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1.  A Positron Tomographic Emission Study of Olfactory Induced Emotional Recall in Veterans with and without Combat-related Posttraumatic Stress Disorder 
Psychopharmacology bulletin  2007;40(1):8-30.
OBJECTIVE
Memory for odors is often associated with highly emotional experiences, and odors have long been noted by clinicians to be precipitants of trauma symptoms in PTSD. Primitive brain systems involved in fear responsivity and survival also mediate smell, including the olfactory cortex and amygdala. The purpose of this study was to measure neural correlates of olfaction in PTSD.
METHODS
We exposed male combat veterans with PTSD (N=8) and without PTSD (N=8) to a set of smells, including diesel (related to traumatic memories of combat), and three other types of smells: odorless air, vanilla/coconut and hydrogen sulfide (H2S) (resp. a neutral, positive, and negative hedonic non-traumatic smell) in conjunction with PET imaging of cerebral blood flow and assessment of psychophysiological and behavioral symptoms. All subjects also underwent a baseline of olfactory acuity.
RESULTS
PTSD patients rated diesel as unpleasant and distressing, resulting in increased PTSD symptoms and anxiety in PTSD versus combat controls. Exposure to diesel resulted in an increase in regional blood flow (rCBF) in amygdala, insula, medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC), and decreased rCBF in lateral prefrontal cortex (lPFC) in PTSD in comparison to combat controls. Combat controls showed less rCBF changes on any smell, and did not show amygdala activation upon diesel exposure.
CONCLUSIONS
These data support the hypothesis that in PTSD trauma-related smells can serve as strong emotional reminders. The findings indicate the involvement of a neural circuitry that shares olfactory elements and memory processing regions when exposed to trauma-related stimuli.
PMCID: PMC3236699  PMID: 17285093
PTSD; brain imaging techniques; olfaction; memory; amygdala
2.  Comparison of Classical and Clozapine Treatment on Schizophrenia Using Positive and Negative Syndrome Scale of Schizophrenia (PANSS) and SPECT Imaging 
Many neuroimaging studies of schizophrenia have shown abnormalities in the frontal cortex, limbic system, basal ganglia, temporal and parietal lobes. These findings are not specific or consistent enough to build up a coherent theory of the origin of the brain abnormality in schizophrenia. This paper describes a state-of-the-art approach of SPECT to correlate neuropsychological evaluation. PANSS scores and different brain focal abnormalities of two groups of patients receiving Clozapine and classical antipsychotic treatments were observed. A total of 20 drug-free patients, actively psychotic schizophrenic, were selected according to the DSM-IV criteria. Pre-Post-treatment was designed using PANSS and 99mTc- ECD-SPECT to assess regional Cerebral Blood Flow (rCBF). The results showed that after treatment, differences in PANSS scores were significant in both groups, with superior scores resulting from the Clozapine therapy. Results were supported by SPECT, which showed a greater improvement in the Clozapine group. Both positive and negative symptoms were improved with Clozapine as well. Before treatment, hypofrontality was the most common (85%) finding, whereas after treatment hypofrontality was mostly cleared. However, in some areas like temporal and caudate, hyperfrontality was induced. Negative symptoms showed linkage to hypofrontality in both groups before and after treatment, and both positive and negative symptoms were improved more with Clozapine therapy than with classical treatment.
PMCID: PMC1145138  PMID: 15968344
Schizophrenia; SPECT imaging; PANSS scores
3.  Functional Neuro-Imaging and Post-Traumatic Olfactory Impairment 
Objective:
To evaluate via a research literature survey the anterior neurological significance of decreased olfactory functioning following traumatic brain injuries.
Materials and Methods:
A computer literature review was performed to locate all functional neuro-imaging studies on patients with post-traumatic anosmia and other olfactory deficits.
Results:
A convergence of findings from nine functional neuro-imaging studies indicating evidence for reduced metabolic activity at rest or relative hypo-perfusion during olfactory activations. Hypo-activation of the prefrontal regions was apparent in all nine post-traumatic samples, with three samples yielding evidence of reduced activity in the temporal regions as well.
Conclusions:
The practical ramifications include the reasonable hypothesis that a total anosmic head trauma patient likely has frontal lobe involvement.
doi:10.4103/0253-7176.78504
PMCID: PMC3122553  PMID: 21716782
Anosmia; functional neuro-imaging; olfaction; traumatic brain injury
4.  99mTc HMPAO SPECT prediction of conversion from mild cognitive impairment to Alzheimer disease 
Objective
To examine the utility of single photon emission computed tomography (SPECT) to predict conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD).
Design
Longitudinal, prospective study.
Setting
University-based memory disorders clinic.
Participants
127 patients with MCI and 59 healthy comparison subjects followed for 1 to 9 years.
Measurements
Diagnostic evaluation, neuropsychological tests, social/cognitive function, olfactory identification, apolipoprotein E genotype, MRI, and brain 99mTc HMPAO SPECT scan with visual ratings and region of interest (ROI) analyses were done.
Results
Visual ratings of SPECT temporal and parietal blood flow did not distinguish eventual MCI converters to AD (n=31) from non-converters (n=96) but the global rating predicted conversion (41.9% sensitivity and 82.3% specificity, Fisher's exact test p=0.013). Blood flow in each ROI was not predictive, but when dichotomized at the MCI patients' median value, low flow increased the hazard of conversion to AD for parietal (HR 2.96, 95%CI 1.16-7.53, p=0.023) and medial temporal regions (HR 3.12, 95%CI 1.14-8.56, p=0.027). In the 3-year follow-up sample, low parietal (p<0.05) and medial temporal (p<0.01) flow predicted conversion to AD, with or without controlling for age, MMSE, and apolipoprotein E ε4 genotype. These measures lost significance when other strong predictors were included in logistic regression analyses: verbal memory, social/cognitive functioning, olfactory identification deficits, hippocampal and entorhinal cortex volumes.
Conclusions
SPECT visual ratings showed limited utility in predicting MCI conversion to AD. The modest predictive utility of quantified low parietal and medial temporal flow using SPECT may decrease when other stronger predictors are available.
doi:10.1097/JGP.0b013e3181ec8696
PMCID: PMC3103107  PMID: 20808143
Mild cognitive impairment; Alzheimer's disease; prediction; SPECT; clinical utility
5.  Differences at brain SPECT between depressed females with and without adult ADHD and healthy controls: etiological considerations 
Background
Comorbidity between Attention Deficit Hyperactivity Disorder (ADHD) and mood disorders is common. Alterations of the cerebellum and frontal regions have been reported in neuro-imaging studies of ADHD and major depression.
Methods
Thirty chronically depressed adult females of whom 16 had scores below, and 14 scores above, cut-offs on the 25-items Wender Utah Retrospective Scale (WURS-25) and the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) were divided into subgroups designated "Depression" and "Depression + ADHD", respectively. Twenty-one of the patients had some audiological symptom, tinnitus and/or hearing impairment. The patients were investigated with other rating scales and 99mTc-HMPAO SPECT. Controls for 99mTc-HMPAO SPECT were 16 healthy females. SPECT was analyzed by both statistical parametric mapping (SPM2) and the computerized brain atlas (CBA). Discriminant analysis was performed on the volumes of interest generated by the CBA, and on the scores from rating scales with the highest group differences.
Results
The mean score of a depression rating scale (MADRS-S) was significantly lower in the "Depression" subgroup compared to in the "Depression + ADHD" subgroup. There was significantly decreased tracer uptake within the bilateral cerebellum at both SPM and CBA in the "Depression + ADHD" subgroup compared to in the controls. No decrease of cerebellar tracer uptake was observed in "Depression". Significantly increased tracer uptake was found at SPM within some bilateral frontal regions (Brodmann areas 8, 9, 10, 32) in the "Depression + ADHD" subgroup compared to in "Depression". An accuracy of 100% was obtained for the discrimination between the patient groups when thalamic uptake was used in the analysis along with scores from Socialization and Impulsivity scales.
Conclusion
The findings confirm the previous observation of a cerebellar involvement in ADHD. Higher bilateral frontal 99mTc-HMPAO uptake in "Depression + ADHD" compared to in "Depression" indicate a difference between these subgroups. 99mTc-HMPAO uptake mechanisms are discussed.
doi:10.1186/1744-9081-5-37
PMCID: PMC2753339  PMID: 19723308
6.  PERVASIVE OLFACTORY IMPAIRMENT AFTER BILATERAL LIMBIC SYSTEM DESTRUCTION 
What pattern of brain damage could completely obliterate the sense of olfaction in humans? We had an opportunity to address this intriguing question in patient B., who has extensive bilateral damage to most of the limbic system, including the medial and lateral temporal lobes, orbital frontal cortex, insular cortex, anterior cingulate cortex, and basal forebrain, caused by herpes simplex encephalitis. The patient demonstrated profound impairments in odor identification and recognition. Moreover, he could not discriminate between olfactory stimuli and he had severe impairments in odor detection. Reliable stimulus detection was obtained only for solutions of the organic solvent acetone and highly concentrated solutions of ethanol. In contrast to the more circumscribed olfactory deficits demonstrated in patients with damage confined to either the temporal lobes or orbitofrontal cortex (which tend to involve odor identification but not odor detection), patient B. demonstrates a strikingly severe and complete anosmia. This contrast in olfactory abilities and deficits as a result of different anatomical pathology affords new insights into the neural substrates of olfactory processing in humans.
doi:10.1080/13803395.2011.633897
PMCID: PMC3269190  PMID: 22220560
7.  PET and SPECT in whiplash syndrome: a new approach to a forgotten brain? 
Whiplash associated disorders are a medicolegally controversial condition becoming increasingly worrisome in the western world. This study was designed to evaluate perfusion and glucose metabolism in whiplash brain. Using Tc-99m-bicisate (ECD) single photon emission computed tomography (SPECT) and F-18-fluorodeoxyglucose (FDG) PET, six clinically and neuropsychologically controlled patients (patient group) with whiplash syndrome and 12 normal controls (control group) were investigated. Standardised elliptical regions of interest (ROIs) were determined in three adjacent transaxial slices in the frontal, parietal, temporal, and parieto-occipital cortex, cerebellum, brain stem, basal ganglia, and thalamus. For PET, the glucose metabolic index (GMI; =ROI uptake/global uptake at the level of the basal ganglia) and, for SPECT, the perfusion index (PI; =ROI/global) were calculated. In the patient group there was significant hypometabolism and hypoperfusion in the parieto-occipital regions (on the right (R) and left (L) side) compared with the control group: PET data: GMI parieto-occipital R: control 1.066 (0.081) (mean (SD)), patient 0.946 (0.065); P=0.0092, Mann Whitney. GMI parieto-occipital L: control 1.034 (0.051), patient 0.922 (0.073); p=0.0067. SPECT data: PI parieto-occipital R: control 1.262 (0.066), patient 1.102 (0.063); P=0.0039. PI parieto-occipital L: control 1.226 (0.095), patient 1.098 (0.075); P=0.0273. In some patients there was hypometabolism (>2 SD of control) in regions other than the parieto-occipital region. It is hypothesised that parieto-occipital hypometabolism may be caused by activation of nociceptive afferent nerves from the upper cervical spine.


PMCID: PMC2169690  PMID: 9328255
8.  Evaluation of both perfusion and atrophy in multiple system atrophy of the cerebellar type using brain SPECT alone 
BMC Medical Imaging  2010;10:17.
Background
Partial volume effects in atrophied areas should be taken into account when interpreting brain perfusion single photon emission computed tomography (SPECT) images of neurodegenerative diseases. To evaluate both perfusion and atrophy using brain SPECT alone, we developed a new technique applying tensor-based morphometry (TBM) to SPECT.
Methods
After linear spatial normalization of brain perfusion SPECT using 99mTc-ethyl cysteinate dimer (99mTc-ECD) to a Talairach space, high-dimension-warping was done using an original 99mTc-ECD template. Contraction map images calculated from Jacobian determinants and spatially normalized SPECT images using this high-dimension-warping were compared using statistical parametric mapping (SPM2) between two groups of 16 multiple system atrophy of the cerebellar type (MSA-C) patients and 73 age-matched normal controls. This comparison was also performed in conventionally warped SPECT images.
Results
SPM2 demonstrated statistically significant contraction indicating local atrophy and decreased perfusion in the whole cerebellum and pons of MSA-C patients as compared to normal controls. Higher significance for decreased perfusion in these areas was obtained in high-dimension-warping than in conventional warping, possibly due to sufficient spatial normalization to a 99mTc-ECD template in high-dimensional warping of severely atrophied cerebellum and pons. In the present high-dimension-warping, modification of tracer activity remained within 3% of the original tracer distribution.
Conclusions
The present new technique applying TBM to brain SPECT provides information on both perfusion and atrophy at the same time thereby enhancing the role of brain perfusion SPECT
doi:10.1186/1471-2342-10-17
PMCID: PMC2927477  PMID: 20701753
9.  Alleviation of Brain Hypoperfusion after Preventative Treatment with Lomerizine in an Elderly Migraineur with Aura 
Previous studies of brain single-photon emission tomography (SPECT) showed changes of regional cerebral blood flow (rCBF) in migraineurs during prodromes or headache attacks. Little is known about how successful medication of migraine prevention can reflect rCBF in migraineurs. We highlighted alternation of brain SPECT findings in a migraineur with aura before and after prophylactic treatment with lomerizine, a calcium channel blocker. A 70-year-old man with migraine developed visual disturbance frequently at walking exercise for the recent 3 months. After this visual attack, a mild-degree of throbbing headache occured occasionally. Brain SPECT using 99mTc-ethyl cysteinate dimer was performed at interictal time of migraine. Brain SPECT before lomerizine treatment revealed hypoperfusion in the frontal, parietal, and occipital regions. He was diagnosed with recurrence of migraine with aura (MA). Lomerizine (10 mg/day, po) was administered for 3 months. MA and visual aura without headache were dramatically improved. Migraine attacks and visual disturbance were not induced at exercise. At 3 months after lomerizine medication, brain SPECT showed remarkable increase of rCBF. These SPECT changes of our patient indicated that antimigraine mechanism of lomerizine could contribute to restoration of cerebral hypoperfusion.
doi:10.1155/2011/782758
PMCID: PMC3065840  PMID: 21490733
10.  Efficacy of 99mTc-EDDA/HYNIC-TOC SPECT/CT scintigraphy in Graves’ ophthalmopathy 
The aim of this study was to investigate the predictive role of the orbital somatostatin receptor scintigraphy with 99mTc-EDDA/HYNIC-TOC (99mTc-TOC) to detect clinical stage of Graves’ ophthalmopathy and the response to corticosteroid therapy. The subjects of the experiment were 46 patients with Graves’ ophthalmopathy (GO) and four volunteers without eye disease or GO as the normal group (NG). Single photon emission computed tomography (SPECT), computed tomography (CT) and the left and right lateral position planar imaging of the heads of the all subjects were obtained 4 h after the intravenous injection of 555 MBq of 99mTc-TOC. The 99mTc-TOC SPECT/CT was repeated 3 months later. 35 (35/46) patients were received corticosteroid therapy (prednisolone, 10 mg po tid ) for 3 months, however, the other 11 patients as control groups did not receive any treatment. The treatment effect was evaluated both by the orbital 99mTc-TOC uptake and NOSPECS. A significant decrease in the O/OC ratio was observed in 22 GO patients between pre- and post-treatment (1.64 ± 0.13 vs. 1.21 ± 0.09, P < 0.05). There were neither significant difference of the O/OC ratio in 13 GO patients between pre- and post-treatment periods, nor significant difference in the 9 (9/11) patients before and after three months. Orbital 99mTc-TOC scintigraphy is a feasible technique to estimate the Graves’ ophthalmopathy activity and predict the response to subsequent corticosteroid therapy in GO patients. The technique could be a useful tool for physicians not familiar with CAS determination.
PMCID: PMC3477727  PMID: 23133815
Graves’ ophthalmopathy; single photon emission computed tomography (SPECT); somatostatin receptor; 99mTc-TOC
11.  A SPECT Imaging Study Of Driving Impairment In Patients With Alzheimer's Disease 
Single photon emission computed tomography (SPECT) was used in this study to examine the neurophysiologic basis of driving impairment in 79 subjects with dementia. Driving impairment, as measured by caregiver ratings, was significantly related to regional reduction of right hemisphere cortical perfusion on SPECT, particularly in the temporo-occipital area. With increased severity of driving impairment, frontal cortical perfusion was also reduced. Clock drawing was more significantly related to driving impairment than the Mini-Mental State Examination. Driving impairment in Alzheimer's disease is related to changes in cortical function which vary according to severity of disease. Cognitive tests of visuoperceptual and executive functions may be more useful screening tools for identifying those at greatest risk for driving problems than examinations like the Mini-Mental State Examination, that are weighted toward left hemisphere based verbal tasks.
PMCID: PMC3292192  PMID: 10765046
SPECT; driving; Alzheimer's disease; dementia
12.  SPECT, MRI and cognitive functions in multiple sclerosis. 
Seventeen patients with relapsing remitting multiple sclerosis (MS) and mild physical disability had neuropsychological testing, magnetic resonance imaging (MRI) and single photon emission computerised tomography (SPECT) using technetium 99m (99mTc) hexamethyl-propyleneamine oxime (HMPAO). Performance in verbal fluency, naming and memory testing appeared to be impaired in MS patients compared with 17 age-sex and education matched normal controls. Weighted periventricular and confluent lesion scores and the width of the third ventricle, proved to be the most sensitive MRI measures in differentiating more cognitively impaired patients from those who were relatively unimpaired. Ratios of regional to whole brain activity, measured by SPECT, showed significant reduction in the frontal lobes and in the left temporal lobe of MS patients. A relationship was found between left temporal abnormality in 99mTc-HMPAO uptake and deficit in verbal fluency and verbal memory. Finally, asymmetrical lobar activity indicated a predominant left rather than right temporo-parietal involvement.
PMCID: PMC1014343  PMID: 2019835
13.  Recovery of olfactory function after nine years of post-traumatic anosmia: a case report 
Introduction
Olfactory loss due to head trauma is a common condition. Depending on the severity of the head trauma, anosmia might occur in up to 30% of patients. The period of time until recovery has been reported to be a couple of months in most cases. However, recovery from post-traumatic olfactory loss might occur much later. We present a rare case of recovery from anosmia nine years after the initial trauma.
Case presentation
We report the case of a 54-year-old Caucasian man who suffered complete anosmia from a severe car accident. Smell function as well as flavor perception during eating and drinking were also completely lost. After nine years, the patient had his first olfactory impressions, with his sense of smell gradually improving over a period of three years. We confirmed recovery of olfactory function using psychophysical and electrophysiological techniques.
Conclusion
In most cases, recovery of smell function occurs relatively soon after the head trauma and seems to rarely occur more than two years after the incident. However, patients should be informed that there is a small chance of recovery a long time after the trauma.
doi:10.4076/1752-1947-3-9283
PMCID: PMC2767158  PMID: 19918296
14.  Cellular and Behavioral Effects of Cranial Irradiation of the Subventricular Zone in Adult Mice 
PLoS ONE  2009;4(9):e7017.
Background
In mammals, new neurons are added to the olfactory bulb (OB) throughout life. Most of these new neurons, granule and periglomerular cells originate from the subventricular zone (SVZ) lining the lateral ventricles and migrate via the rostral migratory stream toward the OB. Thousands of new neurons appear each day, but the function of this ongoing neurogenesis remains unclear.
Methodology/Principal Findings
In this study, we irradiated adult mice to impair constitutive OB neurogenesis, and explored the functional impacts of this irradiation on the sense of smell. We found that focal irradiation of the SVZ greatly decreased the rate of production of new OB neurons, leaving other brain areas intact. This effect persisted for up to seven months after exposure to 15 Gray. Despite this robust impairment, the thresholds for detecting pure odorant molecules and short-term olfactory memory were not affected by irradiation. Similarly, the ability to distinguish between odorant molecules and the odorant-guided social behavior of irradiated mice were not affected by the decrease in the number of new neurons. Only long-term olfactory memory was found to be sensitive to SVZ irradiation.
Conclusion/Significance
These findings suggest that the continuous production of adult-generated neurons is involved in consolidating or restituting long-lasting olfactory traces.
doi:10.1371/journal.pone.0007017
PMCID: PMC2737283  PMID: 19753118
15.  Abnormal regional cerebral blood flow on 99mTc ECD brain SPECT in patients with primary Sjögren's syndrome and normal findings on brain magnetic resonance imaging 
Annals of the Rheumatic Diseases  2002;61(9):774-778.
Objective: Technetium-99m ethyl cysteinate dimer (99mTc ECD) single photon emission computed tomography (SPECT) of the brain was used to detect abnormal regional cerebral blood flow (rCBF) in patients with primary Sjögren's syndrome (pSS) and normal findings on brain magnetic resonance imaging (MRI).
Methods: 99mTc ECD brain SPECT was performed to detect brain lesions showing hypoperfusion in 32 female patients with pSS and definite neuropsychiatric symptoms or signs. Seventeen female patients with pSS without neuropsychiatric symptoms and signs were included as a control group for comparison. All of the 49 patients with pSS had normal findings on brain MRI.
Results: 99mTc ECD brain SPECT showed brain regions with hypoperfusion in 18 (56.3%) of the 32 patients, and parietal lobes were the most common areas with such lesions. By contrast, 99mTc ECD brain SPECT showed brain regions with hypoperfusion in only three (17.6%) of the 17 patients with pSS without neuropsychiatric symptoms or signs.
Conclusion: This study suggests that 99mTc ECD SPECT is a sensitive tool for detecting regions of hypoperfusion in the brains of patients with pSS and neuropsychiatric symptoms or signs and normal findings on brain MRI. However, a review of the literature showed that the 99mTc ECD SPECT findings in patients with pSS were non-specific.
doi:10.1136/ard.61.9.774
PMCID: PMC1754217  PMID: 12176800
16.  Functional brain abnormalities localized in 55 chronic tinnitus patients: fusion of SPECT coincidence imaging and MRI 
Tinnitus is often defined as the perception of sounds or noise in the absence of any external auditory stimuli. The pathophysiology of subjective idiopathic tinnitus remains unclear. The aim of this study was to investigate the functional brain activities and possible involved cerebral areas in subjective idiopathic tinnitus patients by means of single photon emission computerized tomography (SPECT) coincidence imaging, which was fused with magnetic resonance imaging (MRI). In this cross-sectional study, 56 patients (1 subject excluded) with subjective tinnitus and 8 healthy controls were enrolled. After intravenous injection of 5 mCi F18-FDG (fluorodeoxyglucose), all subjects underwent a brain SPECT coincidence scan, which was then superimposed on their MRIs. In the eight regions of interest (middle temporal, inferotemporal, medial temporal, lateral temporal, temporoparietal, frontal, frontoparietal, and parietal areas), the more pronounced values were represented in medial temporal, inferotemporal, and temporoparietal areas, which showed more important proportion of associative auditory cortices in functional attributions of tinnitus than primary auditory cortex. Brain coincidence SPECT scan, when fused on MRI is a valuable technique in the assessment of patients with tinnitus and could show the significant role of different regions of central nervous system in functional attributions of tinnitus.
doi:10.1038/jcbfm.2009.254
PMCID: PMC2949154  PMID: 20068582
magnetic resonance imaging; SPECT coincidence imaging; tinnitus
17.  Olfactory Processing, Sex Effects and Heterogeneity in Schizophrenia 
Schizophrenia Research  2011;135(1-3):144-151.
Introduction
Smell identification deficits are associated with negative symptoms in schizophrenia, particularly in males. Far less information is known about the relationship of odor detection sensitivity (acuity) and negative symptoms in schizophrenia, and currently there is a dearth in sex-stratified research specifically examining odor sensitivity and smell identification.
Methods
Fifty-eight individuals with schizophrenia and 42 healthy comparison subjects were assessed on tests of odor sensitivity, smell identification and cognition. Negative symptoms were assessed with the Positive and Negative Syndrome Scale and the Schedule for the Deficit Syndrome.
Results
In healthy males, increased odor detection sensitivity predicted better smell identification scores. In contrast, male schizophrenia patients showed a significant inverse relationship, in which increased odor sensitivity predicted lower smell identification scores. Odor sensitivity and smell identification were unrelated in both schizophrenia and healthy females. Olfactory processing was strongly linked to negative symptoms, but the relationships differed by sex. Emotional expression deficits were related to odor detection hypersensitivity in female patients, whereas smell identification deficits predicted these emotional deficits in male cases.
Conclusion
Sex differences in olfactory functioning were identified in healthy subjects and in schizophrenia patients. Smell identification was related to negative symptoms in males with schizophrenia, whereas odor detection sensitivity predicted these features in females. Sex differences should be considered in future analyses that employ odor stimuli for neuropsychiatric research.
doi:10.1016/j.schres.2011.11.025
PMCID: PMC3288877  PMID: 22177347
Schizophrenia; sex differences; negative symptoms; odor sensitivity; smell identification
18.  Ventral frontal cortex functions and quantified MRI in traumatic brain injury 
Neuropsychologia  2007;46(2):461-474.
Ventral frontal cortex is commonly involved in traumatic brain injury (TBI). The Smell Identification Test (SIT), Object Alternation (OA), and the Iowa Gambling Task (IGT) are associated with this brain region in experimental and neuropsychological research. We examined the relationship of performance on these tests to residual structural brain integrity quantified from MRI in 58 TBI patients, including 18 patients with focal cortical contusions and 40 patients with diffuse injury only. Image analysis yielded regional volumetric measures of gray matter, white matter and cerebrospinal fluid. Multivariate analyses identified distributed patterns of regional volume loss associated with test performance across all three behavioral measures. The tasks were sensitive to effects of TBI. In multivariate analyses, performance in all three tasks was related to gray matter loss including ventral frontal cortex, but the SIT was most sensitive to ventral frontal cortex damage, even in patients without focal lesions. The SIT was further related to temporal lobe and posterior cingulate/retrosplenial volumes. OA and the IGT were associated with superior medial frontal volumes. Complex tasks, such as OA and the IGT, do not consistently localize to a single cortical region. The SIT is associated with the integrity of ventral frontal regions, but it is also affected by distributed damage, although the contribution of undetected olfactory tract or bulb damage could not be ruled out. This study illustrates the scope and limitations of functional localization in human ventral frontal cortex.
doi:10.1016/j.neuropsychologia.2007.08.027
PMCID: PMC2287189  PMID: 17976665
Head injury; diffuse axonal injury; focal lesions; neuropsychology; orbitofrontal cortex; partial least squares analysis
19.  Decreases in blood perfusion of the anterior cingulate gyri in Anorexia Nervosa Restricters assessed by SPECT image analysis 
BMC Psychiatry  2001;1:2.
Background
It is possible that psychopathological differences exist between the restricting and bulimic forms of anorexia nervosa. We investigated localized differences of brain blood flow of anorexia nervosa patients using SPECT image analysis with statistic parametric mapping (SPM) in an attempt to link brain blood flow patterns to neurophysiologic characteristics.
Methods
The subjects enrolled in this study included the following three groups: pure restrictor anorexics (AN-R), anorexic bulimics (AN-BP), and healthy volunteers (HV). All images were transformed into the standard anatomical space of the stereotactic brain atlas, then smoothed. After statistical analysis of each brain image, the relationships among images were evaluated.
Results
SPM analysis of the SPECT images revealed that the blood flow of frontal area mainly containing bilateral anterior cingulate gyri (ACC) was significantly decreased in the AN-R group compared to the AN-BP and HV groups.
Conclusions
These findings suggest that some localized functions ofthe ACCare possibly relevant to the psychopathological aspects of AN-R.
doi:10.1186/1471-244X-1-2
PMCID: PMC32312  PMID: 11407997
20.  Localized 1H-MR Spectroscopy in Moyamoya Disease before and after Revascularization Surgery 
Korean Journal of Radiology  2003;4(2):71-78.
Objective
To evaluate, using localized proton magnetic resonance spectroscopy (1H-MRS), the cerebral metabolic change apparent after revascularization surgery in patients with moyamoya disease.
Materials and Methods
Sixteen children with moyamoya disease and eight age-matched normal controls underwent MR imaging, MR angiography, conventional angiography, and 99mTc-ECD SPECT. Frontal white matter and the basal ganglia of both hemispheres were subjected to localized 1H-MRS, and after revascularization surgery, four patients underwent follow-up 1H-MRS.
Results
Decreased NAA/Cr ratios (1.35±0.14 in patients vs. 1.55±0.24 in controls) and Cho/Cr ratios (0.96±0.13 in patients vs. 1.10±0.11 in controls) were observed in frontal white matter. After revascularization surgery, NAA/Cr and Cho/Cr ratios in this region increased. In the basal ganglia, there is no abnormal metabolic ratios.
Conclusion
Localized 1H-MRS revealed abnormal metabolic change in both hemispheres of children with moyamoya disease. Because of its non-invasive nature, 1H-MRS is potentially useful for the preoperative evaluation of metabolic abnormalities and their postoperative monitoring.
doi:10.3348/kjr.2003.4.2.71
PMCID: PMC2698073  PMID: 12845301
Magnetic resonance (MR), spectroscopy; Brain, infarction; Moyamoya disease
21.  Olfactory Hedonic Judgment in Patients With Deficit Syndrome Schizophrenia 
Schizophrenia Bulletin  2009;36(4):860-868.
Olfactory perception was examined in deficit syndrome (DS) and nondeficit syndrome (ND) schizophrenia patients. Participants included 22 controls (CN) and 41 patients with schizophrenia who were divided into DS (n = 15) and ND (n = 26) subtypes using the Schedule for the Deficit Syndrome (SDS). Olfactory perception for pleasant and unpleasant odors was assessed using the Brief Smell Identification Test. Participants were instructed to identifying each smell as well as provide hedonic judgment ratings of each smell on a 7-point scale (1 = extremely pleasant, 4 = neutral, and 7 = extremely unpleasant). Results indicated that when compared with the ND patients, the DS patients rated pleasant smells as being significantly less pleasant, although no difference between the groups was present for unpleasant smells, and both ND and DS groups significantly differed from CN on rating and identifying pleasant and unpleasant items. Additionally, lower smell identification accuracy was negatively correlated with SDS symptom severity, and valence ratings for pleasant odors were positively correlated with SDS diminished emotional range. Findings suggest that the DS is characterized by a unique pattern of olfactory valence judgment that is characterized by abnormalities in processing positively valenced stimuli.
doi:10.1093/schbul/sbn178
PMCID: PMC2894582  PMID: 19223658
negative symptoms; olfaction; emotion; valence
22.  Mice with a “Monoclonal” Nose: Perturbations in an Olfactory Map Impair Odor Discrimination 
Neuron  2008;60(6):1068-1081.
SUMMARY
The recognition of odors is accomplished in the sensory epithelium where individual olfactory neurons express only one of 1,300 odorant receptor genes. Neurons expressing a given receptor project to two spatially invariant glomeruli in the olfactory bulb such that each odor elicits a distinct and sparse pattern of glomerular activity. We have altered the neural representation of odors in the brain by generating a mouse with a “monoclonal nose” in which greater than 95% of the sensory neurons express a single odorant receptor, M71. As a consequence, the frequency of sensory neurons expressing endogenous receptor genes is reduced twenty-fold. We observe that these mice can smell but odor discrimination and performance in associative olfactory learning tasks are impaired. However, these mice cannot detect the M71 ligand acetophenone despite the observation that virtually all sensory neurons and glomeruli are activated by this odor. The M71 transgenic mice readily detect other odors in the presence of acetophenone. These observations have implications for how receptor activation in the periphery is represented in the brain and how these representations encode odors.
doi:10.1016/j.neuron.2008.10.046
PMCID: PMC2732586  PMID: 19109912
23.  Olfactory dysfunction in Parkinson’s disease: Benefits of quantitative odorant examination 
Olfactory involvement is well recognized in patients with Parkinson’s disease (PD). The purpose of this study was to examine smell function quantitatively, using different types and concentrations of odorants in PD patients. We aimed to elucidate whether a specific odor can affect the severity and duration of PD patients. A total of 89 nondemented PD patients and 20 age-matched controls participated in the study. Quantitative evaluation of smell function was performed using the T and T olfactometer test. This test contains five kinds of odorants at different concentrations. Recognition threshold (RT) scores for all five odorants and for each individual odorant were measured in five groups of PD patients with Hoehn and Yale (HY) stages I (n = 12), II (n = 24), III (n = 43), and IV (n = 10), as well as in control subjects (n = 20). One-way analysis of variance and Ryan’s method were used for statistical comparison between the five groups. Compared with controls and HY I patients, total RT scores were significantly higher in HY II, III, and IV patients. There were no statistically significant differences in RT scores between HY I patients and controls. However, total RT scores for three HY I patients (25%) were higher than the mean + two standard deviations of controls. On single odorant testing, significant higher RT scores for methylcyclopentenolone and skatol were found in HY II, III, and IV patients, in comparison with controls and HY I patients. The remaining three odorants did not differ statistically between PD patients and control subjects. The present study indicated that hyposmia in PD patients increased from HY II onwards. A single odorant of methyl cyclopentenolone or skatol had benefits for olfactory evaluation in PD patients. Our data also clarified that olfactory deficits occurred in a subset of HY I patients. Further prospective study is needed to elucidate whether a distinct profile of PD exists between HY I patients with and without hyposmia.
PMCID: PMC2915529  PMID: 20689691
Parkinson’s disease; Hoehn and Yale stage; olfactory dysfunction; odorants
24.  (99mTc)-HM-PAO SPECT and cognitive impairment in Parkinson's disease: a comparison with dementia of the Alzheimer type. 
Regional cerebral perfusion was evaluated by single photon emission tomography (SPECT) using (99mTc)-HM-PAO as a tracer, in thirty Parkinsonian patients with (n = 15) or without (n = 15) dementia, nineteen patients with dementia of the Alzheimer type (DAT) and thirteen control subjects. HM-PAO uptake was measured in the frontal, parietal, temporal and occipital cortex and tracer perfusion was expressed as cortical/cerebellar activity ratios. Regional HM-PAO ratios in nondemented Parkinsonian patients did not differ from controls, whereas in demented patients with Parkinson's disease (DPD) a significant reduction was found in the parietal, temporal and occipital cortex. Tracer uptake ratios were significantly reduced in all regions in the DAT group. Thus DPD and DAT shared a common pattern of marked posterior hypoperfusion, although the perfusion defect was greater and more extensive in the DAT patients.
Images
PMCID: PMC1014518  PMID: 1955897
25.  Asymmetric Cerebral Blood Flow in Patients with Mild Cognitive Impairment: Possible Relationship to Further Cognitive Deterioration 
Aim
To explore patterns of cerebral blood flow in patients with mild cognitive impairment (MCI), who (1) eventually deteriorate into overt dementia, with no particular focus on the type of dementia, or (2) do not appear to further deteriorate in their cognitive functions.
Methods
Thirty-seven MCI patients, with or without vascular pathology, were studied prospectively. The patients underwent 99mTc-HMPAO SPECT analysis at baseline. Possible clinical conversion into dementia within a 2-year period was assessed.
Results
Nineteen patients had progressive MCI (PMCI), while 18 patients were considered clinically stable (SMCI). PMCI patients had more often abnormally low cerebral blood flow in at least one of the frontal, temporal, parietal or occipital lobes compared to SMCI patients (12/19 vs. 5/18; p = 0.049). At least one of the temporal regions was found to be abnormal in 9 PMCI patients in contrast to only 1 SMCI patient (p = 0.008). More specifically, blood flow in the medial portion of the left temporal region was abnormal in 8 PMCI patients, a pattern seen in 1 SMCI patient only (p = 0.019).
Conclusion
The results suggest that blood flow reductions particularly in the left medial temporal region indicate an elevated risk of further cognitive decline in MCI patients.
doi:10.1159/000329447
PMCID: PMC3199881  PMID: 22163247
Cerebral blood flow; Cognitive decline; Mild cognitive impairment; Progressive dementia; SPECT

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