Functional neuroimaging of the olfactory system in humans.

Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have begun to provide unique information regarding the neural underpinnings of olfactory functioning in humans. We review the relative strengths and weaknesses of PET and fMRI techniques for studying olfaction. We then review PET and fMRI studies relating to the olfactory functions of the pyriform cortex, orbitofrontal cortex, amygdala and the entorhinal/hippocampal region. A pixelwise correlational analysis of PET data is also presented in order to clarify the relationship between blood flow in the medial temporal lobes and psychoperceptual variables.     

Methods on Skull Stripping of MRI Head Scan Images—a Review

The high resolution magnetic resonance (MR) brain images contain some non-brain tissues such as skin, fat, muscle, neck, and eye balls compared to the functional images namely positron emission tomography (PET), single photon emission computed tomography (SPECT), and functional magnetic resonance imaging (fMRI) which usually contain relatively less non-brain tissues. The presence of these non-brain tissues is considered as a major obstacle for automatic brain image segmentation and analysis techniques. Therefore, quantitative morphometric studies of MR brain images often require a preliminary processing to isolate the brain from extra-cranial or non-brain tissues, commonly referred to as skull stripping. This paper describes the available methods on skull stripping and an exploratory review of recent literature on the existing skull stripping methods.     

Reliability and Validity of Functional Neuroimaging Techniques for Identifying Language-Critical Areas in Children and Adults

Advances in neuroimaging technologies over the last 15 years have prompted their relatively widespread use in the study of brain mechanisms supporting language function in children and adults. We reviewed reliability and external validity studies of 3 of the most common functional imaging methods, functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and positron emission tomography (PET). Although reliability and validity reports for fMRI are generally quite favorable, significant variability was found across studies with respect to methodology, preventing in some cases either the assessment of the reliability of individual datasets, or cross-study comparisons. Reliability and validity reports of MEG are strong, yet methodological questions regarding optimal modeling techniques remain. PET investigators report good concordance of language maps with data from more invasive brain mapping techniques, but its use of radioactive tracers and poorer spatial and temporal resolution make it the least optimal of the 3 methods for language mapping. Investigations of the cortical networks supporting language function during development and into adulthood should be viewed in the context of the validity and reliability of the methods used, with careful attention to details regarding the methodologies employed in the acquisition and analysis of statistical maps.     

Reliability and validity of functional neuroimaging techniques for identifying language-critical areas in children and adults

Advances in neuroimaging technologies over the last 15 years have prompted their relatively widespread use in the study of brain mechanisms supporting language function in children and adults. We reviewed reliability and external validity studies of 3 of the most common functional imaging methods, functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and positron emission tomography (PET). Although reliability and validity reports for fMRI are generally quite favorable, significant variability was found across studies with respect to methodology, preventing in some cases either the assessment of the reliability of individual datasets, or cross-study comparisons. Reliability and validity reports of MEG are strong, yet methodological questions regarding optimal modeling techniques remain. PET investigators report good concordance of language maps with data from more invasive brain mapping techniques, but its use of radioactive tracers and poorer spatial and temporal resolution make it the least optimal of the 3 methods for language mapping. Investigations of the cortical networks supporting language function during development and into adulthood should be viewed in the context of the validity and reliability of the methods used, with careful attention to details regarding the methodologies employed in the acquisition and analysis of statistical maps.     

What does neuroimaging tell us about the role of prefrontal cortex in memory retrieval?

The past five years have seen an outpouring of neuroimaging studies of memory — using both positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). These studies have convincingly demonstrated that neuroimaging can be used to study the functional anatomy of normal human memory and that neuroimaging can precisely localize memory related brain activations within small areas of cortex. As one illustration of the application of neuroimaging in the study of memory, this review shows how several laboratories have produced data that converge on the notion that specific areas in the prefrontal cortex are active during long-term memory retrieval. Moreover, the data further suggest that distinct prefrontal brain areas might make differential contributions to different kinds of long-term memory retrieval.     

Recent advances in investigations into brain function and its clinical application

Recent advances in investigations into brain function and its clinical application are described. The investigations were divided into three method groups consisting of the examinations of; 1) brain electric activity; 2) imaging techniques on activated brain tissue; and 3) collation of the metabolic information on the area of brain focused on. The first group included electroencephalogram(EEG), dipole tracing(DT) and magnetoencephalogram(MEG). The second one, single photon emission computed tomography(SPECT), positron emission tomography(PET) and functional magnetic resonance imaging(fMRI), and the third, magnetic resonance spectrometry(MRS). Here I overview these examinations and report some cases diagnosed with these technologies.     

Functional neuroimaging findings in healthy middle-aged adults at risk of Alzheimer’s disease

It is well established that the neurodegenerative process of Alzheimer's disease (AD) begins many years before symptom onset. This preclinical phase provides a crucial time-window for therapeutic intervention, though this requires biomarkers that could evaluate the efficacy of future disease-modification treatments in asymptomatic individuals. The last decade has witnessed a proliferation of studies characterizing the temporal sequence of the earliest functional and structural brain imaging changes in AD. These efforts have focused on studying individuals who are highly vulnerable to develop AD, such as those with familial genetic mutations, susceptibility genes (i.e. apolipoprotein epsilon-4 allele), and/or a positive family history of AD. In this paper, we review the rapidly growing literature of functional imaging changes in cognitively intact individuals who are middle-aged: positron emission tomography (PET) studies of amyloid deposition, glucose metabolism, as well as arterial spin labeling (ASL), task-dependent, resting-state functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) studies. The prevailing evidence points to early brain functional changes in the relative absence of cognitive impairment and structural atrophy, although there is marked variability in the directionality of the changes, which could, in turn, be related to antagonistic pleiotropy early in life. A common theme across studies relates to the spatial extent of these changes, most of which overlap with brain regions that are implicated in established AD. Notwithstanding several methodological caveats, functional imaging techniques could be preferentially sensitive to the earliest events of AD pathology prior to macroscopic grey matter loss and clinical manifestations of AD. We conclude that while these techniques have great potential to serve as biomarkers to identify at-risk individuals, more longitudinal studies with greater sample size and robust correction for multiple comparisons are still warranted to establish their utility.     

Rodent functional and anatomical imaging of pain

Human brain imaging has provided much information about pain processing and pain modulation, but brain imaging in rodents can provide information not attainable in human studies. First, the short lifespan of rats and mice, as well as the ability to have homogenous genetics and environments, allows for longitudinal studies of the effects of chronic pain on the brain. Second, brain imaging in animals allows for the testing of central actions of novel pharmacological and nonpharmacological analgesics before they can be tested in humans. The two most commonly used brain imaging methods in rodents are magnetic resonance imaging (MRI) and positron emission tomography (PET). MRI provides better spatial and temporal resolution than PET, but PET allows for the imaging of neurotransmitters and non-neuronal cells, such as astrocytes, in addition to functional imaging. One problem with rodent brain imaging involves methods for keeping the subject still in the scanner. Both anesthetic agents and restraint techniques have potential confounds. Some PET methods allow for tracer uptake before the animal is anesthetized, but imaging a moving animal also has potential confounds. Despite the challenges associated with the various techniques, the 31 studies using either functional MRI or PET to image pain processing in rodents have yielded surprisingly consistent results, with brain regions commonly activated in human pain imaging studies (somatosensory cortex, cingulate cortex, thalamus) also being activated in the majority of these studies. Pharmacological imaging in rodents shows overlapping activation patterns with pain and opiate analgesics, similar to what is found in humans. Despite the many structural imaging studies in human chronic pain patients, only one study has been performed in rodents, but that study confirmed human findings of decreased cortical thickness associated with chronic pain. Future directions in rodent pain imaging include miniaturized PET for the freely moving animal, as well as new MRI techniques that enable ongoing chronic pain imaging.     

Positron Emission Tomography Molecular Imaging of Dopaminergic System in Drug Addiction

Dopamine (DA) is involved in drug reinforcement, but its role in drug addiction remains unclear. Positron emission tomography (PET) is the first technology used for the direct measurement of components of the dopaminergic system in the living human brain. In this article, we reviewed the major findings of PET imaging studies on the involvement of DA in drug addiction, especially in heroin addiction. Furthermore, we summarized PET radiotracers that have been used to study the role of DA in drug addiction. To investigate presynaptic function in drug addiction, PET tracers have been developed to measure DA synthesis and transport. For the investigation of postsynaptic function, several radioligands targeting dopamine one (D1) receptor and dopamine two (D2) receptor are extensively used in PET imaging studies. Moreover, we also summarized the PET imaging findings of heroin addiction studies, including heroin‐induced DA increases and the reinforcement, role of DA in the long‐term effects of heroin abuse, DA and vulnerability to heroin abuse and the treatment implications. PET imaging studies have corroborated the role of DA in drug addiction and increase our understanding the mechanism of drug addiction. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.     

A comparison of in vivo and in vitro neuroimaging of 5-HT 1A receptor binding sites in the cat brain

To validate the cat as a suitable model for positron emission tomography imaging (PET) and to gain further knowledge on the anatomical distribution of the serotonin-1A receptor (5-HT 1A) in the feline brain, we used PET with [18F]MPPF and in vitro autoradiography with [3H]MPPF, [3H]8-OH-DPAT and [3H]paroxetine. PET radioactivity curves with [18F]MPPF were very reproducible in anaesthetized cats, with the highest radioactivity uptakes recorded in the hippocampus, cingulate cortex, septum, infralimbic cortex and raphe nucleus, whereas the lowest were found in the cerebellum. [3H]8-OH-DPAT binding displayed a comparable, albeit lower, regional distribution than with [3H]MPPF. Autoradiography also revealed the presence of 5-HT 1A receptor binding sites in the cortex and in the interpeduncular nucleus, due to its greater sensitivity and spatial resolution compared with PET imaging. The cat constitutes an interesting experimental model for PET imaging, as many physiological concepts have been well established with this animal. Our study also shows the advantages of combining complementary neuroimaging techniques such as in vivo PET imaging and in vitro autoradiography to visualize the distribution of the 5-HT 1A receptors.     

Imaging biomarkers in Parkinson's disease

Parkinson's disease (PD) is characterized by a progressive loss of nigrostriatal dopaminergic neurons associated with intracellular Lewy inclusion bodies. The result is poverty of movement, increased muscle rigidity, and tremor at rest and on posture. Midbrain/nigral structural abnormalities can be demonstrated in vivo with both transcranial sonography (TCS) and diffusion tensor magnetic resonance imaging (DTI) while positron emission tomography (PET) and single photon emission computed tomography (SPECT) ligands exist to demonstrate dopamine terminal dysfunction. These radiotracers are markers of dopamine storage capacity, vesicular monoamine and dopamine transporter availability. While loss of putamen dopaminergic function leads to motor disability, Lewy bodies not only target dopamine neurons but have also been observed in serotoninergic, noradrenergic, and cholinergic neurons. As a consequence, non-dopaminergic neurotransmission is also impaired resulting in non-motor symptoms including sleep disturbance, fatigue, depression, dementia, and autonomic dysfunction. PET and SPECT ligands exist to interrogate the function of monoaminergic and cholinergic neurons. Cortical and limbic Lewy body disease is seen in more advanced PD and this can be detected with FDG PET as abnormal covariance between levels of resting brain metabolism in these regions. Additionally, widespread microglial activation can be detected in PD with PET. This review discusses the role of structural and functional imaging for understanding parkinsonian syndromes and aiding in their diagnosis and management.     

Positron emission tomography and migraine]

Positron emission tomography (PET) is a brain imaging technique that allows in vivo studies of numerous physiological parameters. There have been few PET studies in migraine patients. Cerebral blood flow changes with no variations in brain oxygen consumption have been reported in patients with prolonged neurologic manifestations during migraine attacks. Parenteral administration of reserpine during migraine headache has been followed by a fall in the overall cerebral uptake of glucose. The small sample sizes and a number of methodologic problems complicate the interpretation of these results. Recent technical advances and the development of new PET tracers can be expected to provide further insight into the pathophysiology of migraine. Today cerebral cortex 5 HT2 serotonin receptors can be studied in migraine patients with PET.     

D2 dopamine receptor polymorphism and brain regional glucose metabolism

Positron emission tomography (PET) studies have shown decreased glucose metabolism in brain regions of detoxified alcoholics and cocaine abusers. However, it is not clear whether this decrease is due to chronic drug abuse or a pre-existing condition. Molecular genetic studies have found an association of the D₂ dopamine receptor (DRD2) A1 allele with alcoholism and drug abuse. Moreover, reduced central dopaminergic function has been suggested in subjects who carry the A1 allele (A1⁺) compared with those who do not (A1⁻). In the present study, using ¹⁸F-deoxyglucose, regional glucose metabolism was determined in healthy nonalcohol/nondrug-abusing subjects with the A1⁺ or A1⁻ allele. The mean relative glucose metabolic rate (GMR) was significantly lower in the A1⁺ than the A1⁻ group in many brain regions, including the putamen, nucleus accumbens, frontal and temporal gyri and medial prefrontal, occipito-temporal and orbital cortices. Decreased relative GMR in the A1⁺ group was also found in Broca's area, anterior insula, hippocampus, and substantia nigra. A few brain areas, however, showed increased relative GMR in the A1⁺ group. Since polymorphism of the DRD² gene is commonly observed in humans, the importance of differentiating A1⁺ and A1⁻ alleles subjects in PET studies is suggested. Am. J. Med. Genet. 74:162–166, 1997. © 1997 Wiley-Liss, Inc.     

PET studies of [18F]methyl-MK-801, a potential NMDA receptor complex radioligand.

Using positron emission tomography (PET), the potential of 18F-labelled fluoro-methyl-MK-801([18F]FMM) as a radioligand for in vivo studies of the NMDA receptor complex was investigated in baboons. In baseline conditions, there was a slight differential retention of [18F]FMM in cerebral cortex and striatum relative to cerebellum, compatible with specific binding. However, neither pretreatment with pharmacological doses of MK-801 or phencyclidine, nor severe, transient brain hypoxia, were able to clearly alter [18]FMM brain regional kinetics, indicating limited usefulness of this radioligand for in vivo PET investigations of the NMDA receptor.     

Oxidative metabolism and the detection of neuronal activation via imaging

Recent years have witnessed a great growth of interest in non-invasive imaging methods, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), permitting identification of brain structures that mediate specific cognitive and behavioural tasks in humans. Because these techniques use physiological responses such as increased perfusion or metabolism as surrogate indicators of evoked neuronal electrical activity, understanding the role of these processes in sustaining the information processing function of neurons is vital to the proper interpretation of functional neuroimaging data. An ultimate goal of these non-invasive techniques is to approach the sensitivity and spatial resolution of earlier autoradiographic methods, which have repeatedly demonstrated exquisitely detailed delineations of neuronal response patterns using metabolic glucose uptake as a physiological tag. Although glucose is generally metabolized in conjunction with oxygen, technical challenges in imaging tissue oxygen consumption in vivo have limited the use of this complementary process in the detection of neuronal activation. In this article we review concepts linking cerebral blood flow and metabolism to neuronal activation, and compare functional imaging techniques that exploit these relationships. We also describe recently introduced MRI based methods for measurement of oxygen consumption and assess the relative contributions of different metabolic pathways during neuronal activation. Our calculations suggest that the bulk of the energy demand evoked during stimulation of neurons in visual cortex is met through oxidative metabolism of glucose, supporting the use of oxygen uptake as a marker for increased neuronal electrical activity.     

Right parietal cortex is involved in the perception of sound movement in humans

Changes in the delay (phase) and amplitude of sound at the ears are cues for the analysis of sound movement. The detection of these cues depends on the convergence of the inputs to each ear, a process that first occurs in the brainstem. The conscious perception of these cues is likely to involve higher centers. Using novel stimuli that produce different perceptions of movement in the presence of identical phase and amplitude modulation components, we have demonstrated human brain areas that are active specifically during the perception of sound movement. Both functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) demonstrated the involvement of the right parietal cortex in sound movement perception with these stimuli.     

Molecular imaging in neuroscience research with small-animal PET in rodents

Cognitive neuroscience, which studies the biological basis of mental processes, widely uses neuroimaging technologies like functional magnetic resonance imaging and positron emission tomography (PET) to study the human brain. Small laboratory animals, like rodents, are commonly used in brain research and provide abundant models of human brain diseases. The development of high-resolution small-animal PET and various radiotracers together with sophisticated methods for analyzing functional brain imaging data have accelerated research on brain function and neurotransmitter release during behavioral tasks in rodents. In this review, we first summarize advances in the methodology of cognitive research brought about by the development of sophisticated methods for whole-brain imaging analysis and improvements in neuroimaging protocols. Then, we discuss basic mechanisms related to metabolic changes and the expression of neurotransmitters in various brain areas during task-induced neural activity. In particular, we discuss glucose metabolism imaging and brain receptor imaging for various receptor systems. Finally, we discuss the current status and future perspectives. Mechanisms of neurotransmitter expression will probably become an increasingly important field of study in the future, leading to more collaboration between investigators in fields such as computational and theoretical neuroscience.     

Possible role of an error detection mechanism in brain processing of deception: PET-fMRI study

To investigate brain maintenance of deliberate deception the positron emission tomography and the event related functional MRI studies were performed. We used an experimental paradigm that presupposed free choices between equally beneficial deceptive or honest actions. Experimental task simulated the “Cheat” card game which aims to defeat an opponent by sequential deceptive and honest claims. Results of both the PET and the fMRI studies revealed that execution of both deliberately deceptive and honest claims is associated with fronto-parietal brain network comprised of inferior and middle frontal gyri, precentral gyrus (BA 6), caudate nucleus, and inferior parietal lobule. Direct comparison between those claims, balanced in terms of decision making and action outcome (gain and losses), revealed activation of areas specifically associated with deception execution: precentral gyrus (BA 6), caudate nuclei, thalamus and inferior parietal lobule (BA 39/40). The obtained experimental data were discussed in relation to a possible role of an error detection system in processing deliberate deception.     

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.     

Neuroimaging and ADHD: fMRI,PET, DTI Findings,and Methodological Limitations

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by pervasive and developmentally inappropriate levels of inattention, impulsivity, and hyperactivity. There is no conclusive cause of ADHD although a number of etiologic theories have been advanced. Research across neuroanatomical, neurochemical, and genetic disciplines collectively support a physiological basis for ADHD and, within the past decade, the number of neuroimaging studies concerning ADHD has increased exponentially. The current selective review summarizes research findings concerning ADHD using functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and diffusion tensor imaging (DTI). Although these technologies and studies offer promise in helping to better understand the physiologic underpinnings of ADHD, they are not without methodological problems, including inadequate sensitivity and specificity for psychiatric disorders. Consequently, neuroimaging technology, in its current state of development, should not be used to inform clinical practice.