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1.
J Affect Disord ; 223: 130-138, 2017 12 01.
Article in English | MEDLINE | ID: mdl-28753471

ABSTRACT

BACKGROUND: Traumatic brain injury (TBI) is common in military personnel and associated with high rates of posttraumatic stress disorder (PTSD). TBI impacts widely-distributed neural patterns, some of which influence affective processing. Better understanding how TBI and PTSD/TBI alters affective neural activity may improve our understanding of comorbidity mechanisms, but to date the neural correlates of emotional processing in these groups has been relatively understudied. METHODS: Military controls, military personnel with a history of TBI, and military personnel with both TBI and PTSD (N = 53) completed an emotional face processing task during fMRI. Whole-brain activation and functional connectivity during task conditions were compared between groups. RESULTS: Few whole-brain group differences emerged in planned pairwise contrasts, though the TBI group showed some areas of hypoactivation relative to other groups during processing of faces versus shapes. The PTSD/TBI group compared to the control and TBI groups demonstrated greater connectivity between the amygdala and insula seed regions and a number of prefrontal and posterior cingulate regions. LIMITATIONS: Generalizability to other patient groups, including those with only PTSD, has not yet been established. CONCLUSION: TBI alone was associated with hypoactivation during a condition processing faces versus shapes, but PTSD with TBI was associated altered functional connectivity between amygdala and insula regions and cingulate and prefrontal areas. Altered connectivity patterns across groups suggests that individuals with PTSD/TBI may need to increase frontal connectivity with the insulae in order to achieve similar task-based activity.


Subject(s)
Brain Injuries, Traumatic/physiopathology , Emotions/physiology , Facial Recognition/physiology , Stress Disorders, Post-Traumatic/physiopathology , Adult , Cerebral Cortex/physiopathology , Humans , Magnetic Resonance Imaging , Male , Military Personnel , United States , Veterans
2.
Psychiatry Res ; 226(2-3): 513-4, 2015 Apr 30.
Article in English | MEDLINE | ID: mdl-25724487

ABSTRACT

Harmful use of alcohol is one of the top five risks for burden of disease globally and in Europe; in 2012, 3.3 million net deaths (approximately 6% of all global deaths) were attributable to this risk factor. It is also linked to the development of a wide spectrum of alcohol use disorders, ranging from mild manifestations to a severe disease known as alcohol dependence. Alcohol dependence is a progressive, chronic, and relapsing brain disease resulting from the prolonged effects of alcohol on the brain. Alcohol dependence imposes a significant societal burden, with indirect societal costs reaching up to 0.64% of European countries׳ annual gross domestic product. With these facts in mind, it is important to recognize and manage alcohol dependence. Although the biological mechanisms behind the development of alcohol dependence are not fully known, factors that have been shown to influence its development include genetic predisposition, psychological problems, and social interactions. Alcohol use has also been linked to the development of hypertension, liver cirrhosis, chronic pancreatitis, multiple types of cancer, and psychiatric comorbidities such as depression and anxiety disorders. With such severe effects on both individuals and society, it is important to recognize the characteristic signs and symptoms of alcohol dependence and explore new ways to better manage patients with this brain disease. Effective treatment approaches for alcohol dependence include biological, behavioral, and social components addressing the multiple aspects of this disease. Comprehensive, educational platforms in which to explore the many facets of this disease such as the Progress in Mind: Focus on Alcohol Use Disorders Resource Centre, will provide clinicians with the tools necessary for recognizing patients with alcohol dependence and managing their disease along with related comorbidities. Online Access: http://progressinmind.elsevierresource.com.


Subject(s)
Alcohol-Related Disorders/diagnosis , Alcohol-Related Disorders/therapy , Alcohol Drinking/genetics , Alcohol Drinking/therapy , Alcohol-Related Disorders/genetics , Alcoholism/diagnosis , Alcoholism/genetics , Alcoholism/therapy , Comorbidity , Genetic Predisposition to Disease/genetics , Humans , Risk Factors
3.
Mol Genet Metab ; 87(3): 272-7, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16343970

ABSTRACT

Classic phenylketonuria (PKU) is characterized by severe mental retardation in untreated individuals and mild neurocognitive abnormalities in some early treated adults. The exact biochemical mechanisms underlying this neurotoxicity remain undetermined. Several theories implicate abnormal cerebral energy utilization and alterations in biochemical pathways that involve glucose metabolism. This pilot study was undertaken to investigate whether 18F-deoxyglucose positron emission tomography (PET) is an effective tool to study cerebral glucose metabolism in early treated PKU. After PET coregistration with SPGR MRI, relative glucose metabolic rates (rGMR) at the center of standard atlas positions was determined. Repeated measures MANOVA was used to assess regional metabolic differences, which were then correlated with age-specific and day-of-scan plasma phenylalanine and age. Patients with PKU in comparison to controls had decreased rGMR in cortical regions including the prefrontal, somatosensory, and visual cortices, and increased activity in subcortical regions including the striatum and limbic system. Day-of-scan phenylalanine correlated with abnormal activity in subcortical structures, and older age was associated with decreased activity in the prefrontal and visual cortices. The clinical significance of these abnormalities of glucose metabolism in specific areas of the brain remains unknown.


Subject(s)
Cerebral Cortex/metabolism , Glucose/metabolism , Phenylketonurias/metabolism , Phenylketonurias/therapy , Adult , Aging , Case-Control Studies , Female , Fluorodeoxyglucose F18 , Humans , Male , Phenylalanine/metabolism , Pilot Projects , Positron-Emission Tomography , Time Factors
4.
J Neuropsychiatry Clin Neurosci ; 13(4): 486-91, 2001.
Article in English | MEDLINE | ID: mdl-11748317

ABSTRACT

This study evaluates electroencephalography (EEG) and positron emission tomography (PET) in the same subjects. Fourteen murderers were assessed by using both PET (while they were performing the continuous performance task) and EEG during a resting state. EEG revealed significant increases in slow-wave activity in the temporal, but not frontal, lobe in murderers, in contrast to prior PET findings that showed reduced prefrontal, but not temporal, glucose metabolism. Results suggest that resting EEG shows empirical utility distinct from PET activation findings.


Subject(s)
Arousal/physiology , Blood Glucose/metabolism , Electroencephalography , Homicide , Temporal Lobe/physiopathology , Tomography, Emission-Computed , Adult , Beta Rhythm , Brain Mapping , Delta Rhythm , Female , Frontal Lobe/physiopathology , Humans , Insanity Defense , Male , Neuropsychological Tests , Psychomotor Performance/physiology , Reference Values , Theta Rhythm
5.
Neuropsychopharmacology ; 25(5 Suppl): S50-6, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11682274

ABSTRACT

Positron emission tomography with deoxyglucose-F18 was obtained during nighttime sleep in 36 normal volunteers, 12 studied in rapid eye movement sleep (REM period 2), 12 in nonREM sleep, and 12 while awake with eyes closed. Metabolic rate was higher throughout the cortex in REM than nonREM sleep, with differences most marked in the cingulate and frontal cortex, thalamus, and visual association areas. Whole-brain metabolic rates in the waking condition were intermediate between those in REM and nonREM sleep. Metabolism in the primary visual cortex and parts of the lateral temporal lobe was relatively constant in the REM/nonREM conditions. REM sleep did not differ from either the nonREM or waking conditions in hemispheric lateralization of metabolic activity. Compared with REM sleep, nonREM sleep was associated with significantly lower metabolic rates in the temporal and occipital regions, as well as the thalamus.


Subject(s)
Brain/metabolism , Sleep/physiology , Adult , Brain/diagnostic imaging , Fluorodeoxyglucose F18 , Humans , Male , Radiopharmaceuticals , Sleep, REM , Tomography, Emission-Computed , Wakefulness
6.
Neuropsychopharmacology ; 25(5 Suppl): S74-8, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11682278

ABSTRACT

The antidepressant and cerebral metabolic effects of total sleep deprivation (TSD) or partial sleep deprivation (PSD) for one night has been studied with functional neuroimaging in seven publications from five different groups. Despite the variations in methods and techniques, the over-all findings were relatively consistent. First, before sleep deprivation, responders have significantly elevated metabolism compared with non-responders and normal controls, in the orbital medial prefrontal cortex, and especially the ventral portions of the anterior cingulate cortex. Second, after sleep deprivation, these hyperactive areas normalize in the responders. One functional imaging study suggested that synaptic dopamine release was associated with the antidepressant effects of TSD. The neurochemical implications of these findings are explored. Possible dopaminergic and serotonergic mechanisms are discussed.


Subject(s)
Cerebral Cortex/metabolism , Depressive Disorder/therapy , Gyrus Cinguli/metabolism , Sleep Deprivation , Cerebral Cortex/diagnostic imaging , Depressive Disorder/diagnostic imaging , Depressive Disorder/metabolism , Dopamine/metabolism , Gyrus Cinguli/diagnostic imaging , Humans , Psychiatric Status Rating Scales , Serotonin/metabolism , Tomography, Emission-Computed , Treatment Outcome
7.
Depress Anxiety ; 14(1): 37-49, 2001.
Article in English | MEDLINE | ID: mdl-11568981

ABSTRACT

This paper reviews the functional brain imaging studies in depressed patients treated with sleep deprivation. Sleep deprivation is an excellent experimental model of antidepressant treatments which offer new opportunities to understand the basic neural mechanisms. Its antidepressant effects are efficacious and rapid; sleep deprivation is easy to administer, inexpensive, and relatively safe; it can be studied in patients, normal controls, and animals; and it may lead to new treatments and new paradigms for antidepressant therapies. Seven published papers, coming from five different research centers, using either positron emission tomography (PET) with 18fluorodeoxyglucose (FDG) or single photon emission computerized tomography (SPECT) with Technetium-99-bexamethyl propyleneamine oxime (HMPAO) have relatively consistent findings. First, before sleep deprivation, responders have significantly elevated metabolism compared with non-responders, and usually the normal controls, in the orbital medial prefrontal cortex, and especially in the ventral portions of the anterior cingulate cortex. Secondly, after sleep deprivation, these hyperactive areas normalize in the responders. The magnitude of the clinical improvement was significantly correlated with decreased local glucose metabolic rate or cerebral blood flow in three studies. The results are consistent with some but not all functional brain imaging studies of antidepressant medications in depressed patients. Finally, a SPECT study using a radioactively labeled D2 receptor antagonist suggests that the antidepressant benefits of sleep deprivation are correlated with endogenous release of dopamine.


Subject(s)
Brain/diagnostic imaging , Depressive Disorder/diagnostic imaging , Depressive Disorder/therapy , Sleep Deprivation , Humans , Models, Psychological , Tomography, Emission-Computed , Tomography, Emission-Computed, Single-Photon , Treatment Outcome
8.
Horm Behav ; 40(2): 86-92, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11534967

ABSTRACT

The interstitial nuclei of the human anterior hypothalamus (INAH1-4) have been considered candidates for homology with the sexually dimorphic nucleus of the preoptic area of the rat. Volumetric sexual dimorphism has been described for three of these nuclei (INAH1-3), and INAH3 has been reported to be smaller in homosexual than heterosexual men. The current study measured the INAH in Nissl-stained coronal sections in autopsy material from 34 presumed heterosexual men (24 HIV- and 10 HIV+), 34 presumed heterosexual women (25 HIV- and 9 HIV+), and 14 HIV+ homosexual men. HIV status significantly influenced the volume of INAH1 (8% larger in HIV+ heterosexual men and women relative to HIV- individuals), but no other INAH. INAH3 contained significantly more neurons and occupied a greater volume in presumed heterosexual males than females. No sex difference in volume was detected for any other INAH. No sexual variation in neuronal size or density was observed in any INAH. Although there was a trend for INAH3 to occupy a smaller volume in homosexual men than in heterosexual men, there was no difference in the number of neurons within the nucleus based on sexual orientation.


Subject(s)
HIV Infections/pathology , Hypothalamus/physiology , Sexual Behavior/physiology , Adult , Aged , Brain/anatomy & histology , Brain/pathology , Female , HIV Seronegativity/physiology , HIV Seropositivity/pathology , Humans , Hypothalamus/anatomy & histology , Hypothalamus/pathology , Male , Middle Aged , Organ Size/physiology , Sex Characteristics
9.
Arch Gen Psychiatry ; 58(9): 877-84, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11545672

ABSTRACT

BACKGROUND: Schizotypal personality disorder (SPD) shares social deficits and cognitive impairment with schizophrenia, but is not typically characterized by frank psychosis. Because striatal size and functional activity have both been shown to be associated with psychotic symptoms, we carried out the first study of SPD to assess the caudate and putamen for comparison with findings in schizophrenia. METHODS: Patients with SPD (n = 16), schizophrenic patients (n = 42), and age- and sex-matched normal control subjects (n = 47) were assessed with magnetic resonance imaging. All of the patients with SPD and subsamples of the schizophrenic patients (n = 27) and control subjects (n = 32) were also assessed with positron emission tomography using fluorodeoxyglucose F-18. RESULTS: The relative size of the putamen in controls was significantly larger than in patients with SPD and significantly smaller than in schizophrenic patients, while the relative size of the caudate was similar in all 3 groups. Compared with control values, relative glucose metabolic rate in the ventral putamen was significantly elevated in patients with SPD and reduced in schizophrenic patients. When subsamples of schizophrenic patients (n = 10) and patients with SPD (n = 10) both of whom never received medication were compared, this pattern was more marked, with the highest value for the putamen being found in patients with SPD for the ventral slice and the lowest value for the right dorsal putamen. CONCLUSIONS: Patients with SPD showed reduced volume and elevated relative glucose metabolic rate of the putamen compared with both schizophrenic patients and controls. These alterations in volume and activity may be related to the sparing of patients with SPD from frank psychosis.


Subject(s)
Corpus Striatum/anatomy & histology , Corpus Striatum/metabolism , Glucose/metabolism , Schizophrenia/diagnosis , Schizotypal Personality Disorder/diagnosis , Adult , Caudate Nucleus/anatomy & histology , Caudate Nucleus/diagnostic imaging , Caudate Nucleus/metabolism , Corpus Striatum/diagnostic imaging , Diagnosis, Differential , Female , Fluorodeoxyglucose F18 , Humans , Magnetic Resonance Imaging/statistics & numerical data , Male , Putamen/anatomy & histology , Putamen/diagnostic imaging , Putamen/metabolism , Schizophrenia/diagnostic imaging , Schizophrenia/metabolism , Schizophrenic Psychology , Schizotypal Personality Disorder/diagnostic imaging , Schizotypal Personality Disorder/metabolism , Tomography, Emission-Computed/statistics & numerical data
10.
Front Biosci ; 6: D1069-72, 2001 Sep 01.
Article in English | MEDLINE | ID: mdl-11532605

ABSTRACT

Patients with schizophrenia exhibit (a) deficient sensorimotor gating as indexed by impaired prepulse inhibition (PPI) of the startle eyeblink reflex suggesting abnormal automatic information processing and (b) abnormal attentional modulation of PPI suggesting impaired controlled information processing. Here we test the hypothesis of deficient attentional modulation of PPI in schizophrenia as a defect in the interrelationship between frontal lobe functions of planning and executive action and posterior function of processing of sensory stimulation using positron emission tomography (PET). Consistent with the literature, our findings indicate that unmedicated schizophrenia patients exhibit lower frontal/occipital ratios (termed "hypofrontality") compared with healthy controls (n=15 in each group) during a standard tone-length-judgment (attention-to-prepulse) task. Moreover, better attentional modulation of PPI was associated with higher frontal/occipital ratios in the control, but not the patient group. These findings extend animal models to humans by demonstrating the importance of frontal and occipital lobe coordination in the modulation of PPI.


Subject(s)
Frontal Lobe/physiopathology , Motor Neuron Disease/physiopathology , Schizophrenia/physiopathology , Animals , Attention/physiology , Glucose/metabolism , Humans , Neural Inhibition/physiology , Reflex, Startle/physiology , Review Literature as Topic , Schizophrenia/diagnosis , Schizophrenia/metabolism , Schizophrenic Psychology , Tomography, Emission-Computed
11.
Biol Psychiatry ; 50(4): 281-91, 2001 Aug 15.
Article in English | MEDLINE | ID: mdl-11522263

ABSTRACT

BACKGROUND: Prepulse inhibition (PPI) of the startle reflex reflects early stages of information processing and is modulated by selective attention. Animal models indicate medial frontal-thalamic circuitry is important in PPI modulation. We report data from the first functional magnetic resonance imaging (fMRI) study examining whether attending to or ignoring a prepulse differentially activates brain areas within this circuitry. METHODS: Ten healthy subjects received structural and functional MRI. During fMRI acquisition, subjects heard intermixed attended and ignored tones serving as prepulses to the startle stimulus. Regions of interest were traced on structural MRI and coregistered to fMRI images. RESULTS: Greater amplitude fMRI blood-oxygen-level-dependent response to attended than ignored PPI conditions occurred in the right thalamus, and bilaterally in the anterior and mediodorsal thalamic nuclei, whereas the startle-alone condition showed deactivation. In transitional medial cortex (Brodmann Area 32), which is involved in affective processing of noxious stimuli, the startle-alone condition elicited the greatest response, the attended-PPI condition showed the smallest response, and the ignored-PPI condition was intermediate. CONCLUSIONS: These findings extend animal models to humans by indicating thalamic involvement in the modulation of PPI. Further fMRI investigations may elucidate other key structures in the circuitry underlying normal and disordered modulation of PPI.


Subject(s)
Attention/physiology , Magnetic Resonance Imaging , Reflex, Startle/physiology , Thalamus/anatomy & histology , Thalamus/physiology , Adult , Female , Frontal Lobe/anatomy & histology , Frontal Lobe/blood supply , Frontal Lobe/physiology , Humans , Male , Neural Inhibition/physiology , Oxygen/blood , Thalamus/blood supply
12.
Int J Neuropsychopharmacol ; 4(2): 119-25, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11466160

ABSTRACT

The regional metabolic effects of fluoxetine were examined in patients with autism spectrum disorders. Six adult patients with DSM-IV and Autism Diagnostic Interview (ADI) diagnoses of autism (n = 5) and Asperger's syndrome (n = 1), entered a 16-wk placebo-controlled cross-over trial of fluoxetine. The patients received (18)F-deoxyglucose positron emission tomography with co-registered magnetic resonance imaging at baseline and at the end of the period of fluoxetine administration. After treatment, the patients showed significant improvement on the scores of the Yale--Brown Obsessive--Compulsive Scale -- Obsessions subscale and the Hamilton Anxiety Scale; Clinical Global Impressions -- Autism scores showed 3 of the patients much improved and 3 unchanged. Relative metabolic rates were significantly higher in the right frontal lobe following fluoxetine, especially in the anterior cingulate gyrus and the orbitofrontal cortex. Patients with higher metabolic rates in the medial frontal region and anterior cingulate when unmedicated were more likely to respond favourably to fluoxetine. These results are consistent with those in depression indicating that higher cingulate gyrus metabolic rates at baseline predict SRI response.


Subject(s)
Antidepressive Agents, Second-Generation/therapeutic use , Asperger Syndrome/drug therapy , Asperger Syndrome/metabolism , Autistic Disorder/drug therapy , Autistic Disorder/metabolism , Brain/metabolism , Fluoxetine/therapeutic use , Selective Serotonin Reuptake Inhibitors/therapeutic use , Adult , Analysis of Variance , Asperger Syndrome/diagnostic imaging , Autistic Disorder/diagnostic imaging , Brain/diagnostic imaging , Cross-Over Studies , Female , Frontal Lobe/metabolism , Gyrus Cinguli/metabolism , Humans , Male , Pilot Projects , Psychiatric Status Rating Scales , Radionuclide Imaging , Treatment Outcome
13.
Neuropsychobiology ; 43(4): 265-72, 2001.
Article in English | MEDLINE | ID: mdl-11340367

ABSTRACT

Positron emission tomography with uptake of [(18)F]fluorodeoxyglucose (FDG) and quantitative EEG were simultaneously performed in 18 medication-free patients with schizophrenia and in 13 normal volunteers. Subjects performed the Continuous Performance Task (CPT) during FDG uptake. Correlations were calculated between alpha power during the CPT and glucose metabolic rate (GMR) in thalamic regions and between alpha power during the CPT and GMR in occipital cortices. Regression analyses were used to describe the prediction of GMR in the occipital cortices and in the thalamic regions of occipital alpha power. In normal controls, we found (1) significant negative correlations between absolute alpha power and GMR in the left occipital cortex, (2) significant positive correlations between normalized alpha power and GMR in the right and left lateral thalamus and (3) combined effects of GMR in the thalamic regions and the occipital cortices on alpha power, which accounted for 98% of the variance of alpha power. In patients with schizophrenia, we found no significant correlations between alpha power and GMR in the occipital cortices or between alpha power and GMR in the thalamic regions. Correlation coefficients between absolute alpha power and GMR in the left occipital cortex and between normalized alpha power and GMR in the left lateral thalamus were significantly different in normal subjects compared to schizophrenic patients. The present findings provide evidence for involvement of the thalamus in the generation of alpha rhythm in humans. Furthermore, the present results suggest differences in thalamocortical circuits between normal controls and schizophrenic subjects.


Subject(s)
Alpha Rhythm , Glucose/metabolism , Schizophrenia/metabolism , Schizophrenia/physiopathology , Thalamus/metabolism , Adult , Basal Metabolism/physiology , Female , Humans , Kinetics , Male , Occipital Lobe/metabolism , Psychiatric Status Rating Scales , Psychomotor Performance/physiology , Schizophrenia/diagnostic imaging , Thalamus/diagnostic imaging , Tomography, Emission-Computed
14.
Neuroimage ; 13(6 Pt 1): 1140-5, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11352619

ABSTRACT

Deformation-based morphometry (DBM) is a useful technique to detect morphological differences over the entire brain since it analyses positional differences between every voxel and a standard brain. In this report we compare DBM to semimanual tracing of brain ventricles in a population of 39 patients with schizophrenia. High-resolution T(1)-weighted magnetic resonance images were obtained and processed with DBM and interactive tracing software. We evaluate the validity of the DBM in two different approaches. First, we divide subjects into two groups based on the mean ventricular/brain ratios and compute statistical maps of displacement vectors and their spatial derivatives. This analysis demonstrates a striking consistency of the DBM and visual tracing results. We show that restricting the information about the deformation fields by computing the local Jacobian determinant (as a measure of volume change) provides evidence of the shape of ventricular deformation which is unavailable from ventricular volume measures alone. Second, we compute a mean measure of the Jacobian values over the entire ventricles and observe a correlation of r = 0.962 with visual tracing based ventricular/brain ratios. The results support the usefulness and validity of DBM for the local and global examination of brain morphology.


Subject(s)
Cerebral Ventricles/pathology , Magnetic Resonance Imaging , Schizophrenia/diagnosis , Adolescent , Adult , Aged , Brain/pathology , Female , Humans , Image Enhancement , Image Processing, Computer-Assisted , Male , Mathematical Computing , Middle Aged , Schizophrenia/pathology
15.
Schizophr Res ; 48(2-3): 187-99, 2001 Mar 30.
Article in English | MEDLINE | ID: mdl-11295372

ABSTRACT

The volumes of the whole temporal lobe, the superior temporal gyrus and the corpus callosum were measured on magnetic resonance images from 13 patients with schizotypal personality disorder (SPD), 27 patients with schizophrenia, and 31 age- and sex-matched controls. Temporal lobe structures were traced on consecutive 1.2mm thick SPGR images. Both patient groups had smaller temporal lobes than normal volunteers, a difference that was more marked for the area outside the superior temporal gyrus than for the STG. Correcting for brain volume diminished differences between normal subjects and schizophrenia patients, but the differences between normal subjects and SPD patients remained. Normal volunteers and SPD patients showed significant correlations between the sagittal section area of the posterior portion of the corpus callosum, which carries temporal interhemispheric connections, and the white matter volume of the temporal lobe. While the sample size is modest, taken together, these results suggest that the psychopathological symptoms of SPD may be related to temporal gray matter loss with relatively intact white matter connectivity, while the cognitive and psychotic symptoms of schizophrenia may be related to temporal gray loss combined with disruption of normal patterns of white matter development.


Subject(s)
Magnetic Resonance Imaging , Schizophrenia/diagnosis , Schizotypal Personality Disorder/diagnosis , Temporal Lobe/abnormalities , Adult , Agenesis of Corpus Callosum , Anthropometry , Female , Humans , Male
16.
Biol Psychiatry ; 49(5): 426-36, 2001 Mar 01.
Article in English | MEDLINE | ID: mdl-11274654

ABSTRACT

BACKGROUND: Declarative memory changes are the hallmark of Alzheimer's disease, although their functional neuroanatomy is not restricted to a single structure. Factor analysis provides statistical methods for evaluating patterns of cerebral changes in regional glucose uptake. METHODS: Thirty-three Alzheimer's patients and 33 age- and gender-matched control subjects were studied with magnetic resonance imaging and positron emission tomography with [(18)F] deoxyglucose. During the tracer-uptake period, subjects performed a serial verbal learning task. Cortical activity was measured in 32 regions of interest, four in each lobe on both hemispheres. RESULTS: Factor analysis with varimax rotation identified seven factors explaining 80% of the variance ("parietal cortex," "occipital cortex," "right temporo-prefrontal areas," "frontal cortex," "motor strip," "left temporal cortex," and "posterior temporal cortex"). Relative to control subjects, Alzheimer's patients showed significantly reduced values on the factors occipital cortex, right temporo-prefrontal areas, frontal cortex, and left temporal cortex. The factor temporo-prefrontal areas showed large differences between patients with good and poor performance, but little difference when control subjects were similarly divided. CONCLUSIONS: Findings suggest that Alzheimer's disease is characterized by altered patterns of cortical activity, rather than deficits in a single location, and emphasize the importance of right temporo-prefrontal circuitry for understanding memory deficits.


Subject(s)
Alzheimer Disease/metabolism , Cerebral Cortex/blood supply , Cerebral Cortex/metabolism , Memory Disorders/diagnosis , Aged , Brain/anatomy & histology , Cerebrovascular Circulation/physiology , Female , Fluorodeoxyglucose F18/pharmacokinetics , Functional Laterality/physiology , Humans , Magnetic Resonance Imaging , Male , Neuropsychological Tests , Prefrontal Cortex/blood supply , Prefrontal Cortex/metabolism , Radiopharmaceuticals/pharmacokinetics , Temporal Lobe/blood supply , Temporal Lobe/metabolism , Time Factors , Tomography, Emission-Computed
17.
Neuropsychologia ; 39(6): 556-73, 2001.
Article in English | MEDLINE | ID: mdl-11257281

ABSTRACT

This study used fMRI to examine the response of the amygdala in the evaluation and short-term recognition memory of unpleasant vs. neutral words in nine right-handed healthy adult women. To establish specificity of the amygdala response, we examined the fMRI BOLD signal in one control region (visual cortex). Alternating blocks of unpleasant and neutral trials were presented. During the emotional decision task, subjects viewed sets of three unpleasant or three neutral words while selecting the most unpleasant or neutral word, respectively. During the memory task, subjects identified words that were presented during the emotional decision task (0.50 probability). Images were detrended, filtered, and coregistered to standard brain coordinates. The Talairach coordinates for the center of the amygdala were chosen before analysis. The BOLD signal at this location in the right hemisphere revealed a greater amplitude signal for the unpleasant relative to the neutral words during the emotional decision but not the memory task, confirmed by Time Course x Word Condition ANOVAs. These results are consistent with the memory modulatory view of amygdala function, which suggests that the amygdala facilitates long-term, but not short-term, memory consolidation of emotionally significant material. The control area showed only an effect for Time Course for both the emotional decision and memory tasks, indicating the specificity of the amygdala response to the evaluation of unpleasant words. Moreover, the right-sided amygdala activation during the unpleasant word condition was strongly correlated with the BOLD response in the occipital cortex. These findings corroborate those by other researchers that the amygdala can modulate early processing of visual information in the occipital cortex. Finally, an increase in subject's state anxiety (evaluated by questionnaire) while in the scanner correlated with amygdala activation under some conditions.


Subject(s)
Affect/physiology , Amygdala/anatomy & histology , Amygdala/physiology , Decision Making/physiology , Magnetic Resonance Imaging , Memory/physiology , Recognition, Psychology , Vocabulary , Adult , Female , Functional Laterality/physiology , Humans , Speech Perception/physiology
18.
Acad Emerg Med ; 8(2): 196-9, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11157301

ABSTRACT

OBJECTIVE: Patients with a low risk of coronary artery disease (CAD) presenting to the emergency department (ED) with chest pain pose a diagnostic dilemma because a small percentage will suffer an acute myocardial infarction (MI) and sudden death. The authors conducted this study to determine whether exercise stress echocardiography (ESE) could be used to further support the safe discharge of these low-risk patients. METHODS: A convenience sample of patients > or =30 years of age without a prior cardiac history who presented to an academic community hospital with chest pain, normal initial creatine kinase, and electrocardiography without ischemic changes underwent ESE within 6 +/- 1.7 hours (mean +/- SD). Abnormal ESE was defined as regional wall motion abnormality at rest or after exercise. The ED disposition and three- and six-month follow-up for cardiac events were recorded. This was a prospective observational cohort study. RESULTS: Of a total of 149 eligible patients, 145 completed the study. The mean age (+/-SD) was 47 +/- 9 years; 56% were male. No adverse events were noted during ESE. Seven patients (5%) had abnormal ESE (2 with rest wall motion abnormalities and 5 with exercise-induced wall motion abnormalities). Five of the seven underwent cardiac catheterization; three had CAD. All patients received telephone follow-up at three months and six months. Of the 138 patients with a normal ESE, all were free of cardiac events at three months. One patient had a non-Q-wave MI at six months (negative predictive value = 99.3%, 95% CI = 97.8% to 100%). CONCLUSIONS: Exercise stress echocardiography can be used to evaluate low-risk chest pain patients in the ED. Patients with a normal ESE may be considered for discharge with minimal risk of sequelae.


Subject(s)
Chest Pain/diagnosis , Coronary Disease/diagnosis , Emergency Service, Hospital , Adult , Algorithms , Chest Pain/drug therapy , Coronary Disease/diagnostic imaging , Diagnosis, Differential , Electrocardiography , Exercise Test , Female , Humans , Male , Middle Aged , Myocardial Infarction/diagnosis , Myocardial Infarction/diagnostic imaging , Nitroglycerin/therapeutic use , Predictive Value of Tests , Prospective Studies , Risk Factors , Ultrasonography , Vasodilator Agents/therapeutic use
19.
AJNR Am J Neuroradiol ; 22(1): 136-42, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11158899

ABSTRACT

BACKGROUND AND PURPOSE: We used quantitative diffusion MR imaging to investigate the microstructural changes that occur in white matter during normal aging in order to identify regional changes in anisotropy and to quantify global microstructural changes by use of whole-brain diffusion histograms. METHODS: Full diffusion tensor MR imaging was performed in 20 healthy volunteers, 20 to 91 years old. Thirteen subjects also underwent high-resolution T1-weighted imaging, so that diffusion images could be coregistered and standardized to normal coordinates for statistical probability mapping. Relative anisotropy (RA) was calculated, as was linear regression of RA with age for each pixel; pixels with a significant correlation coefficient were displayed. For histographic analysis, the average apparent diffusion coefficient (ADC) histograms were calculated on a pixel-by-pixel basis. Subjects were divided into two equal groups by the median age (55 years) of the population and plotted for statistical comparison. RESULTS: Regional analysis showed statistically significant decreases in RA with increasing age in the periventricular white matter, frontal white matter, and genu and splenium of the corpus callosum, despite the absence of signal abnormalities on visual inspection of conventional images. Significant increases in RA were found in the internal capsules bilaterally. ADC histograms showed higher mean ADC and reduced peak height and skew in the older age group on group comparisons. CONCLUSION: Quantitative diffusion histograms correlate with normal aging and may provide a global assessment of normal age-related changes and serve as a standard for comparison with neurodegenerative diseases.


Subject(s)
Aging/physiology , Brain/anatomy & histology , Brain/growth & development , Magnetic Resonance Imaging/methods , Adult , Aged , Aged, 80 and over , Anisotropy , Diffusion , Female , Humans , Male , Middle Aged , Reference Values
20.
Arch Gen Psychiatry ; 58(2): 133-40, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11177115

ABSTRACT

BACKGROUND: The importance of neuronal interactions in development, the cortical dependence of many thalamic nuclei, and the phenomenon of transsynaptic degeneration suggest possible abnormalities in thalamic nuclei with connections to other brain regions implicated in schizophrenia. Because frontal and temporal lobe volumes are diminished in schizophrenia, volume loss could characterize their primary thalamic relay nuclei (mediodorsal nucleus [MDN] and pulvinar). METHODS: Tracers delineated the thalamus, MDN, and pulvinar on contiguous 1.2-mm magnetic resonance images in 12 schizophrenic patients, 12 with schizotypal personality disorder (SPD), and 12 normal control subjects. The MDN and pulvinar were rendered visible by means of a Sobel intensity-gradient filter. RESULTS: Pixel overlap for delineation of all structures by independent tracers was at least 80%; intraclass correlations were r = 0.78 for MDN and r = 0.83 for pulvinar. Pulvinar volume was smaller in schizophrenic (1.22 +/- 0.24 cm(3)) and SPD (1.20 +/- 0.23 cm(3)) patients than controls (1.37 +/- 0.25 cm(3)). Differences for MDN were not statistically significant; however, when expressed as percentage of total brain volume, pulvinar and MDN together were reduced in SPD (0.14%) and schizophrenic (0.15%) patients vs controls (0.16%). Reductions were more prominent in the left hemisphere, with MDN reduced only in the schizophrenic group, and pulvinar in both patient groups. Total thalamic volume did not differ among the 3 groups. CONCLUSIONS: Measurement of MDN and pulvinar in magnetic resonance images is feasible and reproducible. Schizophrenic and SPD patients have volume reduction in the pulvinar, but only schizophrenic patients show reduction relative to brain volume in MDN.


Subject(s)
Magnetic Resonance Imaging/statistics & numerical data , Mediodorsal Thalamic Nucleus/anatomy & histology , Pulvinar/anatomy & histology , Schizophrenia/diagnosis , Schizotypal Personality Disorder/diagnosis , Adult , Brain/anatomy & histology , Diagnosis, Differential , Female , Humans , Male , Neural Pathways/anatomy & histology , Psychiatric Status Rating Scales/statistics & numerical data , Reproducibility of Results , Thalamus/anatomy & histology
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