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A neuroimaging approach to inborn errors of metabolism.

There are numerous neurodegenerative and neurometabolic disorders of childhood. Individually, however, they are quite rare. Some may be seen only once in a lifetime at a given medical center, even one devoted to the specialized care of children. This article presents the classic neuroimaging features of some of the more commonly seen entities and of some of the more recently described metabolic disorders.

Brain↗

New insights help define the pathophysiology of bipolar affective disorder: neuroimaging and neuropathology findings.

Bipolar affective disorder (BD) is a severe mental illness, characterized by episodes of mania and depression. With the development of Magnetic Resonance Imaging (MRI), neuroimaging methods are now allowing investigation of the neurocircuitry involved in this disorder. This in turn has aided further neuropathological exploration of the brain. Structural MRI and Magnetic Resonance Spectroscopy studies suggest that brain abnormalities in BD are mostly regional, as global measures (cerebral, white and gray matter and ventricular volumes) do not seem to be affected in the majority of patients. The prefrontal and anterior cingulate cortices, and amygdalae are consistently implicated in BD, whilst the evidence for hippocampal involvement is less convincing. Functional studies have found that the activity of the dorsal prefrontal cortex and the anterior cingulate are closely associated with mood symptoms. Activity in the ventral and orbital prefrontal cortex appears reduced both during episodes and in remission. In contrast, amygdala activity shows a persistent increase. We suggest that abnormal interaction between the amygdala and the ventral/orbitofrontal cortex may be a central feature of the pathophysiology of BD.

Animals↗

A meta-analysis of functional neuroimaging in obsessive-compulsive disorder.

Recent neurobiological models of obsessive-compulsive disorder (OCD) posit that a dysfunction in orbitofrontal-subcortical circuitry underlies the etiology of this disorder. Much of the empirical support for these theories comes from studies using neuroimaging techniques to compare brain activity in OCD patients with that in non-OCD controls. Qualitative reviews of this literature implicate the orbitofrontal cortex, caudate nuclei, and thalamus. In this study, a meta-analysis was conducted to summarize the results of studies using positron emission tomography (PET) and single photon emission computed tomography (SPECT) to investigate brain activity in OCD. Results suggest that differences in radiotracer uptake between patients with OCD and healthy controls have been found consistently in the orbital gyrus and the head of the caudate nucleus. No other significant differences were found. The implications of these results for theories regarding the etiology of OCD are discussed.

Caudate Nucleus↗

Social brain dysfunctions in schizophrenia: a review of neuroimaging studies.

Several studies have indicated that schizophrenic patients show impaired performance in various aspects of social cognition, including theory of mind, emotion processing, and agency judgments. Neuroimaging studies that have compared patients and healthy subjects during such mental activity indicate an abnormal hemodynamic response in the medial prefrontal cortex, the prefrontal cortex, the amygdala, the inferior parietal lobe, i.e., a set of regions known to be critically involved in social cognition. This paper addresses a number of issues raised by schizophrenia research into theory of mind, emotion perception and self-agency with regards to the neural systems that mediate social cognition. In healthy subjects, typical brain patterns are associated with theory of mind, emotion perception and self-agency; some activated clusters overlap, while others are distinct. For instance, activations in the paracingulate gyrus are almost systematically associated with theory of mind tasks, while the amygdala is mainly involved in emotion perception tasks. Additional foci are frequently found activated during those tasks: superior temporal sulcus, inferior frontal area. Moreover, the inferior parietal lobe is thought to contribute to agency judgments. In the light of the data on brain abnormalities and neurochemical dysfunctions in schizophrenia, we discuss the interaction of social cognitive dysfunction with the supposed information processing abnormalities caused by dopamine dysregulation.

Amygdala↗

Functional neuroimaging studies in restless legs syndrome.

Functional neuroimaging studies may contribute to elucidate pathophysiological mechanisms of the restless legs syndrome (RLS) which still remain unclear. Studies in patients with RLS have been performed using functional magnetic resonance imaging (fMRI), single photon emission computed tomography (SPECT) and, more recently, positron emission tomography (PET). SPECT and PET studies revealed some controversial results of the pre- and postsynaptic dopaminergic neurotransmission system and cerebral metabolism in RLS probably reflecting a dysfunction of the central dopaminergic system. However, it still has to be determined whether these alterations affect the nigrostriatal and/or other central dopaminergic systems like the diencephalospinal or mesolimbic pathway and whether they are the primary mechanisms or only secondary phenomena within the manifestation of RLS symptoms. A subtle receptor dysfunction or a synaptic dopaminergic deficit may play a major role. fMRI investigations of RLS patients revealed an activation in the red nuclei and brainstem close to the reticular formation during the symptomatic period, suggesting that subcortical cerebral generators are involved in the pathogenesis of RLS. However, both techniques are not yet clinically relevant methods to differentiate RLS from other movement disorders during sleep. Further investigations, especially at night when RLS symptoms are most pronounced, will lead to a better understanding of the mechanisms underlying RLS.

Brain↗

Advances in neuroimaging of the visual pathways.

PURPOSE: To provide a practical review for the ophthalmologist of advances in neuroimaging of the visual pathways. METHODS: We reviewed recent advances in computed tomography, magnetic resonance imaging, and angiography that are applicable to visual pathways imaging. RESULTS: For detailed ocular imaging, computed tomography complements ocular sonography for imaging of calcification, trauma, and masses. Magnetic resonance imaging may be helpful for localization and characterization of ocular masses in the setting of hemorrhage. For orbital imaging, computed tomography is most appropriate in the evaluation of suspected thyroid ophthalmopathy, infection, and trauma; otherwise, either computed tomography or magnetic resonance imaging is useful for detection and characterization of abnormality. For disorders affecting the sellar, retrochiasmal, and brainstem pathways, magnetic resonance imaging is the study of choice, except for acute hemorrhage, for which noncontrast computed tomography is preferable. Although magnetic resonance angiography has a role in the elective evaluation of cerebrovascular disease, conventional angiography is the definitive study for suspected aneurysm and for surgical planning. CONCLUSIONS: A practical approach for selection of the most appropriate imaging modalities by the ophthalmologist is suggested on the basis of the anatomic location and type of disease suspected.

Adult↗

Neuroimaging studies of mood disorders.

Neuroimaging studies of major depression have identified neurophysiologic abnormalities in multiple areas of the orbital and medial prefrontal cortex, the amygdala, and related parts of the striatum and thalamus. Some of these abnormalities appear mood state-dependent and are located in regions where cerebral blood flow increases during normal and other pathologic emotional states. These neurophysiologic differences between depressives and control subjects may thus implicate areas where physiologic activity changes to mediate or respond to the emotional, behavioral, and cognitive manifestations of major depressive episodes. Other abnormalities persist following symptom remission, and are found in orbital and medial prefrontal cortex areas where postmortem studies demonstrate reductions in cortex volume and histopathologic changes in primary mood disorders. These areas appear to modulate emotional behavior and stress responses, based upon evidence from brain mapping, lesion analysis, and electrophysiologic studies of humans and/or experimental animals. Dysfunction involving these regions is thus hypothesized to play a role in the pathogenesis of depressive symptoms. Taken together, these findings implicate interconnected neural circuits in which pathologic patterns of neurotransmission may result in the emotional, motivational, cognitive, and behavioral manifestations of primary and secondary affective disorders.

Amygdala↗

The anatomy of mood disorders--review of structural neuroimaging studies.

The structural neuroimaging findings in mood disorders were reviewed, to evaluate evidence for a neuroanatomic model of pathophysiology, involving the prefrontal cortex, the basal ganglia, the amygdala-hippocampus complex, thalamus, and connections among these structures. Global atrophy is not consistently found. The best replicated finding is an increased rate of white matter and periventricular hyperintensities. A smaller frontal lobe, cerebellum, caudate, and putamen appear present in unipolar depression. A larger third ventricle, and smaller cerebellum and perhaps temporal lobe appear present in bipolar disorder. These localized structural changes involve regions that may be critical in the pathogenesis of mood disorders. Generalized and localized anatomic alterations may be related to age or vascular disease. The clinical and biological correlates of these changes need to be investigated to allow development of a more complete model of pathophysiology of mood disorders.

Atrophy↗

PET neuroimaging of clomipramine challenge in humans: focus on the thalamus.

PET neuroimaging of serotonin responsivity relied previously mainly on fenfluramine, but that drug has been withdrawn from the market. Therefore, we determined whether clomipramine, which stimulates serotonergic mechanisms by inhibiting serotonin reuptake, has reliable effects in the healthy human brain as measured by [15O]H2O PET. The clomipramine challenge markedly reduced the relative rate of blood flow in the selected region of interest, namely the dorsomedial nucleus of the thalamus, a limbic region rich in serotonin uptake sites. These findings show similarities between effects of fenfluramine and clomipramine in the healthy human brain, and support the use of the clomipramine challenge in conjunction with PET for studying cerebral serotonergic mechanisms.

Aged↗

Neuroimaging of performance monitoring: error detection and beyond.

The ability to monitor performance and behavior is crucial for goal-directed, adaptive behavior in a changing environment. Performance monitoring has been extensively investigated using behavioral, electrophysiological and hemodynamic measures, and is still in the focus of many research projects. This paper gives an overview on neuroimaging of performance monitoring and the models which arose from several research approaches, taking into account the knowledge stemming from electrophysiological and lesion studies. Particular emphasis is put on error detection and response conflict monitoring, but also at motivational factors. Furthermore, the paper presents and discusses data from an fMRI study investigating the influence of error relevance on the hemodynamic correlates of error processing. By instruction and financial reward manipulation, the relevance of errors were block-wise modulated in a flanker paradigm. The results suggest that the engagement of the posterior frontomedian wall (pFMC) previously shown to be involved in performance monitoring is dependent on error relevance.

Adult↗

Evidence against functionalism from neuroimaging of the alien colour effect in synaesthesia.

Coloured hearing synaesthetes experience colours to heard words, as confirmed by reliability of self-report, psychophysical testing and functional neuroimaging data. Some also describe the 'alien colour effect' (ACE): in response to colour names, they experience colours different from those named. We have previously reported that the ACE slows colour naming in a Stroop task, reflecting cognitive interference from synaesthetically induced colours, which depends upon their being consciously experienced. It has been proposed that the hippocampus mediates such consciously experienced conflict. Consistent with this hypothesis, we now report that, in functional magnetic resonance imaging of the Stroop task, hippocampal activation differentiates synaesthetes with the ACE from those without it and from non-synaesthete controls. These findings confirm the reality of coloured hearing synaesthesia and the ACE, phenomena which pose major challenges to the dominant contemporary account of mental states, functionalism. Reductive functionalism identifies types of mental states with causal roles: relations to inputs, outputs and other states. However, conscious mental states, such as experiences of colour, are distinguished by their qualitative properties or qualia. If functionalism is applied to conscious mental states, it identifies the qualitative type of an experience with its causal role or function. This entails both that experiences with disparate qualitative properties cannot have the same functional properties, and that experiences with disparate functional properties cannot have the same qualitative properties. Challenges to functionalism have often denied the first entailment. Here, we challenge the second entailment on empirical grounds. In coloured hearing synaesthesia, colour qualia are associated with both hearing words and seeing surfaces; and, in the ACE, these two functions act in opposition to one another. Whatever its merits as an account of other mental states, reductive functionalism cannot be the correct account of conscious experiences.

Adult↗

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.

Brain Mapping↗

The contribution of functional neuroimaging to recovery after brain damage: a review.

The introduction of functional neuroimaging techniques has contributed to understanding the neural correlates of recovery of motor, sensory and cognitive functions after brain damage. In this paper, we review the literature of the past twenty years, with particular emphasis on quantitative studies of cerebral blood flow and metabolism. Studies are presented that examine recovery from hemiparesis, aphasia, spatial hemineglect and sensory disorders. The contribution of this research is critically discussed in a methodological perspective. A basic distinction is made between cerebral plasticity and recovery of functions. It is also argued that the most frequently used experimental designs do not permit directly relating changes in brain activity to functional recovery. The importance of accurate behavioural measures is underlined. Alternative experimental designs are proposed, based on correlations between behavioural performance and brain activations.

Brain↗

Neuroimaging of aging and estrogen effects on central nervous system physiology.

OBJECTIVE: To review the literature on neuroimaging studies focusing on gender differences in the aging process and on the effects of postmenopausal estrogen use on the brain. DESIGN: Pertinent studies were identified through a computer MEDLINE search. References of selected articles were hand-searched for additional citations. CONCLUSION(S): The current literature suggests that estrogen replacement may decrease brain white matter lesions, increase cerebral blood flow, alter regional brain activation patterns during cognitive processing, and have modulatory effects on various neurotransmitter systems. Overall, this points to a functional plasticity in higher order brain processing that can be altered by gonadal steroids.

Aging↗

A review of functional neuroimaging studies of vagus nerve stimulation (VNS).

Vagus nerve stimulation (VNS) is a new method for preventing and treating seizures, and shows promise as a potential new antidepressant. The mechanisms of action of VNS are still unknown, although the afferent direct and secondary connections of the vagus nerve are well established and are the most likely route of VNS brain effects. Over the past several years, many groups have used functional brain imaging to better understand VNS effects on the brain. Since these studies differ somewhat in their methodologies, findings and conclusions, at first glance, this literature may appear inconsistent. Although disagreement exists regarding the specific locations and the direction of brain activation, the differences across studies are largely due to different methods, and the results are not entirely inconsistent. We provide an overview of these functional imaging studies of VNS. PET (positron emission tomography) and SPECT (single photon emission computed tomography) studies have implicated several brain areas affected by VNS, without being able to define the key structures consistently and immediately activated by VNS. BOLD (blood oxygen level dependent) fMRI (functional magnetic resonance imaging), with its relatively high spatio-temporal resolution, performed during VNS, can reveal the location and level of the brain's immediate response to VNS. As a whole, these studies demonstrate that VNS causes immediate and longer-term changes in brain regions with vagus innervations and which have been implicated in neuropsychiatric disorders. These include the thalamus, cerebellum, orbitofrontal cortex, limbic system, hypothalamus, and medulla. Functional neuroimaging studies have the potential to provide greater insight into the brain circuitry behind the activity of VNS.

Brain↗

[The internationalization of scientific production in the fields of radiology and neuroimaging in Spain (1996-2003)].

The situation of Research in radiology in Spain is analysed by examining the number of publications by Spanish authors in main stream international journals. The scientific production of Spanish researchers in journals included in the Science Citation Index (SCI) under the headings "Radiology, Nuclear Medicine, and Medical Imaging" and "Neuroimaging" during the years 1996-2003. During this period the scientific production in these fields comprised 1,562 documents (3.5% of the total production for Spanish clinical medicine); scientific production in these fields increased by 40% in this period in comparison to 24% for all clinical medicine. The bulk of the production was concentrated in the autonomous communities of Catalonia (35%), Madrid (28%), and Valencia (10%). The autonomous communities of Navarra and Cantabria had a high relative production after the results were adjusted for population. The healthcare sector is the most active, with the Hospital de la Santa Creu i Sant Pau, the Hospital Clinic de Barcelona, and the Hospital Vall d'Hebron being outstanding in that they not only lead the country in the number of publications but also publish more in journals with high impact factors. Among centers other than hospitals, the Center for Research in Energy, the Environment, and Technologies (CIEMAT) and the Medical School of the Universidad Complutense de Madrid are the most important. A high degree of collaboration is evident: 68% of the documents were produced by more than one institution, foreign centers were involved in 20%, and the documents were signed by an average of six authors. Conclusions. In summary, the data show that Spanish radiological research is becomin increasingly international, although this process is still in the initial stage, with the percentage of documents published in the most prestigious journals for this specialty being lower than in other disciplines. The relative activity and production of Spain is slightly below the average of the European Union, but the country shows a rising trend for both production and impact.

Bibliometrics↗

[Neuroimaging characteristics of cerebral infarcts].

Over the last years, technical advances in neuroimaging have allowed drastic improvements in the assessment of acute ischemic cerebral events. Beyond conventional morphological analysis, diffusion-weighted and perfusion-weighted MRI now enable routine functional assessment of brain tissue; spectroscopy and diffusion tensor imaging still remains in the domain of clinical research. During acute ischemia events, diffusion-weighted MRI can detect the movements of water molecules and cytotoxic edema related to cell injury enabling rapid diagnosis and early assessment of cerebral ischemia. In conjunction with perfusion imaging, which detects hypoperfusion areas, diffusion-weighted MRI provides a means to identify areas of penumbra ischemia. More recent multislice computed tomographic (CT) scans with multimodal analysis are also very competitive for assessment of cerebral ischemia (non-enhanced CT, CT angiography and perfusion CT). The purpose of this paper is to describe the CT and MRI patterns during the different stages of cerebral infarcts.

Acute Disease↗