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What psychological testing and neuroimaging tell us about the treatment of Posttraumatic Stress Disorder by Eye Movement Desensitization and Reprocessing.

To better understand the pathophysiology and treatment of Posttraumatic Stress Disorder (PTSD), standard psychological testing, Rorschach Ink Blot testing, and neuroimaging using Single Photon Emission Computed Tomography (SPECT) were administered to subjects with PTSD prior to and following three sessions of Eye Movement Desensitization and Reprocessing (EMDR). Using this within-subject design, data from one of six subjects in our series is presented as a case report. Following EMDR, the subject experienced improvement in his level of distress, which correlated with decrements in PTSD and depressive symptomatology on psychological testing. Analysis of the Rorschach data corroborated these changes. Among other findings, the Hypervigilance Index went from positive to negative, indicating that the subject was spending less time scanning the environment for threats, and available ego resources also increased, as measured by the Experience Actual variable. Upon recall of the traumatic memory during SPECT scanning, two areas of the brain were hyperactive post-EMDR treatment relative to pretreatment: the anterior cingulate gyrus and the left frontal lobe. These changes were consistent with summed data from four out of six subjects in the ongoing study. An important implication of these findings is that successful treatment of PTSD does not reduce arousal at the limbic level, but instead, enhances the ability to differentiate real from imagined threat. The psychology and neurophysiology of PTSD are discussed in greater detail.

Adult↗

Agyria-pachygyria: clinical, neuroimaging, and neurophysiologic correlations.

Agyria-pachygyria complex is a disorder of neuronal migration and organization. Patients suffer either motor or intellectual retardation. We report our experiences of 10 patients with agyria-pachygyria complex and evaluate their clinical features, electroencephalography, and evoked potentials. Of nine electroencephalography examinations, five patients demonstrated characteristically high-amplitude fast activity. One of nine patients had an abnormal brainstem auditory-evoked potential. Three of seven patients had abnormal goggled visual-evoked potential. Six patients received somatosensory-evoked potential examinations, and five of these were abnormal, including four with prolonged central conduction times. Of the 10 patients, eight survived with variable intellectual and motor retardation; two died of sepsis. Patients with grades 1-4 agyria-pachygyria had high incidences of somatosensory-evoked potential abnormalities and also suffered worse neurologic outcomes. Normal brainstem auditory-evoked potential but abnormal cortical somatosensory-evoked potential components and prolonged central conduction time in these patients indicate that agyria-pachygyria is a supratentorial disease. We conclude that somatosensory-evoked potential examination is supplemental to neuroimaging in predicting the neurologic prognosis of patients with agyria-pachygyria.

Adolescent↗

Neuroimaging in the evaluation of children and adolescents with intractable epilepsy: I. Magnetic resonance imaging and the substrates of epilepsy.

Recent advances in neuroimaging, particularly the magnetic resonance imaging (MRI) scan, have greatly enhanced our ability to visualize intraparenchymal anatomy. With the linkage between intracranial pathology and epilepsy now clearly established, the MRI data provides detailed information for the clinician treating patients with epilepsy. This article supplies the reader with an overview of the new techniques in MRI brain imaging that allow us to identify intracranial abnormalities, and a survey of some of the MRI-identified substrates of epilepsy.

Adolescent↗

Neuroimaging findings of four patients with Sandhoff disease.

Sandhoff disease is a severe form of GM2 gangliosidosis that is caused by the deficiency of both hexosaminidase A and B. Startle reaction, hypotonia, psychomotor retardation, and blindness are the main clinical features. Presented are computed tomography and magnetic resonance imaging findings of four patients with Sandhoff disease diagnosed by enzymatic analyses. Bilateral homogeneous thalamic hyperdensity was evident on computed tomography. Magnetic resonance imaging scans revealed mild cortical atrophy, a thin corpus callosum, and abnormal signal intensities in the caudate nucleus, globus pallidum, putamen, cerebellum, and brainstem. No correlation was evident between the severity of the central nervous system imaging findings and the clinical pictures. In this article the neuroimaging findings of four patients with Sandhoff disease are discussed.

Adolescent↗

Mild head injury in children: identification, clinical evaluation, neuroimaging, and disposition.

Pediatric head injury presents in various degrees of severity. Early intervention in the patient with a severe head injury is the key to preventing secondary central nervous system damage. Patients with a head injury are easily identified, often by clinical examination alone. However, patients with a mild head injury present a challenge to practitioners, particularly in identification, knowing what is important in the clinical evaluation, deciding whether to use neuroimaging, and knowing where to send the child for observation. Use of the Glasgow Coma Score, primary survey, and identification of historic and clinical features that are suggestive of severe head injury may guide pediatric nurse practitioners in providing appropriate medical care and disposition.

Adolescent↗

[11C]Mirtazapine for PET neuroimaging: radiosynthesis and initial evaluation in the living porcine brain.

We radiolabelled mirtazapine, a tetracyclic, atypical, antidepressant drug, for positron emission tomography (PET) and evaluated its regional kinetics in the living porcine brain. We produced [N-methyl-11C]mirtazapine with a radiochemical-purity >98% in a 21% decay-corrected radiochemical yield by alkylation of N-desmethyl mirtazapine with [11C]methyl iodide, followed by HPLC purification and formulation. [N-Methyl-11C]mirtazapine entered the brain readily and, under baseline conditions, it had an apparent volume of distribution (V(e)') of 9-13 in the basal ganglia, thalamus, and frontal cortex. Reference region and graphical analyses based on a one-compartment model showed that the binding of [N-methyl-11C]mirtazapine was reversible, with an apparent binding potential of more than two in thalamus and frontal cortex. Infusion of unlabelled mirtazapine markedly displaced [N-methyl-11C]mirtazapine from binding sites in the basal ganglia, thalamus and frontal cortex, but not in reference regions (cerebellum and olfactory tubercle). Thus, [N-methyl-11C]mirtazapine showed rapid passage into the living brain, slow metabolism in blood, and reversible, competitive binding, which may make it useful for PET neuroimaging of neuroreceptors involved in antidepressant actions.

Animals↗

Neuroimaging of hallucinations: a review of the literature.

While hallucinations have been described for over two millennia, their cause remains unclear. Brain-based models suggest that abnormal cerebral excitation and a lack of normal cerebral inhibition may play primary roles, but evaluation of these hypotheses has been hampered by difficulty in studying the hallucinatory state. Recent advances in neuroimaging have provided researchers with tools to study a variety of mental states, including hallucinations. We review the literature regarding the structural and functional neural correlates of hallucinations. Despite small sample sizes and methodological differences, several studies describe similar results: hallucinations are associated with sensory modality-specific activation in cerebral areas involved in normal sensory processing. Furthermore, neural activation may be specifically related to distinct phenomenological features of the hallucinatory experience. Further work is needed to better understand the neural basis of hallucinations.

Adult↗

An evaluation of methods for detecting brain activations from functional neuroimages.

Brain activation studies based on PET or fMRI seek to explore neuroscience questions by statistically analyzing the acquired images to produce statistical parametric images (SPIs). An increasingly wide range of univariate and multivariate analysis techniques are used to generate SPIs in order to detect mean-signal activations and/or long-range spatial interactions. However, little is known about the comparative detection performance of even simple techniques in finite data sets. Our aims are (1) to empirically compare the detection performance of a range of techniques using simulations of a simple image phantom and receiver operating characteristics (ROC) analysis, and (2) to construct two near-optimal detectors, both generalized likelihood ratio tests as upper performance bounds. We found that for finite samples of (10-100) images, even when the t-test with single-voxel variance estimates (single-voxel t-test) is the "correct" (i.e. unbiased) model for simple local additive signals, better detection performance is obtained using pooled variance estimates or adaptive, multivariate covariance-based detectors. Normalization by voxel-based variance estimates causes significantly decreased detection performance using either single-voxel t-tests or correlation-coefficient thresholding compared to pooled-variance t-tests or covariance thresholding, respectively. Moreover, we found that SVD by itself, or followed by an adaptive Fisher linear discriminant, provides a detector that is (1) more sensitive to mean differences than a single-voxel t-test, (2) insensitive to the large local signal variances detected by covariance thresholding, and (3) much more sensitive to signal correlations than correlation-coefficient thresholding. Adaptive, multivariate covariance-based approaches and pooled-variance t-tests represent promising directions for obtaining optimal signal detection in functional neuroimaging studies.

Brain↗

Finding related functional neuroimaging volumes.

We describe a content-based image retrieval technique for finding related functional neuroimaging experiments by voxelization of sets of stereotactic coordinates in Talairach space, comparing the volumes and reporting related volumes in a sorted list. Voxelization is accomplished by convolving each coordinate with a Gaussian kernel. The scheme allows us to compare experiments represented as either lists of coordinates or volumes, and we introduce alternative entrances to databases by image-based indices constructed via novelty measures and singular value decomposition.

Brain↗

Classical fear conditioning in functional neuroimaging.

Classical conditioning, the simplest form of associative learning, is one of the most studied paradigms in behavioural psychology. Since the formal description of classical conditioning by Pavlov, lesion studies in animals have identified a number of anatomical structures involved in, and necessary for, classical conditioning. In the 1980s, with the advent of functional brain imaging techniques, particularly positron emission tomography (PET), it has been possible to study the functional anatomy of classical conditioning in humans. The development of functional magnetic resonance imaging (fMRI)--in particular single-trial or event-related fMRI--has now considerably advanced the potential of neuroimaging for the study of this form of learning. Recent event-related fMRI and PET studies are adding crucial data to the current discussion about the putative role of the amygdala in classical fear conditioning in humans.

Acoustic Stimulation↗

Neuroimaging of visual awareness in patients and normal subjects.

The immediacy and directness of our visual experience belies the complexity of the underlying neural mechanisms, which remain incompletely understood. Recent neuroimaging studies suggest that activity in ventral visual cortex is necessary but not sufficient for visual awareness. Experiments in both patients and normal subjects indicate that parietal and frontal areas make an important contribution to visual awareness, suggesting that reciprocal interactions between dorsal frontoparietal areas and ventral visual cortex may provide a fundamental neural substrate for conscious visual experience.

Animals↗

Neuroimaging of cognitive functions in human parietal cortex.

Functional neuroimaging has proven highly valuable in mapping human sensory regions, particularly visual areas in occipital cortex. Recent evidence suggests that human parietal cortex may also consist of numerous specialized subregions similar to those reported in neurophysiological studies of non-human primates. However, parietal activation generalizes across a wide variety of cognitive tasks and the extension of human brain mapping into higher-order "association cortex" may prove to be a challenge.

Animals↗

Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders.

Neuroimaging technology has provided unprecedented opportunities for elucidating the anatomical correlates of major depression. The knowledge gained from imaging research and from the postmortem studies that have been guided by imaging data is catalyzing a paradigm shift in which primary mood disorders are conceptualized as illnesses that involve abnormalities of brain structure, as well as of brain function. These data suggest specific hypotheses regarding the neural mechanisms underlying pathological emotional processing in mood disorders. They particularly support a role for dysfunction within the prefrontal cortical and striatal systems that normally modulate limbic and brainstem structures involved in mediating emotional behavior in the pathogenesis of depressive symptoms.

Amygdala↗

Distinct systems for automatic and cognitively controlled time measurement: evidence from neuroimaging.

A recent review of neuroimaging data on time measurement argued that the brain activity seen in association with timing is not influenced by specific characteristics of the task performed. In contrast, we argue that careful analysis of this literature provides evidence for separate neural timing systems associated with opposing task characteristics. The 'automatic' system draws mainly upon motor circuits and the 'cognitively controlled' system depends upon prefrontal and parietal regions.

Animals↗

Prefrontal cortex involvement in preattentive auditory deviance detection: neuroimaging and electrophysiological evidence.

Previous electrophysiological and neuroimaging studies suggest that the mismatch negativity (MMN) is generated by a temporofrontal network subserving preattentive auditory change detection. In two experiments we employed event-related brain potentials (ERP) and event-related functional magnetic resonance imaging (fMRI) to examine neural and hemodynamic activity related to deviance processing, using three types of deviant tones (small, medium, and large) in both a pitch and a space condition. In the pitch condition, hemodynamic activity in the right superior temporal gyrus (STG) increased as a function of deviance. Comparisons between small and medium and between small and large deviants revealed right prefrontal activation in the inferior frontal gyrus (IFG; BA 44/45) and middle frontal gyrus (MFG; BA 46), whereas large relative to medium deviants led to left and right IFG (BA 44/45) activation. In the ERP experiment the amplitude of the early MMN (90-120 ms) increased as a function of deviance, by this paralleling the right STG activation in the fMRI experiment. A U-shaped relationship between MMN amplitude and the degree of deviance was observed in a late time window (140-170 ms) resembling the right IFG activation pattern. In a subsequent source analysis constrained by fMRI activation foci, early and late MMN activity could be modeled by dipoles placed in the STG and IFG, respectively. In the spatial condition no reliable hemodynamic activation could be observed. The MMN amplitude was substantially smaller than in the pitch condition for all three spatial deviants in the ERP experiment. In contrast to the pitch condition it increased as a function of deviance in the early and in the late time window. We argue that the right IFG mediates auditory deviance detection in case of low discriminability between a sensory memory trace and auditory input. This prefrontal mechanism might be part of top-down modulation of the deviance detection system in the STG.

Acoustic Stimulation↗

Effect of emergency department CT on neuroimaging case volume and positive scan rates.

RATIONALE AND OBJECTIVES: The authors performed this study to determine the effect a computed tomographic (CT) scanner in the emergency department (ED) has on neuroimaging case volume and positive scan rates. MATERIALS AND METHODS: The total numbers of ED visits and neuroradiology CT scans requested from the ED were recorded for 1998 and 2000, the years before and after the installation of a CT unit in the ED. For each examination type (brain, face, cervical spine), studies were graded for major findings (those that affected patient care), minor findings, and normal findings. The CT utilization rates and positive study rates were compared for each type of study performed for both years. RESULTS: There was a statistically significant increase in the utilization rate after installation of the CT unit (P < .001). The fractions of studies with major findings, minor findings, and normal findings changed significantly after installation of the CT unit for facial examinations (P = .002) but not for brain (P = .12) or cervical spine (P = .24) examinations. In all types of studies, the percentage of normal examinations increased. In toto, there was a significant decrease in the positive scan rate after installation of the CT scanner (P = .004). CONCLUSION: After installation of a CT scanner in the ED, there was increased utilization and a decreased rate of positive neuroradiologic examinations, the latter primarily due to lower positive rates for facial CT scans.

Cervical Vertebrae↗

Functional neuroimaging of gastric distention.

This study aimed to measure brain activation during gastric distention as a way to investigate short-term satiety. We estimated regional cerebral blood flow with positron emission tomography (15O-water) during gastric balloon inflation and deflation in 18 healthy young women. The contrast between inflated minus deflated conditions showed activation in the following four key regions that were identified a priori: dorsal brain stem; left inferior frontal gyrus; bilateral insula; and right subgenual, anterior cingulate cortex. Extant neuroimaging literature provides context for these areas as follows: the brain stem represents vagal projection zones for visceral afferent processing; the inferior frontal gyrus serves as a convergence zone for processing food-related stimuli; and both the insula and subgenual anterior cingulate cortex respond to emotional stimulation. The identification of neural correlates of gastric distention is a key step in the discovery of new treatments for obesity. New therapies could intervene by modifying the perception of gastric distention, an important contributor to meal termination and short-term satiety. This first study of brain activation during nonpainful, proximal gastric distention provides the groundwork for future research to discover novel treatments for obesity.

Brain↗

Clinical Value of Neuroimaging in the Diagnosis of Dementia. Sensitivity and Specificity of Regional Cerebral Metabolic and Other Parameters for Early Identification of Alzheimer's Disease.

Dementing illnesses such as Alzheimer's disease (AD) progressively devastate human brain tissue and consequently the health and lives of people afflicted by these disorders. One of the greatest clinical challenges posed by dementia is establishing an approach to ensure its early identification and accurate diagnosis-thus making it possible to treat and, potentially, arrest the development of disease before a substantial amount of brain tissue has been permanently destroyed. The data generated by neuroimaging studies conducted over the past two decades show PET with [(18)F]fluorodeoxyglucose (FDG) to be exceptionally well-suited to meeting this challenge. The regional metabolic patterns imaged with FDG-PET enable sensitive diagnosis of AD, and reveal pathophysiologic alterations even before they lead to symptomatic expression. The accuracy of PET in identifying early AD, and distinguishing it from other etiologies of cognitive impairment, exceeds that of CT, MRI (qualitative or quantitative), and SPECT, as well as that of expert clinical evaluation based on history, physical examination, cognitive testing, and blood laboratory values. Recent developments in instrumentation and radiopharmaceutical distribution have made obtaining scans of cerebral metabolism achievable in routine clinical settings, including most hospitals in which Nuclear Medicine services are provided, for less than the cost of a single year of anticholinesterase therapy or a single month of lost productivity. The need and opportunity are thus present for making a fundamental change in the current approach to evaluating patients for dementia.

Journal Article↗