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Non-invasive mapping of brain functions and brain recovery: applying lessons from cognitive neuroscience to neurorehabilitation.

Modern cognitive neuroscience provides a powerful framework in which biological models of recovery and neurorehabilitation can be constructed and tested. The widespread availability, relatively low cost and informativeness of functional magnetic resonance imaging (fMRI) has made it the most popular of the techniques available to help with this task. Here, on the basis of functional imaging studies of stroke, diffuse microvascular disease and multiple sclerosis, we argue that processes of motor control and learning in the healthy brain share common mechanisms with those for adaptive functional reorganisation during spontaneous recovery after brain injury or with neurorehabilitation. Relatively stringent criteria can be met to confirm that adaptive functional reorganisation limits disability even in the adult brain: functional brain changes are related to disease burden, can be found in patients with demonstrable pathology but no clinical deficits and can be defined (in motor cortex) even in the absence of volitional recruitment. Initial studies of neurorehabilitation responses using fMRI and transcranial magnetic stimulation demonstrate that adaptive reorganisation can be manipulated directly with both pharmacological and behavioural interventions. The combination of strategies based on a strong biological rational with monitoring their effects using highly informative functional brain imaging methods heralds a new era of scientifically-founded neurorehabilitation.

Brain Mapping↗

Volumetric neuroimaging in children with neurodevelopmental disorders--mapping the brain and behavior.

The recent volumetric neuroimaging studies in children with fragile X syndrome, Down syndrome (DS), Rett syndrome (RS), and Tourette syndrome (TS) were reviewed. Neuroimaging studies and cognitive and behavioral phenotypes pertinent to each disorder were reviewed within the context of current knowledge of their neurobiological mechanisms. The mainly involved brain regions in fragile X syndrome are the cerebellar vermis, temporal areas, and the caudate nucleus which may be related to autistic tendency, problems of memory and language and deficits in executive function, respectively. The preferential involvement of frontal lobe, cerebellum and mesial temporal areas may correspond to the selective language and speech deficits in DS children. There was significantly generalized cerebral volume reduction with greater loss of gray matter in comparison to white matter, consistent with the extensive clinical features of RS. Right side predominance of basal ganglia supported the suggestion that the basal ganglia is related to pathogenesis of TS, which may also be related to the impaired executive function and the absence of functional asymmetry. Further prospectives for integrating neuroanatomic findings and neurobehavioral studies also were discussed.

Brain↗

Motor rehabilitation and brain plasticity after hemiparetic stroke.

This review intends to begin to build a bridge between our understanding of the effect of motor rehabilitation and brain plasticity on recovery after hemiparetic stroke. It discusses the impact of intensive post-stroke motor rehabilitation on motor recovery. This is followed by an overview of our current understanding, based on human brain mapping technologies, of brain plasticity underlying spontaneous recovery after hemiparetic stroke. These discussions lead to a descriptive review of human brain mapping studies that have begun to provide an understanding of the neural basis of rehabilitation-induced gains in motor function after stroke. Finally, it speculates on how a solid understanding of the neural underpinnings of spontaneous and rehabilitation-induced motor recovery will permit brain mapping technologies to be applied toward optimizing post-stroke motor rehabilitation.

Brain↗

Mapping cortical change in Alzheimer's disease, brain development, and schizophrenia.

This paper describes algorithms that can identify patterns of brain structure and function associated with Alzheimer's disease, schizophrenia, normal aging, and abnormal brain development based on imaging data collected in large human populations. Extraordinary information can be discovered with these techniques: dynamic brain maps reveal how the brain grows in childhood, how it changes in disease, and how it responds to medication. Genetic brain maps can reveal genetic influences on brain structure, shedding light on the nature-nurture debate, and the mechanisms underlying inherited neurobehavioral disorders. Recently, we created time-lapse movies of brain structure for a variety of diseases. These identify complex, shifting patterns of brain structural deficits, revealing where, and at what rate, the path of brain deterioration in illness deviates from normal. Statistical criteria can then identify situations in which these changes are abnormally accelerated, or when medication or other interventions slow them. In this paper, we focus on describing our approaches to map structural changes in the cortex. These methods have already been used to reveal the profile of brain anomalies in studies of dementia, epilepsy, depression, childhood- and adult-onset schizophrenia, bipolar disorder, attention-deficit/hyperactivity disorder, fetal alcohol syndrome, Tourette syndrome, Williams syndrome, and in methamphetamine abusers. Specifically, we describe an image analysis pipeline known as cortical pattern matching that helps compare and pool cortical data over time and across subjects. Statistics are then defined to identify brain structural differences between groups, including localized alterations in cortical thickness, gray matter density (GMD), and asymmetries in cortical organization. Subtle features, not seen in individual brain scans, often emerge when population-based brain data are averaged in this way. Illustrative examples are presented to show the profound effects of development and various diseases on the human cortex. Dynamically spreading waves of gray matter loss are tracked in dementia and schizophrenia, and these sequences are related to normally occurring changes in healthy subjects of various ages.

Algorithms↗

Event-related potential maps depend on prestimulus brain electric microstate map.

The brain functional microstate immediately before each of about 3000 identical tone stimuli was classified using extracted reference-free descriptors (locations of maximal and minimal potential) of the landscape of the brain's momentary electric field, in 8 volunteers. Six prestimulus microstate map classes occurred more than 30 times in each subject, and were clustered into two map class types (totals of 242 and 283 cases, respectively, on the average per subject). Event-related potential (ERP) map series were averaged for each subject and prestimulus map class. Map descriptors were extracted from the ERP maps at times of maximal Global Field Power during the component time windows N100, P200 and P330. Discriminant functions were estimated; for the maps of N100 and P330, the discriminant scores differed significantly between the maps associated with the two prestimulus map class types (paired t-tests, df = 7, p = .014 and p = .005, respectively). The dominant axis of the poststimulus class type II ERP maps deviated clockwise from that of the type I ERP maps in all components. We conclude that subtle changes in the brain's spontaneous momentary functional microstate (as classified by spatial descriptors of a single map) influence event-related information processing by the brain, following common rules over subjects.

Adult↗

Auditory perception of music measured by brain electrical activity mapping.

The brain electrical activity of right-handed normal subjects was studied while they were exposed to auditory stimulation of the music type. The material presented was a note, a scale and a melody, recorded on magnetic tape. Each stimulus condition lasted 45 sec. The first 30 sec were analysed using brain electrical activity mapping in the delta (1-4 Hz), alpha (8-12 Hz) and beta 2 (18-24 Hz) frequency bands. The results showed significant bilateral reaction differences for all conditions, showing a left midtemporal activation predominance for the note and scale conditions, but a right midtemporal and frontal predominance for the melody. The results are discussed in terms of functional specialization for different levels of processing.

Adult↗

Alterations in EEG amplitude, personality factors, and brain electrical mapping after alpha-theta brainwave training: a controlled case study of an alcoholic in recovery.

A controlled case study was conducted of effects of EEG alpha and theta brainwave training with a recovering alcoholic patient who experienced craving and fear of relapse after 18 months of abstinence. Training consisted of six sessions of thermal biofeedback to increase central nervous system (CNS) relaxation. Effects were documented with pretreatment and post-treatment personality testing, 20-channel digitized EEG evaluations both under relaxed conditions and under stress, minute-by-minute physiologic recordings of autonomic and EEG data during each training session, blood pressure, and heart rate indications taken both during relaxation and under stress, and by clinical observation. Results replicated those of a previous controlled study with chronic alcoholic patients not abstinent prior to treatment. New findings include post-treatment indications of more relaxed CNS functioning under stress, and of reduced autonomic activation both during relaxation and under stress. Brain-mapping indications of anxiety associated with painful cold-pressor stimulation were seen only in the pretest readings; at post-test the brain map indicated pain-associated EEG activity in the contralateral somatosensory area, but no apparent anxiety-associated EEG activity. At 4 months post-treatment the patient's wife and colleagues report the patient appears to function in a more relaxed way under the impact of stress, and he reports no longer experiencing craving for alcohol. Overall, support is provided for the possibility that alpha and theta brainwave training may be a useful intervention for the abstinent alcoholic experiencing stress-related craving and fear of relapse.

Adult↗

Topographic maps of brain electrical activity--pitfalls and precautions.

Topographic mapping of brain electrical activity is a popular, powerful, and potentially misleading technique. The map lies at the end of a long chain of physiological, technical, electronic, and mathematical processes and is vulnerable to artifact, error, and distortion at many points. Close attention must be paid to data collection parameters, subject cooperation, minimization of artifact, limitations of resolutions, selection, and transformation of parameters for display, and map generation strategy to yield an accurate, physiologically interpretable map. Review of the data at each step of analysis, from the paper electroencephalogram (EEG) to sets of maps on video display, may be necessary for optimum understanding. Development of more sophisticated qualitative and quantitative concepts of "normal" physiology is needed. These improvements in electrophysiological data analysis demand, rather than obviate, sophistication on the part of the user.

Arousal↗

Regulation of axial patterning of the retina and its topographic mapping in the brain.

Topographic maps are a fundamental organizational feature of axonal connections in the brain. A prominent model for studying axial polarity and topographic map development is the vertebrate retina and its projection to the optic tectum (or superior colliculus). Linked processes are controlled by molecules that are graded along the axes of the retina and its target fields. Recent studies indicate that ephrin-As control the temporal-nasal mapping of the retina in the optic tectum/superior colliculus by regulating the topographically-specific interstitial branching of retinal axons along the anterior-posterior tectal axis. This branching is mediated by relative levels of EphA receptor repellent signaling. A major recent advance is the demonstration that EphB receptor forward signaling and ephrin-B reverse signaling mediate axon attraction to control dorsal-ventral retinal mapping along the lateral-medial tectal axis. In addition, several classes of regulatory proteins have been implicated in the control of the axial patterning of the retina, and its ultimate readout of topographic mapping.

Animals↗

Event-related functional MRI: past, present, and future.

The past two decades have seen an enormous growth in the field of human brain mapping. Investigators have extensively exploited techniques such as positron emission tomography and MRI to map patterns of brain activity based on changes in cerebral hemodynamics. However, until recently, most studies have investigated equilibrium changes in blood flow measured over time periods upward of 1 min. The advent of high-speed MRI methods, capable of imaging the entire brain with a temporal resolution of a few seconds, allows for brain mapping based on more transient aspects of the hemodynamic response. Today it is now possible to map changes in cerebrovascular parameters essentially in real time, conferring the ability to observe changes in brain state that occur over time periods of seconds. Furthermore, because robust hemodynamic alterations are detectable after neuronal stimuli lasting only a few tens of milliseconds, a new class of task paradigms designed to measure regional responses to single sensory or cognitive events can now be studied. Such "event related" functional MRI should provide for fundamentally new ways to interrogate brain function, and allow for the direct comparison and ultimately integration of data acquired by using more traditional behavioral and electrophysiological methods.

Brain↗

Mapping the brain in autism. A voxel-based MRI study of volumetric differences and intercorrelations in autism.

Autism is a disorder of neurodevelopment resulting in pervasive abnormalities in social interaction and communication, repetitive behaviours and restricted interests. There is evidence for functional abnormalities and metabolic dysconnectivity in 'social brain' circuitry in this condition, but its structural basis has proved difficult to establish reliably. Explanations for this include replication difficulties inherent in 'region of interest' approaches usually adopted, and variable inclusion criteria for subjects across the autism spectrum. Moreover, despite a consensus that autism probably affects widely distributed brain regions, the issue of anatomical connectivity has received little attention. Therefore, we planned a fully automated voxel-based whole brain volumetric analysis in children with autism and normal IQ. We predicted that brain structural changes would be similar to those previously shown in adults with autism spectrum disorder and that a correlation analysis would suggest structural dysconnectivity. We included 17 stringently diagnosed children with autism and 17 age-matched controls. All children had IQ >80. Using Brain Activation and Morphological Mapping (BAMM) software, we measured global brain and tissue class volumes and mapped regional grey and white matter differences across the whole brain. With the expectation that volumes of interconnected regions correlate positively, we carried out a preliminary exploration of 'connectivity' in autism by comparing the nature of inter-regional grey matter volume correlations with control. Children with autism had a significant reduction in total grey matter volume and significant increase in CSF volume. They had significant localized grey matter reductions within fronto-striatal and parietal networks similar to findings in our previous study, and additional decreases in ventral and superior temporal grey matter. White matter was reduced in the cerebellum, left internal capsule and fornices. Correlation analysis revealed significantly more numerous and more positive grey matter volumetric correlations in controls compared with children with autism. Thus, using similar diagnostic criteria and image analysis methods in otherwise healthy populations with an autistic spectrum disorder from different countries, cultures and age groups, we report a number of consistent findings. Taken together, our data suggest abnormalities in the anatomy and connectivity of limbic-striatal 'social' brain systems which may contribute to the brain metabolic differences and behavioural phenotype in autism.

Adolescent↗

Mapping function in the human brain with magnetoencephalography, anatomical magnetic resonance imaging, and functional magnetic resonance imaging.

Integrated analyses of human anatomical and functional measurements offer a powerful paradigm for human brain mapping. Magnetoencephalography (MEG) and EEG provide excellent temporal resolution of neural population dynamics as well as capabilities for source localization. Anatomical magnetic resonance imaging (MRI) provides excellent spatial resolution of head and brain anatomy, whereas functional MRI (fMRI) techniques provide an alternative measure of neural activation based on associated hemodynamic changes. These methodologies constrain and complement each other and can thereby improve our interpretation of functional neural organization. We have developed a number of computational tools and techniques for the visualization, comparison, and integrated analysis of multiple neuroimaging techniques. Construction of geometric anatomical models from volumetric MRI data allows improved models of the head volume conductor and can provide powerful constraints for neural electromagnetic source modeling. These approaches, coupled to enhanced algorithmic strategies for the inverse problem, can significantly enhance the accuracy of source-localization procedures. We have begun to apply these techniques for studies of the functional organization of the human visual system. Such studies have demonstrated multiple, functionally distinct visual areas that can be resolved on the basis of their locations, temporal dynamics, and differential sensitivity to stimulus parameters. Our studies have also produced evidence of internal retinotopic organization in both striate and extrastriate visual areas but have disclosed organizational departures from classical models. Comparative studies of MEG and fMRI suggest a reasonable but imperfect correlation between electrophysiological and hemodynamic responses. We have demonstrated a method for the integrated analysis of fMRI and MEG, and we outline strategies for improvement of these methods. By combining multiple measurement techniques, we can exploit the complementary strengths and transcend the limitations of the individual neuro-imaging methods.

Brain↗

Circulatory basis of fMRI signals: relationship between changes in the hemodynamic parameters and BOLD signal intensity.

Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) is widely used as a tool for functional brain mapping. During brain activation, increases in the regional blood flow lead to an increase in blood oxygenation and a decrease in paramagnetic deoxygenated hemoglobin (deoxy-Hb), causing an increase in the MR signal intensity at the site of brain activation. However, not a few studies using fMRI have failed to detect activation of areas that ought to have been activated. We assigned BOLD-positive (an increase in the signal intensity), BOLD-negative (a decrease in the signal intensity), and BOLD-silent (no change) brain activation to respective circulatory conditions through a description of fMRI signals as a function of the concentration of oxygenated Hb (oxy-Hb) and deoxy-Hb obtained with near-infrared optical imaging (NIOI). Using this model, we explain the sensory motor paradox in terms of BOLD-positive, BOLD-negative, and BOLD-silent brain activation.

Adult↗

Obesity-specific circuits in the human brain: exploration by dynamic Brain Self-Reference (dynBSR).

In the last decade many efforts have been made in order to identify brain regions that may be abnormal in obese subjects. Most of the lines of research have examined links between brain circuits, behavioral processing, and overweight. We introduce here a novel analysis to the brain mapping, 'dynamic Brain Self-Reference' (dynBSR), based on the electrical response evoked during passively viewing a simple stimulus. Hypothetically, it should be possible to monitor both task-related networks and task-irrelevant networks during a mental state with low cognitive demand, as shown previously by others using fMRI and establishing the latter as the neural correlates of an 'inherent' brain activation pattern. However, this fact has been usually ignored. Our results showed that a distinct set of interconnected brain regions including, frontal areas (middle, inferior, orbitofrontal, and dorsolateral), dorsal/ventral striatum, thalamus, superior temporal region, insula cortex, post-central gyrus, left supramarginal gyrus, and parietal regions, whose activities seem to be tonically maintained, displays cohesive functional state in obesity during passively viewing a simple stimulus. This organized network is maintained in a dynamic equilibrium with the transient activation of the right supramarginal gyrus. These brain areas have been previously implicated in the regulation of taste, reward, and behavioral processing and most of them have also structural abnormalities regarding normal-weight subjects. Although exploratory, the most important result here is that the evaluation of the visual-evoked responses with dynBSR provides a foundation for investigating the brain circuits in obesity, and becomes the first attempt, to our knowledge, to imply task-irrelevant networks in these individuals.

Adult↗

[Reorganization of the pattern of the brain somatosensory evoked potentials after spinal cord injury].

Recordings of somatosensory evoked potentials (SEPs) and SEP brain maps of 23 patients with vertebral injury were analyzed. All patients were operated at the Clinic of Military Traumatology and Orthopedics, Military Medical Academy. SEPs (19 sites) were recorded in real time and mapped with "Brain surveyor" neuromapper. Brain lesions were localized before surgery by of MR imaging and CT standard techniques. The results demonstrate that electrical stimulation of peripheral nerves produces a substantially variable SEP pattern. It was shown that SEP formation in more than 60% of recordings suggests a favorable prognosis for rehabilitation, whereas if more than 50% of recording sites are unresponsive, the rehabilitation prognosis is unfavorable. The amplitude of early components (below 60 ms) increases, and that of the late waves reduces.

Adult↗

Spatiotemporal maps of brain activity underlying word generation and their modification during repetition priming.

Spatiotemporal maps of brain activity based on magnetoencephalography were used to observe sequential stages in language processing and their modification during repetition priming. Subjects performed word-stem completion and produced either novel or repeated (primed) words across trials. Activation passes from primary visual cortex (activated at approximately 100 msec after word presentation), to left anteroventral occipital ( approximately 180 msec), to cortex in and near Wernicke's ( approximately 210 msec) and then Broca's ( approximately 370 msec) areas. In addition, a posteroventral temporal area is activated simultaneously with posterosuperior temporal cortex. This area shows an early ( approximately 200-245 msec) increase in activation to repeated word stems. In contrast, prefrontal and anterior temporal regions showed activity reductions to repeated word stems late ( approximately 365-500 msec) in processing. These results tend to support classical models of language and suggest that an effect of direct item repetition is to allow word-form processing to increase its contribution to task performance while concurrently allowing reductions in time-consuming frontal temporal processing.

Brain↗