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New perspectives in EEG/MEG brain mapping and PET/fMRI neuroimaging of human pain.

With the maturation of EEG/MEG brain mapping and PET/fMRI neuroimaging in the 1990s, greater understanding of pain processing in the brain now elucidates and may even challenge the classical theory of pain mechanisms. This review scans across the cultural diversity of pain expression and modulation in man. It outlines the difficulties in defining and studying human pain. It then focuses on methods of studying the brain in experimental and clinical pain, the cohesive results of brain mapping and neuroimaging of noxious perception, the implication of pain research in understanding human consciousness and the relevance to clinical care as well as to the basic science of human psychophysiology. Non-invasive brain studies in man start to unveil the age-old puzzles of pain-illusion, hypnosis and placebo in pain modulation. The neurophysiological and neurohemodynamic brain measures of experimental pain can now largely satisfy the psychophysiologist's dream, unimaginable only a few years ago, of modelling the body-brain, brain-mind, mind-matter duality in an inter-linking 3-P triad: physics (stimulus energy); physiology (brain activities); and psyche (perception). For neuropsychophysiology greater challenges lie ahead: (a) how to integrate a cohesive theory of human pain in the brain; (b) what levels of analyses are necessary and sufficient; (c) what constitutes the structural organisation of the pain matrix; (d) what are the modes of processing among and across the sites of these structures; and (e) how can neural computation of these processes in the brain be carried out? We may envision that modular identification and delineation of the arousal-attention, emotion-motivation and perception-cognition neural networks of pain processing in the brain will also lead to deeper understanding of the human mind. Two foreseeable impacts on clinical sciences and basic theories from brain mapping/neuroimaging are the plausible central origin in persistent pain and integration of sensory-motor function in pain perception.

Brain↗

Neuroimaging studies in post-traumatic stress disorder.

The authors review some of the advances that have been made in understanding the structural, biochemical, and functional neuroanatomy of post-traumatic stress disorder (PTSD). First, the authors review the primary brain regions that had been hypothesized a priori, from the phenomenology and neurobiology of PTSD, to be implicated in the pathophysiology. Next, they review findings from neuroimaging studies of these brain regions in PTSD, and explain the various experimental methods and imaging technologies used in these studies. A broader perspective, including a discussion of additional brain areas that may be involved in PTSD, is synthesized. The authors conclude with a rationale and approach for studies testing sharply defined hypotheses and those using multidisciplinary strategies that integrate neuroimaging data with other cognitive, biologic, and genetic tools to study this complex disorder.

Amygdala↗

Neuroimaging and neuropsychology of the striatum. Bridging basic science and clinical practice.

Neuroimaging and neuropsychology are complementary disciplines that provide powerful means for assessing the structure and function of corticostriatal systems. Findings from four model basal ganglia disorders--OCD, TS, HD, and PD--are reviewed. This survey is intended as a vehicle for illustrating the breadth of current clinical and research applications, as well as the potential for future advances. The perspectives brought by neuroimaging and neuropsychology serve as a natural bridge from the basic neuroscience to the clinical practice articles in this issue.

Cognition Disorders↗

The role of neuroimaging in the initial management of patients with minor head injury.

STUDY OBJECTIVE: To determine whether omitting neuroimaging in the primary assessment of patients with minor head injuries in the emergency department is safe. DESIGN: Prospective cohort study. SETTING: University hospital, Copenhagen County Hospital, Glostrup, Denmark. PARTICIPANTS: The study group consisted of 2,204 patients presenting to the ED after sustaining minor head injuries. Only patients able to talk and walk were included. MEASUREMENTS AND MAIN RESULTS: The decision to admit was based exclusively on clinical guidelines in which the findings in the ED were of highest priority. Seven patients (0.3%) had a skull radiograph; computed tomography was not used in the primary evaluation. Four hundred thirty patients (19.5%) were admitted. After hospitalization, four patients developed intracranial complications. One required surgery, two required hyperventilation, and one was observed. Follow-up demonstrated that no patient with an intracranial complication had been missed. CONCLUSION: We found it safe to exclude neuroimaging in the primary assessment of patients with minor head injuries in the ED, and to rely instead on clinical criteria.

Adolescent↗

[Functional neuroimaging in patients with rapid cycling bipolar depression].

Bipolar patients with a rapid cycling clinical course constitute an interesting sub-group for studies focused on the pathophysiology of the disorder, since several switches can be studied by the investigators in a short period of time. At present, functional neuroimaging techniques, as SPECT and PET, may be used for the neurobiological study of affective disorders. Few longitudinal functional neuroimaging studies assessing the different phases of bipolar disorder have been carried out. However, the published data suggest an asymmetrical temporal lobe dysfunction in depressive and manic phases of bipolar depression. Further studies with larger samples of patients are needed in order to improve our knowledge of the pathophysiology of bipolar disorder.

Bipolar Disorder↗

Neuroimaging studies of priming.

This article reviews functional neuroimaging studies of priming, a behavioural change associated with the repeated processing of a stimulus. Using the haemodynamic techniques of functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), priming-related effects have been observed in numerous regions of the human brain, with the specific regions depending on the type of stimulus and the manner in which it is processed. The most common finding is a decreased haemodynamic response for primed versus unprimed stimuli, though priming-related response increases have been observed. Attempts have been made to relate these effects to a form of implicit or "unconscious" memory. The priming-related decrease has also been used as a tool to map the brain regions associated with different stages of stimulus-processing, a method claimed to offer superior spatial resolution. This decrease has a potential analogue in the stimulus repetition effects measured with single-cell recording in the non-human primate. The paradigms reviewed include word-stem completion, masked priming, repetition priming of visual objects and semantic priming. An attempt is made to relate the findings within a "component process" framework, and the relationship between behavioural, haemodynamic and neurophysiological data is discussed. Interpretation of the findings is not always clear-cut, however, given potential confounding factors such as explicit memory, and several recommendations are made for future neuroimaging studies of priming.

Adaptation, Physiological↗

Neural correlates of attention and arousal: insights from electrophysiology, functional neuroimaging and psychopharmacology.

Attention and arousal are multi-dimensional psychological processes, which interact closely with one another. The neural substrates of attention, as well as the interaction between arousal and attention, are discussed in this review. After a brief discussion of psychological and neuropsychological theories of attention, event-related potential correlates of attention are discussed. Essentially, attention acts to modulate stimulus-induced electrical potentials (N100/P100, P300, N400), rather than generating any unique potentials of its own. Functional neuroimaging studies of attentional orienting, selective attention, divided attention and sustained attention (and its inter-dependence on underlying levels of arousal) are then reviewed. A distinction is drawn between the brain areas which are crucially involved in the top-down modulation of attention (the 'sources' of attention) and those sensory-association areas whose activity is modulated by attention (the 'sites' of attentional expression). Frontal and parietal (usually right-lateralised) cortices and thalamus are most often associated with the source of attentional modulation. Also, the use of functional neuroimaging to test explicit hypotheses about psychological theories of attention is emphasised. These experimental paradigms form the basis for a 'new generation' of functional imaging studies which exploit the dynamic aspect of imaging and demonstrate how it can be used as more than just a 'brain mapping' device. Finally, a review of psychopharmacological studies in healthy human volunteers outlines the contributions of the noradrenergic, cholinergic and dopaminergic neurotransmitter systems to the neurochemical modulation of human attention and arousal. While, noradrenergic and cholinergic systems are involved in 'low-level' aspects of attention (e.g. attentional orienting), the dopaminergic system is associated with more 'executive' aspects of attention such as attentional set-shifting or working memory.

Animals↗

Slit ventricle syndrome after cyst-peritoneal shunting for temporal arachnoid cyst in children--a clinical entity difficult to detect on neuroimaging study.

Slit ventricle syndrome, known to occur from malfunction of the shunt procedure for hydrocephalus, is reported after cyst-peritoneal shunt for temporal arachnoid cyst. Two children aged 12 and 10 years, who underwent cyst-peritoneal shunting for a large temporal arachnoid cyst at the age of 10 and 5 years, respectively, recently experienced several episodes of severe headache. Prior to admission, repeated CT scans did not reveal any morphological change in either of these two patients. Evidence of high intracranial pressure by lumbar tap revealed shunt malfunction. Both patients became free of neurological complaints and deficits after shunt revision. Despite elevated intracranial pressure due to shunt malfunction, neuroimaging studies showed no morphological changes in slit ventricle syndrome. Delay in both the diagnosis and prompt treatment may result in complete loss of visual acuity and even death. It is important to suspect this complication in patients with persistent elevated intracranial pressure symptoms and signs after any shunting procedure, regardless of unchanged neuroimaging studies. Once this is suspected, lumbar tap may be necessary and the choice of treatment is shunt revision.

Arachnoid Cysts↗

The role of neuroimaging in dementia.

Potential new therapies for the treatment of Alzheimer's disease demand early and accurate diagnosis. Although clinical evaluation is generally sufficient when the disease is well established, neuroimaging tools are helpful to detect the earliest changes of Alzheimer's disease or differentiate Alzheimer's disease from the other forms of dementia. This article reviews the basic concepts of brain imaging and clinical application. It concludes with a brief discussion of future directions in neuroimaging for the diagnosis and longitudinal follow-up of Alzheimer's disease.

Aftercare↗

Working memory and executive function: evidence from neuroimaging.

Traditional theories of working memory and executive function, when mapped in straightforward ways into the neural domain, yield predictions that are only partly supported by the recent neuroimaging studies. Neuroimaging studies suggest that some constituent functions, such as maintaining information in active form and manipulating it, are not discretely localized in prefrontal regions. Some hypothesized executive processes, such as goal management, have effects in several cortical regions, including posterior regions. Such results suggest a more dynamic and distributed view of the cortical organization of working memory and executive functions.

Brain Mapping↗

Neuroimaging and neurocircuitry models pertaining to the neurosurgical treatment of psychiatric disorders.

Neurocircuitry models of obsessive-compulsive disorder (OCD) and major depression (MD) are described, focusing on relevant supporting neuroimaging data. Corticostriatothalamocortical circuitry is implicated in OCD. In MD, the relation between "dorsal" and "ventral" cortical compartments is emphasized; the amygdala, hippocampus, and pregenual anterior cingulate are implicated in the pathophysiology of MD and are potential targets for treatment. The neuroanatomy of psychiatric neurosurgical procedures and related neuroimaging findings are reviewed. Finally, anticipated future directions of research in this field are discussed.

Brain↗

Valence, gender, and lateralization of functional brain anatomy in emotion: a meta-analysis of findings from neuroimaging.

We performed quantitative meta-analyses on 65 neuroimaging studies of emotion. In an earlier report (NeuroImage 16 (2002), 331). we examined the effects of induction method, specific emotions, and cognitive demand in emotional tasks. This paper focuses on the effects of emotional valence (positive vs negative and approach vs withdrawal) and gender on regional brain activations, with particular emphasis on hypotheses concerning lateralization of brain function in emotion. Overall, we found no support for the hypothesis of overall right-lateralization of emotional function, and limited support for valence-specific lateralization of emotional activity in frontal cortex. In addition, we found that males showed more lateralization of emotional activity, and females showed more brainstem activation in affective paradigms. The study provides evidence that lateralization of emotional activity is more complex and region-specific than predicted by previous theories of emotion and the brain.

Brain↗

Evaluation of the dual route theory of reading: a metanalysis of 35 neuroimaging studies.

Numerous studies concerned with cerebral structures underlying word reading have been published during the last decade. A few controversies, however, together with methodological or theoretical discrepancies between laboratories, still contribute to blurring the overall view of advances effected in neuroimaging. Carried out within the dual route of reading framework, the aim of this metanalysis was to provide an objective picture of these advances. To achieve this, we used an automated analysis method based on the inventory of activation peaks issued from word or pseudoword reading contrasts of 35 published neuroimaging studies. A first result of this metanalysis was that no cluster of activations has been found more recruited by word than pseudoword reading, implying that the first steps of word access may be common to word and word-like stimuli and would take place within a left occipitotemporal region (previously referred to as the Visual Word Form Area-VWFA) situated in the ventral route, at the junction between inferior temporal and fusiform gyri. The results also indicated the existence of brain regions predominantly involved in one of the two routes to access word. The graphophonological conversion seems indeed to rely on left lateralized brain structures such as superior temporal areas, supramarginal gyrus, and the opercular part of the inferior frontal gyrus, these last two regions reflecting a greater load in working memory during such an access. The lexicosemantic route is thought to arise from the coactivation of the VWFA and semantic areas. These semantic areas would encompass a basal inferior temporal area, the posterior part of the middle temporal gyrus, and the triangular part of inferior frontal gyrus. These results confirm the suitability of the dual route framework to account for activations observed in nonpathological subjects while they read.

Clinical Trials as Topic↗

Neuroimaging of children with partial seizures.

The predictive value of abnormal neurological findings on neuroimaging (NI) of children with partial seizures (PS) was studied. The sample comprised 143 children and adolescents with PS from 1979 to 1996. Fifty patients had the following abnormal NI findings: diffuse atrophy and porencephalic cyst (5.6% each), hemiatrophy, tumors, neurocutaneous syndrome brain lesions, and dysgenesis (4.2% each), and arachnoid cyst and hydrocephalus (2.1% each). There were significantly more NI abnormalities among those with simple PS than among the other groups of complex PS or PS with secondary generalization. All cases of porencephalic cyst (n = 8), and hemiatrophy (n = 6) were in the hemiparetic group, all cases of tumor (n = 6) were in the normal group, while most cases of diffuse atrophy were in the mentally retarded group. Patients with abnormal NIs had a significantly earlier age of seizure onset than the others. The chance of finding a treatable abnormality in neuroimaging was 5% for tumors and 2% for arachnoid cysts in the group of patients with PS and normal neurological findings. Neither an abnormality detected in a neurological examination nor the type of seizure are predictive parameters for suggesting the presence of a resectable brain tumor. All patients with newly diagnosed PS should undergo an MRI.

Adolescent↗

A symbolic environment for visualizing activated foci in functional neuroimaging datasets.

This paper presents a symbolic visualization environment known as the Corner Cube environment, which was developed to facilitate rapid examination and comparison of activated foci defined by analyses of functional neuroimaging datasets. We have performed a comparative evaluation of this environment against maximum-intensity projection and 'gallery of slices' displays, and the results suggest that the Corner Cube environment has definite advantages over both conventional display techniques. We conclude that the Corner Cube is an effective tool for summarizing the spatial characteristics of activated foci within an easily understood visual context and is especially useful for displaying the similarities and differences in functional neuroimaging datasets.

Brain↗

Functional neuroimaging of headaches.

Functional neuroimaging, mainly PET and functional MRI, is the main tool that allows the capturing of neurovascular events during a headache attack. In migraine, functional imaging has clarified the underlying pathophysiology of the visual aura, whereas in migraine without aura, brainstem findings suggest a dysfunctional pain system. In cluster headache, the activation and morphological changes seen in a region posterior and inferior to the hypothalamus has provided a useful therapeutic target using deep-brain stimulation. We will discuss the main neuroimaging findings pertaining to the pathophysiology of these two common headache disorders, migraine and cluster headache.

Headache Disorders↗

Neuroimaging in hepatic encephalopathy.

Hepatic encephalopathy (HE) is a poorly defined, complex neuropsychological disorder that often accompanies portal hypertension. Although the mechanisms underlining HE and the characterization of HE are still under investigation, the information derived from functional neuroimaging of patients with HE complemented by laboratory investigation and neuropsychological and neurophysiological studies have clarified much of the neuroanatomical defects. In this review, we have provided an outline of the understood mechanisms of HE and the associated findings on neuroimaging.

Ammonia↗

Frequency and clinical, neuropsychological and neuroimaging correlates of apathy following stroke - the Sydney Stroke Study.

BACKGROUND: The frequency and clinical, neuropsychological and neuroimaging correlates of apathy in patients who have had a stroke are inadequately defined. METHOD: A total of 167 consecutive patients admitted to the stroke units of two university hospitals after an ischaemic stroke and 109 controls received extensive medical, psychiatric and neuropsychological assessments; a subset received a magnetic resonance imaging (MRI) scan. The groups were matched for sex and age. Patients were assessed 3-6 months after their stroke. The sample for this study comprised 135 patients and 92 controls who completed the Apathy Evaluation Scale (AES). RESULTS: Apathy was present in 26.7% of stroke patients compared to 5.4% of controls. Apathetic stroke patients were older, more functionally dependent and had lower Mini-Mental State Examination (MMSE) scores than those without apathy. Apathy was not associated with risk factors for cerebrovascular disease or stroke severity. There was a weak but significant correlation between apathy and self-reported depression but not with clinician-rated depression. Neuropsychologically, after correction for age, premorbid intelligence (IQ) and depression, apathy was associated with reduced attention and speed of information processing. On neuroimaging there were trends for associations of apathy with the extent of hyperintensities in the right hemisphere and right fronto-subcortical circuit, but not with total stroke volume or number of strokes. CONCLUSIONS: Apathy is common following a cerebrovascular event. Presence of apathy may be related to older age and right fronto-subcortical pathway pathology, rather than stroke severity. It is associated with functional impairment and cognitive deficits.

Aged↗