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Right hemispheric dysfunction in a case of pure progressive aphemia: fusion of multimodal neuroimaging.

This article describes the unusual case of a 60-year-old woman suffering from pure progressive aphemia. The fusion of multimodal neuroimaging (MRI, perfusion SPECT) implicated the right frontal lobe, especially the inferior frontal gyrus. This area also showed the greatest functional MRI activation during the performance of a covert phonemic fluency task. Results are discussed in terms of bihemispheric language representation. The fusion of three sets of neuroimages has aided in the interpretation of the patient's cognitive brain dysfunction.

Aphasia, Broca↗

Review of longitudinal functional neuroimaging studies of drug treatments in patients with schizophrenia.

We systematically reviewed twenty-one functional neuroimaging studies that used longitudinal designs to investigate the effects of medication treatments on brain functioning among patients with schizophrenia. The studies reviewed were comprised of functional magnetic resonance imaging and positron emission tomography research using a baseline and at least one follow-up. The present review summarizes the different effects of medication and disease status on brain function, with attention to functional normalization, specific drug effects, and comparisons of typical versus atypical antipsychotics. Particular emphasis is given to methodological limitations in the existing literature, including lack of reliability data, clinical heterogeneity among studies, and inadequate study designs and statistics. Suggestions are made for improving future longitudinal neuroimaging studies of treatment effects in schizophrenia.

Antipsychotic Agents↗

Can cognitive processes be inferred from neuroimaging data?

There is much interest currently in using functional neuroimaging techniques to understand better the nature of cognition. One particular practice that has become common is 'reverse inference', by which the engagement of a particular cognitive process is inferred from the activation of a particular brain region. Such inferences are not deductively valid, but can still provide some information. Using a Bayesian analysis of the BrainMap neuroimaging database, I characterize the amount of additional evidence in favor of the engagement of a cognitive process that can be offered by a reverse inference. Its usefulness is particularly limited by the selectivity of activation in the region of interest. I argue that cognitive neuroscientists should be circumspect in the use of reverse inference, particularly when selectivity of the region in question cannot be established or is known to be weak.

Brain↗

Forward inference using functional neuroimaging: dissociations versus associations.

Many people are excited by functional neuroimaging as a new tool for cognitive science; many others are sceptical. In this opinion article, I describe a 'forward inference' that one can make from patterns of brain activity to distinguish between cognitive theories. I give an example of forward inferences in research on recognition memory, and outline some statistical criteria for a 'qualitative difference' in brain activity. Forward inferences resemble the dissociation logic long-used in behavioural studies of healthy and brain-damaged people, although I argue that dissociations in neuroimaging data can go beyond behavioural dissociations. Nonetheless, forward inferences are only as good as the cognitive theories to which they pertain, and are most valuable in conjunction with other types of inference.

Association↗

Mapping form and function in the human brain: the emerging field of functional neuroimaging in cortical malformations.

Malformations of cortical development (MCDs) are increasingly being recognized as a common cause of epilepsy in cases previously felt to be cryptogenic. MCDs occur when the normal process of cerebral cortical development is disrupted, and include disorders of neuronal proliferation, migration, and organization. Many have a genetic basis and the genes responsible for some MCDs have been identified. MCDs represent a unique and valuable substrate in functional brain mapping studies, since as developmental lesions they provide complementary information to studies performed on patients with acquired brain lesions. In recent years an increasing number of functional neuroimaging methods, including positron emission tomography, single photon emission computed tomography, magnetic resonance spectroscopy, and functional magnetic resonance imaging, have been applied to patients with MCDs. In this review we highlight some of the prominent findings in this emerging field by presenting the functional neuroimaging characteristics of selected MCDs.

Brain Diseases↗

Neuroimaging in chronic fatigue syndrome.

The diagnosis of chronic fatigue syndrome (CFS) is made difficult by the absence of specific biomedical markers, and depends primarily on determining whether subjective information provided by the patient meets the clinical case definition of this syndrome. Reported cognitive difficulties and/or complaints of headache may instigate referral for brain imaging. This article will discuss the value of neuroimaging in evaluating CFS, specifically reviewing studies that (1) used static magnetic resonance imaging (MRI) to assess structural abnormalities; and (2) assessed regional cerebral blood flow (rCBF) via detection of Tc-99m hexamethylpropyl-eneamine oxime distribution by single-photon emission computed tomography (SPECT). Future research design considerations are explored including (1) the utilization of positron emission tomography (PET) and other emerging neuroimaging technologies; and (2) methodological concerns, i.e., the influence of psychopathology (such as depression) and neurologic disease (such as multiple sclerosis) as possible confounding factors.

Fatigue Syndrome, Chronic↗

Atypical features prompting neuroimaging in acute optic neuropathy in adults.

BACKGROUND: Acute optic neuropathy due to an intracranial lesion may masquerade as optic neuritis or nonarteritic anterior ischemic optic neuropathy (NAION). We reviewed the records of patients who presented with acute unilateral optic neuropathy that was initially diagnosed as optic neuritis or NAION but who ultimately proved to have an underlying structural lesion. METHODS: Retrospective observational case series. We reviewed the records of patients with the initial diagnosis of optic neuritis or NAION in whom the diagnosis was changed to an intracranial etiology at four tertiary care neuro-ophthalmology centres between 1995 and 1998. RESULTS: Eight cases were identified in which atypical features prompted further investigation, including neuroimaging, leading to the diagnosis of an intracranial etiology for the optic neuropathy. Five patients were discovered to have neoplasms (a tuberculum sellae meningioma in two cases, an optic nerve sheath meningioma in two cases and a metastatic lesion in one case), and three patients had intracranial sarcoidosis. Atypical features for optic neuritis included a progressive course, absence of pain, optic atrophy at presentation, lack of significant visual improvement and age over 40 years. For NAION, the atypical features included progressive course, optic atrophy on presentation, absence of vasculopathic risk factors and preceding transient visual loss. INTERPRETATION: Clinicians should be aware that patients with intracranial lesions may present with acute optic neuropathy mimicking optic neuritis or NAION and that certain atypical features should warrant consideration for neuroimaging.

Acute Disease↗

Neuroimaging studies of speech an overview of techniques and methodological approaches.

UNLABELLED: Over the past two decades, there has been an explosion in the use of imaging technology to study the structure and function of the human brain. The purpose of this article is to explore how functional neuroimaging has been applied to the study of speech production. This article begins with a brief review of neuroimaging methods and limitations. Then, two approaches that can be used to study the brain areas that support speech production are illustrated. The first approach is based upon comparisons across different types of language production tasks; the second approach is based upon comparing the effects of different types of stimuli within a single task. Results obtained using these approaches will be used to dissociate the contributions of different brain regions involved in speech production. For example, evidence will be presented that Broca's area contributes to phonological encoding, whereas motor cortex, the supplementary motor area (SMA), and the cerebellum support phonetic encoding and articulation. LEARNING OUTCOMES: As a result of this activity, the participant will be able to describe basic methods for conducting a positron emission tomography study and a functional magnetic resonance imaging study. The participant will also be introduced to two approaches for fractionating the brain regions involved in speech production: (1) comparisons between tasks, and (2) manipulations of stimulus materials. Finally, the participant will be able to summarize a cognitive model of the components of speech production that will be introduced, and potential mappings between these components and particular brain regions will be discussed.

Brain↗

Emergence of optic pathway gliomas in children with neurofibromatosis type 1 after normal neuroimaging results.

We report the appearance of gliomas of the optic nerve or chiasm in four young children with neurofibromatosis type 1 whose previous neuroimaging studies showed no abnormalities; the age range of the children was 1 year 8 months to 5 years 9 months at the time the tumors were detected. Normal neuroimaging findings in an infant or young child with neurofibromatosis type 1 does not provide assurance that the optic nerves and chiasm will remain healthy.

Child, Preschool↗

Autosomal dominant early onset dementia and leukoencephalopathy in a Japanese family: clinical, neuroimaging and genetic studies.

We report here the results of clinical, neuroimaging and genetic studies of autosomal dominant dementia and leukoencephalopathy in a Japanese family. Twenty-two individuals in this family were examined clinically (17 living, 5 deceased), neuroradiologically and genetically (16 of 17 living members). Ten (5 deceased) of 22 individuals had early onset dementia (age of onset: 45.2 +/- 12.1 years on average) and four of them had multiple white matter lesions and brain atrophy on brain MRI without history of brain ischemic attack. Another four individuals had abnormal white matter lesions on brain MRI without dementia. Linkage studies for chromosome 1q31-42, 14q24.3 and 21q21 responsible for Alzheimer's disease, chromosome 19p13.1-13.2 for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and chromosome 3 for familial non-specific dementia suggested no specific haplotypes cosegregated with the disease. Apo E genotypes were E2/2 and E2/3 in this family. Clinical, neuroimaging and genetic studies revealed that the disease in this family was distinguished from known familial dementia. This is the first report of a large Japanese family with autosomal dominant early onset dementia and leukoencephalopathy.

Adult↗

Functional neuroimaging.

Functional neuroimaging represents an area of brain imaging that has undergone tremendous advancements in the last decade. It is now possible to design experiments that elucidate the functional interplay between brain regions that give rise to specific human cognitive processes. Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) form the core technologies that have allowed such studies. This article reviews the basis of these techniques, their strengths and limitations, the underlying neurophysiology, and the future of functional neuroimaging.

Brain↗

A combined neuropsychological and neuroimaging study of topographical and non-verbal memory in semantic dementia.

A combined neuropsychological and neuroimaging investigation was carried out on a patient (O.I.) with semantic dementia who had asymmetrical temporal lobe atrophy, greater on the left. His performance on tests of verbal memory was gravely impaired. Similarly, his visual memory as indexed by recognition of unfamiliar faces was impaired. By contrast, his recognition memory for topographical memoranda (e.g. buildings, landscapes) and ability to find his way around was preserved. In order to identify the neural substrates supporting the preserved recognition of static topographical memoranda, O.I. was scanned using positron emission tomography (PET) during the encoding and recognition of building and landscape stimuli. In common with control subjects, during encoding O.I. activated parahippocampal cortex bilaterally, along with bilateral temporo-parietal, retrosplenial and left frontal cortices. During recognition, both patient and controls activated right parahippocampal, right superior parietal and right frontal cortices. Notably, control subjects, but not O.I., also activated at encoding the precuneus and at recognition the retrosplenial cortex. This allows the conclusion that these two areas while involved may not be necessary for topographical memory. Interestingly, the patient also activated regions that were not evident in control subjects both during encoding and recognition. These additional areas of activation may be necessary in a compensatory role. Overall, these data represent the first reported assessment of the functional integrity of degenerating brain tissue and its contribution to preserved topographical memory. The combination of the neuropsychological and neuroimaging approaches may provide insights into the functional-anatomy of memory while having clinical utility for the assessment of residual brain tissue.

Aged↗

Hypotheses from functional neuroimaging studies.

Functional neuroimaging, especially positron emission tomography (PET) using various tracers, provided new insights into the pathophysiology of West syndrome in the past decade. Glucose PET studies revealed a unique corticosubcortical circuitry assumed to be involved in the age-dependent generalization of seizure activity leading to symmetric spasms. The findings strongly suggested that cortical abnormalities, mostly consistent with dysplastic lesions or diffuse cortical dysfunction due to an underlying systemic disorder, trigger brain stem nuclei and activate basal ganglia bilaterally. PET is also able to investigate developmental abnormalities of serotonergic and GABAergic neurotransmitter systems in vivo. Involvement of these systems in the pathophysiology of infantile spasms is strongly supported by animal data and can be further elucidated by future PET studies. In addition, the development of new PET tracers (such as neurotracers for imaging NMDA receptors) could help further clarify the role of altered neurotransmission in generation of spasms. This review of the most important functional neuroimaging findings illustrates how human PET and single photon emission computed tomography data help answer basic questions regarding the pathomechanisms involved in this often devastating condition and how these findings might facilitate development of a useful animal model of West syndrome.

Brain Diseases↗

Functional neuroimaging during altered states of consciousness: how and what do we measure?

The emergence of functional neuroimaging has extended the doctrine of functional specificity of the brain beyond the primary stages of perception, language, and motor systems to high-level cognitive, personality, and affective systems. This chapter applies functional magnetic resonance imaging to another high-level realm of cognition and neurology to characterize cortical function in patients with disorders of consciousness. At first pass, this objective appears paradoxical because conventional investigations of a cognitive process require experimental manipulation. For example, to map the location of language-sensitive cortex, a language-related task is performed according to a temporal sequence that alternates the task with rest (no-task) periods. Application of this approach to the study of consciousness would require that levels of consciousness be similarly varied, this is an unlikely technique. Alternatively, another strategy is presented here where the focus is on functional brain activity elicited during various passive stimulations of patients who are minimally conscious. Comparisons between patients with altered states of consciousness due to brain injury and healthy subjects may be employed to infer readiness and potential to sustain awareness. As if a behavioral microscope, fMRI enables a view of occluded neural processes to inform medical practitioners about the health of the neurocircuity-mediating cognitive processes. An underlying point of view is that assessment of recovery potential can be enhanced by neuroimaging techniques that reveal the status of residual systems specialized for essential cognitive and volitional tasks for each patient. Thus, development of imaging techniques that assess the functional status of individual unresponsive patients is a primary goal. The structural integrity of injured brains is often compromised depending on the specific traumatic event, and, therefore, images cannot be grouped across patients, as is the standard practice for investigations of cognitive systems in healthy volunteers. This chapter addresses these challenges and discusses technique adaptations associated with passive stimulation, paradigm selection, and individual patient assessments, where there is "zero tolerance for error," and confidence in the results must meet the highest standards of care. Similar adaptations have been previously developed for the purpose of personalized planning for neurosurgical procedures by mapping the locations of essential functional systems such as language, perception, and sensory-motor functions for each individual patient. Rather than addressing the question of "how does the brain do consciousness" with these techniques, this chapter presents methods for assessment of neurocognitive health in specific patients with disorders of consciousness.

Attention↗

A review of MRI pulse sequences and techniques in neuroimaging.

BACKGROUND: The unmatched soft tissue contrast provided by magnetic resonance imaging (MRI) has made it the modality of choice for many neuroimaging examinations. The fact that signal intensity in MRI depends on many parameters, including spin-lattice and spin-spin relaxation times, proton density, and velocity, makes it possible to highlight various pathologies by appropriate choice of pulse sequences and pulse sequence parameters. It is somewhat overwhelming however, to filter through various pulse sequences and parameters in order to understand how their selection affects image contrast. This brief review is intended to highlight common pulse sequences and parameters as well as introduce new techniques currently being released for clinical use. MATERIALS: Basic pulse sequences are described and the influence of the acquisition parameters on image contrast are illustrated. Such basic sequences include the ubiquitous spin echo, fast spin echo, and gradient echo sequences. Specialized techniques for fat suppression and magnetic resonance angiography are also presented. Currently approved contrast agents for use in MRI are briefly reviewed, and various advanced pulse sequences, such as those for diffusion and magnetization transfer contrast imaging, are briefly outlined. RESULTS: The utility of basic and advanced pulse sequences are demonstrated by clinical examples and images of normal brain and spine. New sequences and techniques are briefly outlined with regard to their potential for improving neuroimaging examinations. CONCLUSIONS: This brief review outlines how the choice of pulse sequence and acquisition parameters influences the resulting image contrast for a variety of basic and advanced imaging techniques.

Humans↗

Relationships between cognition and structural neuroimaging findings in adults with human immunodeficiency virus type-1.

Infection of the central nervous system with human immunodeficiency virus type-1 (HIV) is associated with cognitive impairments that range from mild cognitive and motor difficulties to dementia. Structural neuroimaging abnormalities are also common in HIV-infected patients both with and without cognitive disturbances. The most common abnormalities include high signal intensities in the white matter and atrophy. Research over the past 12 years has helped define the relationship between these neuroimaging abnormalities and the manifestation of cognitive disturbance in HIV. In the present paper, we provide a synopsis of these studies and report the current state of the literature. Our review revealed that atrophy of the caudate nucleus is most consistently associated with cognitive impairment in HIV. The current literature does not support a strong relationship between cortical atrophy or white matter abnormalities and cognitive dysfunction in this population, though methodological issues may have influenced the results. Suggestions for study design and new research directions are provided.

Acquired Immunodeficiency Syndrome↗

[Pediatric neuroimaging emergencies].

The notion of emergency with regards to pediatric neuroimaging requires a strong knowledge of clinical indications. In children under 2 years of age, head trauma requires a CT scan in case of repeated or prolonged or rapidly increasing vomiting, focal signs, loss of consciousness, unusual behavior, seizures, clinical signs of skull fracture or polytrauma. The "shaken baby syndrome" is usually suspected in case of loss of consciousness or seizures before 8 months of age. The hematomas that are observed are subdural in location, diffuse and deeply located. Imaging is only mandatory for headache suggesting underlying space occupying lesion: permanent or increasing pain, nocturnal headache, headache during postural changes or efforts, associated to seizures or abnormal neurological examination. No imaging is indicated in case of first epileptic seizure associated to normal neurological examination and without any particular context. The presence of trauma, intracranial hypertension, persisting disturbances of consciousness or associated focal sign necessitates urgent neuroimaging. No imaging is indicated in case of typical febrile seizures, i.e. generalized, brief and occurring between 1 and 5 years of age. Spinal cord symptoms require immediate MRI evaluation. The most frequent tumor is neuroblastoma. In the absence of spinal tumor, brain abnormalities must be excluded (inflammatory disease). In neonates, CT scan or MRI must be readily performed in case of seizures or loss of consciousness to exclude ischemic, traumatic or infectious lesions.

Age Factors↗

The retrosplenial cortex and emotion: new insights from functional neuroimaging of the human brain.

Little is known about the function of the retrosplenial cortex and until recently, there was no evidence that it had any involvement in emotional processes. Surprisingly, recent functional neuroimaging studies show that the retrosplenial cortex is consistently activated by emotionally salient words. A review of the functional neuroimaging literature reveals a previously overlooked pattern of observations: the retrosplenial cortex is the cortical region most consistently activated by emotionally salient stimuli. Evidence that this region is also involved in episodic memory suggests that it might have a role in the interaction between emotion and episodic memory. Recognition that the retrosplenial cortex has a prominent role in the processing of emotionally salient stimuli invites further studies to define its specific functions and its interactions with other emotion-related brain regions.

Brain Mapping↗