The functional connectivity of the human claustrum, according to the Human Connectome Project database

The claustrum is an irregular and fine sheet of grey matter in the basolateral telencephalon present in almost all mammals. The claustrum has been the object of several studies using animal models and, more recently, in human beings using neuroimaging. One of the most extended cognitive processes attributed to the claustrum is the salience process, which is also related to the insular cortex. In the same way, studies with human subjects and functional magnetic resonance imaging have reported the coactivation of the claustrum/insular cortex in the integration of sensory signals. This coactivation has been reported in the left claustrum/insular cortex or in the right claustrum/insular cortex. The asymmetry has been reported in task studies and literature related to neurological disorders such as Alzheimer’s disease and schizophrenia, relating the severity of delusions with the reduction in left claustral volume. We present a functional connectivity study of the claustrum. Resting-state functional and anatomical MRI data from 100 healthy subjects were analyzed; taken from the Human Connectome Project (HCP, NIH Blueprint: The Human Connectome Project), with 2x2x2 mm3 voxel resolution. We hypothesize that 1) the claustrum is a node involved in different brain networks, 2) the functional connectivity pattern of the claustrum is different from the insular cortex’s pattern, and 3) the asymmetry is present in the claustrum’s functional connectivity. Our findings include at least three brain networks related to the claustrum. We found functional connectivity between the claustrum, frontoparietal network, and the default mode network as a distinctive attribute. The functional connectivity between the right claustrum with the frontoparietal network and the dorsal attention network supports the hypothesis of claustral asymmetry. These findings provide functional evidence, suggesting that the claustrum is coupled with the frontoparietal network serving together to instantiate new task states by flexibly modulating and interacting with other control and processing networks.

Annotations for: The functional connectivity of the human claustrum, according to the Human Connectome Project database

✅ Key Points

Claustrum has an irregular form. I like the use of the words here concavity of the insula and convexity of the putamen [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 12]

irregular form taking the concavity form of the insular cortex and the convexity of the putamen [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 12]

Background

The claustrum is an irregular and fine sheet of grey matter in the basolateral telencephalon present in almost all mammals [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 1]

Research in healthy subjects using diffusion tensor imaging (DTI) has revealed cortical connections with the claustrum, which possesses projections to A) prefrontal cortex, BA 8, 9, 10, 11, 12, and 34; B) visual cortex, BA 17, 18, 19 and 39; C) sensorimotor cortex, BA 7, 5, 1/2/3, 4, 6 and 8; and D) language areas BA 44, 45 and 31; as well as with orbitofrontal cortex, temporal cortex, basal ganglia and amygdala [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 2]

Human claustrum is the most interconnected brain region [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 2]

DTI in 100 healthy subjects, Torgerson et al. [8] found that the claustrum has the highest connectivity in the brain by regional volume [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 2]

the claustrum has been described as a “cornerstone of sensory integration [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 2]

Claustrum important in integrating sensory information [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 2]

integrating motor and sensory information from different modalities to assemble them in a single experience [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 2]

Its hard to image the claustrum in humans [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 3]

challenging issues in studying the human claustrum is its intricate anatomical location and its irregular form [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 3]

Hypothesis

we carried out a seed-driven resting-state functional connectivity analysis of the claustrum in a sample of 100 healthy subjects. [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 10]

Methods

assessing the claustrum’s whole brain resting state functional connectivity using the WU-Minn Human Connectome Project [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 3]

spatial resolution of 2 mm isotropic and a temporal resolution of 720ms at 3T [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 3]

used HCP dataset to explore the claustrum resting-state functional connectivity [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 3]

we aimed to explore, by a seed-driven analysis, the resting-state functional connectivity of the human claustrum based on a large cohort of healthy subjects [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 3]

100 healthy young adults (53 females) with ages between 22 and 35 years old [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 3]

Only a 32 channel head coil used not a 64 [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 3]

3T “Connectome Skyra” with a standard 32-channel head coil [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 3]

High-res anatomical images [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 3]

T1-weighted (T1w) and T2-weighted (T2w) images with 0.7 mm isotropic resolution, FOV = 224x224 mm, matrix = 320, 256 sagittal slices in a single slab TR = 2400 ms, TE = 2.14 ms, TI = 1000 ms, FA = 8 ̊ [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 3]

Only 2mm voxel sizes at 3T, but perhaps it is needed to go to lower resolutions at 3T to be able to image the claustrum accurately as we have seen for Carmens data [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 3]

2 mm isotropic resolution, TR = 720ms, TE = 33.1 ms, slice thickness of 2.0 mm, 72 slices [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 3]

Sort of normal preprocessing methods used here, nothing special [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 3]

HCP include spatial distortion correction, motion correction, spatial registration and normalization to MNI coordinates, high pass filtering [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 3]

Nuisance regressors used in the model basically [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 4]

confound regressors BOLD signal from the white matter, cerebrospinal fluid (CSF) mask, realignment and scrubbing parameters, and band-pass filtering (0.01–0.08 Hz) [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 4]

Used CONN toolbox, again a standard tool to be used in connectivity research, so nothing special here. But CONN requires MATLAB which is a bit shit to be honest [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 4]

CONN toolbox [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 4]

They manually delineated the right and left claustrum in eacho subject? (n = 100). This is quite impressive [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 4]

T1 anatomical volumes were used to manually delineate right and left claustrum masks for each subject [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 4]

The transformation of the mask was a linear transformation, Tri-linear interpolation method and was carried out by the Linear Image Registration Tool (FLIRT) [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 4]

So in connectivity you can determine what is connected to what area of the brain by seeing from the seed-to-ROI and also seed-to-voxel [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 5]

seed-to-voxel and seed-to-ROI analysis [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 5]

Number of ROIs used [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 5]

132 ROIs combining FSL Harvard-Oxford atlas cortical and subcortical areas and AAL atlas cerebellar areas [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 5]

Results

Similar claustrum sized mask dimensions to Kapakin, although I would estimate the mask to be smaller than the actual claustrum itself. [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 5]

whose dimensions are 31mm x 1 mm x 17 mm., which closely coincides with the dimension described by Kapakin [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 5]

Intersect all claustrum masks and the idea behind this is to increase the accuracy of the mask [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 6]

averaged mask used in the analysis, our effective claustrum seed, was estimated from the intersection of all subjects’ claustrum [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 6]

These are a list of regions that were found to be connected to the left claustrum [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 6]

functional connectivity of the left claustrum (p<0.05 p-FDR corrected) with the following clusters: a) Left claustrum with a t–score 23.44, including left and right (l, r) precentral gyrus, postcentral gyrus (l, r), insular cortex (l, r), opercular cortex (l, r), anterior cingulate cortex, supramarginal gyrus (l, r), supplementary motor cortex (l, r), planum temporale (l, r), putamen (l, r), amygdala (l). b) Left lingual gyrus (t–score 7.92), including intracalcarine cortex (l, r), precuneous cortex, cuneal cortex (r). c) Left occipital fusiform gyrus (t–score 6.79). d) Left cuneal cortex (t–score 6.87). [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 6]

What regions were found to be connected to the right claustrum. There are some areas that ovberlap that are connected to both the left and right claustrum respectively [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 6]

right claustrum and the following clusters: a) Right claustrum (t–score 18.40) including precentral gyrus (r), postcentral gyrus (r), insular cortex (r), opercular cortex (r), supramarginal gyrus (r), anterior cingulate cortex, supplementary motor cortex (r), inferior frontal gyrus (r), planum temporale (r), putamen (r), amygdala (r). b) Left planum polare (t–score 9.53) including opercular cortex (l), precentral gyrus (l), postcentral gyrus (l), insular cortex (l), planum temporale (l). c) Right lingual gyrus (t–score 7.04), precuneous cortex, intracalcarine cortex (r), cuneal cortex (r) [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 6]

A summary of all the regions that the claustrum is connected to. Interesting that the auditory cortex is not seen here but it could be because the auditory cortex is too close to the seed region especially with using 2mm voxel sizes [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 10]

Left and right claustrum are mainly connected with precentral gyrus, postcentral gyrus, insular cortex, opercular cortex, supplementary motor area, anterior cingulate cortex, paracingulate cortex, frontal cortex, temporal and occipital cortex, putamen, hippocampus, and amygdala [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 10]

Conclusions

We found that the human claustrum is widely connected with cortical and subcortical brain areas. [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 10]

The regions connected to the claustrum implicated in saliency, attention and default mode network (and frontoparietal network and sensorimotory and language networks) [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 10]

functional connectivity with specific nodes of well characterized brain networks such as salience (SN), sensorimotor, language, dorsal attention, default mode (DMN), and frontoparietal network (FPN) [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 10]

consistent with previous studies [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 10]

There is asymmertry in resting state date in healthy participants [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 11]

results of our seed-driven functional connectivity analysis of the claustrum show features of lateral asymmetry in resting state healthy subjects [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 11]

left and right claustrum show ipsilateral and contralateral asymmetries [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 11]

Basic conclusion of this work in one sentence [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 12]

we present an approximation of the resting-state functional connectivity of the claustrum, which maintains positive functional connectivity not only with cortical brain areas but also subcortical and different brain networks such as salience, default mode network, dorsal attention, and frontoparietal network. [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 12]

Implications

Our analyses are limited to the resting state and do not include task-related functional imaging [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 12]

presenting the connectivity of the average claustrum [@rodriguez-vidalFunctionalConnectivityHuman2024, p. 12]

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