Aberrant corticospinal tract characteristics in prodromal PD: A diffusion tensor imaging study.

Introduction: Parkinson's disease (PD) is typically diagnosed when motor symptoms first occur. However, PD-related non-motor symptoms may appear several years before diagnosis. REM sleep behaviour disorder (RBD) and olfactory deficits (hyposmia) are risk factors, but they are not specific for predicting progression towards PD. Other PD-related markers, for example brain imaging markers, may help to identify preclinical PD in hyposmic RBD patients. Studies have reported abnormal structural characteristics in the corticospinal tract (CST) of PD patients, but it is unclear whether hyposmic RBD patients have similar abnormalities that may help to predict PD in these individuals. This study examined whether CST abnormalities may be a potential marker of PD risk by using diffusion tensor imaging (DTI) measures. Methods: Twenty hyposmic RBD patients, 31 PD patients, and 29 healthy controls (HCs) were studied. DTI data were collected on a 1.5 T MRI scanner and CST characteristics (FA, MD, AD, and RD) were evaluated using probabilistic tractography (with seed regions in the bilateral primary motor cortex and mediolateral cerebral peduncles). Olfactory function was assessed with the University of Pennsylvania Smell Identification Test (UPSIT). Results: Hyposmic RBD patients showed significantly higher mean diffusivity (MD) values of the right CST compared to HCs but did not differ from PD patients. PD patients showed a trend of higher MD values compared to HCs. Conclusions: Altered diffusivity in the CST seems to be associated with RBD. The combination of RBD, hyposmia, and CST alterations may be related to later development of PD with comorbid RBD.

Analyzing the experiences of adolescent control rats: Effects of the absence of physical or social stimulation on anxiety-like behaviour are dependent on the test.

The present study was designed to systematically assess the control experience routinely used in our laboratory as part of studies on predator odour stress. Specifically, we examined effects of the physical and social components of this control experience on measures of anxiety-like behaviour in adolescent rats. Adolescent animals are at increased susceptibility to environmental perturbations and have been used for such studies much less often. Long-Evans rats of both sexes were subjected to physical stimulation (Exposed or Unexposed) and social stimulation (Single-Housed or Pair-Housed), resulting in four groups. Exposed rats received six 30-min exposures to an enclosed arena containing an unscented piece of cat collar occurring between adolescence and early adulthood, while Unexposed remained in the home cage. Groups of Exposed and Unexposed animals were housed singly (Single-Housed) from early adolescence to early adulthood or Pair-Housed during this time. Experimental procedures began in adolescence and involved repeated assessment of startle amplitude (measure of anxiety-like behaviour) and prepulse inhibition (PPI; a measure of sensorimotor gating) to gauge the short-term impact of social and/or physical stimulation. All animals were re-paired in adulthood prior to a final startle/PPI session to assess if isolation limited to adolescence could impose long-term effects that were not reversible. We also measured anxiety-like behaviour in adulthood using an extended open field test (EOFT; addition of novel objects to the open field on later days), and the elevated plus maze task (EPM), as well as a sucrose preference test (SPT) to measure anhedonia. An absence of social or physical stimulation resulted in increased startle amplitude and some measures of anxiety-like behaviour in the EOFT, but a reduction in such anxiety-like behaviour in the EPM task. These results suggest common neural substrates for the physical and social experiences. Performance in the SPT was unaltered by any experimental treatments. Sensorimotor gating, as measured by PPI, was increased in the absence of physical stimulation with no short-term effect of isolation, or of re-pairing. These results indicate the importance of considering individual components of the rearing environment of rats, while showing the need to use multiple assays of anxiety-like behaviour.

Diffusion tensor imaging and olfactory identification testing in early-stage Parkinson's disease.

Evidence from imaging, clinical studies, and pathology suggests that Parkinson's disease is preceded by a prodromal stage that predates clinical diagnosis by several years but there is no established method for detecting this stage. Olfactory impairment, which is common in Parkinson's disease and often predates clinical diagnosis, may be a useful biomarker for early Parkinson's. Evidence is emerging that diffusion imaging parameters might be altered in olfactory tract and substantia nigra in the early stages of clinical Parkinson's disease, possibly reflecting pathological changes. However, no study has examined olfaction and diffusion imaging in olfactory tract and substantia nigra in the same group of patients. The present study compared newly diagnosed Parkinson's disease patients with a matched control group using both olfactory testing and diffusion tensor imaging of the substantia nigra and anterior olfactory structures. Fourteen patients with stage 1-2 Hoehn & Yahr Parkinson's disease were matched to a control group by age and sex. All subjects then completed the University of Pennsylvania Smell Identification Test, as well as a series of MRI scans designed to examine diffusion characteristics of the olfactory tract and the substantia nigra. Olfactory testing revealed significant impairment in the patient group. Diffusion tensor imaging revealed significant group differences in both the substantia nigra and anterior olfactory region, with fractional anisotropy of the olfactory region clearly distinguishing the Parkinson's subjects from controls. This study suggests that there may be value in combining behavioral (olfaction) and MRI testing to identify early Parkinson's disease. Since loss of olfaction often precedes the motor symptoms in Parkinson's disease, the important question raised is "will the combination of olfactory testing and MRI (DTI) testing identify pre-motor Parkinson's disease?"

Minimal illumination for direct laryngoscopy and intubation in different ambient light settings.

OBJECTIVES: This study sought to investigate the minimal laryngoscope illumination required for proper laryngoscopy and intubation in different ambient light settings as determined by paramedics. METHODS: Paramedics qualified to intubate patients in the field were recruited to intubate a cadaver embalmed with a minimal fixation technique designed to maintain tissue integrity. All paramedic participants intubated the cadaver under three different ambient light settings representing possible out-of-hospital settings: an outdoor night setting, an indoor setting, and an outdoor day setting. Paramedics were asked to determine the minimal illumination required for intubation of the cadaver under each of these settings. RESULTS: Twenty-three paramedics participated in the study. The mean (+/-SD) minimal illumination required for intubation was 39.1 (+/-35.4) lux at the night setting, 92.5 (+/-57.3) lux at the indoor setting, and 209.7 (+/-117.4) lux at the day setting. There was a statistically significant difference in minimal illumination required between each of the three light settings (p < 0.0001). CONCLUSIONS: Minimal illumination requirements in the out-of-hospital setting may be lower than previously recommended. Ambient light intensity affects this minimal illumination requirement, with brighter ambient light conditions necessitating more laryngoscope light output. Further studies assessing out-of-hospital laryngoscope illumination should consider ambient light conditions.

Pituitary gland volume in adolescent and young adult bipolar and unipolar depression.

OBJECTIVES: Few studies have examined pituitary gland size in mood disorders, particularly in adolescents. We hypothesized increase in the pituitary gland size in early-onset mood disorders. METHODS: Thirty subjects between the ages of 13 and 20 years participated in the study. Three groups (control, bipolar I depression and unipolar depression) of 10 subjects each (4 male, 6 female) underwent volumetric magnetic resonance imaging at 1.5 T. RESULTS: Analysis of covariance (covarying for age, sex and intracranial volume) revealed a significant difference in pituitary gland volume amongst the groups [F(2,24) = 7.092, p = 0.014]. Post hoc analysis revealed that controls had a significantly smaller pituitary gland volume than both bipolar patients (p = 0.019) and depressed patients (p = 0.049). Bipolar and depressed subjects did not differ significantly from each other with regard to pituitary gland volume (p = 0.653). Control females had larger pituitary glands than control males [F(1,8) = 10.523, p = 0.012], but no sex differences were noted in the mood disorder groups. CONCLUSIONS: Pituitary glands are enlarged in adolescents with mood disorders compared to controls. Healthy young females have larger pituitary glands than males, but such a difference is not evident in individuals with unipolar depression or bipolar disorder. These findings provide new evidence of abnormalities of the pituitary in early onset mood disorders, and are consistent with neuroendocrine dysfunction in early stages of such illnesses.

Cognitive impairments in the STOP null mouse model of schizophrenia.

Cognitive dysfunction is a primary and persisting core deficit of schizophrenia that is marginally improved by antipsychotic treatment. Adult mice that lack the stable tubule-only polypeptide (STOP) have neurochemical and behavioral abnormalities that model some features of schizophrenia. Recognition and long-term memory in the STOP null mouse were tested with the novel object recognition task and an olfactory discrimination task, respectively. Researchers examined the brains from STOP null mice to determine whether differences in task performance were associated with alterations in brain morphology. STOP null mice displayed deficits in both recognition and long-term memory. These behavioral deficits were accompanied by a massive enlargement of the cerebral ventricular system as well as by reductions in volume of cortical and diencephalic structures. In addition to deficits in recognition and long-term memory, STOP null mice displayed exaggerated neuroanatomical deficits somewhat reminiscent of those observed among individuals with schizophrenia.

Sex differences in olfactory function in young patients with psychotic disorders.

Female superiority on many measures of olfactory function is well established, but debate remains as to whether this pattern extends to patients with psychotic disorders. The purpose of this large retrospective study was to re-examine whether male vs. female differences in olfactory identification exist in patients with psychotic disorders, and if so, whether any such differences were related to features of the psychotic disorder or could be explained by a generalized male-female difference. We examined 353 relatively young patients, recently diagnosed with a psychotic illness, (258 males and 95 females) and compared these with 89 healthy control subjects (45 males and 44 females). All individuals had been assessed birhinally using the University of Pennsylvania Smell Identification Test (UPSIT). Overall, females were superior to males, and patients underperformed healthy controls. No interaction was noted between these two variables, and there was no significant effect found as a result of age of the subjects. The data suggested that sex differences in olfactory identification ability exist in young patients with psychotic disorders. They do not appear to be related to exposure to antipsychotic medication or smoking habit. Therefore, it is likely that they represent basic male vs. female differences and not diagnosis-specific sex differences in olfactory performance-at least in those who are in the early stages of illness.

5-HT6 receptor binding sites in schizophrenia and following antipsychotic drug administration: autoradiographic studies with [125I]SB-258585.

The 5-hydroxytryptamine (5-HT; serotonin)-6 receptor (5-HT6R) is a putative target of atypical antipsychotic drugs and its mRNA expression is altered in schizophrenia. [125I]SB-258585 is a selective 5-HT6R antagonist which has been well characterized for use in the rat brain. The present study evaluated its suitability for receptor autoradiography in the human brain and its application to quantitative studies. The affinity (K(d) approximately 1.2 nM) and relative distribution of binding sites (striatum >> cortex approximately hippocampus) were similar to the rat. The distribution of [125I]SB-258585 binding in these regions was also consistent with that of 5-HT6R mRNA, determined in parallel using in situ hybridization. [125I]SB-258585 binding site densities were measured in dorsolateral prefrontal cortex of 20 patients with chronic schizophrenia and compared with 17 normal subjects. No differences were seen between groups. Neither were [125I]SB-258585 binding site densities affected in the frontal cortex or striatum of rats following 2 weeks' administration of the antipsychotic drugs haloperidol, chlorpromazine, olanzapine, risperidone, or clozapine. In summary, [125I]SB-258585 is a suitable radioligand for studies of human brain 5-HT6R binding sites and shows that their distribution is broadly similar to that of the rodent. The lack of effect of schizophrenia or antipsychotic drug administration on [125I]SB-258585 binding suggests that an altered receptor density does not contribute to any involvement which the 5-HT6R may have in the disease or its treatment.

The distribution of 5-HT(6) receptors in rat brain: an autoradiographic binding study using the radiolabelled 5-HT(6) receptor antagonist [(125)I]SB-258585.

We used the highly selective 5-HT(6) receptor radioligand [(125)I]SB-258585 (4-iodo-N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzene-sulfonamide) to perform autoradiographic binding studies on the rat brain. High levels of specific binding occurred in the corpus striatum, nucleus accumbens, Islands of Calleja and the olfactory tubercle. A high level of binding also appeared in the choroid plexus. Moderate levels occurred in several regions of the hippocampal formation and in certain regions of the cerebral cortex, thalamus, hypothalamus, and substantia nigra; and very low levels in the globus pallidus, cerebellum, other mesencephalic regions, and the rhombencephalon. Displacement of total binding with 10 microM unlabelled SB-214111 (4-bromo-N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzene-sulfonamide), another selective 5-HT(6) receptor antagonist, or 10 microM unlabelled methiothepin, reduced binding to barely discernible levels. Some animals received unilateral injections of 6-hydroxydopamine (6-OHDA) into the median forebrain bundle to lesion the nigro-striatal pathway before autoradiographic examination. Effectiveness of the 6-OHDA lesions in the substantia nigra and striatum was confirmed with tyrosine hydroxylase immunohistochemistry. Such lesions resulted in no significant changes in [(125)I]SB-SB258585 binding in any brain region examined, suggesting that 5-HT(6) receptors in the striatum are not located on dendritic, somatic or terminal elements of dopaminergic neurones. Thus, the striatal binding sites seen in this study may be on intrinsic GABAergic or cholinergic neurones, or on terminals of projection neurones from the thalamus or cerebral cortex. The 5-HT(6) receptor ligand binding seen here in the striatum, accumbens, olfactory tubercle, Islands of Calleja, cerebral cortex and hippocampus are in concordance with previous immunohistochemical studies, and suggest a possible involvement of 5-HT(6) receptors in locomotor control, cognition, memory, and control of affect. The high levels of binding observed in the choroid plexus in this study have not been reported before. This finding suggests that 5-HT(6) receptors could play a role in the control of cerebrospinal fluid dynamics.