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The role of neuroimaging in the discovery of processing stages. A review.

In this contribution we show how neuroimaging methods can augment behavioural methods to discover processing stages. Event Related Brain Potentials (ERPs), Brain Electrical Source Analysis (BESA) and regional changes in cerebral blood flow (rCBF) do not necessarily require behavioural responses. With the aid of rCBF we are able to discover several cortical and subcortical brain systems (processors) active in selective attention and memory search tasks. BESA describes cortical activity with high temporal resolution in terms of a limited number of neural generators within these brain systems. The combination of behavioural methods and neuroimaging provides a picture of the functional architecture of the brain. The review is organized around three processors: the Visual, Cognitive and Manual Motor Processors.

Arousal↗

Neuroimaging.

Recent advances in neuroimaging have led to an increase in the types of studies possible in the field of cognitive neuroscience. Researchers are now using neuroimaging to enhance classic approaches, such as lesion-behavior studies, as well as provide information about normal functions at levels that were previously difficult to assess.

Animals↗

Functional neuroimaging of attention-deficit/hyperactivity disorder: a review and suggested future directions.

Over the past few decades, functional neuroimaging techniques have begun to provide unprecedented windows on the neurobiology of attention-deficit/hyperactivity disorder (ADHD) and the neural effects of medications used to treat the disorder. Convergent data from neuroimaging, neuropsychological, genetics, and neurochemical studies have implicated dysfunction of fronto-striatal structures (lateral prefrontal cortex, dorsal anterior cingulate cortex, caudate, and putamen) as likely contributing to the pathophysiology of ADHD. This review 1) provides an overview of the main imaging techniques being used to study ADHD; 2) discusses their relative strengths and weaknesses, highlighting how they can complement one another; 3) shows how the functional imaging literature, which has built on the structural imaging data, is now being used to test focused hypotheses regarding the neurobiological substrate of ADHD; and 4) suggests guidelines for improving future functional imaging studies. Although at present there are no accepted uses for functional imaging in diagnosing ADHD, this article mentions possible future clinical uses of imaging in ADHD.

Attention Deficit Disorder with Hyperactivity↗

Neurocircuitry models of posttraumatic stress disorder and extinction: human neuroimaging research--past, present, and future.

The prevailing neurocircuitry models of anxiety disorders have been amygdalocentric in form. The bases for such models have progressed from theoretical considerations, extrapolated from research in animals, to in vivo human imaging data. For example, one current model of posttraumatic stress disorder (PTSD) has been highly influenced by knowledge from rodent fear conditioning research. Given the phenomenological parallels between fear conditioning and the pathogenesis of PTSD, we have proposed that PTSD is characterized by exaggerated amygdala responses (subserving exaggerated acquisition of fear associations and expression of fear responses) and deficient frontal cortical function (mediating deficits in extinction and the capacity to suppress attention/response to trauma-related stimuli), as well as deficient hippocampal function (mediating deficits in appreciation of safe contexts and explicit learning/memory). Neuroimaging studies have yielded convergent findings in support of this model. However, to date, neuroimaging investigations of PTSD have not principally employed conditioning and extinction paradigms per se. The recent development of such imaging probes now sets the stage for directly testing hypotheses regarding the neural substrates of fear conditioning and extinction abnormalities in PTSD.

Amygdala↗

Neuroimaging of interval timing.

Exactly how the brain is able to measure the durations of events lasting from seconds to minutes while maintaining time-scale invariance remains largely a mystery. Neuroimaging studies are only now beginning to unravel the nature of interval timing and reveal whether different timing mechanisms are required for the perception and production of sub- and supra-second intervals that can be defined by different stimulus modalities. We here review the impact that neuroimaging studies have had on the field of timing and time perception and outline the major challenges that remain to be addressed before a physiologically realistic theory of interval timing can be established involving cortico-striatal circuits.

Animals↗

Neuroimaging studies of obsessive-compulsive disorder in adults and children.

Obsessive-compulsive disorder (OCD) is a severe, highly prevalent and chronically disabling disorder that usually emerges during childhood or adolescence. Neuroimaging studies play an important role in advancing our understanding of the pathophysiology of OCD and in developing neurocircuitry models of this psychiatric illness. This paper provided an updated, comprehensive review and analysis of the relevant literature on baseline functional and structural neuroimaging studies of OCD in both paediatric and adult patients. The neuroanatomical findings were presented in the context of two models: executive dysfunction, which implicates the dorsolateral prefrontal cortex, caudate nucleus, thalamus, and striatum; and modulatory control, which implicates the orbitofrontal and medial prefrontal cortex and the cingulate gyrus. Neuroanatomical findings were not consistent across all studies, and limitations were examined. Recommendations for future research directions and the implications of the results for improved treatment were explored.

Adolescent↗

Post-lesional cerebral reorganisation: evidence from functional neuroimaging and transcranial magnetic stimulation.

Reorganisation of cerebral representations has been hypothesised to underlie the recovery from ischaemic brain infarction. The mechanisms can be investigated non-invasively in the human brain using functional neuroimaging and transcranial magnetic stimulation (TMS). Functional neuroimaging showed that reorganisation is a dynamic process beginning after stroke manifestation. In the acute stage, the mismatch between a large perfusion deficit and a smaller area with impaired water diffusion signifies the brain tissue that potentially enables recovery subsequent to early reperfusion as in thrombolysis. Single-pulse TMS showed that the integrity of the cortico-spinal tract system was critical for motor recovery within the first four weeks, irrespective of a concomitant affection of the somatosensory system. Follow-up studies over several months revealed that ischaemia results in atrophy of brain tissue adjacent to and of brain areas remote from the infarct lesion. In patients with hemiparetic stroke activation of premotor cortical areas in both cerebral hemispheres was found to underlie recovery of finger movements with the affected hand. Paired-pulse TMS showed regression of perilesional inhibition as well as intracortical disinhibition of the motor cortex contralateral to the infarction as mechanisms related to recovery. Training strategies can employ post-lesional brain plasticity resulting in enhanced perilesional activations and modulation of large-scale bihemispheric circuits.

Animals↗

Neuroimaging in psychiatry: An update.

The introduction of neuroimaging techniques in the 1960s has revolutionized the study of the biology of psychiatric disorders with implications for psychiatric practice. These comprise structural (computerized axial tomography, magnetic resonance imaging) and functional (including neurochemical/neuropharmacological techniques such as single-photon emission computerized tomography, positron emission tomography, functional magnetic resonance imaging, and magnetic resonance spectroscopy) techniques. As a result, we now have a better understanding of the morbid anatomy, pathophysiology, and chemical pathology of organic brain disease, schizophrenia, addictions, and affective disorders. This selective review will focus on recent advances in the use and application of neuroimaging techniques in the study of addictions, schizophrenia, and depression. Reference will be made to studies conducted in the United Arab Emirates on Arab patients with depression, schizophrenia, and alcohol dependence. The refinement of these techniques and their application in the study of psychiatric disorders will redefine these disorders, promising their deconstruction and the development of novel and more specific treatments.

Antidepressive Agents↗

Neuroimaging and fetal alcohol spectrum disorders.

Heavy prenatal alcohol exposure causes permanent structural alterations to the brain and can lead to numerous cognitive and behavioral outcomes. Consistent with many of the neuropsychological and behavioral deficits that have been reported, neuroimaging studies reveal a pattern of structural abnormalities associated with prenatal alcohol exposure. This chapter systematically reviews structural anomalies by brain region, identifying cognitive and behavioral correlates when relevant. The consensus shows that in addition to the overall reduction of brain size, prominent brain shape abnormalities have been observed, with narrowing in the parietal region and reduced brain growth in portions of the frontal lobe. Commensurating with these anomalies, volumetric and tissue density findings cite disproportionate reductions in the parietal lobe, cerebellar vermis, corpus callosum, and the caudate nucleus, suggesting that certain areas of the brain may be especially vulnerable to prenatal alcohol exposure. In sum, neuroimaging techniques have greatly advanced our understanding of brain-behavior relationships in fetal alcohol spectrum disorders (FASD), and hopefully will lead to improved diagnosis and treatment options for those affected by prenatal exposure to alcohol.

Brain↗

Volumetric neuroimaging and low-dose early-life exposures: loose coupling of pathogenesis-brain-behavior links.

The interface of developmental neuroimaging with developmental neurotoxicology can, broadly speaking, address two complementary concerns. The first is to study the impact of specific exposures on brain development. The second is to study known neurobehavioral disorders with an eye to discerning toxicological contributions to pathogenesis. Pathogenesis targets brain based upon physical properties (receptors, growth factors, etc.) while behavior is modulated by regional and neural systems alterations. The distribution of pathogenesis-brain relationships overlaps only partially with that of brain-behavior relationships. The goal of this paper is to highlight methodological issues involved in designing and interpreting volumetric neuroimaging studies in the light of this loose coupling.

Behavior↗

Relating neuronal dynamics for auditory object processing to neuroimaging activity: a computational modeling and an fMRI study.

We investigated the neural basis of auditory object processing in the cerebral cortex by combining neural modeling and functional neuroimaging. We developed a large-scale, neurobiologically realistic network model of auditory pattern recognition that relates the neuronal dynamics of cortical auditory processing of frequency modulated (FM) sweeps to functional neuroimaging data of the type obtained using PET and fMRI. Areas included in the model extend from primary auditory to prefrontal cortex. The electrical activities of the neuronal units of the model were constrained to agree with data from the neurophysiological literature regarding the perception of FM sweeps. We also conducted an fMRI experiment using stimuli and tasks similar to those used in our simulations. The integrated synaptic activity of the neuronal units in each region of the model, convolved with a hemodynamic response function, was used as a correlate of the simulated fMRI activity, and generally agreed with the experimentally observed fMRI data in the brain areas corresponding to the regions of the model. Our results demonstrate that the model is capable of exhibiting the salient features of both electrophysiological neuronal activities and fMRI values that are in agreement with empirically observed data. These findings provide support for our hypotheses concerning how auditory objects are processed by primate neocortex.

Adult↗

Neuroimaging studies of shifting attention: a meta-analysis.

This paper reports a meta-analysis of neuroimaging studies of attention shifting and executive processes in working memory. We analyzed peak activation coordinates from 31 fMRI and PET studies of five types of shifting using kernel-based methods [NeuroImage 19 (2003) 513]. Analyses collapsing across different types of shifting gave more consistent results overall than analysis within individual types, suggesting a commonality across types of shifting. These areas shared substantial, significant overlap with regions derived from kernel-based analyses of reported peaks for executive processes in working memory (WM). The results suggest that there is a common set of brain regions active in diverse executive control operations, including medial prefrontal, superior and inferior parietal, medial parietal, and premotor cortices. However, within several of these regions, different types of switching produced spatially discriminable activation foci. Precise locations of meta analysis-derived regions from both attention shifting and working memory are defined electronically and may be used as regions of interest in future studies.

Arousal↗

Partial least squares analysis of neuroimaging data: applications and advances.

Partial least squares (PLS) analysis has been used to characterize distributed signals measured by neuroimaging methods like positron emission tomography (PET), functional magnetic resonance imaging (fMRI), event-related potentials (ERP) and magnetoencephalography (MEG). In the application to PET, it has been used to extract activity patterns differentiating cognitive tasks, patterns relating distributed activity to behavior, and to describe large-scale interregional interactions or functional connections. This paper reviews the more recent extension of PLS to the analysis of spatiotemporal patterns present in fMRI, ERP, and MEG data. We present a basic mathematical description of PLS and discuss the statistical assessment using permutation testing and bootstrap resampling. These two resampling methods provide complementary information of the statistical strength of the extracted activity patterns (permutation test) and the reliability of regional contributions to the patterns (bootstrap resampling). Simulated ERP data are used to guide the basic interpretation of spatiotemporal PLS results, and examples from empirical ERP and fMRI data sets are used for further illustration. We conclude with a discussion of some caveats in the use of PLS, including nonlinearities, nonorthogonality, and interpretation difficulties. We further discuss its role as an important tool in a pluralistic analytic approach to neuroimaging.

Adult↗

Wavelet variance components in image space for spatiotemporal neuroimaging data.

Neuroimaging studies place great emphasis on not only the estimation but also the standard error estimates of underlying parameters derived from a temporal model. This allows inferences to be made about the signal estimates and resulting conclusions to be drawn about the underlying data. It can often be advantageous to interrogate temporal models after spatial transformation of the data into the wavelet domain. Wavelet bases provide a multiresolution decomposition of the spatial data dimension and an ensuing reduction in spatial correlation. However, widespread acceptance of these wavelet techniques has been hampered by the limited ability to reconstruct both parametric and error estimates into the image domain after analysis of temporal models in the wavelet domain. This paper introduces a derivation and a fast implementation of a method for the calculation of the variance of the parametric images obtained from wavelet filters. The technique is proposed for a class of estimators that have been shown to be useful in neuroimaging studies. The techniques are demonstrated for both functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) data sets.

Analysis of Variance↗

Control of end-tidal PCO2 reduces middle cerebral artery blood velocity variability: implications for physiological neuroimaging.

Breath-by-breath variability of the end-tidal partial pressure of CO2 (Pet(CO2)) has been shown to be associated with cerebral blood flow (CBF) fluctuations. These fluctuations can impact neuroimaging techniques that depend on cerebrovascular blood flow. We hypothesized that controlling Pet(CO2) would reduce CBF variability. Dynamic end-tidal forcing was used to control Pet(CO2) at 1.5 mm Hg above the resting level and to hold the end-tidal partial pressure of oxygen (Pet(O2)) at the resting level. Peak blood velocity in the middle cerebral artery (MCA) was measured by transcranial Doppler ultrasound (TCD) as an index of CBF. Blood velocity parameters and timing features were determined on each waveform and the variance of these parameters was compared between Normal (air breathing) and Forcing (end-tidal gas control) sessions. The variability of all velocity parameters was significantly reduced in the Forcing session. In particular, the variability of the average velocity over the cardiac cycle was decreased by 18.2% (P < 0.001). For the most part, the variability of the timing parameters was unchanged. Thus, we conclude that controlling Pet(CO2) is effective in reducing CBF variability, which would have important implications for physiologic neuroimaging.

Adult↗

Determining significant connectivity by 4D spatiotemporal wavelet packet resampling of functional neuroimaging data.

An active area of neuroimaging research involves examining functional relationships between spatially remote brain regions. When determining whether two brain regions exhibit significant correlation due to true functional connectivity, one must account for the background spatial correlation inherent in neuroimaging data. We define background correlation as spatiotemporal correlation in the data caused by factors other than neurophysiologically based functional associations such as scanner induced correlations and image preprocessing. We develop a 4D spatiotemporal wavelet packet resampling method which generates surrogate data that preserves only the average background spatial correlation within an axial slice, across axial slices, and through each voxel time series, while excluding the specific correlations due to true functional relationships. We also extend an amplitude adjustment algorithm which adjusts our surrogate data to closely match the amplitude distribution of the original data. Our method improves upon existing wavelet-based methods and extends them to 4D. We apply our resampling technique to determine significant functional connectivity from resting state and motor task fMRI datasets.

Adult↗

What have we learned about cognitive development from neuroimaging?

Changes in many domains of cognition occur with development. In this paper, we discuss neuroimaging approaches to understanding these changes at a neural level. We highlight how modern imaging methods such as functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) are being used to examine how cognitive development is supported by the maturation of the brain. Some reports suggest developmental changes in patterns of brain activity appear to involve a shift from diffuse to more focal activation, likely representing a fine-tuning of relevant neural systems with experience. One of the challenges in investigating the interplay between cognitive development and maturation of the brain is to separate the contributions of neural changes specific to development and learning. Examples are given from the developmental neuroimaging literature. The focus is on the development of cognitive control, as the protracted developmental course of this ability into adolescence raises key issues. Finally, the relevance of normative studies for understanding neural and cognitive changes in developmental disorders is discussed.

Adolescent↗

Correlation of surgical outcome with neuroimaging findings in periocular lymphangiomas.

PURPOSE: To evaluate the results of surgical intervention and rate of recurrence in patients with periocular lymphangioma with respect to the anatomic extent of tumor involvement determined by neuroimaging studies. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Eighteen patients with periocular lymphangioma. METHODS: All patients underwent complete ocular examination and preoperative orbital imaging with either computed tomography or magnetic resonance imaging. Tumor location in the orbit was defined as intraconal, extraconal, or diffuse. For extraconal cases, a further classification was made as intraorbital, extraorbital, or mixed. All patients underwent orbitotomy via either a conjunctival or a skin-crease approach, depending on the tumor location. The indications for surgical intervention were varied and included preservation of visual function or cosmetic appearance in some cases and exploration of an unidentified orbital mass in others. The diagnosis of lymphangioma was established histopathologically in each case. Cases that showed recurrence at follow-up also were treated using an orbitotomy approach. MAIN OUTCOME MEASURES: Anatomic extent of tumor location in the orbit as determined by neuroimaging studies, completeness of surgical excision, pathological findings, recurrence, and visual outcome. RESULTS: Seven patients had extraconal tumors; 4, intraconal tumors, and 7, diffuse tumors. Of the patients with extraconal tumors, 4 had mixed lymphangioma and 3 had extraorbital lymphangioma. In 5 cases, the extraconal lymphangiomas were totally resected. In the remaining 13 cases with diffuse, intraconal, and infiltrating extraconal lymphangiomas, the tumors were treated with a subtotal resection procedure. At a mean follow-up of 29.4 months (range: 3-77), 2 patients with diffuse tumors developed 4 recurrences and underwent further surgical intervention for 3 recurrent events. The mean interval between treatment and recurrence was 16 months (range: 12-20). Two patients experienced decreased visual acuity due to compressive optic neuropathy in one case and operative damage in the other. CONCLUSIONS: Surgically well-delineated extraconal lymphangiomas can be resected totally with no clinical recurrence at short-term follow-up. Although intraconal, diffuse, and some extraconal lymphangiomas were treated with a subtotal resection procedure, many such cases did not demonstrate recurrence. These results are encouraging because they demonstrate that many periocular lymphangiomas can be treated successfully with good visual outcome and satisfactory cosmesis.

Adolescent↗