Neuroplasticity in human callosal dysgenesis: a diffusion tensor imaging study

Callosal dysgenesis (CD) is observed in many neurodevelopmental conditions, but its subjacent mechanisms are unknown, despite extensive research on animals. Here we employ magnetic resonance diffusion tensor imaging and tractography in human CD to reveal the aberrant circuitry of these brains. We searched particularly for evidence of plasticity. Four main findings are described--1) in the presence of a callosal remnant or a hypoplastic corpus callosum (CC), fibers therein largely connect the expected neocortical regions; 2) callosal remnants and hypoplastic CCs display a fiber topography similar to normal; 3) at least 2 long abnormal tracts are formed in patients with defective CC: the well-known Probst bundle (PB) and a so far unknown sigmoid, asymmetrical aberrant bundle connecting the frontal lobe with the contralateral occipitoparietal cortex; and 4) whereas the PB is topographically organized and has an ipsilateral U-connectivity, the sigmoid bundle is a long, heterotopic commissural tract. These observations suggest that when the developing human brain is confronted with factors that hamper CC fibers to cross the midline, some properties of the miswired fibers are maintained (such as side-by-side topography), whereas others are dramatically changed, leading to the formation of grossly abnormal white matter tracts.     

Parasagittal asymmetries of the corpus callosum

Significant relationships have been reported between midsagittal areas of the corpus callosum and the degree of interhemispheric transfer, functional lateralization and structural brain asymmetries. No study, however, has examined whether parasagittal callosal asymmetries (i.e. those close to the midline of the brain), which may be of specific functional consequence, are present in the human brain. Thus, we applied magnetic resonance imaging and novel computational surface-based methods to encode hemispheric differences in callosal thickness at a very high resolution. Discrete callosal areas were also compared between the hemispheres. Furthermore, acknowledging the frequently reported sex differences in callosal morphology, parasagittal callosal asymmetries were examined within each gender. Results showed significant rightward asymmetries of callosal thickness predominantly in the anterior body and anterior third of the callosum, suggesting a more diffuse functional organization of callosal projections in the right hemisphere. Asymmetries were increased in men, supporting the assumption of a sexually dimorphic organization of male and female brains that involves hemispheric relations and is reflected in the organization and distribution of callosal fibers.     

The size of corpus callosum correlates with functional activation of medial motor cortical areas in bimanual and unimanual movements

Effects of the size of corpus callosum measured from in vivo magnetic resonance imaging (MRI) recordings on cortical activations evaluated using functional MRI (fMRI) were analyzed during motor tasks. Twelve right-handed men performed unilateral finger movements and bilateral movements either with or without a temporal delay between left and right fingers. The size of the rostral part of corpus callosum and the anterior and posterior callosal truncus explained 11.9 and 15.2% of activation in the mesial frontal cortex in unimanual left and right finger movements, respectively. In bimanual simultaneous movements, 34.2% of the activated voxels in the mesial frontal cortex were related to the size of corpus callosum. In bimanual movements in which left finger movement preceded the onset of the right finger movement, the callosal size accounted for 88.7% of activation in the mesial frontal cortex. In contrast, when the right finger movement preceded the left, callosal size accounted for only 31.3% of the mesial frontal cortex activation. The correlations between callosal parameters and activation over the lateral cortex were sparse and occurred only in bimanual movements. The results suggest that corpus callosum modulates the activity of the supplementary motor and cingulate cortical areas depending on temporal complexity of bimanual movements.     

Selective age-related degradation of anterior callosal fiber bundles quantified in vivo with fiber tracking

The corpus callosum, the principal white matter structure enabling interhemispheric information transfer, is heterogeneous in its microstructural composition, heterotopic in its anteroposterior cortical connectivity, and differentially susceptible to aging. In vivo characterization of callosal features is possible with diffusion tensor imaging (DTI), a magnetic resonance imaging method sensitive to the detection of white matter's linear structure. We implemented a quantitative fiber tracking approach to examine age-related variation in regional microstructural characteristics [fractional anisotropy (FA) and apparent diffusion coefficient (ADC)] of callosal fibers in 10 younger (29 +/- 5 years) and 10 older (72 +/- 5 years) healthy adults. Fiber tracking was performed on 2.5 mm isotropic voxels collected at 3 T. Fiber targets comprised the midsagittal corpus callosum, divided into six regions based on known callosal anatomical projections. FA and ADC for each voxel of each fiber identified were determined; lower FA and higher ADC reflect degraded microstructural tissue integrity. Older subjects had lower FA (P < 0.002), higher ADC (P < 0.006), and fewer (P < 0.005) fibers than younger subjects. Group x region interactions indicated disproportionately lower FA (P = 0.0001) and higher ADC (P < 0.006) in the older than younger group in frontal fiber bundles relative to posterior bundles. As a test of the functional significance of the fiber bundle metrics, the older subjects were administered the Stroop Task, which showed significant correlations between regional fiber bundle integrity and performance. These results validate this quantitative fiber tracking approach and confirm the selective vulnerability of frontal white matter systems to normal aging, likely substrates of age-related declines in cognitive processes dependent on prefrontal circuitry integrity.     

Dissociated pathways for successful memory retrieval from the human parietal cortex: anatomical and functional connectivity analyses

The parietal cortex has traditionally been implicated in spatial attention and eye-movement processes. Recent functional neuroimaging studies have found that activation in the parietal cortex is related to successful recognition memory. The activated regions consistently include the intraparietal sulcus in the lateral parietal cortex and the precuneus in the medial parietal cortex. However, little is known about the functional differences between lateral and medial parietal cortices in the memory retrieval process. In this study, we examined whether the human lateral and medial parietal lobes have differential anatomical and functional connectivity with the temporal lobe. To this end, we used functional magnetic resonance imaging to constrain the analysis of anatomical connectivity obtained by diffusion tensor imaging (DTI). Both DTI tractography and functional connectivity analysis showed that the lateral parietal region has anatomical and functional connections with the lateral temporal lobe, and the medial parietal region has connections with the medial temporal lobe. These results suggest the existence of segregated lateral and medial parieto-temporal pathways in successful memory retrieval.     

Diffusion tensor imaging reveals white matter reorganization in early blind humans

Multiple functional methods including functional magnetic resonance imaging, transcranial magnetic stimulation, and positron emission tomography have shown cortical reorganization in response to blindness. We investigated microanatomical correlates of this reorganization using diffusion tensor imaging and diffusion tensor tractography (DTT). Five early blind (EB) were compared with 7 normally sighted (NS) persons. DTT showed marked geniculocalcarine tract differences between EB and NS participants. All EB participants showed evidence of atrophy of the geniculocortical tracts. Connections between visual cortex and the orbital frontal and temporal cortices were relatively preserved in the EB group. Importantly, no additional tracts were found in any EB participant. Significant alterations of average diffusivity and relative anisotropy were found in the white matter (WM) of the occipital lobe in the EB group. These observations suggest that blindness leads to a reorganization of cerebral WM and plausibly support the hypothesis that visual cortex functionality in blindness is primarily mediated by corticocortical as opposed to thalamocortical connections.     

Diffusion tensor imaging in the corpus callosum in children after moderate to severe traumatic brain injury

Diffusion tensor imaging (DTI) is a recent imaging technique that assesses the microstructure of the cerebral white matter (WM) based on anisotropic diffusion (i.e., water molecules move faster in parallel to nerve fibers than perpendicular to them). Fractional anisotropy (FA), which ranges from 0 to 1.0, increases with myelination of WM tracts and is sensitive to diffuse axonal injury (DAI) in adults with traumatic brain injury (TBI). However, previous DTI studies of pediatric TBI were case reports without detailed outcome measures. Using mean FA derived from DTI fiber tractography, we compared DTI findings of the corpus callosum for 16 children who were at least 1 year (mean 3.1 years) post-severe TBI and individually matched, uninjured children. Interexaminer and intraexaminer reliability in measuring FA was satisfactory. FA was significantly lower in the patients for the genu, body, and splenium of the corpus callosum. Higher FA was related to increased cognitive processing speed and faster interference resolution on an inhibition task. In the TBI patients, higher FA was related to better functional outcome as measured by the dichotomized Glasgow Outcome Scale (GOS). FA also increased as a function of the area of specific regions of the corpus callosum such as the genu and splenium, and FA in the splenium was reduced with greater volume of lesions in this region. DTI may be useful in identifying biomarkers related to DAI and outcome of TBI in children.     

高定义角度纤维追踪技术重建人脑颞顶枕区短纤维束连接

目的观察人脑颞顶枕区短纤维束连接的空间走行、皮质连接及三维空间关系。方法对10名健康志愿者进行MR扫描。下载90名健康志愿者的弥散谱成像(DSI)综合数据模板(NTU-90)。应用高定义角度纤维束追踪技术(HDFT)对所收集数据进行人脑颞顶枕区3条短纤维束连接[上纵束的垂直部(SLF-V)、枕纵束(VOF)和颞顶束(TP)]重建,并分析其纤维走行、皮质连接、空间三维关系及左右侧别差异。结果 3条纤维束在10名志愿者和NTU-90中均重建成功。SLF-V纤维束起源于颞中回和颞下回后部,终止于角回和缘上回;VOF纤维束起源于下枕叶和梭状回,少量纤维来源于颞下回的后部和枕极前部,终止点位于角回和上枕叶外侧部;TP纤维束主要起源于颞中回、颞下回、梭状回和下颞-下枕结合部,连接于顶上小叶;左右侧SLF-V、VOF和TP的纤维束体积差异无统计学意义(P均0.05)。结论应用HDFT纤维束成像技术成功重建了SLF-V、VOF和TP,可为脑功能研究和神经外科手术提供解剖学依据。     

Corpus callosal microstructural integrity influences interhemispheric processing: a diffusion tensor imaging study

Normal aging and chronic alcoholism result in disruption of brain white matter microstructure that does not typically cause complete lesions but may underlie degradation of functions requiring interhemispheric information transfer. We examined whether the microstructural integrity of the corpus callosum assessed with diffusion tensor imaging (DTI) would relate to interhemispheric processing speed. DTI yields estimates of fractional anisotropy (FA), a measure of orientation and intravoxel coherence of water diffusion usually in white matter fibers, and diffusivity (), a measure of the amount of intracellular and extracellular fluid diffusion. We tested the hypothesis that FA and would be correlated with (i) the crossed-uncrossed difference (CUD), testing visuomotor interhemispheric transfer; and (ii) the redundant targets effect (RTE), testing parallel processing of visual information presented to each cerebral hemisphere. FA was lower and higher in alcoholics than in controls. In controls but not alcoholics, large CUDs correlated with low FA and high in total corpus callosum and regionally in the genu and splenium. In alcoholics but not controls, small RTEs, elicited with equiluminant stimuli, correlated with low FA in genu and splenium and high in the callosal body. The results provide in vivo evidence for disruption of corpus callosum microstructure in normal aging and alcoholism that has functional ramifications for efficiency in interhemispheric processing.     

White matter pathway asymmetry underlies functional lateralization

Structural and functional asymmetry of the human brain has been well documented using techniques such as magnetic resonance imaging (MRI). However, asymmetry of underlying white matter connections is less well understood. We applied an MRI technique known as diffusion tensor tractography to reveal the morphology of the white matter in vivo by mapping directions of maximum water diffusion in brain tissue. White matter pathway asymmetry was investigated in a normalized image data set of 30 right-handed young healthy individuals. We identified, for the first time, a rightwardly asymmetric pathway connecting the posterior temporal lobe to the superior parietal lobule. This pathway may be related to auditory spatial attention and working memory for which there is evidence for a rightward laterality from functional imaging studies. Additional leftward asymmetries connecting the parietal and frontal lobes to the temporal lobe may be more closely related to laterality of language.     

The relation between connection length and degree of connectivity in young adults: a DTI analysis

Using diffusion tensor imaging and tractography to detail the patterns of interhemispheric connectivity and to determine the length of the connections, and formulae based on histological results to estimate degree of connectivity, we show that connection length is negatively correlated with degree of connectivity in the normal adult brain. The degree of interhemispheric connectivity--the ratio of interhemispheric connections to total corticocortical projection neurons--was estimated for each of 5 subregions of the corpus callosum in 22 normal males between 20 and 45 years of age (mean 31.68; standard deviation 8.75), and the average length of the longest tracts passing through each point of each subregion was calculated. Regression analyses were used to assess the relation between connection length and the degree of connectivity. Connection length was negatively correlated with degree of connectivity in all 5 subregions, and the regression was significant in 4 of the 5, with an average r(2) of 0.255. This is contrasted with previous analyses of the relation between brain size and connectivity, and connection length is shown to be a superior predictor. The results support the hypothesis that cortical networks are optimized to reduce conduction delays and cellular costs.     

Anatomical landmarks for hemispherotomy and their clinical application

OBJECT: The authors introduce the surgical concept of the central core of a hemisphere, from which anatomical structures are disconnected during most current hemispherotomy techniques. They also propose key anatomical landmarks for hemispherotomies that can be used to disconnect the hemisphere from its lateral surface around the insula, through the lateral ventricle toward the midline. METHODS: This anatomical study was performed in five adult cadaveric heads following perfusion of the cerebral arteries and veins with colored latex. Anatomical landmarks were used in five hemispheric deafferentations. The central core of a hemisphere consists of extreme, external, and internal capsules; claustrum; lentiform and caudate nuclei; and thalamus. Externally, this core is covered by the insula and surrounded by the fornix, choroid plexus, and lateral ventricle. During most hemispherotomies, the surgeon reaches the lateral ventricle through the frontoparietal opercula or temporal lobe; removes the mesial temporal structures; and disconnects the frontal lobe ahead, the parietal and occipital lobes behind, and the intraventricular fibers of the corpus callosum above the central core. After a temporal lobectomy, the landmarks include the choroid plexus and posterior/ascending portion of the tentorium to disconnect the parietal and occipital lobes, the callosal sulcus or distal anterior cerebral artery (ACA) to sever the intraventricular fibers of the corpus callosum, and the head of the caudate nucleus and ACA to detach the frontal lobe. CONCLUSIONS. These landmarks can be used in any hemispherotomy during which a cerebral hemisphere is disconnected from its lateral surface. Furthermore, they can be used to perform any resection around the central core of the hemisphere and the tentorial incisura.     

Fiber connections between the cerebral cortex and the corpus callosum in Alzheimer's disease: a diffusion tensor imaging and voxel-based morphometry study

Regional cortical atrophy in Alzheimer's disease (AD) most likely reflects the loss of cortical neurons. Several diffusion tensor imaging studies reported reduced fractional anisotropy (FA) in the corpus callosum in AD. The aim of this study was to investigate the association between reduced FA in the corpus callosum and gray matter atrophy in AD. Thirteen patients with AD with a mean (+/-standard deviation) age of 68.3 years (+/-11.5) and mean Mini Mental State Examination (MMSE) score of 21.8 (+/-4.8) were recruited. There were 13 control subjects with a mean age of 66.7 years (+/-6.4) and MMSE of 29.1 (+/-0.7). We used voxel-based morphometry of gray matter maps and region of interest-based analysis of FA in the corpus callosum. FA values of the anterior corpus callosum in AD patients were significantly correlated with gray matter volume in the prefrontal cortex and left parietal lobes. FA values of the posterior corpus callosum were significantly correlated with gray matter volume in the bilateral frontal, temporal, right parietal, and occipital lobes. In control subjects, no correlations were detected. Our findings suggest that decline of FA in the corpus callosum may be related to neuronal degeneration in corresponding cortical areas.     

Emotional voice areas: anatomic location, functional properties, and structural connections revealed by combined fMRI/DTI

We determined the location, functional response profile, and structural fiber connections of auditory areas with voice- and emotion-sensitive activity using functional magnetic resonance imaging (fMRI) and diffusion tensor imaging. Bilateral regions responding to emotional voices were consistently found in the superior temporal gyrus, posterolateral to the primary auditory cortex. Event-related fMRI showed stronger responses in these areas to voices-expressing anger, sadness, joy, and relief, relative to voices with neutral prosody. Their neural responses were primarily driven by prosodic arousal, irrespective of valence. Probabilistic fiber tracking revealed direct structural connections of these "emotional voice areas" (EVA) with ipsilateral medial geniculate body, which is the major input source of early auditory cortex, as well as with the ipsilateral inferior frontal gyrus (IFG) and inferior parietal lobe (IPL). In addition, vocal emotions (compared with neutral prosody) increased the functional coupling of EVA with the ipsilateral IFG but not IPL. These results provide new insights into the neural architecture of the human voice processing system and support a crucial involvement of IFG in the recognition of vocal emotions, whereas IPL may subserve distinct auditory spatial functions, consistent with distinct anatomical substrates for the processing of "how" and "where" information within the auditory pathways.     

Lesions of the corpus callosum in hydrocephalic patients with ventricular drainage — a CT-study

Summary Patients with ventricular drainage may develop lesions of the corpus callosum. In order to study frequency, pathogenesis and clinical relevance of callosal lesions, 301 routine CT investigations of 79 patients with ventricular drainage were reviewed. Hypodense lesions in the anterior part of the corpus callosum were observed in 7 patients with longstanding hydrocephalus of variable origin, in 2 cases the corpus callosum was slightly swollen. All 7 patients showed signs of forced ventricular drainage. The callosal alterations were clinically inapparent and potentially reversible. Knowledge of these lesions is important to avoid misinterpretation.     

Neural substrates of phonemic perception

The temporal lobe in the left hemisphere has long been implicated in the perception of speech sounds. Little is known, however, regarding the specific function of different temporal regions in the analysis of the speech signal. Here we show that an area extending along the left middle and anterior superior temporal sulcus (STS) is more responsive to familiar consonant-vowel syllables during an auditory discrimination task than to comparably complex auditory patterns that cannot be associated with learned phonemic categories. In contrast, areas in the dorsal superior temporal gyrus bilaterally, closer to primary auditory cortex, are activated to the same extent by the phonemic and nonphonemic sounds. Thus, the left middle/anterior STS appears to play a role in phonemic perception. It may represent an intermediate stage of processing in a functional pathway linking areas in the bilateral dorsal superior temporal gyrus, presumably involved in the analysis of physical features of speech and other complex non-speech sounds, to areas in the left anterior STS and middle temporal gyrus that are engaged in higher-level linguistic processes.     

The claustrum and its projection system in the human brain: a microsurgical and tractographic anatomical study

OBJECT: The goal in this study was to examine the microsurgical and tractographic anatomy of the claustrum and its projection fibers, and to analyze the functional and surgical implications of the findings. METHODS: Fifteen formalin-fixed human brain hemispheres were dissected using the Klingler fiber dissection technique, with the aid of an operating microscope at x 6-40 magnification. Magnetic resonance imaging studies of 5 normal brains were analyzed using diffusion tensor (DT) imaging-based tractography software. RESULTS: Both the claustrum and external capsule have 2 parts: dorsal and ventral. The dorsal part of the external capsule is mainly composed of the claustrocortical fibers that converge into the gray matter of the dorsal claustrum. Results of the tractography studies coincided with the fiber dissection findings and showed that the claustrocortical fibers connect the claustrum with the superior frontal, precentral, postcentral, and posterior parietal cortices, and are topographically organized. The ventral part of the external capsule is formed by the uncinate and inferior occipitofrontal fascicles, which traverse the ventral part of the claustrum, connecting the orbitofrontal and prefrontal cortex with the amygdaloid, temporal, and occipital cortices. The relationship between the insular surface and the underlying fiber tracts, and between the medial lower surface of the claustrum and the lateral lenticulostriate arteries is described. CONCLUSIONS: The combination of the fiber dissection technique and DT imaging-based tractography supports the presence of the claustrocortical system as an integrative network in humans and offers the potential to aid in understanding the diffusion of gliomas in the insula and other areas of the brain.     

Functional-anatomical validation and individual variation of diffusion tractography-based segmentation of the human thalamus

Parcellation of the human thalamus based on cortical connectivity information inferred from non-invasive diffusion-weighted images identifies sub-regions that we have proposed correspond to nuclei. Here we test the functional and anatomical validity of this proposal by comparing data from diffusion tractography, cytoarchitecture and functional imaging. We acquired diffusion imaging data in eleven healthy subjects and performed probabilistic tractography from voxels within the thalamus. Cortical connectivity information was used to divide the thalamus into sub-regions with highest probability of connectivity to distinct cortical areas. The relative volumes of these connectivity-defined sub-regions correlate well with volumetric predictions based on a histological atlas. Previously reported centres of functional activation within the thalamus during motor or executive tasks co-localize within atlas regions showing high probabilities of connection to motor or prefrontal cortices, respectively. This work provides a powerful validation of quantitative grey matter segmentation using diffusion tractography in humans. Co-registering thalamic sub-regions from 11 healthy individuals characterizes inter-individual variation in segmentation and results in a population-based atlas of the human thalamus that can be used to assign likely anatomical labels to thalamic locations in standard brain space. This provides a tool for specific localization of functional activations or lesions to putative thalamic nuclei.     

Mapping morphology of the corpus callosum in schizophrenia

The nature and extent of callosal morphological alterations in schizophrenia remain unresolved. A parametric surface modeling approach using magnetic resonance (MR) images was employed. This provided spatially accurate representations of midsagittal callosal surfaces in schizophrenic patients (n = 25; 15 males) and normal controls (n = 28; 15 males). Areas of functionally relevant callosal channels and measures reflecting callosal shape were visualized and compared across groups. To register neuroanatomical landmarks surrounding the corpus callosum, each three-dimensional MR volume was scaled according to Talairach AC-PC distance, and raw distances included as covariates in multivariate analyses. Results revealed: (i) a marked vertical displacement of the corpus callosum in patients (P < 0.01); (ii) increases in curvature of superior and inferior callosal surfaces (P < 0.001); and (iii) significant increases in maximum widths in anterior and posterior regions in male patients compared to male controls; as well as (iv) increased patterns of callosal variability in female patients but no effects of diagnosis between female groups. These findings demonstrate a clear index of structural neuropathology in male schizophrenic patients. Displacement and curvature increases were highly correlated with structural differences in surrounding neuroanatomical regions, including increased volume of the lateral ventricles (P < 0.01).     

Clinicopathological study of multiple gliomas--report of three cases.

Three cases of multiple gliomas with postmortem findings including a rare case of multicentric glioma are presented. A 59-year-old female was hospitalized with decreased mental activity and gait disturbance. Computed tomographic (CT) scans and magnetic resonance (MR) images showed two independent mass lesions in the left frontal and the right temporal lobes, shown by postmortem to have no communication. Histologically, they were a gemistocytic astrocytoma and an anaplastic astrocytoma, respectively. Therefore, multicentric glioma was diagnosed. A 66-year-old male was admitted with slow mentation and gait disturbance. CT scans and MR images demonstrated two mass lesions; one overriding the bilateral frontal lobes through the corpus callosum and the other in the left temporal lobe. Postmortem examination showed that both lesions were glioblastoma and the left temporal tumor was accompanied by subarachnoid dissemination. A 29-year-old male was hospitalized with gustatory hallucination and convulsions of the right upper extremity. CT scans revealed two mass lesions in the right frontal and the left temporal lobes. MR images demonstrated communication between the two lesions through the corpus callosum. The left temporal tumor developed into the occipital lobe and another new lesion appeared in the right temporal lobe despite chemotherapy and irradiation. Postmortem examination revealed communication between the three masses through the corpus callosum. Histologically, all three tumors were glioblastoma. Multicentric gliomas have been reported at various incidences from 2.3 to 9.1%. However, multicentric gliomas with multiple tumors of different histologies are very rare and only 16 cases have been reported. MR imaging is more valuable than CT scanning to detect communication between two or more lesions.