Immunologic privilege in the central nervous system and the blood–brain barrier

The brain is in many ways an immunologically and pharmacologically privileged site. The blood–brain barrier (BBB) of the cerebrovascular endothelium and its participation in the complex structure of the neurovascular unit (NVU) restrict access of immune cells and immune mediators to the central nervous system (CNS). In pathologic conditions, very well-organized immunologic responses can develop within the CNS, raising important questions about the real nature and the intrinsic and extrinsic regulation of this immune privilege. We assess the interactions of immune cells and immune mediators with the BBB and NVU in neurologic disease, cerebrovascular disease, and intracerebral tumors. The goals of this review are to outline key scientific advances and the status of the science central to both the neuroinflammation and CNS barriers fields, and highlight the opportunities and priorities in advancing brain barriers research in the context of the larger immunology and neuroscience disciplines. This review article was developed from reports presented at the 2011 Annual Blood-Brain Barrier Consortium Meeting.     

Rational approaches to the neurobiologic study of youth at risk for bipolar disorder and suicide

Objectives:  The aims of this paper are to provide an overview of neuroimaging findings specific to bipolar disorder and suicide, and to consider rational approaches to the design of future in vivo studies in youth at risk.
Methods:  Neuroimaging and related neurobiological literature pertaining to bipolar disorder and suicide in adult and pediatric samples was reviewed in a non-quantitative manner.
Results:  Specific structural and functional brain findings in bipolar disorder are described, where possible in the context of relevant current neurobiological theories of etiology. Diagnostic and prognostic implications are discussed.
Conclusions:  The simultaneous use of complementary neurobiological approaches may be a powerful way of identifying and validating factors reliably associated with bipolar disorder and suicide. A profile of neurobiological markers with which to screen for bipolar disorder and suicide risk may provide for earlier and more accurate diagnosis, perhaps even in the pre- or subsyndromal stages in high-risk youth.     

Calcified cysticercotic lesions and intractable epilepsy: a cross sectional study of 512 patients

Background

Neurocysticercosis is a major cause of epilepsy in developing countries and is endemic in Brazil. To test the hypothesis that the aetiological profile of patients with intractable epilepsy in Brazil includes neurocysticercosis, we conducted a cross sectional study investigating the aetiology of intractable epilepsy.

Methods

A total of 512 patients evaluated at the outpatient clinic for intractable epilepsy at the Ribeirão Preto School of Medicine were included in the survey. Medical intractability was determined on the basis of seizure incidence and severity, and response to appropriate epilepsy management. Neuroimaging included brain CT with non‐contrasted and contrasted phases and high resolution MRI. Patients were divided into neurocysticercosis and non‐neurocysticercosis groups according to previous diagnostic criteria.

Results

The most common epileptogenic lesions were mesial temporal sclerosis (MTS; 56.0%), malformations of cortical development (12.1%), and brain tumours (9.9%). Neuroimaging was normal in 8.7% of patients. Calcifications were found in 27% of patients and were significantly more common in patients with MTS than in those without MTS (p<0.001). Isolated neurocysticercosis was found in only eight patients (1.56%).

Conclusions

These data suggest that neurocysticercosis is an uncommon cause of intractable epilepsy, even in an endemic region such as Brazil, and that it may only represent a coexistent pathology. However, an analysis of our findings reveals that neurocysticercosis was more common in patients with MTS. This finding could suggest either that there is a cause‐effect relationship between MTS and neurocysticercosis, or that MTS and neurocysticercosis co‐vary with a missing variable, such as socio‐economic status.     

What can't functional neuroimaging tell the cognitive psychologist?

In this paper, I critically review the usefulness of functional neuroimaging to the cognitive psychologist. All serious cognitive theories acknowledge that cognition is implemented somewhere in the brain. Finding that the brain "activates" differentially while performing different tasks is therefore gratifying but not surprising. The key problem is that the additional dependent variable that imaging data represents, is often one about which cognitive theories make no necessary predictions. It is, therefore, inappropriate to use such data to choose between such theories. Even supposing that fMRI were able to tell us where a particular cognitive process was performed, that would likely tell us little of relevance about how it was performed. The how-question is the crucial question for theorists investigating the functional architecture of the human mind. The argument is illustrated with particular reference to Henson (2005) and Shallice (2003), who make the opposing case.     

Caudate nucleus volume and cognitive performance: Are they related in childhood psychopathology?

BACKGROUND: Impaired neuropsychological test performance, especially on tests of executive function and attention, is often seen in children diagnosed with autism spectrum disorders (ASD). Structures involved in fronto-striatal circuitry, such as the caudate nucleus, may support these cognitive abilities. However, few studies have examined caudate volumes specifically in children with ASD, or correlated caudate volumes to cognitive ability. METHODS: Neuropsychological test scores and caudate volumes of children with ASD were compared to those of children with bipolar disorder (BD) and of typically developing (TD) children. The relationship between test performance and caudate volumes was analyzed. RESULTS: The ASD group displayed larger right and left caudate volumes, and modest executive deficits, compared to TD controls. While caudate volume inversely predicted performance on the Wisconsin Card Sorting Test in all participants, it differentially predicted performance on measures of attention across the ASD, BD and TD groups. CONCLUSIONS: Larger caudate volumes were related to impaired problem solving. On a test of attention, larger left caudate volumes predicted increased impulsivity and more omission errors in the ASD group as compared to the TD group, however smaller volume predicted poorer discriminant responding as compared to the BD group.     

Neuroimaging and neurogenetics of epilepsy in humans

In the past decade, several genetic mutations have been associated with different forms of familial focal and generalized epilepsies. Most of these genes encode ion-channel subunits. Based on neurophysiological in vitro and in vivo animal studies, substantial progress has been made in understanding the functional consequences of gene defects associated with epilepsies. However, the knowledge transition from animal studies to patients carrying a mutation, or even suffering from a nonfamilial form of epilepsy, is very limited. This review will illustrate how neuroimaging studies in humans may help to bridge the gap between genotype and phenotype. We will be presenting examples of familial focal (autosomal dominant nocturnal frontal lobe epilepsy), idiopathic generalized epilepsies (severe myoclonic epilepsy of infancy). Such studies will help to better understand functional consequences of genetic alterations and may contribute to a better phenotype characterization.     

Anatomically informed basis functions in multisubject studies

We describe the use of anatomically informed basis functions (AIBF) in the analysis of multisubject functional imaging studies. AIBF are used to specify an anatomically informed spatial model that embodies anatomical knowledge for the statistical analysis of neuroimaging data. In a previous communication, we showed how AIBF can be used to incorporate prior anatomical constraints in single subject functional magnetic resonance image (fMRI) analyses to augment their anatomical precision. In this paper, we extend AIBF such that it can be applied to multisubject studies using fMRI or PET. The key concept is that, after spatial normalization, a canonical cortical surface can be used to generate a forward model of signal sources for all subjects. By estimating the hemodynamic signal in this canonical AIBF-space and then projecting it back into the voxel-space, one effectively extracts functional activity that is smooth, within and only within, the cortical sheet while attenuating other components unrelated to the physiological process of interest. The ensuing procedure can be considered as a highly non-stationary, anisotropic anatomically informed [de]convolution or smoothing. It is shown that this procedure offers various advantages compared to existing conventional methods for the analysis of multisubject studies, in particular it is more sensitive to underlying activations.     

Comparison of automated and manual MRI volumetry of hippocampus in normal aging and dementia

PURPOSE: To determine whether automatic and manual measurements of hippocampal volume differences on MRI between normal aging, cognitive impairment (CI), and Alzheimer's disease (AD) yield similar results. MATERIALS AND METHODS: Reliability was determined for an automatic and a manual method on nine volunteers (22-83 years old) who underwent MRI twice in 1 day. Hippocampal volumes of 20 cognitively normal subjects (mean age 74.0 +/- 6.2 years) and age-matched patients (20 CI and 20 AD) were compared. RESULTS: The intraclass correlation for automatic calculations of hippocampal volume was 0.94; for manual tracing it was 0.99. Volume differences between cognitively normal, CI, and AD subjects from the automatic and manual methods were similar. CONCLUSION: Because the automatic calculations were faster and less susceptible to rater bias than manual tracing, this automated method is expected to be very useful for analyzing hippocampal changes in studies of aging and dementia.     

脑静脉窦血栓形成的诊断和治疗（附3例报告）

目的探讨脑静脉窦血栓形成的临床表现及影像学特征,减少该病误诊率及死亡率。方法描述我院收治的3例患者临床表现、辅助检查及治疗情况。结果3例患者均有非特异性的头痛和神经功能障碍。3例均行头颅磁共振成像及磁共振静脉血管显影检查,明确诊断为静脉窦血栓形成,1例行数字减影血管显影检查的患者,证实有静脉窦血栓形成。所有患者均行降颅压及抗凝治疗,同时给病因治疗及对症支持治疗,1例行尿激酶局部溶栓,3例患者均好转。结论脑静脉窦血栓形成的临床表现缺乏特异性,误诊率高,确诊有赖于影像学检查,抗凝治疗是一种安全有效的方法。     

Addiction and its brain science

AIMS: To illustrate how modern neurobiological approaches will help to identify the neurocircuits and genes involved in addictive behavior. BACKGROUND: The current disorder concept of addiction includes neurobiological foundations and neurobiological research assuming irreversible molecular and structural changes within the brain dopamine reinforcement system, constituting the 'molecular and structural switch' from controlled drug intake to compulsive drug abuse. However, those irreversible changes have not so far been identified and it is suggested that in addition to the mesolimbic dopamine system, other brain systems including the mesocortical and nigrostriatal pathways as well as their non-dopaminergic feedback-loops might be involved in addictive behavior. NEUROBIOLOGICAL APPROACH: A three-step neurobiological approach is described that allows in a first step via novel animal models and imaging techniques to identify the neuroanatomical sites mediating voluntary drug intake, reinstatement of drug-seeking behavior, relapse, loss of control and drug intake despite negative consequences. In a subsequent step, forward genetic approaches including quantitative trait loci (QTL)-analysis and gene expression profiling are helpful in identifying so-called candidate genes. In a final step, conditional animal mutants and selective pharmacological tools are used to functionally validate candidate genes. Following this validation process, the transfer to the human situation has to be made and candidate genes have to be verified further in well-phenotyped cohorts of addicted patients. CONCLUSION: This three-step neurobiological approach, that must involve an interdisciplinary team including experimental psychologists, geneticists, molecular biologists and finally clinical addiction researchers, will allow us to understand where and how the addicted brain goes awry.