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The number of functional olfactory receptor genes and the relative size of olfactory brain structures are poor predictors of olfactory discrimination performance with enantiomers.

The ability of four squirrel monkeys and three pigtail macaques to distinguish between nine enantiomeric odor pairs sharing an isopropenyl group at the chiral center was investigated in terms of a conditioning paradigm. All animals from both species were able to discriminate between the optical isomers of limonene, carvone, dihydrocarvone, dihydrocarveole and dihydrocarvyl acetate, whereas they failed to distinguish between the (+)- and (-)-forms of perillaaldehyde and limonene oxide. The pigtail macaques, but not the squirrel monkeys, also discriminated between the antipodes of perillaalcohol and isopulegol. A comparison of the across-task patterns of discrimination performance shows a high degree of similarity among the two primate species and also between these nonhuman primates and human subjects tested in an earlier study on the same tasks. These findings suggest that between-species comparisons of the relative size of olfactory brain structures or of the number of functional olfactory receptor genes are poor predictors of olfactory discrimination performance with enantiomers.

Animals↗

Eicosapentaenoic acid in treatment-resistant depression associated with symptom remission, structural brain changes and reduced neuronal phospholipid turnover.

The n-3 essential fatty acid eicosapentaenoic acid (EPA) was added to the conventional antidepressant treatment of a treatment-resistant severely depressed and suicidal male patient with a seven-year history of unremitting depressive symptoms. The niacin skin flush test and cerebral magnetic resonance scanning were carried out at baseline and nine months later. The addition of ethyl-EPA led to a dramatic and sustained clinical improvement in all the symptoms of depression, including a cessation of previously unremitting severe suicidal ideation, within one month. Symptoms of social phobia also improved dramatically. During the nine-month period the volumetric niacin response increased by 30%, the relative concentration of cerebral phosphomonesters increased by 53%, and the ratio of cerebral phosphomonesters to phosphodiesters increased by 79%, indicating reduced neuronal phospholipid turnover. Registered difference images showed that the EPA treatment was accompanied by structural brain changes including, in particular, a reduction in the lateral ventricular volume.

Adult↗

Unawareness of illness in chronic schizophrenia and its relationship to structural brain measures and neuropsychological tests.

The present study seeks to elucidate the relationship between unawareness of illness in schizophrenia and frontal lobe dysfunction, in addition to investigating the relationship between lack of insight and sociodemographic and clinical variables. Twenty-one medicated schizophrenic patients, recruited from in- and out-patient wards at Ullevâl Hospital, underwent the Scale to Assess Unawareness of Mental Disorder (SUMD), neuropsychological testing, psychiatric symptom ratings and neuroimaging procedures (CT). Also, 21 matched normal controls were neuropsychologically tested. CT data were assessed blindly by two experienced neuroradiologists, according to the degree of ventricular enlargement and/or sulcal widening, and an assessment of localisation of atrophy was made. Unawareness of illness was correlated with neuropsychological measures related to executive functioning, but not with other neuropsychological measures. Five patients showed slight frontal atrophy, while two showed moderate frontal atrophy. The remaining 13 patients did not show signs of frontal lobe atrophy. Frontal lobe atrophy documented by structural brain measures was associated with poor insight in schizophrenia. Furthermore, Anergia (BPRS), GAF score and 'undifferentiated' sub-diagnosis correlated with SUMD scores. Unawareness of illness in schizophrenia may be related to frontal lobe deficit. Also, awareness of illness may not be related to general psychopathology, but rather to specific aspects.

Adult↗

Effect of stress on activity of the serotoninergic system in limbic brain structures and its correlation with pituitary-adrenal function in the rat.

Fifteen min after ether stress, the 5-hydroxytryptamine (5-HT) content of the rat hypothalamus decreased, while after electric shock no decline was noted in the mesencephalon and the hypothalamus. At 30 min an increase occurred in the mesencephalon and amygdala and at 60 min in the hypothalamus after both stressors. Fifteen min after electric shock the 5-hydroxyindoleacetic acid (5-HIAA) content was increased in the amygdala, while after both stressors in the mesencephalon and hypothalamus 30 min and after ether stress in the amygdala. In the hippocampus and the septum the 5-HT or 5-HIIA content was unaffected by either type of stress. 5-HT turnover decreased between 10 and 20 min after ether stress in the hypothalamus and after electric shock in the mesencephalon and hypothalamus. Between 50 and 60 min after electric shock, 5-HT turnover increased in the mesencephalon. Other brain areas showed no significant difference from the control 5-HT value. 3H-5-HT uptake decreased in the mesencephalon and hypothalamus 20 min after ether stress, but returned to normal after 60 min. The plasma corticosterone level was highest at 30 min after both stressors and returned to normal 90 min after stress. Therefore, the stress-induced decrease of serotoninergic activity in certain limbic brain structures, especially in the hypothalamus, suggests an inverse relationship with pituitary-adrenal activity. This finding would further support the concept that the serotoninergic system plays an inhibitory role in pituitary-adrenal function.

Animals↗

Structural brain CT changes and cognitive deficits in elderly depressives with and without reversible dementia ('pseudodementia').

Twenty-six elderly (greater than 60 yrs) patients with DSM-III major depression were compared to 13 patients with NINCDS/ADRDA probable Alzheimer's disease (AD), and to 31 screened normal controls. Subjects were matched on age and sex. Fifteen of the 26 depressed patients were cognitively impaired on the Mini-Mental State Examination (MMSE) upon admission, but after treatment returned to the normal range. These 15 patients were defined as having the dementia syndrome of depression (DOD). The remaining 11 depressed patients were termed depressed, cognitively normal (DCN). All subjects received standardized cranial CT scans for assessment of ventricular brain ratio (VBR) and CT attenuation numbers. Subjects also received neuropsychological evaluation. CT values for the 26 depressed patients lay between those of AD patients and normal controls. CT values for the DOD subgroup clustered near those of AD patients. Patterns of cognitive deficits and correlations of CT attenuation values with cognitive measures were also similar in AD and DOD. Most patients were reassessed at a mean of two years after initial testing; of the 11 of the 15 DOD re-examined, only one had undergone cognitive decline. By contrast, all AD patients retested had declined significantly. Episodes of DOD and DCN tended to 'breed true'. This study suggests that while patients with DOD may have underlying structural brain abnormalities, obvious short-term progression to AD does not commonly occur.

Aged↗

Evidence for a common network of brain structures involved in parkinsonian tremor and voluntary repetitive movement.

Repeated measurements of regional cerebral blood flow (rCBF) were obtained in 7 patients who underwent a stereotactic thalamic electrode implantation in the nucleus ventralis intermedius (nVIM) of the thalamus for severe hemi-parkinsonian tremor. Using positron emission tomography and oxygen-15 labelled water, rCBF was studied in each patient in two conditions: in absence of tremor, e.g. under nVIM electrical stimulation, and in presence of tremor. X-ray tomograms permitted individual definition of anatomical regions of interest. In presence of tremor, normalized rCBF increases were observed in the following regions: postcentral (13.6 +/- 8.4%, P = 0.0003), precentral (7.7 +/- 8.8%, P = 0.016), paracentral (7.7 +/- 8.4%), supplementary motor (8.2 +/- 10.4%, P = 0.025), caudate nucleus (5.7 +/- 7.6%, P = 0.03), vermis (9.7 +/- 7.3%, P = 0.007), cerebellar grey nuclei (9 +/- 6%, P = 0.016) on the electrode side and on the contralateral vermis (17.8 +/- 7.5%, P = 0.0003) and cerebellar grey nuclei (22 +/- 6.3%, P = 0.0004). These results clearly indicate an activation of the sensory-motor cortex, as well as an involvement of the supplementary motor area and the cortico-cerebellar pathways in Parkinsonian resting tremor (PRT). They demonstrate that PRT shares common network of brain structures with repetitive voluntary movement.

Aged↗

Zeta waves, an unusual EEG finding in structural brain lesions: report of two patients.

We report two patients with acute cerebral conditions and zeta waves on their EEGs. The first patient, a 48-year-old lady, had acute disseminated encephalomyelitis (ADEM)following afebrile illness. Neurological examination showed expressive dysphasia and a mild right hemiparesis. The magnetic resonance imaging (MRI) scan of the brain showed multiple, bilateral, subcortical white matter hyperintensities, predominantly in the centrum semiovale region of the left hemisphere, and also in the corpus callosum. An EEG done 21 days after the onset of the neurological deficit showed intermittent, sharply contoured, predominantly biphasic delta waves (zeta waves) over the left frontotemporal region. The second patient was a 2-year-old child, who had a head-injury resulting in bilateral, frontoparietal fractures of the skull; acute epidural hematoma on the left frontoparietal region; and a cerebral contusion on the right frontotemporal region. An EEG done one day after the evacuation of the hematoma showed zeta waves over the right frontal region. To the best of our knowledge, the association of zeta waves and ADEM has not been previously reported. The EEG findings in our patients again supports the hypothesis that these waves are seen predominantly in patients with structural brain lesions. Other conditions causing zeta waves in the EEG are briefly reviewed.

Brain↗

Persistent epileptiform activity induced by low Mg2+ in intact immature brain structures.

We have determined the properties of seizures induced in vitro during the first postnatal days using intact rat cortico-hippocampal formations (CHFs) and extracellular recordings. Two main patterns of activity were generated by nominally Mg2+-free ACSF in hippocampal and cortical regions: ictal-like events (ILEs) and late recurrent interictal discharges (LRDs). They were elicited at distinct developmental periods and displayed different pharmacological properties. ILEs were first observed in P1 CHFs 52 +/- 7 min after application of low-Mg2+ ACSF (frequency 1.5 +/- 0.3 h-1, duration 86 +/- 3 s). There is a progressive age-dependent maturation of ILEs characterized by a decrease in their onset and an increase in their frequency and duration. ILEs were abolished by d-APV and Mg2+ ions. From P7, ILEs were followed by LRDs that appeared 89 +/- 8 min after application of low-Mg2+ ACSF (frequency approximately 1 Hz, duration 0.66 s, amplitude 0.31 +/- 0.03 mV). LRDs were no longer sensitive to d-APV or Mg2+ ions and persisted for at least 24 h in low-Mg2+ or in normal ACSF. ILEs and LRDs were synchronized in limbic and cortical regions with 10-40 ms latency between the onsets of seizures. Using a double chamber that enables independent superfusion of two interconnected CHFs, we report that ILEs and LRDs generated in one CHF propagated readily to the other one that was being kept in ACSF. Therefore, at a critical period of brain development, recurrent seizures induce a permanent form of hyperactivity in intact brain structures and this preparation provides a unique opportunity to study the consequences of seizures at early developmental stages.

Age Factors↗

Antibodies against viruses and structural brain components in oligoclonal IgG obtained from multiple sclerosis brain.

Immunoglobulin G (IgG) was isolated from three multiple sclerosis (MS) and two control brains by Protein A Sepharose affinity chromatography and was characterized by thin-layer polyacrylamide gel isoelectric focusing (PAG IEF) and antiserum immunofixation. The three MS brains contained oligoclonal IgG. Immunofixation with measles, herpes simplex, varicella, rubella, mumps and cytomegalovirus as antigens and autoradiography revealed that some of the oligoclonal IgG bands separated by PAG IEF contained antibodies against herpes simplex in one, measles in two and varicella virus in all three MS brains. No antibodies were detected with this technique against structural human (crude saline, lipid-proteolipid, ganglioside, and myelin basic protein extracts of MS and normal human brain) and bovine (purified myelin myelin basic protein and oligodendrocytes of bovine brain) brain components. The finding of viral antibodies and the absence of antibodies against structural brain proteins in oligoclonal MS brain IgG is similar to that previously recorded in MS cerebrospinal fluid (CSF).

Antibodies, Viral↗

Structural brain changes in tinnitus.

Tinnitus is a common but poorly understood disorder characterized by ringing or buzzing in the ear. Central mechanisms must play a crucial role in generating this auditory phantom sensation as it persists in most cases after severing the auditory nerve. One hypothesis states that tinnitus is caused by a reorganization of tonotopic maps in the auditory cortex, which leads to an overrepresentation of tinnitus frequencies. Moreover, the participation of the limbic system in generating tinnitus has been postulated. Here we aimed at identifying brain areas that display structural change in tinnitus. We compared tinnitus sufferers with healthy controls by using high-resolution magnetic resonance imaging and voxel-based morphometry. Within the auditory pathways, we found gray-matter increases only at the thalamic level. Outside the auditory system, gray-matter decrease was found in the subcallosal region including the nucleus accumbens. Our results suggest that reciprocal involvement of both sensory and emotional areas are essential in the generation of tinnitus.

Adult↗

Using automated morphometry to detect associations between ERP latency and structural brain MRI in normal adults.

Despite the clinical significance of event-related potential (ERP) latency abnormalities, little attention has focused on the anatomic substrate of latency variability. Volume conduction models do not identify the anatomy responsible for delayed neural transmission between neural sources. To explore the anatomic substrate of ERP latency variability in normal adults using automated measures derived from magnetic resonance imaging (MRI), ERPs were recorded in the visual three-stimulus oddball task in 59 healthy participants. Latencies of the P3a and P3b components were measured at the vertex. Measures of local anatomic size in the brain were estimated from structural MRI, using tissue segmentation and deformation morphometry. A general linear model was fitted relating latency to measures of local anatomic size, covarying for intracranial vault volume. Longer P3b latencies were related to contractions in thalamus extending superiorly into the corpus callosum, white matter (WM) anterior to the central sulcus on the left and right, left temporal WM, the right anterior limb of the internal capsule extending into the lenticular nucleus, and larger cerebrospinal fluid volumes. There was no evidence for a relationship between gray matter (GM) volumes and P3b latency. Longer P3a latencies were related to contractions in left temporal WM, and left parietal GM and WM near the interhemispheric fissure. P3b latency variability is related chiefly to WM, thalamus, and lenticular nucleus, whereas P3a latency variability is not related as strongly to anatomy. These results imply that the WM connectivity between generators influences P3b latency more than the generators themselves do.

Adult↗

Effect of repeated treatment with antidepressant drugs and electroconvulsive shock (ECS) on [3H] prazosin binding to different rat brain structures.

The influence of acute and repeated treatment with imipramine, amitriptyline, mianserin, citalopram and ECS on alpha 1-adrenoceptors in different structures of the rat brain (cerebral cortex, hippocampus and thalamus) was measured using [3H] prazosin as a ligand. Repeated, but not acute, treatment with all the above antidepressant drugs and ECS induced an increase in the density of alpha 1-adrenoceptors in the cerebral cortex. On the other hand, no changes were found in the hippocampus and thalamus, with an exception of the increased number of [3H] prazosin binding sites in the thalamus after imipramine. The results suggest that the up-regulation of alpha 1-adrenoceptors following repeated antidepressant treatment is not a general phenomenon within the central nervous system.

Animals↗

Improving whole brain structural MRI at 4.7 Tesla using 4 irregularly shaped receiver coils.

Both higher magnetic field strengths (> or =3 T) and multiple receiver "array coils" can provide increased signal-to-noise ratio (SNR) for MRI. This increase in SNR can be used to obtain images with higher resolution, enabling better visualisation of structures within the human brain. However, high field strength systems also suffer from increased B(1) non-uniformity and increased power deposition, reaching specific absorption rate (SAR) limits more quickly. For these problems to be mitigated, a careful choice of both the pulse sequence design and transmit RF coil is required. This paper describes the use of a prototype array coil consisting of 4 irregularly shaped coils within a standard configuration for neuroimaging at 4.7 T (a head transmit/receive volume coil to minimise SAR and a head gradient insert for maximum gradient performance). With a fast spin echo (FSE) pulse sequence optimised for 4.7 T, this provides dramatically increased quality and resolution over a large brain volume. Using the array coil, a SNR improvement relative to the volume coil of 1-1.5 times in central brain areas and 2-3 times in cortical regions was obtained. Array coil images with a resolution of 352 x 352 x 2000 mum had a SNR of 16.0 to 26.2 in central regions and 19.9 to 34.8 in cortical areas. Such images easily demonstrate cortical myeloarchitecture, while still covering most of the brain in a approximately 12 min scan.

Algorithms↗

Zinc and glutamate dehydrogenase in putative glutamatergic brain structures.

A certain topographic parallelism between the distribution of histochemically (TIMM staining) identified zinc and putative glutamatergic structures in the rat brain was demonstrated. Glutamate dehydrogenase as a zinc containing protein is in consideration to be an enzyme synthesizing transmitter glutamate. In a low concentration range externally added zinc ions (10(-9) to 10(-7) M) induced an increase in the activity of glutamate dehydrogenase (GDH) originating from rat hippocampal formation, neocortex, and cerebellum up to 142.4%. With rising molarity of Zn(II) in the incubation medium, the enzyme of hippocampal formation and cerebellum showed a biphasic course of activation. Zinc ions of a concentration higher than 10(-6) M caused a strong inhibition of GDH. The effect of Zn(II) on GDH originating from spinal ganglia and liver led only to a decrease of enzyme activity. These results are discussed in connection with a functional correlation between zinc and putatively glutamatergic system.

Animals↗

Can amnesia be caused by damage of a single brain structure?

The relation of amnesia and damage to some particular brain regions is discussed by reviewing the main findings of selected human case reports. It is argued that frequently a too straightforward and unidimensional interpretation of the relations between brain damage and a behavioral deficit is formulated in such reports. Evidence obtained by modern anatomical techniques as well as the widespread and time-dependent effects of lesions make it necessary to consider a lesion of a particular structure of the brain and correlated mnemonic disturbances as possibly due to an altered equilibrium in an extensive network of the brain. The primary lesion of one or the other specific structure may lead to severe and lasting amnesia or may fail to do so depending on its influence on other brain regions.

Adult↗

Structural brain aging in inbred mice: potential for genetic linkage.

To identify genetic factors involved in brain aging, we have initiated studies assessing behavioral and structural changes with aging among inbred mouse strains. Cognitive performance of C57BL/6J mice is largely maintained with aging, and stereological analysis revealed no significant age-related change in neuron number, synaptic bouton number or glial number in the hippocampus. Moreover, no change in cortical neuron number and cholinergic basal forebrain neuron number has been found in this strain. 129Sv/J mice have more pronounced age-related cognitive deficits, although hippocampal and basal cholinergic forebrain neuron number also appear unchanged with aging. Differences in neurogenesis and neuron vulnerability in the adult CNS of C57BL/6, 129/Sv and other inbred strains have been reported, which in turn may have important consequences for brain aging. Age-related lesions, such as thalamic eosinophilic inclusions and hippocampal clusters of polyglucosan bodies also vary greatly among inbred strains although the functional significance of these lesions is not clear. The continued assessment of such age-related structural and behavioral changes among inbred mouse strains offers the potential to identify genes that control age-related changes in brain structure and function.

Aging↗

Digital image reconstruction for the study of brain structure and function.

Functional activity of brain can be defined as the change in physiological activity that accompanies change in behavior. Although the precise relationship between such coupled activity is still being explored, autoradiographic methods for measuring brain blood flow, metabolism and receptor ligand densities have advanced to the point where it is possible to survey the entire brain of an animal for such changes. These developments offer the opportunity for studying brain as a whole--that is, for surveying the entire brain to identify the sites where changes in blood flow, metabolism or receptor chemistry occur with a particular behavior. The development of computer-based image analysis systems offer the possibility for visualizing such holistic brain function. We identified 4 steps which must be accomplished in developing a three-dimensional (3D) display for studying brain function. This paper describes the development and implementation of procedures for these 4 steps. Sectioning and digitizing representative tissue (e.g. autoradiograms, histology, histochemistry) with an adequate sampling frequency. Alignment and reconstruction of the components which make up the whole brain so that the original shape and orientation prior to sectioning is maintained. Projection and surface generation of a 3D model where the shading of the surface is mathematically dependent on the location of light source(s) and the viewer. Localization and quantification of planar cuts through the 3D model. Density data which reference the original autoradiograms are displayed along the exposed surface of the designated plane. The final presentation of data once these 4 steps are completed allows for the identification and visualization of changes in functional activity within the whole brain.

Algorithms↗

[Acetylcholinesterase and monoamine oxidase in various brain structures in chronic alcoholic intoxication].

The authors studied the rat brain after prolonged (up to 18 months) alcohol intoxication as well as the progeny of female rats after alcohol consumption for 4 months. Some changes in the activity of acetyl cholinesterase and monoamine oxidase in different structures of the brain in parents and progeny were unidirectional while others were not. Other findings included a weight loss during alcoholization and a decline in the fertility and viability of the progeny.

Acetylcholinesterase↗