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The investigation of functional brain lateralization by transcranial Doppler sonography.

Functional transcranial Doppler sonography (fTCD) adds to the techniques of functional imaging. fTCD measures cerebral perfusion changes related to neural activation in a way comparable to functional magnetic resonance tomography. fTCD contends itself with comparison of averaged, event-related blood flow velocity changes within the territories of two cerebral arteries, for example the left versus the right middle cerebral artery. It can thus serve to evaluate the functional lateralization of higher cognitive functions like hemispheric language dominance (HLD). We present typical applications of fTCD by summarizing studies employing the technique. Then, the physical and physiological underpinnings of fTCD are reviewed. After a brief description of a prototype paradigm for assessing HLD, a detailed outline of the fTCD data analysis is presented. Caveats for fTCD, like other functional imaging techniques, are that the validity of results depends on adequate control of the task parameters, particularly cooperation and reference conditions. We complete the review with examinations of the reliability and validity of the fTCD technique. We conclude that fTCD can be employed to substitute the invasive amobarbital procedure to determine language lateralization in individual patients before undergoing brain surgery. Because of its easy applicability, robustness and mobility, fTCD can also be used to examine many subjects (including children) to obtain representative data on the variability of lateralization of higher cognitive functions, or to scan for atypical patterns of lateralization.

Algorithms↗

The connection between rhythmicity and brain function.

Although rhythm and music are not entirely synonymous terms, rhythm constitutes one of the most essential structural and organizational elements of music. When considering the effect of music on human adaptation, the profound effect of rhythm on the motor system strongly suggests that the time structure of music is the essential element relating music specifically to motor behavior. Why the motor system appears so sensitive to auditory priming and timing stimulation can only be partially answered so far. The high-performance function of the auditory system regarding processing of time information makes good functional sense within the constraints of auditory sensory processing. Thus, the motor system sensitivity to auditory entrainment may simply be an evolutionary useful function of taking advantage of the specific and unique aspects of auditory information processing for enhanced control and organization of motor behavior; e.g, in the time domain. Unlike processes in the motor system, many other physiological processes cannot be effectively entrained by external sensory stimuli. For example, there is probably a very good protective reason why other cyclical physiological processes (e.g., autonomic processes such as heart rate) have only very limited entrainment capacity to external rhythmic cues. Some of the basic auditory-motor arousal connections may also have their basis in adaptive evolutionary processes related to survival behavior; e.g., in fight or flight reactions. Much of the "why" in auditory-motor interactions, however, remains unknown heuristically. In the absence of this knowledge, great care should be taken to not compensate for this lack of understanding of specific cause and effect processes by assigning anthropomorphic descriptions to the behavior of biological and physical systems. The unraveling of the perceptual, physiological, and neuroanatomical basis of the interaction between rhythm and movement has been, and continues to be, a fascinating endeavor with important ramifications for the study of brain function, sensory perception, and motor behavior. One of the most exciting findings in this research, however, may be the evidence that the interaction between auditory rhythm and physical response can be effectively harnessed for specific therapeutic purposes in the rehabilitation of persons with movement disorders.

Acoustic Stimulation↗

Electroencephalographic imaging of higher brain function.

High temporal resolution is necessary to resolve the rapidly changing patterns of brain activity that underlie mental function. Electroencephalography (EEG) provides temporal resolution in the millisecond range. However, traditional EEG technology and practice provide insufficient spatial detail to identify relationships between brain electrical events and structures and functions visualized by magnetic resonance imaging or positron emission tomography. Recent advances help to overcome this problem by recording EEGs from more electrodes, by registering EEG data with anatomical images, and by correcting the distortion caused by volume conduction of EEG signals through the skull and scalp. In addition, statistical measurements of sub-second interdependences between EEG time-series recorded from different locations can help to generate hypotheses about the instantaneous functional networks that form between different cortical regions during perception, thought and action. Example applications are presented from studies of language, attention and working memory. Along with its unique ability to monitor brain function as people perform everyday activities in the real world, these advances make modern EEG an invaluable complement to other functional neuroimaging modalities.

Brain↗

Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia.

Fluorodeoxyglucose positron emission tomography (PET) studies have found that patients with Alzheimer's dementia (AD) have abnormally low rates of cerebral glucose metabolism in posterior cingulate, parietal, temporal, and prefrontal cortex. We previously found that cognitively normal, late-middle-aged carriers of the apolipoprotein E epsilon4 allele, a common susceptibility gene for late-onset Alzheimer's dementia, have abnormally low rates of glucose metabolism in the same brain regions as patients with probable AD. We now consider whether epsilon4 carriers have these regional brain abnormalities as relatively young adults. Apolipoprotein E genotypes were established in normal volunteers 20-39 years of age. Clinical ratings, neuropsychological tests, magnetic resonance imaging, and PET were performed in 12 epsilon4 heterozygotes, all with the epsilon3/epsilon4 genotype, and 15 noncarriers of the epsilon4 allele, 12 of whom were individually matched for sex, age, and educational level. An automated algorithm was used to generate an aggregate surface-projection map that compared regional PET measurements in the two groups. The young adult epsilon4 carriers and noncarriers did not differ significantly in their sex, age, educational level, clinical ratings, or neuropsychological test scores. Like previously studied patients with probable AD and late-middle-aged epsilon4 carriers, the young epsilon4 carriers had abnormally low rates of glucose metabolism bilaterally in the posterior cingulate, parietal, temporal, and prefrontal cortex. Carriers of a common Alzheimer's susceptibility gene have functional brain abnormalities in young adulthood, several decades before the possible onset of dementia.

Adult↗

Functional brain maturation in neonates as measured by EEG-sleep analyses.

OBJECTIVE: Seven measures of neonatal EEG-sleep behavior were evaluated using multivariate analyses to ascertain if physiologic differences exist between healthy full- and preterm cohorts. METHODS: A total of 381 24-channel EEG-sleep studies were analyzed, including 125 recordings on 50 healthy fullterm and 256 recordings on 59 asymptomatic preterm infants between 28 and 70.6 weeks post-conceptional age. One EEG study for each subject was randomly assigned (109 studies) within the time window of 38-44 weeks post-conceptional age. A multivariate analytic procedure was applied to the data sets, by which a 'dysmaturity index' was assigned for each infant, based on 7 EEG-sleep measures. This index was defined in terms of the distance from the fullterm group's centroid (i.e. Mahalanobis distance). Receiver-operating characteristic curves (ROCs) were calculated for several different combinations of 7 EEG-sleep measures to describe differences between neonatal cohorts. RESULTS: The ROC curve corresponding to all 7 EEG-sleep measures covered the substantially largest area among the curves for the sets of variables considered, suggesting that all 7 measures of sleep behavior were required to best discriminate between cohorts. CONCLUSIONS: This methodology exemplifies how EEG-sleep analyses can be applied to the study of functional brain maturation of infants at risk for neurodevelopment problems. SIGNIFICANCE: Changes in EEG-sleep behavior in the preterm infant may represent altered activity-dependent development of neural circuitry, resulting in remodeling of the immature brain as a reflection of adaptation to conditions of prematurity.

Brain↗

Effects of image resolution on autoradiographic measurements of posterior cingulate activity in PDAPP mice: implications for functional brain imaging studies of transgenic mouse models of Alzheimer's Disease.

Fluorodeoxyglucosepositron emission tomography (PET) studies find that persons with Alzheimer's disease have preferential reductions in posterior cingulate activity. Using fluorodeoxyglucose autoradiography, we found that transgenic mice overexpressing a mutant form of the human amyloid precursor protein have preferentially reduced activity in the same region, providing a potential brain imaging indicator of Alzheimer's disease in these animals. In this study, we considered the feasibility of using in vivo imaging techniques, such as PET, to detect this reduction despite their limitations in spatial resolution. Autoradiographic measurements of posterior cingulate activity were remeasured in the previously studied PDAPP transgenic and littermate control mice after the images were filtered to lower spatial resolutions. We continued to detect significantly lower cingulate activity in the transgenic mice when the images were blurred to 0.50 mm, failed to detect significantly abnormal activity when the images were blurred to 0.75 mm, and, indeed, found significantly higher activity when the images were blurred to 1.0 mm. Reversal in direction of the abnormality appears attributable to a previously observed truncation in the corpus callosum in PDAPP mice. With the possible exception of future in vivo imaging techniques that have a spatial resolution greater than or equal to 0.50 mm and high sensitivity, noninvasive functional brain imaging techniques like PET may not be suitable for detecting declines in regional activity in PDAPP mice. It remains possible that these imaging techniques will prove useful in transgenic mouse lines that do not exhibit the same morphological abnormalities in neighboring white matter regions.

Alzheimer Disease↗

II. Temporal patterns of longitudinal change in aging brain function.

Time-dependent changes in brain activity were assessed in a group of older adults who maintained good physical and cognitive health at years 1, 3, 5, 7, and 9 of the Baltimore Longitudinal Study of Aging neuroimaging study. Each year, these participants underwent PET scans during rest and delayed verbal and figural recognition memory conditions. While memory performance remained stable over the 8 years, both generalized and modality-specific patterns of time-dependent changes in regional cerebral blood flow (rCBF) were found. Many brain regions showed steady, progressive changes in rCBF over the 8 years while others maintained rCBF for a number of years before showing incremental declines or increases in activity. These temporal patterns of change were observed in many regions of the brain, particularly in the frontal and temporal lobes, suggesting that there are distinctive patterns of age-related functional decline and compensatory activity over time. The precise patterns of regional involvement and the temporal dynamics of rCBF change within specific regions vary based on cognitive processing demands.

Aged↗

Functional brain imaging of young, nondemented, and demented older adults.

Brain imaging based on functional MRI (fMRI) provides a powerful tool for characterizing age-related changes in functional anatomy. However, between-population comparisons confront potential differences in measurement properties. The present experiment explores the feasibility of conducting fMRI studies in nondemented and demented older adults by measuring hemodynamic response properties in an event-related design. A paradigm involving repeated presentation of sensory-motor response trials was administered to 41 participants (14 young adults, 14 nondemented older adults, and 13 demented older adults). For half of the trials a single sensory-motor event was presented in isolation and in the other half in pairs. Hemodynamic response characteristics to the isolated events allowed basic response properties (e.g., amplitude and variance) between subject groups to be contrasted. The paired events further allowed the summation properties of the hemodynamic response to be characterized. Robust and qualitatively similar activation maps were produced for all subject groups. Quantitative results showed that for certain regions, such as in the visual cortex, there were marked reductions in the amplitude of the hemodynamic response in older adults. In other regions, such as in the motor cortex, relatively intact response characteristics were observed. These results suggest caution should be exhibited in interpreting simple main effects in response amplitude between subject groups. However, across all regions examined, the summation of the hemodynamic response over trials was highly similar between groups. This latter finding suggests that, even if absolute measurement differences do exist between subject groups, relative activation change should be preserved. Designs that rely on group interactions between task conditions, parametric manipulations, or group interactions between regions should provide valuable data for making inferences about functional-anatomic changes between different populations.

Adolescent↗

Functional brain networks in DYT1 dystonia.

Early-onset idiopathic torsion dystonia (ITD) is an autosomal dominant hyperkinetic movement disorder with incomplete penetrance, associated with a 3 base-pair deletion in the DYT1 gene on chromosome 9q34. To determine the metabolic substrates of brain dysfunction in DYT1 dystonia, we scanned 7 nonmanifesting and 10 affected DYT1 carriers and 14 normal volunteers with [18F]fluorodeoxyglucose and positron emission tomography. We found that DYT1 dystonia is mediated by the expression of two independent regional metabolic covariance patterns. The first pattern, identified in an analysis of nonmanifesting gene carriers was designated movement free (MF). This abnormal pattern was characterized by increased metabolic activity in the lentiform nuclei, cerebellum, and supplementary motor areas. The MF pattern was present in DYT1 carriers with and without clinical manifestations and persisted in DYT1 dystonia patients in whom involuntary movements were suppressed by sleep. The second pattern, identified in an analysis of affected gene carriers with sustained contractions at rest, was designated movement related (MR). This pattern was characterized by increased metabolic activity in the midbrain, cerebellum, and thalamus. The expression of the MR pattern was increased in waking DYT1 patients with sustained dystonia, compared with DYT1 carriers who were unaffected or who had dystonia only on action, as well as normal controls. MR subject scores declined significantly with sleep in affected DYT1 patients but not in normal controls. These findings indicate the penetrance of the DYT1 gene is considerably greater than previously assumed. ITD is mediated through the interaction of functional brain networks relating separately to gene status and to abnormal movement.

Adolescent↗

Functional brain mapping of psychopathology.

In this paper, we consider the impact that the novel functional neuroimaging techniques may have upon psychiatric illness. Functional neuroimaging has rapidly developed as a powerful tool in cognitive neuroscience and, in recent years, has seen widespread application in psychiatry. Although such studies have produced evidence for abnormal patterns of brain response in association with some pathological conditions, the core pathophysiologies remain unresolved. Although imaging techniques provide an unprecedented opportunity for investigation of physiological function of the living human brain, there are fundamental questions and assumptions which remain to be addressed. In this review we examine these conceptual issues under three broad sections: (1) characterising the clinical population of interest, (2) defining appropriate levels of description of normal brain function, and (3) relating these models to pathophysiological conditions. Parallel advances in each of these questions will be required before imaging techniques can impact on clinical decisions in psychiatry.

Brain↗

Magnetoencephalography in studies of human cognitive brain function.

Magnetoencephalography provides a new dimension to the functional imaging of the brain. The cerebral magnetic fields recorded noninvasively enable the accurate determination of locations of cerebral activity with an uncompromized time resolution. The first whole-scalp sensor arrays have just recently come into operation, and significant advances are to be expected in both neurophysiological and cognitive studies, as well as in clinical practice. However, although the accuracy of locating isolated sources of brain activity has improved, identification of multiple simultaneous sources can still be a problem. Therefore, attempts are being made to combine magnetoencephalography with other brain-imaging methods to improve spatial localization of multiple sources and, simultaneously, to achieve a more complete characterization of different aspects of brain activity during cognitive processing. Owing to its good time resolution and considerably better spatial accuracy than that provided by EEG, magnetoencephalography holds great promise as a tool for revealing information-processing sequences of the human brain.

Brain↗

The EEG, brain function, and Thomson's sampling theory.

If the EEG is regarded as a measure of functional organisation in the brain, it may yet be possible to use it as an independent variable in psychological studies. The method of Maxwell et al. (1974) suggest how this relationship may be quantified. These authors develop the hypothesis that EEG power is proportional to p, the number of brain components involved in cognition. However, evidence is reviewed here to suggest an alternative hypothesis for the case of EEG alpha activity, namely that power is proportional to (1--p).

Alpha Rhythm↗