Mapping Of Anatomical Connections Research Articles

Motor fatigue is associated with asymmetric connectivity properties of the corticospinal tract in multiple sclerosis

Multiple Sclerosis (MS) is characterized by demyelination and neurodegeneration of the central nervous system and causes excessive fatigue in more than 80% of the patients. The pathophysiologic mechanisms causing fatigue are still largely unknown. In 46 right-handed patients with relapsing-remitting MS and 25 right-handed controls, we performed diffusion MRI and applied streamline based probabilistic tractography to derive unilateral anatomical connectivity maps for the white matter of the right and left hemispheres. The maps provide an indication how often a streamline has passed through a given voxel. Since tractography based anatomical connectivity mapping (ACM) is sensitive to disease-induced changes in anatomical connectivity, we used ACM to test whether motor fatigue is associated with altered ipsi-hemispherical anatomical connectivity in the major motor output pathway, the corticospinal tract (CST). Patients had higher mean ACM values in the CST than healthy controls. This indicated that a higher number of streamlines, starting from voxels in the same hemisphere, travelled through the CST and may reflect an accumulated disease-induced disintegration of CST. The motor subscale of the Fatigue Scale for Motor and Cognitive functions (FSMCMOTOR) was used to define sub-groups with (n = 29, FSMCMOTOR score ≥ 27) and without motor fatigue (n = 17, FSMSMOTOR score ≤ 26). Patients without fatigue only showed higher ACM values in right CST, while mean ACM values were unaltered in left CST. The higher the mean ACM values in the left relative to the right CST, the more patients reported motor fatigue. Left-right asymmetry in anatomical connectivity outside the CST did not scale with individual motor fatigue. Our results link lateralized changes of tractography-based microstructural properties in the CST with motor fatigue in relapsing-remitting MS.

Mapping whole brain connectivity changes: The potential impact of different surgical resection approaches for temporal lobe epilepsy

In neurosurgery there are several situations that require transgression of the temporal cortex. For example, a subset of patients with temporal lobe epilepsy require surgical resection (most typically, en-bloc anterior temporal lobectomy). This procedure is the gold standard to alleviate seizures but is associated with chronic cognitive deficits. In recent years there have been multiple attempts to find the optimum balance between minimising the size of resection in order to preserve cognitive function, while still ensuring seizure freedom. Some attempts involve reducing the distance that the resection stretches back from the temporal pole, whilst others try to preserve one or more of the temporal gyri. More recent advanced surgical techniques (selective amygdalo-hippocamptectomies) try to remove the least amount of tissue by going under (sub-temporal), over (trans-Sylvian) or through the temporal lobe (middle-temporal), which have been related to better cognitive outcomes. Previous comparisons of these surgical techniques focus on comparing seizure freedom or behaviour post-surgery, however there have been no systematic studies showing the effect of surgery on white matter connectivity. The main aim of this study, therefore, was to perform systematic ‘pseudo-neurosurgery’ based on existing resection methods on healthy neuroimaging data and measuring the effect on long-range connectivity. We use anatomical connectivity maps (ACM) to determine long-range disconnection, which is complementary to existing measures of local integrity such as fractional anisotropy or mean diffusivity. ACMs were generated for each diffusion scan in order to compare whole-brain connectivity with an ‘ideal resection’, nine anterior temporal lobectomy and three selective approaches. For en-bloc resections, as distance from the temporal pole increased, reduction in connectivity was evident within the arcuate fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and the uncinate fasciculus. Increasing the height of resections dorsally reduced connectivity within the uncinate fasciculus. Sub-temporal amygdalohippocampectomy resections were associated with connectivity patterns most similar to the ‘ideal’ baseline resection, compared to trans-Sylvian and middle-temporal approaches. In conclusion, we showed the utility of ACM in assessing long-range disconnections/disruptions during temporal lobe resections, where we identified the sub-temporal resection as the least disruptive to long-range connectivity which may explain its better cognitive outcome. These results have a direct impact on understanding the amount and/or type of cognitive deficit post-surgery, which may not be obtainable using local measures of white matter integrity.

Transient networks of spatio-temporal connectivity map communication pathways in brain functional systems

The study of brain dynamics enables us to characterize the time-varying functional connectivity among distinct neural groups. However, current methods suffer from the absence of structural connectivity information. We propose to integrate infra-slow neural oscillations and anatomical-connectivity maps, as derived from functional and diffusion MRI, in a multilayer-graph framework that captures transient networks of spatio-temporal connectivity. These networks group anatomically wired and temporary synchronized brain regions and encode the propagation of functional activity on the structural connectome. In a group of 71 healthy subjects, we find that these transient networks demonstrate power-law spatial and temporal size, globally organize into well-known functional systems and describe wave-like trajectories of activation across anatomically connected regions. Within the transient networks, activity propagates through polysynaptic paths that include selective ensembles of structural connections and differ from the structural shortest paths. In the light of the communication-through-coherence principle, the identified spatio-temporal networks could encode communication channels' selection and neural assemblies, which deserves further attention. This work contributes to the understanding of brain structure-function relationships by considering the time-varying nature of resting-state interactions on the axonal scaffold, and it offers a convenient framework to study large-scale communication mechanisms and functional dynamics.

Simultaneous Assessment of White Matter Changes in Microstructure and Connectedness in the Blind Brain

Magnetic resonance imaging (MRI) of the human brain has provided converging evidence that visual deprivation induces regional changes in white matter (WM) microstructure. It remains unclear how these changes modify network connections between brain regions. Here we used diffusion-weighted MRI to relate differences in microstructure and structural connectedness of WM in individuals with congenital or late-onset blindness relative to normally sighted controls. Diffusion tensor imaging (DTI) provided voxel-specific microstructural features of the tissue, while anatomical connectivity mapping (ACM) assessed the connectedness of each voxel with the rest of the brain. ACM yielded reduced anatomical connectivity in the corpus callosum in individuals with congenital but not late-onset blindness. ACM did not identify any brain region where blindness resulted in increased anatomical connectivity. DTI revealed widespread microstructural differences as indexed by a reduced regional fractional anisotropy (FA). Blind individuals showed lower FA in the primary visual and the ventral visual processing stream relative to sighted controls regardless of the blindness onset. The results show that visual deprivation shapes WM microstructure and anatomical connectivity, but these changes appear to be spatially dissociated as changes emerge in different WM tracts. They also indicate that regional differences in anatomical connectivity depend on the onset of blindness.

Neuroanatomical Visualization of the Impaired Striatal Connectivity in Huntington's Disease Mouse Model.

Huntington's disease (HD) is a movement disorder characterized by the early selective degeneration of striatum. For motor control, the striatum receives excitatory inputs from multiple brain regions and projects the information to other basal ganglia nuclei. Despite the pathological importance of the striatal degeneration in HD, there are little anatomical data that show impaired striatal connectivity in HD. For the anatomical mapping of the striatum, we injected here a neurotracer DiD to the dorsal striatum of HD mouse model (YAC128). Compared with littermate controls, the number of the traced inputs to the striatum was reduced dramatically in YAC128 mice at 12 months of age suggesting massive destruction of the striatal connections. Basal ganglia inputs were significantly damaged in HD mice by showing 61 % decrease in substantia nigra pars compacta, 85% decrease in thalamic centromedian nucleus, and 55% decrease in thalamic parafascicular nucleus. Cortical inputs were also greatly decreased by 43% in motor cortex, 48% in somatosensory cortex, and 72% in visual cortex. Besides the known striatal connections, the neurotracer DiD also traced inputs from amygdala and the amygdala inputs were decreased by 68% in YAC128 mice. Considering the role of amygdala in emotion processing, the impairment in amygdalostriatal connectivity strongly suggests that emotional disturbances could occur in HD mice. Indeed, open-field tests further indicated that YAC128 mice exhibited changes in emotional behaviors related to symptoms of depression and anxiety. Although onset of HD is clinically determined on the basis of motor abnormality, emotional deficits are also common features of the disease. Therefore, our anatomical connectivity mapping of the striatum provides a new insight to interpret brain dysfunction in HD.

Secondary progressive and relapsing remitting multiple sclerosis leads to motor-related decreased anatomical connectivity.

Multiple sclerosis (MS) damages central white matter pathways which has considerable impact on disease-related disability. To identify disease-related alterations in anatomical connectivity, 34 patients (19 with relapsing remitting MS (RR-MS), 15 with secondary progressive MS (SP-MS) and 20 healthy subjects underwent diffusion magnetic resonance imaging (dMRI) of the brain. Based on the dMRI, anatomical connectivity mapping (ACM) yielded a voxel-based metric reflecting the connectivity shared between each individual voxel and all other brain voxels. To avoid biases caused by inter-individual brain-shape differences, they were estimated in a spatially normalized space. Voxel-based statistical analyses using ACM were compared with analyses based on the localized microstructural indices of fractional anisotropy (FA). In both RR-MS and SP-MS patients, considerable portions of the motor-related white matter revealed decreases in ACM and FA when compared with healthy subjects. Patients with SP-MS exhibited reduced ACM values relative to RR-MS in the motor-related tracts, whereas there were no consistent decreases in FA between SP-MS and RR-MS patients. Regional ACM statistics exhibited moderate correlation with clinical disability as reflected by the expanded disability status scale (EDSS). The correlation between these statistics and EDSS was either similar to or stronger than the correlation between FA statistics and the EDSS. Together, the results reveal an improved relationship between ACM, the clinical phenotype, and impairment. This highlights the potential of the ACM connectivity indices to be used as a marker which can identify disease related-alterations due to MS which may not be seen using localized microstructural indices.

Brain tissue modifications induced by cholinergic therapy in Alzheimer's disease

A previous preliminary investigation based on a novel MRI approach to map anatomical connectivity revealed areas of increased connectivity in Alzheimer's disease (AD) but not in mild cognitive impairment patients. This prompted the hypothesis tested here, that these areas might reflect phenomena of brain plasticity driven by acetylcholinesterase inhibitors (AChEIs). Thirty-eight patients with probable AD (19 under medication with AChEIs and 19 drug-naïve) were recruited together with 11 healthy controls. All subjects had MRI scanning at 3T, including volumetric and diffusion-weighted scans. Probabilistic tractography was used to initiate streamlines from all parenchymal voxels, and anatomical connectivity maps (ACMs) were obtained by counting, among the total number of streamlines initiated, the fraction passing through each brain voxel. After normalization into standard space, ACMs were used to test for between-group comparisons, and for interactions between the exposure to AChEIs and global level of cognition. Patients with AD had reduced ACM values in the fornix, cingulum, and supramarginal gyri. The ACM value was strongly associated with the AChEI dosage-x-duration product in the anterior limb (non-motor pathway) of the internal capsule. Tractography from this region identified the anterior thalamic radiation as the main white matter (WM) tract passing through it. The reduced connectivity in WM bundles connecting the hippocampi with the rest of the brain (fornix/cingulum) suggests a possible mechanism for the spread of AD pathology. An intriguing explanation for the interaction between AChEIs and ACM is related to the mechanisms of brain plasticity, partially driven by neurotrophic properties of acetylcholine replacement.

High-resolution mapping of anatomical connections in marmoset extrastriate cortex reveals a complete representation of the visual field bordering dorsal V2.

The primate visual cortex consists of many areas. The posterior areas (V1, V2, V3, and middle temporal) are thought to be common to all primate species. However, the organization of cortex immediately anterior to area V2 (the "third tier" cortex) remains controversial, particularly in New World primates. The main point of contention has been whether the third tier cortex consists of a single area V3, representing lower and upper visual quadrants in dorsal and ventral cortex, respectively, or of 2 distinct areas (the dorsomedial [DM] area and a V3-like area). Resolving this controversy is crucial to understand the function and evolution of the third tier cortex. We have addressed this issue in marmosets, by performing high-precision mapping of corticocortical connections in cortex bordering dorsal V2. Multiple closely spaced neuroanatomical tracer injections were placed across the full width of dorsal V2 or adjacent anterior cortex, and the location of resulting labeled cells mapped throughout whole flattened visual cortex. The resulting topographic patterns of labeled connections allowed us to define areas and their boundaries. We found that a complete representation of the visual field borders dorsal V2 and that the third tier cortex consists of 2 distinct areas. These results unequivocally support the DM model.

Group‐averaged anatomical connectivity mapping for improved human white matter pathway visualisation

Anatomical connectivity mapping (ACM) is a measure of anatomical connectivity obtained by initiating streamline diffusion tractography from all parenchymal voxels and then counting the number of streamlines passing through each voxel of the brain. ACM highlights WM structures that present multiple connections to the rest of the brain but not necessarily strong microstructural orientation coherence. In this study, ACM was used to develop an atlas of the human brain. The ACM template was constructed from 3 T diffusion-weighted data from 19 healthy adults. To account for multiple diffusion directions in a voxel, a high angular resolution diffusion imaging (HARDI) technique, namely Q-ball, was used to model diffusion. To bring data from different subjects into a common space, an algorithm for rotating and averaging the principal directions was implemented, which can be generalized to any application requiring algebraic operations on principal directions derived from any HARDI method. ACM from the average dataset was computed and several white matter connections of interest were identified and highlighted. Fractional anisotropy (FA) from standard diffusion tensor modelling was also derived and FA-modulated colour coded images obtained from the mean tensor were also shown for comparison, highlighting differences and similarities. The ACM template can serve for educational purposes and as future reference for studies based on the evaluation of ACM in subjects affected by neurological and psychiatric disorders.

Anatomical connectivity mapping: A new tool to assess brain disconnection in Alzheimer's disease

Previous studies suggest that the clinical manifestations of Alzheimer's disease (AD) are not only associated with regional gray matter damage but also with abnormal functional integration of different brain regions by disconnection mechanisms. A measure of anatomical connectivity (anatomical connectivity mapping or ACM) can be obtained by initiating diffusion tractography streamlines from all parenchymal voxels and then counting the number of streamlines passing through each voxel of the brain. In order to assess the potential of this parameter for the study of disconnection in AD, we computed it in a group of patients with AD (N=9), in 16 patients with amnestic mild cognitive impairment (a-MCI, which is considered the prodromal stage of AD) and in 12 healthy volunteers. All subjects had an MRI scan at 3T, and diffusion MRI data were analyzed to obtain fractional anisotropy (FA) and ACM. Two types of ACM maps, absolute count (ac-ACM) and normalized by brain size count (nc-ACM), were obtained. No between group differences in FA surviving correction for multiple comparison were found, while areas of both decreased (in the supramarginal gyrus) and increased (in the putamen) ACM were found in patients with AD. Similar results were obtained with ac-ACM and nc-ACM. ACM of the supramarginal gyrus was strongly associated with measures of short-term memory in healthy subjects. This study shows that ACM provides information that is complementary to that offered by FA and appears to be more sensitive than FA to brain changes in patients with AD. The increased ACM in the putamen was unexpected. Given the nature of ACM, an increase of this parameter may reflect a change in any of the areas connected to it. One intriguing possibility is that this increase of ACM in AD patients might reflect processes of brain plasticity driven by cholinesterase inhibitors.

Brain Connectivity Is Not Only Lower but Different in Schizophrenia: A Combined Anatomical and Functional Approach

Schizophrenia is hypothesized to involve disordered connectivity between brain regions. Currently, there are no direct measures of brain connectivity; functional and structural connectivity used separately provide only limited insight. Simultaneous measure of anatomical and functional connectivity and its interactions allow for better understanding of schizophrenia-related alternations in brain connectivity. Twenty-seven schizophrenia patients and 27 healthy control subjects underwent magnetic resonance imaging with resting state functional magnetic resonance imaging and diffusion tensor imaging. Separate functional and anatomical connectivity maps were calculated and combined for each subject. Global, regional, and voxel measures and K-means network analysis were employed to identify group differences and correlation with clinical symptoms. A global connectivity analysis indicated that patients had lower anatomical connectivity and lower coherence between the two imaging modalities. In schizophrenia these group differences correlated with clinical symptom severity. Although anatomical connectivity nearly uniformly decreased, functional connectivity in schizophrenia was lower for some connections (e.g., middle temporal gyrus) and higher for others (e.g., cingulate and thalamus). Within the default mode network (DMN) two separate subsystems can be identified. Schizophrenia patients showed decoupling between structural and functional connectivity that can be localized to networks originating in posterior cingulate cortex as well as in the task-positive network and one of the DMN components. Combining two measures of brain connectivity provides more comprehensive descriptions of altered brain connectivity underlying schizophrenia. Patients show deficits in white matter anatomy, but functional connectivity alterations are more complex. Fusion of both methods allows identification of subsystems showing both increased and decreased functional connectivity.

Anatomical Organization of the Blind's Brain: Combined VBM and DTI Analysis.

Purpose: To explore the whole brain grey and white matter organization in a large cohort of congenital blindness (CB) individuals compared to normal-sight (NS) controls using Diffusion Tensor Imaging (DTI) and tractography (DTT). Materials and Methods: Thirteen CB and thirteen NS were scanned in this experiment. T1WI, T2WI, and DTI (61 directions; b=1200 s/mm) were acquired on a Siemens 3T scanner. T1 and T2 images were segmented using the VBM5 toolbox in SPM5. DARTEL was used for high dimensional inter-subject registration. The diffusion tensor was fitted using the RESTORE algorithm. VBM5 was used for voxel-based analysis for comparing the group differences of gray matter, white matter and FA values. Probabilistic tractography (20 streamlines) implemented in FSL was used to generate anatomical connectivity maps (ACM) using a brain mask as seed ROI. DTIstudio was used for DTT to display the fiber tracts related to the visual pathway, in which two regions of interest (ROI) were defined on the coronal plain for both sides: one covered the whole occipital lobe at middle level of occipital lobe and the other covered the inferior fronto-occipital fasciculus (IFO) at the level through middle corpus callosum. Results: All structures belonging to the visual system showed significant volume reductions. All components of the retino-geniculo-striate system including optic nerve, chiasm, lateral geniculate nucleus, optic radiations and visual cortex were reduced. Especially, the volume of the bilateral superior colliculi was decreased (see Fig.1). In the Non-visual areas changes were observed in the posterior hippocampus and parts of the frontal and temporal lobes. All structures belonging to the visual system showed significant reductions of anatomical connectivity (see Fig.2). Most of the NS, 11 of 13, showed the fiber tracts going through the both ROIs. On the contrary, only 2 of 13 CB demonstrated the similar fiber tracts (see Fig.3). Conclusion: We show for the first time large reductions in the midbrain visual structures. The tractography results of CB were consistent with our VBM results. Our VBM data however did not confirm the enlargement of the fronto-occipital and the supra-longitudinal fasciculi previously reported. Fig.1 Group Comparison for the White Matter between the subjects with NS and CB, FDR correction with p<0.005. All structures belonging to the visual system showed significant volume reductions, including optic chiasm, lateral geniculate bodies and primary and secondary visual area (green arrowheads). Especially, the volume reduction was found in both superior colliculi (blue arrow).

Anatomical connections between brain areas activated during rectal distension in healthy volunteers: A visceral pain network

Diffusion Tensor Imaging (DTI) is a promising new imaging method allowing in vivo mapping of anatomical connections in the living human brain. We combined DTI with functional magnetic resonance imaging (fMRI) to investigate the anatomical relationships between areas involved in visceral sensations in humans. Non-painful and moderately painful rectal distensions were performed in 11 healthy women (38.4 ± 3.1 years). fMRI was used to analyse the changes in brain activity during both types of distension. Then, DTI was applied for tracking fibers between the main activated regions. Non-painful distension bilaterally activated the PreFrontal Cortex (PFC), the Anterior Cingulate Cortex (ACC) and the right insula. Painful distension bilaterally activated the primary (S1) and secondary (S2) somatosensory cortices, the motor cortex, the frontal inferior gyrus, the thalamus, the insula, the striatum and the cerebellum. DTI revealed direct connections between insula, and the four areas more frequently activated in this study, i.e. ACC, thalamus, S1, S2 and PFC. The combined use of fMRI and DTI in healthy subjects during rectal distension revealed a neural network of visceral sensory perception involving the insula, thalamus, somatosensory cortices, ACC and PFC.

Diffusion tensor studies dissociated two fronto-temporal pathways in the human memory system

Recent functional neuroimaging studies have shown that multiple cortical areas are involved in memory encoding and retrieval. However, the underlying anatomical connections among these memory-related areas in humans remain elusive due to methodological limitations. Diffusion tensor imaging (DTI) is a technique based on detecting the diffusion of water molecules from magnetic resonance images. DTI allows non-invasive mapping of anatomical connections and gives a comprehensive picture of connectivity throughout the entire brain. By combining functional magnetic resonance imaging (fMRI) and DTI, we show that memory-related areas in the left dorsolateral prefrontal cortex (DLPFC) and the left ventrolateral prefrontal cortex (VLPFC) each connect with memory-related areas in the left temporal cortex. This result suggests there are two pathways between prefrontal cortex and temporal cortex related to the human memory system.