A rostrocaudal pathway connecting the temporal and parietal lobes was described in monkeys using autoradiography and was named the middle longitudinal fasciculus (MdLF). Recently, the use of diffusion tensor tractography has allowed it to be depicted in human volunteers. In the present study, a technique of fiber dissection was used in 18 cadaveric human brains to investigate the presence of this fasciculus and to detail its anatomical relationships. On the basis of our findings, fiber dissection provides evidence for a long horizontal bundle medial to the arcuate fasciculus and extending to the superior temporal gyrus. Its fibers occupy the lateral-most layer of the upper portion of the stratum sagittale and partially cover the inferior fronto-occipital fasciculus, which is situated deeper and slightly inferiorly. Whereas MdLF fibers continue on a relatively superficial level to reach the superior temporal gyrus, the inferior fronto-occipital fasciculus penetrates the deep temporal white matter and crosses the insular lobe. Although diffusion tensor imaging suggests that the MdLF terminates in the angular gyrus, this was not confirmed by the present study. These long association fibers continue onward posteriorly into upper portions of the occipital lobe. Further studies are needed to understand the role of the MdLF in brain function.
anatomy; connectivity; fiber pathways; fiber dissection; white matter
Using diffusion tensor tractography, we quantified the microstructural changes in the association, projection, and commissural compact white matter pathways of the human brain over the lifespan in a cohort of healthy right-handed children and adults aged 6–68 years. In both males and females, the diffusion tensor radial diffusivity of the bilateral arcuate fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, corticospinal, somatosensory tracts, and the corpus callosum followed a U-curve with advancing age; fractional anisotropy in the same pathways followed an inverted U-curve. Our study provides useful baseline data for the interpretation of data collected from patients.
Lifespan; White matter fiber tract development; Association; Projection; Commissural pathways; Aging; Nonlinear trajectories; Diffusion tensor imaging; Tractography
To investigate the relationship between white matter tract integrity and language and memory performances in patients with temporal lobe epilepsy (TLE).
Diffusion tensor imaging (DTI) was performed in 17 patients with TLE and 17 healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) were calculated for six fiber tracts (uncinate fasciculus [UF], arcuate fasciculus [AF], fornix [FORX], parahippocampal cingulum [PHC], inferior fronto-occipital fasciculus [IFOF], and corticospinal tract [CST]). Neuropsychological measures of memory and language were obtained and correlations were performed to evaluate the relationship between DTI and neuropsychological measures. Hierarchical regression was performed to determine unique contributions of each fiber tract to cognitive performances after controlling for age and hippocampal volume (HV).
Increases in MD of the left UF, PHC, and IFOF were associated with poorer verbal memory in TLE, as were bilateral increases in MD of the AF, and decreases in FA of the right AF. Increased MD of the AF and UF, and decreased FA of the AF, UF, and left IFOF were related to naming performances. No correlations were found between DTI measures and nonverbal memory or fluency in TLE. Regression analyses revealed that several fibers, including the AF, UF, and IFOF, independently predicted cognitive performances after controlling for HV.
The results suggest that structural compromise to multiple fiber tracts is associated with memory and language impairments in patients with temporal lobe epilepsy. Furthermore, we provide initial evidence that diffusion tensor imaging tractography may provide clinically unique information for predicting neuropsychological status in patients with epilepsy.
= arcuate fasciculus;
= Boston Naming Test;
= corticospinal tract;
= diffusion tensor imaging;
= fractional anisotropy;
= hippocampal volume;
= intracranial-adjusted HV;
= inferior fronto-occipital fasciculus;
= Logical Memory;
= mean diffusivity;
= mesial temporal sclerosis;
= parahippocampal cingulum;
= temporal lobe epilepsy;
= uncinate fasciculus;
= Wechsler Memory Scale–Third Edition.
To determine whether the major temporal lobe white matter tracts in patients with temporal lobe epilepsy manifest abnormal water diffusion properties.
Diffusion tensor MRI measurements were obtained from tractography for uncinate, arcuate, inferior longitudinal fasciculi and corticospinal tract in 13 children with left temporal lobe epilepsy and normal conventional MRI, and the data were compared to measurements in 12 age-matched normal volunteers. The relationship between tensor parameters and duration of epilepsy was also determined.
All four tracts in the affected left hemisphere showed lower mean anisotropy, planar and linear indices, but higher spherical index in patients versus controls. Diffusion changes in the left uncinate and arcuate fasciculus correlated significantly with duration of epilepsy. Arcuate fasciculus showed a reversal of the normal left-right asymmetry. Various diffusion abnormalities were also seen in the four tracts studied in the right hemisphere.
Our findings indicate abnormal water diffusion in temporal lobe and extra-temporal lobe tracts with robust changes in the direction perpendicular to the axons. Diffusion abnormalities associated with duration of epilepsy suggest progressive changes in ipsilateral uncinate and arcuate fasciculus due to chronic seizure activity. Finally, our results in arcuate fasciculus are consistent with language reorganization to the contralateral right hemisphere.
We acquired diffusion tensor images on 33 normal adults aged 22–64 and 15 adolescents aged 14–21. We assessed relative anisotropy in stereotaxically located regions of interest in the internal capsule, corpus callosum, anterior thalamic radiations, frontal anterior fasciculus, fronto-occipital fasciculus, temporal lobe white matter, cingulum bundle, frontal inferior longitudinal fasciculus, frontal superior longitudinal fasciculus, and optic radiations. All of these structures except the optic radiations, corpus callosum, and frontal inferior longitudinal fasciculus exhibited differences in anisotropy between adolescents and adults. Areas with anisotropy increasing with age included the anterior limb of the internal capsule, superior levels of the frontal superior longitudinal fasciculus and the inferior portion of the temporal white matter. Areas with anisotropy decreasing with age included the posterior limb of the internal capsule, anterior thalamic radiations, fronto-occipital fasciculus, anterior portion of the frontal anterior fasciculus, inferior portion of the frontal superior longitudinal fasciculus, cingulum bundle and superior portion of the temporal axis. Sex differences were found in the majority of areas but were most marked in the cingulum bundle and internal capsule. These results suggest continuing white matter development between adolescence and adulthood.
Age; White matter; Magnetic resonance imaging
Whole-brain diffusion tensor tractography (DTT) at high signal-to-noise ratio and angular and spatial resolutions were utilized to study the effects of age, sex differences, and lateral asymmetries of 6 white matter pathways (arcuate fasciculus [AF], inferior longitudinal fasciculus, inferior fronto-occipital fasciculus [IFOF], uncinate fasciculus [UF], corticospinal tract [CST], and somatosensory pathway [SS]) in 31 right-handed children (6–17 years). Fractional anisotropy (FA), a measure of the orientational variance in water molecular diffusivity, and the magnitude of water diffusivity (parallel, perpendicular, and mean diffusivity) along the pathways were quantified. Three major patterns of maturation were observed: 1) significant increase in FA with age, accompanied by significant decreases in all 3 diffusivities (e.g., left IFOF); 2) significant decreases in all three diffusivities with age without significant changes in FA (e.g., left CST); and 3) no significant age-related changes in FA or diffusivity (e.g., SS). Sex differences were minimal. Many pathways showed lateral asymmetries. In the right hemisphere, the frontotemporal (FT) segment of AF was not visualized in a substantial (29%) number of participants. FA was higher in the left hemisphere in the FT segment of AF, UF, and CST, whereas it was lower in the frontoparietal segment of AF. This study provides normative data essential for the interpretation of pediatric brain DTT measurements in both health and disease.
association and projection pathways; child and adolescent brain development; diffusion tensor tractography; hemispheric asymmetries
Angelman syndrome is a neurogenetic disorder characterized by severe intellectual disability, absent speech, seizures, and outbursts of laughter. The aim of this study was to utilize diffusion tensor imaging (DTI) to examine alterations in white matter pathways in Angelman syndrome, with an emphasis on correlations with clinical severity.
DTI was used to examine the arcuate fasciculus (AF), uncinate fasciculus (UF), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), and the corpus callosum (CC). We enrolled 14 children aged 8 to 17 years (mean age 10y 8mo; SD 2y 7mo) with Angelman syndrome (seven male; seven female) and 13 typically developing children, aged 8 to 17 years, for comparison (five male; eight female; mean age 12y; SD 2y 9mo). Individuals with Angelman syndrome were assessed using standardized measures of development, language, and behaviour.
The children with Angelman syndrome exhibited lower fractional anisotropy and increased radial diffusivity values than the comparison group for the AF, UF, ILF, and CC (p<0.006 corrected for multiple comparisons). They also had lower fractional anisotropy values for the IFOF and higher radial diffusivity values for the left IFOF (p<0.006). Additionally, children with Angelman syndrome had significantly higher apparent diffusion coefficient values in the AF, CC, ILF, and the left IFOF (p<0.006). Significant correlations were noted between DTI parameters and some of the clinical assessment outcomes (e.g. language, socialization, cognition) for three of the temporal pathways (AF, UF, ILF; p<0.05).
Changes in DTI parameters in individuals with Angelman syndrome suggest decreased/delayed myelination, decreased axonal density or diameter, or aberrant axonal organization. Our findings suggest a generalized white matter alteration throughout the brain in those with Angelman syndrome; however, only the alterations in temporal white matter pathways were associated with language and cognitive and social functioning.
Primary progressive aphasia is a clinical syndrome that encompasses three major phenotypes: non-fluent/agrammatic, semantic and logopenic. These clinical entities have been associated with characteristic patterns of focal grey matter atrophy in left posterior frontoinsular, anterior temporal and left temporoparietal regions, respectively. Recently, network-level dysfunction has been hypothesized but research to date has focused largely on studying grey matter damage. The aim of this study was to assess the integrity of white matter tracts in the different primary progressive aphasia subtypes. We used diffusion tensor imaging in 48 individuals: nine non-fluent, nine semantic, nine logopenic and 21 age-matched controls. Probabilistic tractography was used to identify bilateral inferior longitudinal (anterior, middle, posterior) and uncinate fasciculi (referred to as the ventral pathway); and the superior longitudinal fasciculus segmented into its frontosupramarginal, frontoangular, frontotemporal and temporoparietal components, (referred to as the dorsal pathway). We compared the tracts’ mean fractional anisotropy, axial, radial and mean diffusivities for each tract in the different diagnostic categories. The most prominent white matter changes were found in the dorsal pathways in non-fluent patients, in the two ventral pathways and the temporal components of the dorsal pathways in semantic variant, and in the temporoparietal component of the dorsal bundles in logopenic patients. Each of the primary progressive aphasia variants showed different patterns of diffusion tensor metrics alterations: non-fluent patients showed the greatest changes in fractional anisotropy and radial and mean diffusivities; semantic variant patients had severe changes in all metrics; and logopenic patients had the least white matter damage, mainly involving diffusivity, with fractional anisotropy altered only in the temporoparietal component of the dorsal pathway. This study demonstrates that both careful dissection of the main language tracts and consideration of all diffusion tensor metrics are necessary to characterize the white matter changes that occur in the variants of primary progressive aphasia. These results highlight the potential value of diffusion tensor imaging as a new tool in the multimodal diagnostic evaluation of primary progressive aphasia.
primary progressive aphasia; progressive non-fluent aphasia; semantic dementia; logopenic progressive aphasia; diffusion tensor imaging
The objective of this study is to investigate the relationships among frontotemporal fiber tract compromise and task-switching performance in healthy controls and patients with temporal lobe epilepsy (TLE). We performed diffusion tensor imaging (DTI) on 30 controls and 32 patients with TLE (15 left TLE). Fractional anisotropy (FA) was calculated for four fiber tracts [uncinate fasciculus (UncF), arcuate fasciculus (ArcF), dorsal cingulum (CING), and inferior fronto-occipital fasciculus (IFOF)]. Participants completed the Trail Making Test-B (TMT-B) and Verbal Fluency Category Switching (VFCS) test. Multivariate analyses of variances (MANOVAs) were performed to investigate group differences in fiber FA and set-shifting performances. Canonical correlations were used to examine the overall patterns of structural-cognitive relationships and were followed by within-group bivariate correlations. We found a significant canonical correlation between fiber FA and task-switching performance. In controls, TMT-B correlated with left IFOF, whereas VFCS correlated with FA of left ArcF and left UncF. These correlations were not significant in patients with TLE. We report significant correlations between frontotemporal fiber tract integrity and set-shifting performance in healthy controls that appear to be absent or attenuated in patients with TLE. These findings suggest a breakdown of typical structure-function relationships in TLE that may reflect aberrant developmental or degenerative processes.
Diffusion tensor; Uncinate; Cingulate; Frontal lobe; Arcuate; IFOF
Ever since the 19th century, the standard model for spoken language processing has assumed two pathways for repetition—a phonological pathway and a semantic pathway—and this idea has gained further support in the last decade. First, recent in vivo tractography studies have demonstrated both the “dorsal” (via arcuate fasciculus) and “ventral” (via extreme capsule and uncinate fasciculus) pathways connecting from the primary auditory area to the speech-motor area, the latter of which passes through a brain area associated with semantic processing (anterior temporal lobe). Secondly, neuropsychological evidence for the role of semantics in repetition is conduite d'approche, a successive phonological improvement (sometimes non-improvement) in aphasic patients' response by repeating several times in succession. Crucially, conduite d'approche is observed in patients with neurological damage in/around the arcuate fasciculus. Successful conduite d'approche is especially clear for semantically-intact patients and it occurs for real words rather than for non-words. These features have led researchers to hypothesize that the patients' disrupted phonological output is “cleaned-up” by intact lexical-semantic information before the next repetition. We tested this hypothesis using the neuroanatomically-constrained dual dorsal-ventral pathway computational model. The results showed that (a) damage to the dorsal pathway impaired repetition; (b) in the context of recovery, the model learned to compute a correct repetition response following the model's own noisy speech output (i.e., successful conduite d'approche); (c) this behavior was more evident for real words than non-words; and (d) activation from the ventral pathway contributed to the increased rate of successful conduite d'approche for real words. These results suggest that lexical-semantic “clean-up” is key to this self-correcting mechanism, supporting the classic proposal of two pathways for repetition.
repetition; dual dorsal-ventral pathway; conduite d'approche; semantics; computational modeling
There is increasing recognition that many of the core behavioral impairments that characterize autism potentially emerge from poor neural synchronization across nodes comprising dispersed cortical networks. A likely candidate for the source of this atypical functional connectivity in autism is an alteration in the structural integrity of intra- and inter-hemispheric white matter tracts that form large-scale cortical networks. To test this hypothesis, in a group of adults with high functioning autism (HFA) and matched control participants, we used diffusion tensor tractography to compare the structural integrity of three intra-hemispheric visual-association white matter tracts, the inferior longitudinal fasciculus (ILF), the inferior fronto-occipito fasciculus (IFOF) and the uncinate fasciculus (UF), with the integrity of three sub-portions of the major inter-hemispheric fiber tract, the corpus callosum. Compared with the control group, the HFA group evinced an increase in the volume of the intra-hemispheric fibers, particularly in the left hemisphere, and a reduction in the volume of the forceps minor and body of the corpus callosum. The reduction in the volume of the forceps minor also correlated with an increase in repetitive and stereotypical behavior as measured by the Autism Diagnostic Interview. These findings suggest that the abnormalities in the integrity of key inter-and intra-hemispheric white matter tracts may underlie the atypical information processing observed in these individuals.
Autism; White matter; Inferior fronto-occipito fasciculus; Inferior longitudinal fasciculus; Diffusion tensor tractography
Left unilateral neglect, a dramatic condition which impairs awareness of left-sided events, has been classically reported after right hemisphere cortical lesions involving the inferior parietal region. More recently, the involvement of long-range white matter tracts has been highlighted, consistent with the idea that awareness of events occurring in space depends on the coordinated activity of anatomically distributed brain regions. Damage to the superior longitudinal fasciculus (SLF), linking parietal to frontal cortical regions, or to the inferior longitudinal fasciculus (ILF), connecting occipital and temporal lobes, have been described in neglect patients. In this study four right-handed patients with right-hemisphere strokes were submitted to a high-definition anatomical MRI with diffusion tensor imaging (DTI) sequences and to a paper-and-pencil neglect battery. We used DTI tractography to visualize the SLF, the ILF and the inferior fronto-occipital fasciculus (IFOF), a pathway running in the depth of the temporal lobe, not hitherto associated with neglect. Two patients with cortical involvement of the inferior parietal and superior temporal regions, but intact and symmetrical fasciculi, showed no signs of neglect. The other two patients with signs of left neglect had superficial damage to the inferior parietal cortex and white matter damage involving the IFOF. These findings suggest that superficial damage to the inferior parietal cortex per se may not be sufficient to produce visual neglect. In some cases, a lesion to the direct connections between ventral occipital and frontal regions (i.e. IFOF) may contribute to the manifestation of neglect by impairing the top-down modulation of visual areas from frontal cortex.
Aged; 80 and over; Awareness; physiology; Cerebral Cortex; physiopathology; Diffusion Magnetic Resonance Imaging; Dominance; Cerebral; physiology; Female; Humans; Image Processing; Computer-Assisted; Imaging; Three-Dimensional; Kinesthesis; physiology; Male; Middle Aged; Nerve Fibers; Myelinated; physiology; Nerve Net; physiopathology; Perceptual Disorders; diagnosis; physiopathology; Stroke; complications; physiopathology
The primary progressive aphasias (PPA) are a heterogeneous group of language-led neurodegenerative diseases resulting from large-scale brain network degeneration. White matter (WM) pathways bind networks together, and might therefore hold information about PPA pathogenesis. Here we used diffusion tensor imaging and tract-based spatial statistics to compare WM tract changes between PPA syndromes and with respect to Alzheimer's disease and healthy controls in 33 patients with PPA (13 nonfluent/agrammatic PPA); 10 logopenic variant PPA; and 10 semantic variant PPA. Nonfluent/agrammatic PPA was associated with predominantly left-sided and anterior tract alterations including uncinate fasciculus (UF) and subcortical projections; semantic variant PPA with bilateral alterations in inferior longitudinal fasciculus and UF; and logopenic variant PPA with bilateral but predominantly left-sided alterations in inferior longitudinal fasciculus, UF, superior longitudinal fasciculus, and subcortical projections. Tract alterations were more extensive than gray matter alterations, and the extent of alteration across tracts and PPA syndromes varied between diffusivity metrics. These WM signatures of PPA syndromes illustrate the selective vulnerability of brain language networks in these diseases and might have some pathologic specificity.
Primary progressive aphasia; DTI; Networks; White matter
The goals of this study were to first determine whether the fractional anisotropy (FA) and mean diffusivity (MD) of major white matter pathways associate with schizophrenia, and secondly to characterize the extent to which differences in these metrics might reflect a genetic predisposition to schizophrenia. Differences in FA and MD were identified using a comprehensive atlas-based tract mapping approach using diffusion tensor imaging and high resolution structural data from 35 patients, 28 unaffected first-degree relatives of patients, 29 community controls, and 14 first-degree relatives of controls. Schizophrenia patients had significantly higher MD in the following tracts compared to controls: the right anterior thalamic radiations, the forceps minor, the bilateral inferior fronto-occipital fasciculus (IFO), the temporal component of the left superior longitudinal fasciculus (tSLF), and the bilateral uncinate. FA showed schizophrenia effects and a linear relationship to genetic liability (represented by schizophrenia patients, first-degree relatives, and controls) for the bilateral IFO, the left inferior longitudinal fasciculus (ILF), and the left tSLF. Diffusion tensor imaging studies have previously identified white matter abnormalities in all three of these tracts in schizophrenia; however, this study is the first to identify a significant genetic liability. Thus, FA of these three tracts may serve as biomarkers for studies seeking to identify how genes influence brain structure predisposing to schizophrenia. However, differences in FA and MD in frontal and temporal white matter pathways may be additionally driven by state variables that involve processes associated with the disease.
diffusion tensor imaging; endophenotypes; genetic predisposition
By using diffusion tensor magnetic resonance imaging (DTI) and subsequent tractography, a perisylvian language network in the human left hemisphere recently has been identified connecting Brocas's and Wernicke's areas directly (arcuate fasciculus) and indirectly by a pathway through the inferior parietal cortex.
Applying DTI tractography in the present study, we found a similar three-way pathway in the right hemisphere of 12 healthy individuals: a direct connection between the superior temporal and lateral frontal cortex running in parallel with an indirect connection. The latter composed of a posterior segment connecting the superior temporal with the inferior parietal cortex and an anterior segment running from the inferior parietal to the lateral frontal cortex.
The present DTI findings suggest that the perisylvian inferior parietal, superior temporal, and lateral frontal corticies are tightly connected not only in the human left but also in the human right hemisphere.
We used diffusion tensor imaging to investigate fractional anisotropy (FA), a measure of fiber tract integrity, in attention-deficit hyperactivity disorder (ADHD). Using a tract-based atlasing approach on six-direction diffusion tensor imaging data, we examined FA within the cingulum, corpus callosum, corticospinal tract, fornix, optic radiations, superior longitudinal fasciculus, uncinate fasciculus, and the superior and inferior occipitofrontal fasciculi in an all-male sample of17 children and adolescents with ADHD and 16 age-matched controls. ADHD patients had significantly lower FA in the corticospinal tract (P=0.02) and the superior longitudinal fasciculus (P=0.017) compared with controls. Results support that disruptions in motor and attentional networks may contribute toward ADHD pathophysiology. Future research may clarify how ADHD subtype and psychiatric comorbidities affect diffusion measures.
corticospinal tract; diffusion tensor imaging; fractional anisotropy; superior longitudinal fasciculus
Using diffusion tensor imaging tractography and color-coded anisotropy map quantification, we investigated asymmetry of the arcuate fasciculus to determine language laterality in children and compared it with the Wada test. Arcuate fasciculus volume and fractional anisotropy were measured after tractography. We also quantified the fiber orientation distribution in the arcuate fasciculus region, ie, the fraction of arcuate fasciculus fibers oriented in the anteroposterior and mediolateral directions. A Laterality Index was calculated for each of the measured parameters. Volumetric analysis of the arcuate fasciculus showed asymmetry favoring the language dominant hemisphere (P = .02), while fractional anisotropy showed no significant asymmetry (P = .07). The mean anteroposterior and mediolateral components on the language dominant side were significantly higher than on the nondominant side (P = .003 and .002, respectively). The Laterality Index values were concordant with the Wada test results except for 1 case. Fractional anisotropy also falsely lateralized language in 1 case.
Wada test; diffusion tensor imaging; arcuate fasciculus; language laterality
The ability to perform complex as well as simple cognitive tasks engages a network of brain regions that is mediated by the white matter fiber bundles connecting them. Different cognitive tasks employ distinctive white matter fiber bundles. The temporal lobe and its projections subserve a variety of key functions known to deteriorate during aging. In a cohort of 52 healthy subjects (ages 25–82 years), we performed voxel-wise regression analysis correlating performance in higher-order cognitive domains (executive function, information processing speed, and memory) with white matter integrity, as measured by diffusion tensor imaging (DTI) fiber tracking in the temporal lobe projections [uncinate fasciculus (UF), fornix, cingulum, inferior longitudinal fasciculus (ILF), and superior longitudinal fasciculus (SLF)]. The fiber tracts were spatially registered and statistical parametric maps were produced to spatially localize the significant correlations. Results showed that performance in the executive function domain is correlated with DTI parameters in the left SLF and right UF; performance in the information processing speed domain is correlated with fractional anisotropy (FA) in the left cingulum, left fornix, right and left ILF and SLF; and the memory domain shows significant correlations with DTI parameters in the right fornix, right cingulum, left ILF, left SLF and right UF. These findings suggest that DTI tractography enables anatomical definition of region of interest (ROI) for correlation of behavioral parameters with diffusion indices, and functionality can be correlated with white matter integrity.
magnetic resonance imaging; diffusion tensor imaging; executive function; information processing speed; memory; aging; white matter; temporal lobe
The uncinate fasciculus connects limbic structures, such as the hippocampus and amygdala, with frontal regions. This study utilized diffusion tensor imaging to examine the structural integrity of the uncinate fasciculus in late-life depression.
18 elderly depressed and 19 elderly nondepressed subjects were matched for age and sex; 8 subjects had mid- to late-onset of depression while 10 subjects had early-onset depression. 3T diffusion tensor imaging-based fiber tract mapping delineated the uncinate fasciculus in each hemisphere, which guided measurement of the fractional anisotropy of the uncinate fasciculus in the temporal stem. After controlling for age and sex, differences between diagnostic groups were assessed.
After controlling for age and sex, individuals with early onset depression exhibited lower anisotropy of the left uncinate fasciculus than did mid- and late-onset or nondepressed subjects (F2,36 = 4.50, p = 0.02). Analyses of the right uncinate fasciculus were not statistically significant.
This provides preliminary evidence that there is a structural connectivity deficit between left frontal and limbic structures in early-onset depression. Further work is needed to determine if this is seen in younger depressed subjects, and if it influences treatment outcomes.
depression; elderly; magnetic resonance imaging; temporal lobe
Aicardi syndrome is a congenital neurodevelopmental disorder associated with significant cognitive and motor impairment. Diffusion Tensor Imaging was performed on two subjects with Aicardi syndrome, as well as on two matched subjects with callosal agenesis and cortical malformations, but not a clinical diagnosis of Aicardi syndrome. Whole brain three-dimensional fiber tractography was performed, and major white matter tracts were isolated using standard tracking protocols. One Aicardi subject demonstrated an almost complete lack of normal cortico-cortical connectivity, with only the left inferior fronto-occipital fasciculus recovered by diffusion tensor tractography. A second Aicardi subject showed evidence of bilateral cingulum bundles and right uncinate fasciculus, but other cortico-cortical tracts were not recovered. Major subcortical white matter tracts, including corticospinal, pontocerebellar, and anterior thalamic radiation tracts, were recovered in both Aicardi subjects. In contrast, diffusion tensor tractography analysis on the two matched control subjects with callosal agenesis and cortical malformations recovered all major intrahemispheric cortical and subcortical white matter tracts. These results reveal a widespread disruption in the corticocortical white matter organization of individuals with Aicardi syndrome. Furthermore, such disruption in white matter organization appears to be a feature specific to Aicardi syndrome, and not shared by other neurodevelopmental disorders with similar anatomic manifestations.
The statistical reliability of diffusion property measurements was evaluated in ten healthy subjects using deterministic fiber tracking to localize tracts affected in motor neuron disease: corticospinal tract (CST), uncinate fasciculus (UNC), and the corpus callosum in its entirety (CC), and its genu (GE), motor (CCM), and splenium (SP) fibers separately. Measurements of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ1), transverse diffusivity (λ⊥), and volume of voxels containing fibers (VV) were obtained within each tract. To assess intra-rater and inter-rater reliability, two raters carried out fiber tracking five times on each scan. Scan-rescan and longitudinal reliability were assessed in a subset of four subjects who had six scans, with two sets of three scans separated by one year. The statistical reliability of repeated measurements was evaluated using intra-class correlation coefficients (ICC) and coefficients of variation (CV). Spatial agreement of tract shape was assessed using the kappa (κ) statistic.
Repeated same-scan fiber tracking evaluations showed good geometric alignment (intra-rater κ > 0.90, inter-rater κ > 0.76) and reliable diffusion property measurements (intra-rater ICC > 0.92, inter-rater ICC > 0.77). FA, MD, and λ⊥ were highly reliable with repeated scans on different days, up to a year apart (ICC > 0.8). VV also exhibited good reliability, but with higher CVs. We were unable to demonstrate reproducibility of λ1. Longitudinal reliability after one year was improved by averaging measurements from multiple scans at each timepoint. Fiber tracking provides a reliable tool for the longitudinal evaluation of white matter diffusion properties.
diffusion tensor imaging; tractography; fiber tracking; corticospinal tract; corpus callosum; test-retest reliability
Frontal and temporal language areas involved in syntactic processing are connected by several dorsal and ventral tracts, but the functional roles of the different tracts are not well understood. To identify which white matter tract(s) are important for syntactic processing, we examined the relationship between white matter damage and syntactic deficits in patients with primary progressive aphasia, using multimodal neuroimaging and neurolinguistic assessment. Diffusion tensor imaging showed that microstructural damage to left hemisphere dorsal tracts—the superior longitudinal fasciculus including its arcuate component—was strongly associated with deficits in comprehension and production of syntax. Damage to these dorsal tracts predicted syntactic deficits after gray matter atrophy was taken into account, and fMRI confirmed that these tracts connect regions modulated by syntactic processing. In contrast, damage to ventral tracts—the extreme capsule fiber system or the uncinate fasciculus—was not associated with syntactic deficits. Our findings show that syntactic processing depends primarily on dorsal language tracts.
Since the existence of the occipitofrontal fascicle (OFF) in humans has remained controversial, we utilized diffusion tensor imaging (DT-MRI)-based segmentation and tractography to investigate its trajectory in vivo in the human. We found that the OFF is distinct from the subcallosal fasciculus or Muratoff’s bundle (MB) and extends from the dorsal and medial parts of the occipital lobe as well as the dorsal, medial and inferior parietal lobules to the dorsal and medial part of the prefrontal and premotor regions. In most of its course, it remains parallel to the corpus callosum, the caudate nucleus and the lateral ventricle. In the coronal plane, the OFF is discerned in the core of the white matter medial to the corona radiata and the superior longitudinal fascicle II (SLF II) and lateral to MB and the corpus callosum. The volumetric measurements of the stem portion of the OFF indicate that the OFF is smaller than the SLF II and the cingulum bundle. Since DT-MRI allows the visualization of OFF fibers leading to the projection areas but not to the origin or termination of these fibers, this has been extrapolated from the experimental data in non-human primates. The OFF may have a role in visual spatial processing along with SLF II.
DT-MRI; Segmentation; Tractography; Occipitofrontal fascicle; Fronto-occipital fascicle
The human brain uncinate fasciculus (UF) is an important cortico-cortical white matter pathway that directly connects the frontal and temporal lobes, although there is a lack of conclusive support for its exact functional role. Using diffusion tensor tractography, we extracted the UF, calculated its volume and normalized it with respect to each subject’s intracranial volume (ICV) and analyzed its corresponding DTI metrics bilaterally on a cohort of 108 right-handed children and adults aged 7–68 years. Results showed inverted U-shaped curves for fractional anisotropy (FA) with advancing age and U-shaped curves for radial and axial diffusivities reflecting white matter progressive and regressive myelination and coherence dynamics that continue into young adulthood. The mean FA values of the UF were significantly larger on the left side in children (p=0.05), adults (p=0.0012) and the entire sample (p=0.0002). The FA leftward asymmetry (Left > Right) is shown to be due to increased leftward asymmetry in the axial diffusivity (p<0.0001) and a lack of asymmetry (p>0.23) for the radial diffusivity. This is the first study to provide baseline normative macro and microstructural age trajectories of the human UF across the lifespan. Results of this study may lend themselves to better understanding of UF role in future behavioral and clinical studies.
Diffusion tensor imaging; fiber tracking; uncinate fasciculus; child; adult; brain development; aging; lifespan
Cognitive processing slows with age. We sought to determine the importance of white matter integrity, assessed by diffusion tensor imaging (DTI), at influencing cognitive processing speed among normal older adults, assessed using a novel battery of computerized, non-verbal, choice reaction time tasks. We studied 131 cognitively normal adults aged 55–87 using a cross-sectional design. Each participant underwent our test battery, as well as MRI with DTI. We carried out cross-subject comparisons using tract-based spatial statistics. As expected, reaction time slowed significantly with age. In diffuse areas of frontal and parietal white matter, especially the anterior corpus callosum, fractional anisotropy values correlated negatively with reaction time. The genu and body of the corpus callosum, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus were among the areas most involved. This relationship was not explained by gray or white matter atrophy or by white matter lesion volume. In a statistical mediation analysis, loss of white matter integrity mediated the relationship between age and cognitive processing speed.