anosmia; severe, moderate, or mild hyposmia; or normosmia) as determined by olfactory testing. RESULTS: Olfactory testing revealed that 76% of patients had some degree of impairment; 30% had complete anosmia. Thirty-seven percent of patients with olfactory impairment but only 19% of patients without impairment experienced at least 1 olfactory-related hazardous event. Of the hazardous events reported by impaired patients, cooking-related incidents were most common, representing 45%, with ingestion of spoiled food (25%), inability to detect a gas leak (23%), and inability to smell a fire (7%) reported less frequently. There was a significant correlation between frequency of hazardous events and degree of olfactory impairment (Cochran-Armitage trend test, P<.001): at least 1 hazardous event was reported by 45.2% of patients with anosmia, 34.1% with severe hyposmia, 32.8% with moderate hyposmia, 24.2% with mild hyposmia, and 19.0% of patients with with normal olfaction by testing. CONCLUSION: Patients with impaired olfactory function are more likely to experience olfactory-related hazardous events than those with normal olfactory function.

PMID: 15023839 [PubMed - indexed for MEDLINE]

: The neglected sense-olfaction in primate behavior, ecology, and evolution.

Heymann EW.

Abteilung Verhaltensökologie & Soziobiologie, Deutsches Primatenzentrum, Göttingen, Germany. eheyman@gwdg.de

This special issue emerged from a symposium held during the 20th Congress of the International Primatological Society in Torino, Italy, in August 2004. The symposium brought together scientists studying several different aspects of olfaction in primates. The topics addressed ranged from the morphology and physiology of the sensory apparatus, the genetics and chemistry of olfactory signals and the use of such signals in primate communication, to a comparative analysis of the role of olfaction in neural evolution. The papers in this issue reflect a surge of interest in diverse aspects of olfaction-an interest that has been stimulated by the more rigorous theoretical approaches and new techniques that have recently become available. This introduction briefly reviews past research on primate olfaction, summarizes the scope of this special issue, and provides a somewhat speculative glimpse of the future. Copyright 2006 Wiley-Liss, Inc.

PMID: 16715505 [PubMed - indexed for MEDLINE]

19: Epilepsy Behav. 2004 Oct;5(5):775-83.

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Can memories kindle nonconvulsive behavioral seizures in humans? Case report exemplifying the "limbic psychotic trigger reaction".

Pontius AA, Wieser HG.

Department of Psychiatry, Harvard Medical School, Boston, MA, USA. anneliese_pontius@hms.harvard.edu

We present three hypotheses-(1) the limbic psychotic trigger reaction (LPTR) is a form of nonconvulsive behavioral seizures (NCBS), (2) kindling may occur in the LPTR, and (3) kindling may occur with memory stimuli-and report a case that may exemplify a LPTR kindled by memory and triggered by light and smell. The LPTR has a primate model, in which NCBS are kindled by intermittent exposure to actual subthreshold stimuli. In humans, we propose that such triggering stimuli can be revived by memory alone. Thus, individualized stimuli can trigger partial limbic seizures or seizure-like bizarre episodes with a transient loss of frontal control functions. We present a case of paroxysmal episodes of out-of-character, bizarre, unplanned nonvoluntary acts that occurred with flat affect and without drive motivation (e.g., "fire setting"). Implicated is a transient state of limbic "paleo-consciousness" with preserved memory, autonomic arousal, and first-time brief psychosis (e.g., olfactory, visual hallucinations and depersonalization with olfactory attributes). As in kindled primates, LPTR patients do not show a consistent pattern of morphological brain abnormality; half have had an abnormal electroencephalogram, computed tomography scan, or magnetic resonance image at some time during their lives, and half (including the new patient) have had closed head injuries.

Publication Types:

Case Reports

PMID: 15380135 [PubMed - indexed for MEDLINE]

: [A historical introduction to the neuropsychological model]

[Article in Spanish]

Barcia-Salorio D.

Universidad Católica San Antonio, El Palmar, Murcia, Spain.

INTRODUCTION: In this work we outline the different approaches and doctrines that have been successively developed throughout the history of western medicine with the intention of offering an overall view of the matter. DEVELOPMENT: The author believes that the most important facts from a conceptual point of view are centred around F. Gall's notion of the cerebral localisation of the psychic functions; the development of the notion of nerve centres put forward by Fritsch and Hitzig, which was the foundation for the splendid work of D. Ferrier, the true father of scientific neuropsychology; the work of Klest, which gave rise to a new neogallism in the sense that it represented a real effort to locate the higher psychic functions; the fundamental work of J.H. Jackson, especially in relation to the subject we are studying, and his ideas about the levels of functioning and integration of the nervous system, which enabled later developments to be carried out, such as that of MacLean, whose concept of the limbic system is a core matter in this area. Other milestones were W.H. Hess's critique of