Human Functional Brain Imaging Research Articles

Two hierarchically organized neural systems for object information in human visual cortex

The primate visual system is broadly organized into two segregated processing pathways, a ventral stream for object vision and a dorsal stream for space vision. Here, evidence from functional brain imaging in humans demonstrates that object representations are not confined to the ventral pathway, but can also be found in several areas along the dorsal pathway. In both streams, areas at intermediate processing stages in extrastriate cortex (V4, V3A, MT and V7) showed object-selective but viewpoint- and size-specific responses. In contrast, higher-order areas in lateral occipital and posterior parietal cortex (LOC, IPS1 and IPS2) responded selectively to objects independent of image transformations. Contrary to the two-pathways hypothesis, our findings indicate that basic object information related to shape, size and viewpoint may be represented similarly in two parallel and hierarchically organized neural systems in the ventral and dorsal visual pathways.

Dreaming: a neuroimaging view

Our neurobiological knowledge about human dream organisation results primarily from the study of Rapid-Eye-Movement (REM) sleep. In humans, functional neuroimaging techniques, using H 2 15 O or 18 FDG positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), allowed the mapping of the regional cerebral activity during this sleep stage, which is dominated by the activation of the pons, the thalamus,temporo-occipital and limbic/paralimbic areas (including the amygdala, the hippocampal formation and the anterior cingulate cortex), along with a relative quiescence of dorsolateral prefrontal and inferior parietal cortices. These results are in agreement with animal neurophysiological data about REM-sleep generation. They may also explain several hallmarks of dreaming experience that are found in dream reports after awakening from REM sleep. For instance, amygdala activation is consistent with the predominance of threat-related emotions. Temporo-occipital activation is in keeping with visual dream imagery. Prefrontal deactivation is suggestive of the lack of orientational stability, the alteration in time perception, the delusional belief of being awake, the decrease in volitional control and the fragmented episodic memory recall. Inferior parietal deactivation may contribute to the lack of distinction between first-and third-person perspectives. Conversely, specific cognitive and emotional features in individual dreams could be used to predict some aspects of the regional functional organisation of the human brain during dreams, and also inspire the design of future dedicated neuroimaging studies by offering constraints to the analysis and interpretation of sleep data acquired just before dream reports. Therefore, we suggest that future functional brain imaging in humans should be combined with a careful neuropsychological analysis of dream reports, and especially their categorisation based on the presence of specific bizarre features, to test hypotheses about the brain correlates of dreams. As little is known about the physiology of non-REM sleep dreaming, future neuroimaging studies should also attempt to link dreaming experiences during this sleep stage with patterns of regional cerebral activity. Overall, although many questions arising from the study of oneiric behaviour remain unanswered, recent neurophysiological and neuroimaging research about REM sleep offers an increasingly detailed picture of the cerebral correlates of dreaming that might also provide new insights into dream functions.

Hippocampus: cognitive processes and neural representations that underlie declarative memory.

The hippocampus serves a critical role in declarative memory--our capacity to recall everyday facts and events. Recent studies using functional brain imaging in humans and neuropsychological analyses of humans and animals with hippocampal damage have revealed some of the elemental cognitive processes mediated by the hippocampus. In addition, recent characterizations of neuronal firing patterns in behaving animals and humans have suggested how neural representations in the hippocampus underlie those elemental cognitive processes in the service of declarative memory.

Consciousness and neurosurgery.

The neuronal basis of consciousness is the greatest challenge to the scientific worldview. Much relevant empirical work is carried out on the minimal neuronal mechanisms underlying any one specific conscious percept. Two broad approaches are popular among brain scientists: electrophysiological recordings from individual neurons in the cortex of behaving monkeys or behavior combined with functional brain imaging in humans. However, many aspects of consciousness are problematic or remain off-limits to the former approach, while the latter one lacks sufficient spatial and temporal resolution to monitor individual neurons that are key to perception, thought, memory, and action. It is here that neurosurgeons, probing the living human brain on a daily basis, can play a decisive role. This article explores the contributions of neurosurgeons to this quest and outlines some of the results that have already been achieved.

In vivo imaging of anaesthetic action in humans: approaches with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI)

In vivo imaging of anaesthetic action in humans: approaches with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI)

The Preparation and Execution of Self-Initiated and Externally-Triggered Movement: A Study of Event-Related fMRI

Studies of functional brain imaging in humans and single cell recordings in monkeys have generally shown preferential involvement of the medially located supplementary motor area (SMA) in self-initiated movement and the lateral premotor cortex in externally cued movement. Studies of event-related cortical potentials recorded during movement preparation, however, generally show increased cortical activity prior to self-initiated movements but little activity at early stages prior to movements that are externally cued at unpredictable times. In this study, the spatial location and relative timing of activation for self-initiated and externally triggered movements were examined using rapid event-related functional MRI. Twelve healthy right-handed subjects were imaged while performing a brief finger sequence movement (three rapid alternating button presses: index–middle–index finger) made either in response to an unpredictably timed auditory cue (between 8 to 24 s after the previous movement) or at self-paced irregular intervals. Both movement conditions involved similar strong activation of medial motor areas including the pre-SMA, SMA proper, and rostral cingulate cortex, as well as activation within contralateral primary motor, superior parietal, and insula cortex. Activation within the basal ganglia was found for self-initiated movements only, while externally triggered movements involved additional bilateral activation of primary auditory cortex. Although the level of SMA and cingulate cortex activation did not differ significantly between movement conditions, the timing of the hemodynamic response within the pre-SMA was significantly earlier for self-initiated compared with externally triggered movements. This clearly reflects involvement of the pre-SMA in early processes associated with the preparation for voluntary movement.

Searching for a baseline: functional imaging and the resting human brain.

Functional brain imaging in humans has revealed task-specific increases in brain activity that are associated with various mental activities. In the same studies, mysterious, task-independent decreases have also frequently been encountered, especially when the tasks of interest have been compared with a passive state, such as simple fixation or eyes closed. These decreases have raised the possibility that there might be a baseline or resting state of brain function involving a specific set of mental operations. We explore this possibility, including the manner in which we might define a baseline and the implications of such a baseline for our understanding of brain function.

Project title Methods for dynamic imaging of human brain function

Project title Methods for dynamic imaging of human brain function

Time Course of Pharmacodynamic and Pharmacokinetic Effects of Physostigmine Assessed by Functional Brain Imaging in Humans

In imaging studies of brain functions using pharmacological probes, identification of the time point at which central effects of intravenously infused drugs become stable is crucial to separate the effects of experimental variables from the concomitant changes in drug effects over time. We evaluated the time courses of the pharmacokinetics and pharmacodynamics, including butyrylcholinesterase inhibition and central neural responses, of physostigmine in healthy young subjects. Ten positron emission tomography (PET) scans that alternated between a rest condition (eyes open, ears unplugged) and a working memory for faces (WM) task were acquired in healthy subjects. Subjects in the drug group received a saline infusion for the first two scans, providing a baseline measure, then received an infusion of physostigmine for all subsequent scans. Subjects in the control group received a placebo infusion of saline for all scans. Physostigmine plasma levels and percent butyrylcholinesterase inhibition increased over time ( p < 0.0001), and both became stable by 40 min. Physostigmine decreased reaction time (RT) ( p = 0.0005), and this effect was detected after 20 min of infusion and stable thereafter. Physostigmine also decreased regional cerebral blood flow (rCBF) in right prefrontal cortex during task ( p = 0.0002), and this effect was detected after 40 min of infusion and stable thereafter. No change in RT or rCBF was observed in the control group. These results indicate that a 40-min infusion of physostigmine was necessary to obtain stable central effects. More generally, we have demonstrated that experimental effects can vary with time, especially during the initial phases of a drug infusion, indicating that it is critical that these changes are controlled.

Noninvasive functional imaging of human brain using light.

Analysis of photon transit time for low-power light passing into the head, and through both skull and brain, of human subjects allowed for tomographic imaging of cerebral hemoglobin oxygenation based on photon diffusion theory. In healthy adults, imaging of changes in hemoglobin saturation during hand movement revealed focal, contralateral increases in motor cortex oxygenation with spatial agreement to activation maps determined by functional magnetic resonance imaging; in ill neonates, imaging of hemoglobin saturation revealed focal regions of low oxygenation after acute stroke, with spatial overlap to injury location determined by computed tomography scan. Because such slow optical changes occur over seconds and co-localize with magnetic resonance imaging vascular signals whereas fast activation-related optical changes occur over milliseconds and co-localize with EEG electrical signals, optical methods offer a single modality for exploring the spatio-temporal relationship between electrical and vascular responses in the brain in vivo, as well as for mapping cortical activation and oxygenation at the bedside in real-time for clinical monitoring.

Concepts of pain mechanisms: the contribution of functional imaging of the human brain

Functional imaging of the conscious human brain has a solid physiological basis in synaptically induced rCBF responses. We still do not know how these responses are generated, but recent studies have shown that the rCBF response is parametrically positively correlated with functional measures of neuronal activity. Technical advances in both fMRI and PET imaging have improved the spatial and temporal resolution of imaging methods. Further advances may be expected in the near future. Consequently, we now have an important tool to apply to the study of normal and, most importantly, pathological pain. There is a tendency to expect too much of this exciting technique, but the problems we wish to address are complex and will require considerable time, effort, and patience. We now know that the CNS adapts to both peripheral and central nervous system injury, sometimes in beneficial ways, but sometimes with reorganization that is maladaptive. An understanding of the pathophysiology of neuropathic pain is further complicated by the new knowledge, emphasized by functional brain imaging, that pain and pain modulation is mediated, not by a simple pathway with one or a few central targets, but by a network of multiple interacting modules of neuronal activity. Simplified phrenological thinking, with complete psychological functions separate and localized, is appealing, but wildly misleading. It is far more realistic and productive to apply qualitative and quantitative spatial and temporal analyses to the distributed activity of the conscious, communicating human brain. This will not be quick and easy, but there is every reason for optimism in our search for a thorough and useful understanding of both normal and pathological pain.

Human functional brain imaging: The bridge from neurophysiology to the mind

Human brain imaging studies have identified multiple brain regions activated during the experience of pain. Do these complex activation patterns lead to confusion and an “explanatory gap” between classical neurophysiology, psychology, and brain imaging? We propose the contrary, that human functional brain imaging studies can provide a bridge between neurophysiological research and the psychological concept of “pain.” Modern brain imaging techniques allow analysis of the relationship between brain activation patterns and various psychological percepts. However, an essential element in interpreting functional brain imaging observations is a robust psychophysical paradigm that permits the selective manipulation and measurement of individual perceptual features of pain. Functional brain imaging provides a new tool to facilitate our understanding of the complex cognitive, emotional, and sensory experience of pain. Nevertheless, this tool will add little to our knowledge if it is not used wisely.

Neuronal population activity and functional imaging.

Human functional brain imaging detects blood flow changes that are thought to reflect the activity of neuronal populations and, thus, the responses of neurons that carry behaviourally relevant information. Since this relationship is poorly understood, we explored the link between the activity of single neurons and their neuronal population. The functional imaging results were in good agreement with levels of population activation predicted from the known effects of sensory stimulation, learning and attention on single cortical neurons. However, the nature of the relationship between population activation and single neuron firing was very surprising. Population activation was strongly influenced by those neurons firing at low rates and so was very sensitive to the baseline or 'spontaneous' firing rate. When neural representations were sparse and neurons were tuned to several stimulus dimensions, population activation was hardly influenced by the few neurons whose firing was most strongly modulated by the task or stimulus. Measures of population activation could miss changes in information processing given simultaneous changes in neurons' baseline firing, response modulation or tuning width. Factors that can modulate baseline firing, such as attention, may have a particularly large influence on population activation. The results have implications for the interpretation of functional imaging signals and for cross-calibration between different methods for measuring neuronal activity.

Functional brain imaging during anesthesia in humans: effects of halothane on global and regional cerebral glucose metabolism.

Propofol and isoflurane anesthesia were studied previously with functional brain imaging in humans to begin identifying key brain areas involved with mediating anesthetic-induced unconsciousness. The authors describe an additional positron emission tomography study of halothane's in vivo cerebral metabolic effects. Five male volunteers each underwent two positron emission tomography scans. One scan assessed awake-baseline metabolism, and the other scan assessed metabolism during halothane anesthesia titrated to the point of unresponsiveness (mean +/- SD, expired = 0.7+/-0.2%). Scans were obtained using a GE2048 scanner and the F-18 fluorodeoxyglucose technique. Regions of interest were analyzed for changes in both absolute and relative glucose metabolism. In addition, relative changes in metabolism were evaluated using statistical parametric mapping. Awake whole-brain metabolism averaged 6.3+/-1.2 mg x 100 g(-1) x min(-1) (mean +/- SD). Halothane reduced metabolism 40+/-9% to 3.7+/-0.6 mg x 100 g(-1) x min(-1) (P< or =0.005). Regional metabolism did not increase in any brain areas for any volunteer. The statistical parametric mapping analysis revealed significantly less relative metabolism in the basal forebrain, thalamus, limbic system, cerebellum, and occiput during halothane anesthesia. Halothane caused a global whole-brain metabolic reduction with significant shifts in regional metabolism. Comparisons with previous studies reveal similar absolute and relative metabolic effects for halothane and isoflurane. Propofol, however, was associated with larger absolute metabolic reductions, suppression of relative cortical metabolism more than either inhalational agent, and significantly less suppression of relative basal ganglia and midbrain metabolism.

Spatiotemporal imaging of human brain activity using functional MRI constrained magnetoencephalography data: Monte Carlo simulations.

The goal of our research is to develop an experimental and analytical framework for spatiotemporal imaging of human brain function. Preliminary studies suggest that noninvasive spatiotemporal maps of cerebral activity can be produced by combining the high spatial resolution (millimeters) of functional MRI (fMRI) with the high temporal resolution (milliseconds) of electroencephalography (EEG) and magnetoencephalography (MEG). Although MEG and EEG are sensitive to millisecond changes in mental activity, the ability to resolve source localization and timing is limited by the ill-posed "inverse" problem. We conducted Monte Carlo simulations to evaluate the use of MRI constraints in a linear estimation inverse procedure, where fMRI weighting, cortical location and orientation, and sensor noise statistics were realistically incorporated. An error metric was computed to quantify the effects of fMRI invisible ("missing") sources, "extra" fMRI sources, and cortical orientation errors. Our simulation results demonstrate that prior anatomical and functional information from MRI can be used to regularize the EEG/MEG inverse problem, giving an improved solution with high spatial and temporal resolution. An fMRI weighting of approximately 90% was determined to provide the best compromise between separation of activity from correctly localized sources and minimization of error caused by missing sources. The accuracy of the estimate was relatively independent of the number and extent of the sources, allowing for incorporation of physiologically realistic multiple distributed sources. This linear estimation method provides an operator-independent approach for combining information from fMRI, MEG, and EEG and represents a significant advance over traditional dipole modeling.

Neural correlates of perceptual rivalry in the human brain.

When dissimilar images are presented to the two eyes, perception alternates spontaneously between each monocular view, a phenomenon called binocular rivalry. Functional brain imaging in humans was used to study the neural basis of these subjective perceptual changes. Cortical regions whose activity reflected perceptual transitions included extrastriate areas of the ventral visual pathway, and parietal and frontal regions that have been implicated in spatial attention; whereas the extrastriate areas were also engaged by nonrivalrous perceptual changes, activity in the frontoparietal cortex was specifically associated with perceptual alternation only during rivalry. These results suggest that frontoparietal areas play a central role in conscious perception, biasing the content of visual awareness toward abstract internal representations of visual scenes, rather than simply toward space.

Properties and mechanisms of perceptual priming

Recent evidence suggests that the behavioral phenomenon of perceptual priming and the physiological finding of decreased neural responses with item repetition have similar properties. Both the behavioral and neurophysiological effects show graded changes with multiple repetitions, are resistant to manipulations of particular stimulus attributes (e.g. size and location), and occur independently of awareness. These and other recent findings (e.g. from functional brain imaging in humans) suggest that perceptual priming may be mediated by decreased neural responses associated with perceptual learning.

Hippocampal involvement in human topographical memory: evidence from functional imaging.

Functional brain imaging in humans is beginning to reveal a network of brain regions that subserve topographical learning: the medial parietal lobe, the posterior cingulate gyrus, occipitotemporal areas, the parahippocampal gyrus and the right hippocampus. These findings illuminate the patient lesion literature where all of these brain regions have been implicated at one time or another in cases of topographical disorientation. Once topographical information is acquired, the neuroanatomy that supports its use from either episodic or semantic memory is similar to that activated during encoding. The specific contributions of extrahippocampal regions within the topographical memory system are being revealed, such as the role of the right parahippocampal gyrus in object-in-place encoding. The right hippocampus is clearly involved in processing spatial layouts over long as well as short time-courses, and participates in both the encoding and the retrieval of topographical memory. The ventromedial orbitofrontal cortex is recruited when information in the topographical memory system is not sufficient to produce direct navigation to a goal place.

Non-invasive optical spectroscopy and imaging of human brain function

Brain activity is associated with changes in optical properties of brain tissue. Optical measurements during brain activation can assess haemoglobin oxygenation, cytochrome- c-oxidase redox state, and two types of changes in light scattering reflecting either membrane potential (fast signal) or cell swelling (slow signal), respectively. In previous studies of exposed brain tissue, optical imaging of brain activity has been achieved at high temporal and microscopical spatial resolution. Now, using near-infrared light that can penetrate biological tissue reasonably well, it has become possible to assess brain activity in human subjects through the intact skull non-invasively. After early studies employing single-site near-infrared spectroscopy, first near-infrared imaging devices are being applied successfully for low-resolution functional brain imaging. Advantages of the optical methods include biochemical specificity, a temporal resolution in the millisecond range, the potential of measuring intracellular and intravascular events simultaneously and the portability of the devices enabling bedside examinations.

Magnetic Resonance Imaging of Human Brain Function: Principles, Practicalities, and Possibilities

This article presents a review of functional magnetic resonance (fMR) imaging. Included are four sections that address the principles, practicalities, and potentials of fMR imaging. The current types of hemodynamic contrast available with fMR imaging, including blood volume, perfusion, and oxygenation, are discussed. Technical issues of fMR imaging, including interpretability and sensitivity, are described, and several currently unresolved issues are addressed. Also reviewed are commonly used fMR imaging platforms and clinical and research applications.