Schizophrenia-risk variant rs6994992 in the neuregulin-1 gene on brain developmental trajectories in typically developing children.

The neuregulin-1 (NRG1) gene is one of the best-validated risk genes for schizophrenia, and psychotic and bipolar disorders. The rs6994992 variant in the NRG1 promoter (SNP8NRG243177) is associated with altered frontal and temporal brain macrostructures and/or altered white matter density and integrity in schizophrenic adults, as well as healthy adults and neonates. However, the ages when these changes begin and whether neuroimaging phenotypes are associated with cognitive performance are not fully understood. Therefore, we investigated the association of the rs6994992 variant on developmental trajectories of brain macro- and microstructures, and their relationship with cognitive performance. A total of 972 healthy children aged 3-20 years had the genotype available for the NRG1-rs6994992 variant, and were evaluated with magnetic resonance imaging (MRI) and neuropsychological tests. Age-by-NRG1-rs6994992 interactions and genotype effects were assessed using a general additive model regression methodology, covaried for scanner type, socioeconomic status, sex and genetic ancestry factors. Compared with the C-carriers, children with the TT-risk-alleles had subtle microscopic and macroscopic changes in brain development that emerge or reverse during adolescence, a period when many psychiatric disorders are manifested. TT-children at late adolescence showed a lower age-dependent forniceal volume and lower fractional anisotropy; however, both measures were associated with better episodic memory performance. To our knowledge, we provide the first multimodal imaging evidence that genetic variation in NRG1 is associated with age-related changes on brain development during typical childhood and adolescence, and delineated the altered patterns of development in multiple brain regions in children with the T-risk allele(s).

Methods of MRI-based structural imaging in the aging monkey.

Rhesus monkeys, whose typical lifespan can be as long as 30 years in the presence of veterinary care, undergo a cognitive decline as a function of age. While cortical neurons are largely preserved in the cerebral cortex, including primary motor and visual cortex as well as prefrontal association cortex there is marked breakdown of axonal myelin and an overall reduction in white matter predominantly in the frontal and temporal lobes. Whether the myelin breakdown is diffuse or specific to individual white matter fiber pathways is important to be known with certainty. To this end the delineation and quantification of specific frontotemporal fiber pathways within the frontal and temporal lobes is essential to determine which structures are altered and the extent to which these alterations correlate with behavioral findings. The capability of studying the living brain non-invasively with MRI opens up a new window in structural-functional and anatomic-clinical relationships allowing the integration of information derived from different scanning modalities in the same subject. For instance, for any particular voxel in the cerebrum we can obtain structural T1-, diffusion- and magnetization transfer- magnetic resonance imaging (MRI) based information. Moreover, it is thus possible to follow any observed changes longitudinally over time. These acquisitions of multidimensional data in the same individual within the same MRI experimental setting would enable the creation of a data base of integrated structural MRI-behavioral correlations for normal aging monkeys to elucidate the underlying neurobiological mechanisms of functional senescence in the aging non-human primate.

Towards further understanding of the co-morbidity between attention deficit hyperactivity disorder and bipolar disorder: a MRI study of brain volumes.

BACKGROUND: Although attention deficit hyperactivity disorder (ADHD) and bipolar disorder (BPD) co-occur frequently and represent a particularly morbid clinical form of both disorders, neuroimaging research addressing this co-morbidity is scarce. Our aim was to evaluate the morphometric magnetic resonance imaging (MRI) underpinnings of the co-morbidity of ADHD with BPD, testing the hypothesis that subjects with this co-morbidity would have neuroanatomical correlates of both disorders. METHOD: Morphometric MRI findings were compared between 31 adults with ADHD and BPD and with those of 18 with BPD, 26 with ADHD, and 23 healthy controls. The volumes (cm(3)) of our regions of interest (ROIs) were estimated as a function of ADHD status, BPD status, age, sex, and omnibus brain volume using linear regression models. RESULTS: When BPD was associated with a significantly smaller orbital prefrontal cortex and larger right thalamus, this pattern was found in co-morbid subjects with ADHD plus BPD. Likewise, when ADHD was associated with significantly less neocortical gray matter, less overall frontal lobe and superior prefrontal cortex volumes, a smaller right anterior cingulate cortex and less cerebellar gray matter, so did co-morbid ADHD plus BPD subjects. CONCLUSIONS: Our results support the hypothesis that ADHD and BPD independently contribute to volumetric alterations of selective and distinct brain structures. In the co-morbid state of ADHD plus BPD, the profile of brain volumetric abnormalities consists of structures that are altered in both disorders individually. Attention to co-morbidity is necessary to help clarify the heterogeneous neuroanatomy of both BPD and ADHD.

fMRI of sensitization to angry faces.

This study examined what is communicated by facial expressions of anger and mapped the neural substrates, evaluating the motivational salience of these stimuli. During functional magnetic resonance imaging, angry and neutral faces were presented to human subjects. Across experimental runs, signal adaptation was observed. Whereas fearful faces have reproducibly evoked response habituation in amygdala and prefrontal cortex, angry faces evoked sensitization in the insula, cingulate, thalamus, basal ganglia, and hippocampus. Complementary offline rating and keypress experiments determined an aversive rank ordering of angry, fearful, neutral, and happy faces and revealed behavioral sensitization to the angry faces. Subjects rated angry faces, in contrast to other face categories such as fear, as significantly more likely to directly inflict harm. Furthermore, they rated angry faces as significantly less likely to produce positive emotional outcomes than the other face categories. Together these data argue that angry faces, a directly aversive stimulus, produce a sensitization response.

Brain asymmetries in autism and developmental language disorder: a nested whole-brain analysis.

We report a whole-brain MRI morphometric survey of asymmetry in children with high-functioning autism and with developmental language disorder (DLD). Subjects included 46 boys of normal intelligence aged 5.7-11.3 years (16 autistic, 15 DLD, 15 controls). Imaging analysis included grey-white segmentation and cortical parcellation. Asymmetry was assessed at a series of nested levels. We found that asymmetries were masked with larger units of analysis but progressively more apparent with smaller units, and that within the cerebral cortex the differences were greatest in higher-order association cortex. The larger units of analysis, including the cerebral hemispheres, the major grey and white matter structures and the cortical lobes, showed no asymmetries in autism or DLD and few asymmetries in controls. However, at the level of cortical parcellation units, autism and DLD showed more asymmetry than controls. They had a greater aggregate volume of significantly asymmetrical cortical parcellation units (leftward plus rightward), as well as a substantially larger aggregate volume of right-asymmetrical cortex in DLD and autism than in controls; this rightward bias was more pronounced in autism than in DLD. DLD, but not autism, showed a small but significant loss of leftward asymmetry compared with controls. Right : left ratios were reversed, autism and DLD having twice as much right- as left-asymmetrical cortex, while the reverse was found in the control sample. Asymmetry differences between groups were most significant in the higher-order association areas. Autism and DLD were much more similar to each other in patterns of asymmetry throughout the cerebral cortex than either was to controls; this similarity suggests systematic and related alterations rather than random neural systems alterations. We review these findings in relation to previously reported volumetric features in these two samples of brains, including increased total brain and white matter volumes and lack of increase in the size of the corpus callosum. Larger brain volume has previously been associated with increased lateralization. The sizeable right-asymmetry increase reported here may be a consequence of early abnormal brain growth trajectories in these disorders, while higher-order association areas may be most vulnerable to connectivity abnormalities associated with white matter increases.

Bilateral volume reduction of the superior temporal areas in Landau-Kleffner syndrome.

No specific anatomic abnormalities have been detected in typical Landau-Kleffner syndrome (LKS), an acquired epileptic aphasia with language regression in children. In four children with typical LKS without obvious anatomic abnormalities, the authors performed MRI volumetric analysis of various neocortical regions and subcortical substructures. Volume reduction was detected in bilateral superior temporal areas (26 to 51%), specifically in planum temporale (25 to 63%) and superior temporal gyrus (25 to 57%), where receptive language is localized.

Holoprosencephaly--topologic variations in a liveborn series: a general model based upon MRI analysis.

We present an MRI-based anatomic analysis of a series of 9 human brains, representing lobar, semilobar and alobar forms of holoprosencephaly. The analysis of these variable forms of the malformation is based upon a topologic systematics established in a prior analysis of a homogeneous set of semilobar malformations. This systematics has the dual advantage that it serves both as a uniform reference for qualitative description and as a quantitative descriptive base for mathematical correlations between parameters of topology and of growth and development. Within this systematics, the prosencephalic midline is divided from caudal to rostral into diencephalic (DD-right and left, subthalamus through suprachiasmatic junction with telencephalon), telencephalic (TT-right and left, suprachiasmatic border of telencephalon midline to hippocampal commissure) and diencephalic-telencephalic (DT-right and left-hippocampal commissure through temporal limb of choroid fissure) segments. The topologic abnormality of the initial semilobar series was expressed in an orderly rostral to caudal gradient along the TT segment. In each malformation, normal midline topology began with a small posterior corpus callosum. Although the topologic anomaly in the present series invariably also involved the TT segment, this involvement was not continuous and was variably associated with anomalies of the DD in 6 and unilaterally of the DT in 1 brain. In the present as well as with the earlier series of HPE malformations but not in "normative brains," total telencephalic growth is strongly correlated with the length of the midline telencephalic segment. We propose that this system of analysis will be sensitive to the developmental stage and locus of expression of genetic and non-genetic determinants of the formal origin of HPE. For all of the present series, karyotype anlyses were normal. Mutations in the Shh and Zic2 genes were excluded in 2 cases.

Semilobar holoprosencephaly with midline 'seam': a topologic and morphogenetic model based upon MRI analysis.

We present an MRI-based anatomic analysis of a series of seven human brains with the semilobar form of holoprosencephaly. The analysis defines a set of common descriptors for a pattern of topological anomaly which is uniform for the set of seven brains. The core of the anomaly is a rostro-caudally aligned midline gray matter 'seam' that extends from the telencephalic-suprachiasmatic junctional region to abut the posterior aspect of the callosal commissure. The seam forms the ventricular roof throughout its extent. Rostrally it is formed by the conjoined heads of caudate/accumbens nuclei. It continues caudally as a gray matter bridge in the fundus of the interhemispheric fissure, where it bridges right and left neocortex. Fornix, septal nuclei and septal limb of the choroid plexus are absent, and the telencephalic ventricles communicate with the diencephalic via open septal limbs of the choroid fissures. By contrast, the temporal limb of hippocampal formation and the choroid plexus are normal and the temporal limb of the choroid fissure is closed. This topological anomaly of conjoined left and right cortical and nuclear gray matter into a midline seam and absent septal structures is thus confined to the region of the midline telencephalic hemisphere evagination. Total telencephalic growth is strongly correlated with the length of this topologically abnormal midline telencephalic segment. The set of findings is consistent with graded failure of induction of rostral to caudal specification in the midline rostral telencephalic zone.

Anatomy of stroke, Part II: volumetric characteristics with implications for the local architecture of the cerebral perfusion system.

BACKGROUND AND PURPOSE: The margin of a stroke is assumed to approximate a trace of the isobar of the perfusion threshold for infarction at the time that infarction occurred. Working from this hypothesis, we have analyzed stroke topography and volume in MR images obtained at a time remote from the stroke event. We have derived parameters from these images that may give information on local perfusion competence and microvascular architecture because they influenced the contour of stroke at the time infarction occurred. METHODS: MR images were obtained months after presumed embolic middle cerebral artery stroke in 21 subjects. Volumetric analyses of image data were undertaken with respect to the tissue shape of stroke and scaling ratios of anatomic partitions involved in stroke. RESULTS: For stroke confined to a single volume, the 3-dimensional form conforms to a parabola in which the height-to-width ratios are variable. The ratio for cortex is greater than that for underlying white matter. Scaling ratios indicate a close correlation between volume of cortex and radiata destroyed and total volume of stroke, but the relative proportions vary as a function of location within the M4 territory. CONCLUSIONS: Scaling ratios for cortex and radiata to stroke volume are consistent with vascular studies that depict a modular microvascular perfusion architecture for the cortex and underlying white matter. The stroke descriptors are inferred to be related to the competence of collateral perfusion at the time that stroke occurred. This inference may be tested by serial volumetric analysis of the perfusion-diffusion examination mismatch immediately and over the longer-term evolution of stroke.

Anatomy of stroke, Part I: an MRI-based topographic and volumetric System of analysis.

BACKGROUND AND PURPOSE: The clinical diagnosis and treatment of stroke, as well as investigations into the underlying pathophysiology of the disease, hinge on inferences from the anatomy of the stroke lesion. We describe an MRI-based system of topographic and volumetric analysis that considers distribution of infarct with respect to neuroanatomic structures, superficial and deep perfusion compartments, and gray and white matter tissue types. METHODS: MRI-based 3-dimensional topographic and volumetric analysis of presumed MCA embolic stroke was performed months after the acute event in 21 subjects ranging in age from 34 to 75 years. RESULTS: The topography of infarction was greatly variable, with virtually all regions of the MCA territory involved in at least 1 stroke in the series. In 14, there was involvement of the M1 as well as the M2 through M4 territories; in 6, there was involvement of only the M2 through M4 territories; and in 2, there was involvement of only the M1 territory. The volumes varied from 3.1 to 256 cm3, corresponding approximately to a range of 1% to 90% of the total MCA territory. CONCLUSIONS: The system of topographic and volumetric analysis is generally applicable to all strokes in the forebrain where the infarct is visualized in MRI, independent of vascular territory, clinical correlates, and interval between stroke and MRI. The results emphasize the variety of topographic patterns and lesion volumes of strokes. Intended long-range applications include correlation of outcome of stroke with predictions from acute-phase diffusion- and perfusion-weighted imaging and investigations of the potential benefit of therapeutic agents.

Striatal volume loss in HD as measured by MRI and the influence of CAG repeat.

BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease that results from the expansion of a trinucleotide (CAG) repeat on chromosome 4. Progressive degeneration of the striatum is the pathologic hallmark of the disease. Little is known about the regional selectivity of the neurodegeneration and its relationship to the genetic expansion. METHODS: The authors used high-resolution MRI to determine the relationship between the genetic expansion and the degree of striatal degeneration. Morphometric analyses of the striatum from high-resolution MR images from 27 subjects with HD were compared with those of 24 healthy control subjects. RESULTS AND CONCLUSIONS: Striatal volumes were reduced in subjects with HD as compared with control subjects, in agreement with previously published reports. Left-sided volumes were smaller than right-sided volumes in subjects with HD; in healthy subjects, right-sided volumes were smaller. Finally, volume loss was significantly correlated with CAG repeat number. These results have potential implications for the design and assessment of therapeutic agents in the future.

Test-retest reliability of a functional MRI working memory paradigm in normal and schizophrenic subjects.

OBJECTIVE: Repeated functional magnetic resonance imaging (fMRI) studies of schizophrenic subjects may identify brain activity changes in response to interventions. To interpret the findings, however, it is crucial to know the test-retest reliability of the measures used. METHOD: The authors scanned seven normal subjects and seven schizophrenic subjects on two occasions during performance of a working memory task. They quantified the reliability of task performance and brain activation. RESULTS: In both groups, task performance was reliable, and all a priori regions were activated in group-averaged test and retest data. In individual schizophrenic subjects, however, indices of cognitive activation were not reliable across sessions. Normal subjects showed reasonable reliability of activation. CONCLUSIONS: Even given reliable task performance, stable clinical status, and a stable pattern of group-averaged activation, individual subjects showed unreliable brain activation. This suggests that repeated fMRI studies of schizophrenia should control for sources of variation, both artifactual and intrinsic.

Normal sexual dimorphism of the adult human brain assessed by in vivo magnetic resonance imaging.

The etiology and consistency of findings on normal sexual dimorphisms of the adult human brain are unresolved. In this study, we present a comprehensive evaluation of normal sexual dimorphisms of cortical and subcortical brain regions, using in vivo magnetic resonance imaging, in a community sample of 48 normal adults. The men and women were similar in age, education, ethnicity, socioeconomic status, general intelligence and handedness. Forty-five brain regions were assessed based on T(1)-weighted three-dimensional images acquired from a 1.5 T magnet. Sexual dimorphisms of adult brain volumes were more evident in the cortex, with women having larger volumes, relative to cerebrum size, particularly in frontal and medial paralimbic cortices. Men had larger volumes, relative to cerebrum size, in frontomedial cortex, the amygdala and hypothalamus. A permutation test showed that, compared to other brain areas assessed in this study, there was greater sexual dimorphism among brain areas that are homologous with those identified in animal studies showing greater levels of sex steroid receptors during critical periods of brain development. These findings have implications for developmental studies that would directly test hypotheses about mechanisms relating sex steroid hormones to sexual dimorphisms in humans.

A magnetic resonance imaging study of regional cortical volumes following stereotactic anterior cingulotomy.

The purpose of this study was to test the hypothesis that orbitofrontal cortical volume would be reduced following anterior cingulotomy for obsessive-compulsive disorder (OCD). Whole brain cortical parcellation was performed on magnetic resonance imaging (MRI) data from nine patients, before and 9 (+/-6) months following anterior cingulotomy. No significant volumetric reductions were found in the orbitofrontal cortex. Exploratory findings of reduced volume in ventral temporo-fusiform and posterior cingulate regions were consistent with chance differences, in the face of multiple comparisons. Therefore, though the circumscribed lesions of anterior cingulotomy have recently been associated with corresponding volumetric reductions in the caudate nucleus, no comparable volumetric reductions are evident in cortical territories. Taken together, these results are most consistent with a model of cingulo-striatal perturbation as a putative mechanism for the efficacy of this procedure. While limitations in sensitivity may have also contributed to these negative findings, the methods employed have previously proven sufficient to detect cortical volumetric abnormalities in OCD. The current results may reflect a relatively diffuse pattern of cortico-cortical connections involving the neurons at the site of cingulotomy lesions. Future functional neuroimaging studies are warranted to assess possible cortical or subcortical metabolic changes associated with anterior cingulotomy, as well as predictors of treatment response.

Volume reduction in the caudate nucleus following stereotactic placement of lesions in the anterior cingulate cortex in humans: a morphometric magnetic resonance imaging study.

OBJECT: The goal of this study was to test hypotheses regarding changes in volume in subcortical structures following anterior cingulotomy. METHODS: Morphometric magnetic resonance (MR) imaging methods were used to assess volume reductions in subcortical regions following anterior cingulate lesioning in nine patients. Magnetic resonance imaging data obtained before and 9 +/- 6 months following anterior cingulotomy were subjected to segmentation and subcortical parcellation. Significant volume reductions were predicted and found bilaterally within the caudate nucleus, but not in the amygdala, thalamus, lenticular nuclei, or hippocampus. Subcortical parcellation revealed that the volume reduction in the caudate nucleus was principally referrable to the body, rather than the head. Furthermore, the magnitude of volume reduction in the caudate body was significantly correlated with total lesion volume. CONCLUSIONS: Taken together, these findings implicate significant connectivity between a region of anterior cingulate cortex (ACC) lesioned during cingulotomy and the caudate body. This unique data set complements published findings in nonhuman primates, and advances our knowledge regarding patterns of cortical-subcortical connectivity involving the ACC in humans. Moreover, these findings indicate changes distant from the site of anterior cingulotomy lesions that may play a role in the clinical response to this neurosurgical procedure.

Advanced applications of MRI in human brain science.

Magnetic resonance imaging of the brain is now generally indispensable to state of art clinical medicine. Robust, high resolution imaging systems are currently available worldwide. The availability of MRI has, in little more than a decade, revolutionized the certainty and efficiency of clinical diagnosis and management. As a dividend of this revolution, clinicians and radiologists who are expert in the many and varied applications of MRI methods are able to relate this expertise to a confident mastery of the topographic anatomy of the brain as revealed in magnetic resonance images. Whereas the yield to clinical objectives has been massive, the clinician as yet draws upon a relatively limited sampling of the potential informational harvest from this technology which in theory could further enrich both clinical concerns and those of fundamental neuroscience. Here we will review early explorations into these other offerings with the expectation that the coming decade will see them established comfortably with current uses. We will also consider potential offerings of the extended applications of brain MRI to the characterization and insights into biological origins of certain obscure developmental disorders.

High microvascular blood volume is associated with high glucose uptake and tumor angiogenesis in human gliomas.

The purpose of this investigation was to elucidate the association between microvascular blood volume and glucose uptake and to link these measures with tumor angiogenesis. We demonstrate a regionally specific correlation between tumor relative microvascular blood volume (CBV), determined in vivo with functional magnetic resonance imaging techniques, and tumor glucose uptake determined with fluorodeoxyglucose positron emission tomography. Regions of maximum glucose uptake were well matched with maximum CBV across all patients (n = 21; r = 0.572; P = 0.023). High-grade gliomas showed significantly elevated CBV and glucose uptake compared with low-grade gliomas, (P = 0.009 and 0.008, respectively). Correlations between CBV and glucose uptake were then determined on a voxel-by-voxel basis within each patient's glioma. Correlation indices varied widely, but in 16 of 21 cases of human glioma, CBV and glucose uptake were correlated (r > 0.150). These measures were well correlated in all cases when comparing healthy brain tissue in these same patients. Tumor vascularity, as determined immunohistochemically and morphometrically on clinical samples, revealed statistically significant relationships with functional imaging characteristics in vivo. Regional heterogeneities in glucose uptake were well matched with functional magnetic resonance imaging CBV maps. Our findings support the concept that there is an association of microvascular density and tumor energy metabolism in most human gliomas. In addition, the findings are likely to have important clinical applications in the initial evaluation, treatment, and longitudinal monitoring of patients with malignant gliomas.

A twin MRI study of size variations in human brain.

Although it is well known that there is considerable variation among individuals in the size of the human brain, the etiology of less extreme individual differences in brain size is largely unknown. We present here data from the first large twin sample (N=132 individuals) in which the size of brain structures has been measured. As part of an ongoing project examining the brain correlates of reading disability (RD), whole brain morphometric analyses of structural magnetic response image (MRI) scans were performed on a sample of adolescent twins. Specifically, there were 25 monozygotic (MZ) and 23 dizygotic (DZ) pairs in which at least one member of each pair had RD and 9 MZ and 9 DZ pairs in which neither member had RD. We first factor-analyzed volume data for 13 individual brain structures, comprising all of the neocortex and most of the subcortex. This analysis yielded two factors ("cortical" and "subcortical") that accounted for 64% of the variance. We next tested whether genetic and environmental influences on brain size variations varied for these two factors or by hemisphere. We computed intraclass correlations within MZ and DZ pairs in each sample for the cortical and subcortical factor scores, for left and right neocortex, and for the total cerebral volume. All five MZ correlations were substantial (r's=.78 to.98) and significant in both samples, as well as being larger than the corresponding DZ correlations, (r's=0.32 to 0.65) in both samples. The MZ-DZ difference was significant for 3 variables in the RD sample and for one variable in the smaller control sample. These results indicate significant genetic influences on these variables. The magnitude of genetic influence did not vary markedly either for the 2 factors or the 2 hemispheres. There was also a positive correlation between brain size and full-scale IQ, consistent with the results of earlier studies. The total cerebral volume was moderately correlated (r=.42, p<.01, two-tailed) with full-scale IQ in the RD sample; there was a similar trend in the smaller control sample (r=.31, p<.07, two-tailed). Corrections of similar magnitude were found between the subcortical factor and full-scale IQ, whereas the results for the cortical factor (r=.16 and.13) were smaller and not significant. In sum, these results provide evidence for the heritability of individual differences in brain size which do not vary markedly by hemisphere or for neocortex relative to subcortex. Since there are also correlations between brain size and full-scale IQ in this sample, it is possible that genetic influences on brain size partly contribute to individual differences in IQ.

Acupuncture modulates the limbic system and subcortical gray structures of the human brain: evidence from fMRI studies in normal subjects.

Acupuncture, an ancient therapeutic technique, is emerging as an important modality of complementary medicine in the United States. The use and efficacy of acupuncture treatment are not yet widely accepted in Western scientific and medical communities. Demonstration of regionally specific, quantifiable acupuncture effects on relevant structures of the human brain would facilitate acceptance and integration of this therapeutic modality into the practice of modern medicine. Research with animal models of acupuncture indicates that many of the beneficial effects may be mediated at the subcortical level in the brain. We used functional magnetic resonance imaging (fMRI) to investigate the effects of acupuncture in normal subjects and to provide a foundation for future studies on mechanisms of acupuncture action in therapeutic interventions. Acupuncture needle manipulation was performed at Large Intestine 4 (LI 4, Hegu) on the hand in 13 subjects [Stux, 1997]. Needle manipulation on either hand produced prominent decreases of fMRI signals in the nucleus accumbens, amygdala, hippocampus, parahippocampus, hypothalamus, ventral tegmental area, anterior cingulate gyrus (BA 24), caudate, putamen, temporal pole, and insula in all 11 subjects who experienced acupuncture sensation. In marked contrast, signal increases were observed primarily in the somatosensory cortex. The two subjects who experienced pain instead of acupuncture sensation exhibited signal increases instead of decreases in the anterior cingulate gyrus (BA 24), caudate, putamen, anterior thalamus, and posterior insula. Superficial tactile stimulation to the same area elicited signal increases in the somatosensory cortex as expected, but no signal decreases in the deep structures. These preliminary results suggest that acupuncture needle manipulation modulates the activity of the limbic system and subcortical structures. We hypothesize that modulation of subcortical structures may be an important mechanism by which acupuncture exerts its complex multisystem effects.

Structural and functional brain asymmetries in human situs inversus totalis.

OBJECTIVE: To determine whether individuals with situs inversus totalis (SI), a condition in which there is a mirror-image reversal of asymmetric visceral organs, have alterations in brain asymmetries. BACKGROUND: The human brain is asymmetric in structure and function. Although correlations between anatomic asymmetries and functional lateralization in human brain have been demonstrated, it has been difficult to further analyze them. Characterization of asymmetries of brain structure and function in SI might advance the understanding of these relationships. METHODS: Using anatomic and functional MRI techniques, we analyzed asymmetries in the brains of three individuals with SI. RESULTS: Two major anatomic asymmetries of the cerebral hemispheres, the frontal and occipital petalia, were reversed in individuals with SI. In contrast, SI subjects had left cerebral hemisphere language dominance on functional MRI analysis as well as strong right-handedness. CONCLUSION: These observations suggest that the developmental factors determining anatomic asymmetry of the cerebral petalia and viscera are distinct from those producing the functional lateralization of language.