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Tics in Tourette syndrome (TS) are often preceded by sensory urges that drive the motor and vocal symptoms. Many everyday physiological behaviors are associated with sensory phenomena experienced as an urge for action, which may provide insight into the neural correlates of this pathological urge to tic that remains elusive. This study aimed to identify a brain network common to distinct physiological behaviors in healthy individuals, and in turn, examine whether this network converges with a network we previously localized in TS, using novel 'coordinate network mapping' methods. Systematic searches were conducted to identify functional neuroimaging studies reporting correlates of the urge to micturate, swallow, blink, or cough. Using activation likelihood estimation meta-analysis, we identified an 'urge network' common to these physiological behaviors, involving the bilateral insula/claustrum/inferior frontal gyrus/supplementary motor area, mid-/anterior- cingulate cortex (ACC), right postcentral gyrus, and left thalamus/precentral gyrus. Similarity between the urge and TS networks was identified in the bilateral insula, ACC, and left thalamus/claustrum. The potential role of the insula/ACC as nodes in the network for bodily representations of the urge to tic are discussed., Competing Interests: Declaration of Competing Interest The authors report no competing interest to declare regarding this work. Declarations of Interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Copper participates in a range of critical functions in the nervous system and human brain. Disturbances in brain copper content is strongly associated with neurological diseases. For example, changes in the level and distribution of copper are reported in neuroblastoma, Alzheimer's disease, and Lewy body disorders, such as Parkinson disease and dementia with Lewy bodies (DLB). There is a need for more sensitive techniques to measure intracellular copper levels to have a better understanding of the role of copper homeostasis in neuronal disorders. Here, we report a reaction-based near-infrared (NIR) ratiometric fluorescent probe CyCu1 for imaging Cu 2+ in biological samples. High stability and selectivity of CyCu1 enabled the probe to be deployed as a sensor in a range of systems, including SH-SY5Y cells and neuroblastoma tumors. Furthermore, it can be used in plant cells, reporting on copper added to Arabidopsis roots. We also used CyCu1 to explore Cu 2+ levels and distribution in post-mortem brain tissues from patients with DLB. We found significant decreases in Cu 2+ content in the cytoplasm, neurons, and extraneuronal space in the degenerating substantia nigra in DLB compared with healthy age-matched control tissues. These findings enhance our understanding of Cu 2+ dysregulation in Lewy body disorders. Our probe also shows promise as a photoacoustic imaging agent, with potential for applications in bimodal imaging.

The exocyst, an octameric protein complex, is an essential component of the membrane transport machinery required for tethering and fusion of vesicles at the plasma membrane. We report pathogenic variants in an exocyst subunit, EXOC2 (Sec5). Affected individuals have severe developmental delay, dysmorphism, and brain abnormalities; variability associated with epilepsy; and poor motor skills. Family 1 had two offspring with a homozygous truncating variant in EXOC2 that leads to nonsense-mediated decay of EXOC2 transcript, a severe reduction in exocytosis and vesicle fusion, and undetectable levels of EXOC2 protein. The patient from Family 2 had a milder clinical phenotype and reduced exocytosis. Cells from both patients showed defective Arl13b localization to the primary cilium. The discovery of mutations that partially disable exocyst function provides valuable insight into this essential protein complex in neural development. Since EXOC2 and other exocyst complex subunits are critical to neuronal function, our findings suggest that EXOC2 variants are the cause of the patients' neurological disorders., Competing Interests: Disclosures: The authors declare no competing interests exist., (© 2020 Van Bergen et al.)

L-Ornithine-L-aspartate (LOLA), a crystalline salt, is used primarily in the management of hepatic encephalopathy. The degree to which it might penetrate the brain, and the effects it might have on metabolism in brain are poorly understood. Here, to investigate the effects of LOLA on brain energy metabolism we incubated brain cortical tissue slices from guinea pig (Cavea porcellus) with the constituent amino acids of LOLA, L-ornithine or L-aspartate, as well as LOLA, in the presence of [1- 13 C]D-glucose and [1,2- 13 C]acetate; these labelled substrates are useful indicators of brain metabolic activity. L-Ornithine produced significant "sedative" effects on brain slice metabolism, most likely via conversion of ornithine to GABA via the ornithine aminotransferase pathway, while L-aspartate showed concentration-dependent excitatory effects. The metabolic effects of LOLA reflected a mix of these two different processes and were concentration-dependent. We also investigated the effect of an intraperitoneal bolus injection of L-ornithine, L-aspartate or LOLA on levels of metabolites in kidney, liver and brain cortex and brain stem in mice (C57Bl6J) 1 h later. No significant changes in metabolite levels were seen following the bolus injection of L-aspartate, most likely due to rapid metabolism of aspartate before reaching the target tissue. Brain cortex glutamate was decreased by L-ornithine but no other brain effects were observed with any other compound. Kidney levels of aspartate were increased after injection of L-ornithine and LOLA which may be due to interference by ornithine with the kidney urea cycle. It is likely that without optimising chronic intravenous infusion, LOLA has minimal impact on healthy brain energy metabolism due to systemic clearance and the blood - brain barrier.

Pathogenic variants in CDH1 , encoding epithelial cadherin (E-cadherin), have been implicated in hereditary diffuse gastric cancer (HDGC), lobular breast cancer, and both syndromic and non-syndromic cleft lip/palate (CL/P). Despite the large number of CDH1 mutations described, the nature of the phenotypic consequence of such mutations is currently not able to be predicted, creating significant challenges for genetic counselling. This study collates the phenotype and molecular data for available CDH1 variants that have been classified, using the American College of Medical Genetics and Genomics criteria, as at least 'likely pathogenic', and correlates their molecular and structural characteristics to phenotype. We demonstrate that CDH1 variant type and location differ between HDGC and CL/P, and that there is clustering of CL/P variants within linker regions between the extracellular domains of the cadherin protein. While these differences do not provide for exact prediction of the phenotype for a given mutation, they may contribute to more accurate assessments of risk for HDGC or CL/P for individuals with specific CDH1 variants.

Spread of α-synuclein pathology from the peripheral to central nervous system may be an important etiological factor in Parkinson's disease, although there are some unanswered questions about its correlation with neuronal loss. Experimental evidence has highlighted the gastrointestinal tract as a potential starting point for aggregated α-synuclein, with the vagus nerve acting as a "highway" by which pathology may be transmitted to the lower brain stem. This review begins by highlighting the key studies demonstrating that α-synuclein pathology has the ability to spread from certain sites in the gastrointestinal tract to the brain (and vice versa). We go on to assess the recent epidemiological studies that have shown that vagotomy and appendectomy may have the potential to reduce the risk of developing Parkinson's disease. Finally, we discuss the factors in the gastrointestinal tract (such as dysbiosis of the gut microbiota, infection, and inflammation) that may trigger α-synuclein aggregation in the first place, as well as other potential mechanisms underlying the distribution of α-synuclein pathology in the brain. © 2019 International Parkinson and Movement Disorder Society., (© 2019 International Parkinson and Movement Disorder Society.)

Aims: Postsynaptic density - 95 kDa protein (PSD95) is an important molecule on the postsynaptic membrane. It interacts with many other proteins and plays a pivotal role in learning and memory formation. Its distribution in the brain has been studied previously using in situ hybridization as well as immunohistochemistry. However, these studies are based on 2 dimensional (2D) sections and results are presented with a few sections. The present study aims to show PSD-95 distribution in 3 dimensions (3D) without slicing the brain tissue of C57BL/6 mice into sections using the advanced CUBIC technique., Methods: Immunofluorescent staining using a PSD-95 antibody was performed on a half of the mouse brain after clarifying it using the advanced CUBIC protocol. The brain tissue was imaged using a Zeiss Z1 light sheet microscope and 3D reconstruction was completed using the Arivis Vision 4 dimensional (4D) software., Results: The majority of brain nuclei have similar distribution pattern to what has been reported from in situ hybridization and immunohistochemical studies in the mouse. The signal can be easily followed in the 3D and their spatial relationship with adjacent structures clearly demarcated. In the present study, some fiber bundles also showed strong PSD-95 signal, which is different from what was shown in previous studies and need to be confirmed in future studies.

Although advances in neuroimaging have yielded insights into the intrinsic organization of human brain networks and their relevance to psychiatric and neurological disorders, there has been no translation of these insights into clinical practice. One necessary step toward clinical translation is identifying a summary metric of network function that is reproducible, reliable, and has known normative data, analogous to normed neuropsychological tests. Our aim was therefore to establish the proof of principle for such a metric, focusing on the default mode network (DMN). We compared three candidate summary metrics: global clustering coefficient, characteristic path length, and average connectivity. Across three samples totaling 322 healthy, mostly Caucasian adults, average connectivity performed best, with good internal consistency (Cronbach's α=0.69-0.70) and adequate eight-week test-retest reliability (intra-class coefficient=0.62 in a subsample N=65). We therefore present normative data for average connectivity of the DMN and its sub-networks. These proof of principle results are an important first step for the translation of neuroimaging to clinical practice. Ultimately, a normed summary metric will allow a single patient's DMN function to be quantified and interpreted relative to normative peers.

Melatonin, through its different receptors, has pleiotropic functions in mammalian brain. Melatonin is secreted mainly by the pineal gland and exerts its effects via receptor-mediated and non-receptor-mediated actions. With recent advancement in neuroanatomical mapping, we may now understand better the localizations of the two G protein-coupled melatonin receptors MT1 and MT2. The abundance of these melatonin receptors in respective brain regions suggests that receptor-mediated actions of melatonin might play crucial roles in the functions of central nervous system. Hence, this review aims to summarize the distribution of melatonin receptors in the brain and to discuss the putative functions of melatonin in the retina, cerebral cortex, reticular thalamic nucleus, habenula, hypothalamus, pituitary gland, periaqueductal gray, dorsal raphe nucleus, midbrain and cerebellum. Studies on melatonin receptors in the brain are important because cumulative evidence has pointed out that melatonin receptors not only play important physiological roles in sleep, anxiety, pain and circadian rhythm, but might also be involved in the pathogenesis of a number of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and Huntington's disease.

β-Hydroxybutyrate (βOHB), a ketone body, is oxidised as a brain fuel. Although its contribution to energy metabolism in the healthy brain is minimal, it is an interesting metabolite which is not only oxidised but also has other direct and collateral effects which make it a molecule of interest for therapeutic purposes. In brain βOHB can be produced in astrocytes from oxidation of fatty acids or catabolism of amino acids and is metabolised in the mitochondria of all brain cell types although uptake across the blood brain barrier is a metabolic control point. βOHB possesses an intrinsic high heat of combustion, making it an efficient mitochondrial fuel, where it can alter the NAD + /NADH and Q/QH 2 couples and reduce production of mitochondrial reactive oxygen species. It can directly interact as a signalling molecule influencing opening of K + channels and regulation of Ca 2+ channels. βOHB is an inhibitor of histone deacetylases resulting in upregulation of genes involved in protection against oxidative stress and regulation of metabolism. It interacts with an inflammasome in immune cells to reduce production of inflammatory cytokines and reduce inflammation. Use of βOHB as an efficient neurotherapeutic relies on increasing blood βOHB levels so as to encourage entry of βOHB to the brain. While use of βOHB as a sole therapeutic is currently limited, with employment of a ketogenic diet a more widely used approach, recent development and testing of esterified forms of βOHB have shown great promise, with the approach elevating plasma βOHB while allowing consumption of normal diet. An improved understanding of the mechanisms by which βOHB acts will allow better design of both diet and supplemental interventions.

Autism spectrum disorder (ASD) is one of the most heritable neuropsychiatric conditions. The complex genetic landscape of the disorder includes both common and rare variants at hundreds of genetic loci. This marked heterogeneity has thus far hampered efforts to develop genetic diagnostic panels and targeted pharmacological therapies. Here, we give an overview of the current literature on the genetic basis of ASD, and review recent human brain transcriptome studies and their role in identifying convergent pathways downstream of the heterogeneous genetic variants. We also discuss emerging evidence on the involvement of non-coding genomic regions and non-coding RNAs in ASD.

Aims: Neurogenesis in the postnatal human brain occurs in two neurogenic niches; the subventricular zone (SVZ) in the wall of the lateral ventricles and the subgranular zone (SGZ) of the hippocampus. The extent to which this physiological process continues into adulthood is an area of ongoing research. This study aimed to characterize markers of cell proliferation and assess the efficacy of antibodies used to identify neurogenesis in both neurogenic niches of the human brain., Methods: Cell proliferation and neurogenesis were simultaneously examined in the SVZ and SGZ of 23 individuals aged 0.2-59 years, using immunohistochemistry and immunofluorescence in combination with unbiased stereology., Results: There was a marked decline in proliferating cells in both neurogenic niches in early infancy with levels reaching those seen in the adjacent parenchyma by 4 and 1 year of age, in the SVZ and SGZ, respectively. Furthermore, the phenotype of these proliferating cells in both niches changed with age. In infants, proliferating cells co-expressed neural progenitor (epidermal growth factor receptor), immature neuronal (doublecortin and beta III tubulin) and oligodendrocytic (Olig2) markers. However, after 3 years of age, microglia were the only proliferating cells found in either niche or in the adjacent parenchyma., Conclusions: This study demonstrates a marked decline in neurogenesis in both neurogenic niches in early childhood, and that the sparse proliferating cells in the adult brain are largely microglia., Competing Interests: Statement of Conflict of Interest None of the authors have any conflict of interest in respect of the manuscript contents., (© 2016 British Neuropathological Society.)

Importance: Cognitively distinct subgroups of schizophrenia have been defined based on premorbid and current IQ, but little is known about the neuroanatomical differences among these cognitive subgroups., Objectives: To confirm previous findings related to IQ-based subgroups of patients with schizophrenia in an independent sample and extend those findings to determine the extent to which brain volumetric differences correspond to the IQ-based subgroups., Design, Setting, and Participants: A total of 183 participants were assessed at the outpatient settings of Neuroscience Research Australia and Lyell McEwin Hospital from September 22, 2009, to August 1, 2012. Patients were classified using cluster analysis on the basis of current and premorbid IQ differences. Regional magnetic resonance imaging (MRI) brain volumes were compared among the IQ-based subgroups using analysis of covariance with intracranial volume and age as covariates., Main Outcomes and Measures: Wechsler Adult Intelligence Scale, third edition, scores; Wechsler Test of Adult Reading scores; Positive and Negative Syndrome Scale scores; and MRI brain volumes., Results: Ninety-six outpatients (mean [SD] age, 35.7 [8.4] years; age range, 18-51 years; 59 men) with schizophrenia or schizoaffective disorder and 87 healthy controls (mean [SD] age, 31.9 [8.4] years; age range, 20-50 years; 46 men) were studied. Sixty-two patients and 67 healthy controls underwent structural MRI of the brain. Cluster analyses revealed 25 putatively preserved patients (26%), 33 moderately deteriorated patients (34%), 27 severely deteriorated patients (28%), and 11 compromised patients (12%). Negative symptom scores were significantly worse in the severely deteriorated group relative to the putatively preserved group (F2,82 = 13.8, P < .001, effect size [ES] = 1.40). Patient subgroups analyzed revealed significantly reduced inferior parietal volume relative to controls (F3,113 = 9.7, P < .001, ES = 0.85-1.24). The severely deteriorated group had significantly reduced total hippocampal (mean [SEM], 8309.6 [175.0] vs 9024.0 [145.5]; P = .01), lingual gyrus (mean [SEM], 11 996.0 [531.5] vs 13 838.1 [441.9]; P = .05), and superior temporal sulcus (mean [SEM], 4697.8 [192.0] vs 5446.0 [159.6]; P = .05) gray matter volumes relative to the putatively preserved group (ES = 0.91-1.10)., Conclusions and Relevance: Using an independent sample, we obtained proportions in each IQ-based subgroup that were similar to our previous work. Inferior parietal volume reduction was characteristic of schizophrenia relative to controls, and the severely deteriorated IQ group had widespread volumetric reductions. Classifying cognitive heterogeneity in schizophrenia provides a platform to better characterize the neurobiological underpinnings of the illness and its treatment.

Immunohistochemical staining was used to investigate the expression pattern of SEIPIN in the mouse central nervous system. SEIPIN was found to be present in a large number of areas, including the motor and somatosensory cortex, the thalamic nuclei, the hypothalamic nuclei, the mesencephalic nuclei, some cranial motor nuclei, the reticular formation of the brainstem, and the vestibular complex. Double labeling with NeuN antibody confirmed that SEIPIN-positive cells in some nuclei were neurons. Retrograde tracer injections into the spinal cord revealed that SEIPIN-positive neurons in the motor and somatosensory cortex and other movement related nuclei project to the mouse spinal cord. The present study found more nuclei positive for SEIPIN than shown using in situ hybridization and confirmed the presence of SEIPIN in neurons projecting to the spinal cord. The results of this study help to explain the clinical manifestations of patients with Berardinelli-Seip congenital lipodystrophy (Bscl2) gene mutations.

The sex drive hypothesis predicts that stronger selection on male traits has resulted in masculinization of the genome. Here we test whether such masculinizing effects can be detected at the level of the transcriptome and methylome in the adult zebrafish brain. Although methylation is globally similar, we identified 914 specific differentially methylated CpGs (DMCs) between males and females (435 were hypermethylated and 479 were hypomethylated in males compared to females). These DMCs were prevalent in gene body, intergenic regions and CpG island shores. We also discovered 15 distinct CpG clusters with striking sex-specific DNA methylation differences. In contrast, at transcriptome level, more female-biased genes than male-biased genes were expressed, giving little support for the male sex drive hypothesis. Our study provides genome-wide methylome and transcriptome assessment and sheds light on sex-specific epigenetic patterns and in zebrafish for the first time., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objectives: Changes in tissue perfusion can be critically important in the vulnerable neonate, but they are very difficult to assess at the bedside. Spatiotemporal image correlation (STIC) sonography is an exciting concept that allows assessment of blood flow by rearranging and merging multiple 2-dimensional color images to create serial 3-dimensional images showing regional blood flow throughout the cardiac cycle. Variations in tissue blood flow may reflect tissue impedance and perfusion. The aim of this study was to demonstrate that it is possible to use STIC images to evaluate tissue impedance in the neonatal brain., Methods: Spatiotemporal image correlation data sets were acquired by cranial sonography in 19 neonates. Offline data analysis was performed by using virtual organ computer-aided analysis. With the use of STIC images from different phases of the cardiac cycle, impedance indices were calculated, based on maximum (systolic), minimum (diastolic), and mean virtual organ computer-aided analysis values, in the same way that resistive indices are calculated in 2-dimensional sonography., Results: Volumetric indices for tissue impedance were obtained for all neonates. Intraclass correlation coefficients (95% confidence intervals) for volumetric impedance indices were as follows: systolic/diastolic ratio, 0.793 (0.615-0.906); pulsatility index, 0.790 (0.609-0.905); and resistive index, 0.783 (0.598-0.901). Interclass correlation coefficients for image processing and analysis were as follows: systolic/diastolic ratio, 0.868 (0.692-0.947); pulsatility index, 0.904 (0.772-0.962); and resistive index, 0.914 (0.794-0.966)., Conclusions: This study shows that STIC data sets can be used to calculate volumetric impedance indices in the neonatal brain. Preliminary assessment shows that this technique appears reliable and allows evaluation of regional tissue impedance in the neonate., (© 2016 by the American Institute of Ultrasound in Medicine.)

Background and Purpose: Compressing the internal jugular veins can reverse ventriculomegaly in the syndrome of inappropriately low pressure acute hydrocephalus, and it has been suggested that this works by "stiffening" the brain tissue. Jugular compression may also alter blood and CSF flow in other conditions. We aimed to understand the effect of jugular compression on brain tissue stiffness and CSF flow., Materials and Methods: The head and neck of 9 healthy volunteers were studied with and without jugular compression. Brain stiffness (shear modulus) was measured by using MR elastography. Phase-contrast MR imaging was used to measure CSF flow in the cerebral aqueduct and blood flow in the neck., Results: The shear moduli of the brain tissue increased with the percentage of blood draining through the internal jugular veins during venous compression. Peak velocity of caudally directed CSF in the aqueduct increased significantly with jugular compression (P < .001). The mean jugular venous flow rate, amplitude, and vessel area were significantly reduced with jugular compression, while cranial arterial flow parameters were unaffected., Conclusions: Jugular compression influences cerebral CSF hydrodynamics in healthy subjects and can increase brain tissue stiffness, but the magnitude of the stiffening depends on the percentage of cranial blood draining through the internal jugular veins during compression—that is, subjects who maintain venous drainage through the internal jugular veins during jugular compression have stiffer brains than those who divert venous blood through alternative pathways. These methods may be useful for studying this phenomenon in patients with the syndrome of inappropriately low-pressure acute hydrocephalus and other conditions., (© 2015 by American Journal of Neuroradiology.)

Emotional processing has been reported to effect sensory gating as measured by the event-related potential known as P50. Because both P50 and emotional processing are dysfunctional in bipolar disorder (BD), we sought to investigate the impact that concurrent emotional processing has on sensory gating in this psychiatric population. P50 was recorded using a paired-click paradigm. Peak-to-peak amplitudes for stimulus 1 (S1) and stimulus 2 (S2) were acquired during the presentation of disgust and neutral faces to young adults with BD (n = 19) and controls (n = 20). Social functioning and quality-of-life self-reported measures were also obtained. The BD group had significantly larger P50 amplitudes elicited by the S2-disgust response compared with controls, but no significant difference in overall P50 sensory gating was found between the groups. There were also no differences between groups in S1-disgust or in either of the neutral P50 amplitudes. The BD group showed significant associations between sensory gating to disgust and measures of social functioning. Importantly, BD showed impaired filtering of auditory information when paired with an emotionally salient image. Thus, it appears that patients with the greatest impairment in sensory gating also have the most difficulty engaging in social situations., (© EEG and Clinical Neuroscience Society (ECNS) 2014.)

Background: Acute neural effects of antidepressant medication on emotion processing biases may provide the foundation on which clinical outcomes are based. Along with effects on positive and negative stimuli, acute effects on neutral stimuli may also relate to antidepressant efficacy, yet these effects are still to be investigated. The present study therefore examined the impact of a single dose of the selective serotonin reuptake inhibitor escitalopram (20 mg) on positive, negative and neutral stimuli using pharmaco-fMRI., Methods: Within a double-blind, randomized, placebo-controlled crossover design, healthy women completed 2 sessions of treatment administration and fMRI scanning separated by a 1-week washout period., Results: We enrolled 36 women in our study. When participants were administered escitalopram relative to placebo, left amygdala activity was increased and right inferior frontal gyrus (IFG) activity was decreased during presentation of positive pictures (potentiation of positive emotion processing). In contrast, escitalopram was associated with decreased left amygdala and increased right IFG activity during presentation of negative pictures (attenuation of negative emotion processing). In addition, escitalopram decreased right IFG activity during the processing of neutral stimuli, akin to the effects on positive stimuli (decrease in negative appraisal)., Limitations: Although we used a women-only sample to reduce heterogeneity, our results may not generalize to men. Potential unblinding, which was related to the subjective occurrence of side effects, occurred in the study; however, manipulation check analyses demonstrated that results were not impacted., Conclusion: These novel findings demonstrate that a single dose of the commonly prescribed escitalopram facilitates a positive information processing bias. These findings provide an important lead for better understanding effects of antidepressant medication.

We report the case of a 22-year-old woman who presented with self-poisoning by cyanide ingestion. We have elected to pay particular attention to describing the neuropsychological sequelae of cyanide poisoning, and the evolution of these deficits over a 6-month period. Prominent deficits in episodic memory were noted from an early stage, which were consistent with the findings noted on structural neuroimaging. These deficits remained persistent, although improving in severity over the follow-up period. No focal neurological deficits or abnormal involuntary movements emerged, and the patient's overall functional status remained satisfactory. The patient's psychiatric presentation and background history are briefly discussed.

Concussion is an injury of specific interest in collision and contact sports, resulting in a need to develop effective preventive strategies. A detailed finite element model of the human head was used to approximate the regional distribution of tissue deformations in the brain by simulating reconstructions of unhelmeted concussion and no-injury head impacts. The results were evaluated using logistic regression analysis and it was found that angular kinematics, in the coronal plane, and maximum principal strains, in all regions of the brain, were significantly associated with concussion. The results suggested that impacts to the temporal region of the head cause coronal rotations, which render injurious strain levels in the brain. Tentative strain tolerance levels of 0.13, 0.15, and 0.26 in the thalamus, corpus callosum, and white matter, respectively, for a 50% likelihood of concussion were determined by logistic regression. The tentative strain tolerance levels compared well with previously reported results from reconstruction studies of American football and single axon, optic nerve, and brain slice culture model studies. The methods used in the current study provide an opportunity to collect unique kinematic data of sporting impacts to the unprotected head, which can be employed in various ways to broaden the understanding of concussion.

Brain magnetic resonance imaging (MRI) scans on 98 elderly subjects, 62 with a diagnosis of schizophrenia and 36 healthy controls, were independently and blindly rated by two investigators using the visual rating methods of Fazekas et al. (Fazekas, F., Chawluk, J.B., Alavi, A., Hurtig, H.I., Zimmerman, R.A., 1987. MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. American Journal of Neuroradiology 8, 421-426) and Victoroff et al. (Victoroff, J., Mack, W.J., Grafton, S.T., Schreiber, S.S., Chui, H.C., 1994. A method to improve interrater reliability of visual inspection of brain MRI scans in dementia. Neurology 44, 2267-2276) for periventricular, deep white matter and subcortical gray matter signal hyperintensities (SHs) on T2-weighted images. The hyperintense signal volumes were measured by manual delineation of the signals on a workstation using Analyze software (computerised method). The subjects also underwent a detailed neuropsychological assessment. There was a high correlation between two experienced raters for both visual ratings, and the correspondence between the two methods was high. The inter-rater reliability for the computerised method was modest but significant, and the association between the visual and computerised methods was good except for ratings for SHs in subcortical nuclei. The Fazekas and computerised methods, and to a lesser degree the Victoroff method, had modest but significant correlations with some neuropsychological test measures. In conclusion, we did not demonstrate a clear superiority in reliability or validity for one demanding computerised method of rating SHs. Visual ratings should therefore be considered adequate for most clinical and research purposes, but such ratings should be accompanied by adequate training and the provision of standard reference images.

Kynurenine aminotransferase I (KAT-I), which also shows glutamine transaminase K (GTK) activity, catalyses the conversion of kynurenine to kynurenic acid, an endogenous glutamate antagonist. Both the GTK and KAT enzyme activities were found to be significantly reduced in kidney, brain and medulla oblongata homogenates of spontaneously hypertensive (SHR) compared to Wistar-Kyoto (WKY) rats. Enzyme activity stains on native gel separations of partially purified kidney homogenates was associated with two major bands of GTK (KAT-I)-activity in WKY and Wistar rats, KAT-Ia and KAT-Ib. SHR rats however showed only KAT-Ia activity. These findings suggest that the absence of KAT-Ib activity may result in a reduced ability to synthesise kynurenic acid in SHR rats, this may help to explain the enhanced sensitivity to glutamate seen in this strain.

Five pairs of identified 5HT-IR cells in the deutocerebrum of the crayfish Cherax are known to have their synaptic endings in the accessory and olfactory lobes. Two of these cells, one on each side of the brain, are significantly larger than the others. Dye fills of these "giant" cells reveal each to be an interneuron with its branches confined to, but distributed throughout, the olfactory and accessory lobes on the side of the brain ipsilateral to its cell body and with no branches to the contralateral side. Intracellular recordings from the giant cells were made while stimulating the olfactory afferents and tracts within the brain in an attempt to discover the inputs and outputs to the cells. Electrical stimulation of chemoreceptor sensilla on the outer branch of the antennule does not excite the giant 5HT neurons. Focal extracellular electrical stimulation of the olfactory globular tract containing the axons of projection neurons from the olfactory and accessory lobes produces excitatory synaptic potentials and action potentials in the giant cells. Focal extracellular electrical stimulation of the deutocerebral commissure, the axons of which terminate in the glomeruli of the accessory lobes, also results in excitation of the giant cells. We conclude that the input to the giant cells is via axons in the deutocerebral commissure and collaterals from the projection neurons, ending in the glomeruli of the accessory lobes. The output of the giant cells is to the olfactory lobes, where it may serve to modulate olfactory signals.

Lipid peroxidation was measured in brains and lungs from mice which had been exposed to 100% O2 at 445 kPa, 515 kPa and 585 kPa for 30 min. These treatments produced varying degrees of convulsive activity and negligible to moderate lung damage. Lipid peroxidation was estimated by the thiobarbituric acid method and by analysis of Schiff bases. Lipid peroxidation did not increase in either lungs or brains after hyperbaric oxygen exposure, nor was there any difference between tissues from control or hyperoxic mice in the degree of lipid peroxidation which occurred during in vitro incubation of homogenates at 37 degrees in air for 150 min. Similarly, no increased lipid peroxidation was seen in lung tissue from mice exposed to normobaric 100% O2 for either 60 or 72 hr.

Two clusters of red-brown pigmented cell somata lie among other cell somata along the anterior margin of the cerebral ganglion in the crayfish Cherax destructor. Electron micrographs show these cells to contain round electron dense pigment granules and that the cell membranes of two or more adjacent cells fold together to form rhabdom-like structures. The pigmented cells specifically bind a monoclonal antibody against the major species of opsin in R1-7 retinula cells of the compound eye of Cherax. When stimulated with light, the pigmented cells respond with a receptor potential-like depolarization. The axons of the pigmented cells terminate in the neuropil of the protocerebral bridge, together with neuronal elements that label with antibodies against serotonin and substance P. We suggest that the brain photoreceptors of the crayfish are important in the entrainment of circadian rhythms.

In the search for particular neurons that stain selectively and can be identified, the cerebral ganglia (brains) of the crayfish Cherax destructor and the crab Leptograpsus variegatus were immunocytochemically treated with a monoclonal antibody raised against substance P. Four large neurons in the cerebral ganglion of the crayfish and crab label selectively with a monoclonal antibody raised against substance P. Two of the large neurons have their cell bodies in the protocerebrum and two in the deutocerebrum in both animals. Each protocerebral cell in both animals projects through the ipsilateral and contralateral olfactory lobes to end among the lateral cell somata of the olfactory lobe and not in the neuropile. Electron micrographs show the presence of synapses within the cell somata area and on the cell somata themselves. Each deutocerebral cell in both animals projects only ipsilaterally and ends within the neuropile of the olfactory lobes. The immunoreactivity to substance P antibody and the shapes and the unique projections of the four cells suggest that they are homologous in the two species. Synaptic connections between axons and cell somata are rare in the arthropods but have been found on the Kenyon cells of the mushroom bodies of Limulus. This raises questions about homologies between the crustacean olfactory lobe and the mushroom bodies of Limulus and insects.

An atlas of neurons in the brain of the crayfish Cherax destructor that are immunoreactive to antibodies raised against serotonin has been compiled from whole mount preparations. Neuronal networks of serotonin-containing cells are identified in the optic lobes and protocerebrum, in the deutocerebrum, and in the tritocerebrum. The consistency of the whole-mount technique allows 50 out of a total of about 100 immunoreactive cells to be individually identified according to their neuronal architecture or the location of their cell somata or axons. Apart from six neurons with axons in the oesophageal connectives, all the immunoreactive cells are intrinsic to the optic lobes and brain.

The early development of serotonin-containing neurons was studied in wholemounts of the fetal rat brain (E12-E18). The wholemounts were treated immunocytochemically according to an immunoperoxidase technique to reveal a panorama of developing serotoninergic neurons. Serotoninergic neurons were localized to two discrete groups or clusters within the brainstem. Serotonin-containing neurons were identified first at E12 forming a rostral cluster of cells just caudal to the mesencephalic flexure. The more caudal cluster of cells first appeared at E14 in the medulla. During the period from E12 to E18, the immunoreactive cells increased in number and acquired a more complex dendritic tree while migrating to their permanent position. At E16, cells of the rostral group exhibited remarkably uniform mediolateral orientation. The rostral group of immunoreactive neurons gave rise to almost all ascending fibers, whereas the caudal group gave rise to the majority of descending fibers. Growing serotoninergic fibers were tipped by prominent growth cones, which were strongly immunoreactive. The fibers demonstrated prominent orientational selectivity with an almost total separation into ascending and descending bundles. Some of the ascending immunoreactive fibers displayed acute changes in their direction of growth, suggesting that the orientation of serotininergic fibers is mediated by directional cues that are specific to particular populations of serotoninergic fibers. Serotoninergic axons within the medial forebrain bundle were demonstrated particularly well and their ascent and rate of growth toward the forebrain could be easily followed. Immunoreactive fibers entered the telencephalon at E17 two portals, one along the lateral border of the hypothalamus and one rostrally, adjacent to the olfactory tubercle. In wholemounts at E18, fibers arising from this latter location could be followed as two distinct bands within the pallium; a basal band located ventrolaterally, adjacent to the lateral olfactory tract, and a dorsal band located at the medial edge of the telencephalon. Both fascicles were directed toward the occipital pole and contained unbranched fibers. At E18, serotoninergic axons arising from these two loosely organized fascicles covered most of the frontal telencephalon. The results of the present study indicate that wholemounts of embryonic brain can provide novel spaciotemporal data on the development of neuro-transmitter systems and may in the future prove to be useful experimental preparations in developmental neurobiology.