The WU-Minn Human Connectome Project: An overview

May combine two claims.

Claustrophobia and body or head size were among the causes of missing or incomplete imaging data.

“Reasons for partial or complete loss of imaging data include claustrophobia and physical size (body or head).”

Probably not a substantial claim: may not pass S3 (load-bearing).

About six or seven families are screened on average for each family that has a twin pair plus another sibling meeting every criterion and agreeing to take part.

“On average, approximately 6–7 families are screened in order to identify one family with a twin pair and at least one other sibling who meet all inclusion criteria and are willing to participate.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Data from 76 people who came in by November 2012 are part of the Q1 release.

“The Q1 data release includes data from 76 subjects who visited through November, 2012.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In Q1, visits were completed by an average of 2.6 people per family.

“An average of 2.6 subjects per family completed visits in Q1.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The March 2013 Q1 release included imaging and behavioral data from 68 subjects scanned during the first quarter of Phase II.

“This sharing includes the release in March 2013 of data from 68 subjects scanned during the first quarter (Q1) of Phase II data collection.”

May combine two claims.

Because the bore was smaller, the table had to sit higher, leaving the head off the gradient isocenter.

“in the absence of a custom designed patient table, this smaller bore necessitated the placement of the patient table higher in the bore, resulting in the subject’s head not being centered along the gradient isocenter.”

May combine two claims.

The custom 100 mT/m gradient set gave the Siemens 3T Skyra a clear bore of 56 cm, less than the standard 70 cm or the Trio's 60 cm.

“Placing the customized 100 mT/m gradient set into the Siemens 3T Skyra system resulted in a clear inner bore diameter of 56 cm, smaller than the standard Siemens 3T Skyra bore size (70 cm diameter) or a Siemens Trio 3T Trio (60 cm diameter);”

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The standard reconstruction was substantially improved to raise data quality, particularly for dMRI, and to shorten reconstruction time for HCP's large datasets.

“Major improvements to the standard reconstruction process have been made in order to improve the data quality (especially for dMRI, Sotiropoulos et al. 2013c) and to reduce the reconstruction time for the very large HCP datasets (Ugurbil et al., 2013).”

• cites Sotiropoulos et al. 2013cNot checked yet

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• cites Ugurbil et al., 2013 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Several improvements are now part of current FSL, FreeSurfer, and Connectome Workbench releases.

“Some of the refinements have already been incorporated into the latest versions of FSL, FreeSurfer, and Connectome Workbench, three major software packages used by the HCP pipelines.”

May combine two claims.

Spatially more global artifacts, including motion artifacts not fully removed, can remain and may artifactually influence correlation-based functional connectivity estimates.

“Despite the success of the above cleanup process for structured artifacts, spatially more global artifacts can remain in the data. This may include motion artifacts (Power et al., 2012) that are not fully removed by the above processing steps, and which may artifactually influence correlation-based estimates of functional connectivity.”

• cites Power et al., 2012Not checked yet

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In that ICA analysis, component 7 includes the central visual field representation of V1 and V2, while component 3 mainly involves the peripheral visual field representation of these areas.

“ICA Component 7 includes the central visual field representation of V1 and V2, whereas component 3 mainly involves the peripheral visual field representation of these two areas.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Dense connectomes are full correlation matrices of every voxel or grayordinate with every other, and the voxel and grayordinate matrices are 190 GB and 32 GB respectively.

“A dense connectome is the full (voxels X voxels) or (grayordinates X grayordinates) correlation matrix obtained by correlating the timeseries of every brain voxel or every grayordinate with every other. These matrices are massive (190GB and 32GB respectively)”

May combine two claims.

Functional connectivity-based parcellation efforts face two challenges: transitions in connectivity vary in strength and can be influenced by noise and biases, and inter-subject alignment is imperfect in high folding variability, causing misalignment and blurring of connectivity gradients.

“These efforts are still in early stages of development and must cope with two fundamental challenges: (i) the strength, or sharpness of transitions in functional connectivity vary widely and can be influenced by noise and biases in individual subjects; and (ii) the fidelity of inter-subject alignment using shape-based surface registration methods is imperfect in regions of high folding variability”

• cites Van Essen et al., 2012bNot checked yet

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• cites Robinson et al., 2013Not checked yet

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May combine two claims.

Both volume-based and grayordinate-based tfMRI processing indicated excellent quality data from the HCP paradigms, with clear group-level activation and robust activation within individual subjects in many paradigms and contrasts.

“Both approaches indicated excellent quality data from these paradigms, with clear group level activation as well as robust activation within individual subjects in many of the paradigms and contrasts.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

HCP fMRI data include robust task activations and resting-state networks.

“Although not emphasized in the present article, the HCP data do include robust task activations and resting-state networks from the fMRI data (Barch et al., 2013; Smith et al., 2013).”

• cites Barch et al., 2013 sourceNot checked yet

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• cites Smith et al., 2013 sourceNot checked yet

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In group-average task activation from the right-hand movement task in 20 unrelated subjects, activation occurs in expected left motor cortex and in two distinct dorsal and ventral cerebellar locations matching published reports.

“The top row shows the group-average task activation from the right-hand hand movement task, analyzed for the same group of 20 unrelated subjects shown in preceding figures. It includes activation in the expected location in left motor cortex (left panel), and also at two distinct locations in dorsal and ventral cerebellum matching published reports (Buckner et al., 2011).”

• cites Buckner et al., 2011 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

When the article was submitted, the WU-Minn HCP had reached the midpoint of its five-year grant.

“At the time this article was submitted, the WU-Minn HCP is at the midway point of the 5-year grant.”

May combine two claims.

The project's accomplishments so far are substantial, and it is progressing according to its original ambitious timeline.

“Nonetheless, the achievements to date are considerable, and the project remains on track relative to its original ambitious schedule.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Certain advances, for instance the choice to use multiband imaging, had a major effect by themselves.

“Some of the advances, such as the decision to use multiband imaging, have had a large impact on their own.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

These refinements concerned pulse sequences, image reconstruction methods, and preprocessing and analysis pipelines.

“This applies to the extensive efforts to refine pulse sequences, image reconstruction algorithms, and also to the preprocessing and analysis pipelines.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Several of these refinements were adopted into other analysis packages, such as FSL, FreeSurfer, and Connectome Workbench, extending their benefits beyond the HCP.

“A number of these refinements have already been incorporated into other analysis platforms, including FSL, FreeSurfer, and Connectome Workbench, so that the benefits extend well outside the HCP proper.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The consortium currently involves over 100 investigators and technical staff drawn from ten institutions.

“This reflects dedicated efforts and hard work by a large team that currently includes more than 100 investigators and technical staff from ten institutions in the consortium (Supplemental Table S5).”

Probably not a substantial claim: may not pass S3 (load-bearing).

The first-quarter data release represented only about 6% of the planned 1200 subjects.

“The Q1 data release constitutes only ~6% of the target number of 1200 subjects.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The companion papers in the special issue presented many promising preliminary findings and methodological developments, but had not yet reported major neuroscientific discoveries.

“The companion articles in this special issue report many encouraging preliminary results as well as methodological advances, but not surprisingly they do not yet report major neuroscientific discoveries.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The later stages of data analysis needed to characterize structural and functional connectivity were still undergoing refinement and optimization.

“Moreover, the more advanced stages of data analysis that are essential for characterizing structural and functional connectivity are still being refined and optimized.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

At 2 mm resolution, the covariance matrix has about 8 × 10^9 elements, corresponding to about 4 × 10^10 bits if each element carries 2 bits.

“At 2 mm resolution the covariance matrix contains ~8 × 109 (90,0002) elements, or ~4 × 1010 information bits if there are 2 bits per element”

May combine two claims.

Including non-twin siblings increases statistical power for heritability analyses, for separating genetic and environmental influences, and for relating genotype to phenotype.

“Including additional (non-twin) siblings provides a further increase in statistical power for analyzing heritability, distinguishing between genetic and environmental influences (Posthuma and Boomsma, 2000; Van Essen et al., 2012a) and relating genotype to phenotype.”

• cites Posthuma and Boomsma, 2000Not checked yet

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• cites Van Essen et al., 2012aNot checked yet

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May combine two claims.

Although 1200 subjects is small compared with many GWAS studies, the statistical power from studying twins and siblings should enable valuable exploratory genome-wide analyses of how genes and regulatory sequences influence brain connectivity.

“While 1200 subjects is small relative to many GWAS studies, the statistical power gained by studying twins and their siblings should nonetheless enable valuable exploratory genome-wide analyses of how specific genes, interacting genes, and genetic regulatory sequences may influence brain connectivity.”

• AssumptionRests on an assumption: Many features of brain circuitry and behavior probably arise from small effects of many genes rather than from a few dominant genes.

Probably not a substantial claim: may not pass S3 (load-bearing).

16-bit DICOMs give a wider range of signal intensities, useful for multi-channel arrays with large intensity differences.

“The 16 bit DICOMs allow for an extended dynamic range of signal intensity values, which is advantageous with such multi-channel receiver arrays where signal intensity variations can be quite large.”

May combine two claims.

That gain can improve functional SNR, allow more diffusion samples, or raise fMRI/dMRI spatial resolution.

“This efficiency increase can lead to substantially improved functional SNR (Feinberg et al., 2010; (Smith et al., 2011), the ability to acquire more diffusion data points (Sotiropoulos et al., 2013c), and/or increases in spatial resolution for fMRI or dMRI (Ugurbil et al. 2013).”

• cites Feinberg et al., 2010 sourceNot checked yet

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• cites Smith et al., 2011 sourceNot checked yet

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• cites Sotiropoulos et al., 2013cNot checked yet

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May combine two claims.

Choosing the best multiband factor and other sequence settings involves complex trade-offs and required extensive pilot work.

“The optimal multiband factor and other pulse sequence parameters depend on a complex set of trade-offs that entailed extensive piloting and analysis (Ugurbil et al., 2013; Smith et al. 2013; Sotiropoulos et al., 2013c).”

• cites Ugurbil et al., 2013 sourceNot checked yet

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• cites Smith et al. 2013 sourceNot checked yet

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• cites Sotiropoulos et al., 2013cNot checked yet

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May combine two claims.

The 3T HCP protocol does not include prospective motion correction, since the method appeared late and was not tested enough before the protocol was fixed.

“However, prospective motion correction is not part of our 3T HCP acquisition protocol because the technology became available only late in the HCP methods development phase and was not sufficiently tested and developed before the data collection protocol was finalized.”

May combine two claims.

Theory suggests that 100 mT/m helps diffusion imaging substantially more than 40 mT/m, but less than the 300 mT/m system used by MGH/UCLA.

“This specifically benefits diffusion imaging, and on theoretical grounds (Ugurbil et al., 2013) it should provide significant gains over the standard 40 mT/m though not as much as the 300 mT/m customized gradients used by the MGH/UCLA HCP consortium.”

• cites Ugurbil et al., 2013 sourceNot checked yet

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Compared with standard 1 mm scans, the higher resolution makes cortical surface reconstruction more faithful and myelin maps better.

“The higher resolution compared to standard 1 mm structural scans improves the fidelity of cortical surface reconstruction and provides higher quality myelin maps (Glasser et al., 2013a; see below).”

• cites Glasser et al., 2013aNot checked yet

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May combine two claims.

HCP preprocessing fixes these distortions, but users who begin with raw HCP scans must correct them on their own.

“These distortions have been corrected in HCP preprocessed data, but must be carried out separately by anyone starting with the unprocessed (raw) HCP scan data (see below).”

• AssumptionRests on an assumption: Raw MRI images always contain spatial distortions, lack a common anatomical space, and do not align across modalities.

Classified as probably not a substantial claim.

Each HCP structural scan is rated by a trained rater for overall quality based on visual inspection of tissue contrast, blurring, ringing, and other artifacts.

“Each structural scan is evaluated by a trained rater to assess overall quality (poor, fair, good, and excellent), based on visual inspection of tissue contrast, spatial blurring, ringing, and other possible artifacts.”

May combine two claims.

Because 7T images need in-plane acceleration and have shorter T2*, the multiband factor is capped, as multiband also depends on coil sensitivity.

“Further, the requirement of in-plane acceleration, due to the higher resolution images combined with the much shorter T2* at 7T, limits the achievable multiband factor, because it also relies on the coil’s sensitivity profile to accelerate the acquisition.”

May combine two claims.

Optimization compared old and new methods critically, then bundled the best into pipelines meant for uniform, systematic use across HCP data.

“The optimization process entailed critical evaluation and comparisons of how various existing and new methods performed, then packaging the best methods into a set of preprocessing pipelines appropriate for consistent and systematic application to all HCP datasets.”

• AssumptionRests on an assumption: Raw MRI images always contain spatial distortions, lack a common anatomical space, and do not align across modalities.
• AssumptionRests on an assumption: Raw MRI images also contain noise, artifacts, and biases specific to each modality.

May combine two claims.

Compared with lower field strengths, 7T raises image SNR and functional contrast-to-noise.

“7T provides increases in both the image SNR (Vaughan et al., 2001) and functional contrast–to-noise (Yacoub et al., 2001), compared to lower fields.”

• cites Vaughan et al., 2001 sourceNot checked yet

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• cites Yacoub et al., 2001 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Any scan that could show identifiable facial features is defaced, and visual QC checks that defacing worked.

“all scan types containing potentially identifiable facial features are defaced (Milchenko and Marcus, 2013), with visual QC inspection to confirm successful defacing.”

• cites Milchenko and Marcus, 2013Not checked yet

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At higher fields, BOLD images are relatively more sensitive to microvasculature, which narrows the point spread function.

“Additionally, higher fields increase the relative sensitivity to the microvasculature in BOLD-based functional images (Uludag et al., 2009; Ugurbil et al., 2003b; Ogawa et al., 1993), resulting in a smaller point spread function (Shmuel et al., 2007).”

• cites Uludag et al., 2009 sourceNot checked yet

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• cites Ugurbil et al., 2003bNot checked yet

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• cites Ogawa et al., 1993 sourceNot checked yet

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May combine two claims.

Some ICA components represent artifacts such as head motion or cardiac pulsation, while others represent valid neuronally related spontaneous fluctuations.

“Some components represent artifacts such as head motion or cardiac pulsation, while others represent valid neuronally-related spontaneous fluctuations.”

May combine two claims.

FIX was hand-trained and tested on 100 15-minute HCP datasets and achieved better than 99% accuracy in classifying ICA components.

“FIX has been hand-trained and tested on one hundred 15-minute HCP datasets, and has achieved better than 99% accuracy rate in correctly classifying components.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Cortical surface alignment uses surface-based registration to a population-average surface with FreeSurfer, based on matching cortical folding patterns.

“Cortical surface alignment benefits from a subsequent stage of surface-based registration to a population-average surface, using FreeSurfer to register each hemisphere to a separate left and right atlas surfaces based on matching of cortical folding patterns (Fischl et al., 1999).”

• cites Fischl et al., 1999 sourceNot checked yet

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Full and partial correlation matrices are mathematically well-defined, but neither should be regarded as an explicit validated indicator of direct anatomical connectivity, although significant partial correlations may have a high probability of reflecting genuine connections.

“Both the full correlation matrix and the partial correlation matrix represent mathematically well-defined entities; however, as alluded to above, neither should be regarded as an explicit, validated indicator of direct anatomical connectivity, although significant values in the partial correlation matrix will hopefully have a high probability of reflecting genuine connections (Smith, 2012).”

• cites Smith, 2012 sourceNot checked yet

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The V1/V2 connectivity pattern fits evidence for a major mid-eccentricity transition and implies that functional connectivity network boundaries do not always respect classical areal boundaries.

“This fits with evidence for a major transition in functional connectivity that cuts across both V1 and V2 in their mid-eccentricity range (Yeo et al., 2011); it implies that network (parcel) boundaries defined by functional connectivity do not always respect classical areal boundaries”

• cites Yeo et al., 2011 sourceNot checked yet

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• cites Power et al., 2011 sourceNot checked yet

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• cites Van Essen and Glasser, in pressNot checked yet

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The neurobiological interpretation of full correlation, mean-regressed correlation, and partial correlation is not well understood, and none should be considered a perfect measure of direct anatomical connectivity.

“The neurobiological interpretation of different types of representation (full correlation; correlation after mean gray-matter timecourse regression; and the partial correlation approach illustrated below) is not well understood, and none should be considered a perfect measure of direct anatomical connectivity.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Classical parcellations of cortical areas and subcortical nuclei commonly assume that each parcel is topologically contiguous and non-overlapping with neighboring parcels.

“Classical parcellations of cortical areas and subcortical nuclei commonly assume that each parcel is topologically contiguous and is non-overlapping with neighboring parcels (aside from the experimental uncertainties in areal boundaries).”

May combine two claims.

ICA components 12 and 15 include several parts of the default mode network and support the hypothesis that this network includes functionally distinct subregions.

“ICA components 12 and 15 include several parts of the default mode network, and support the hypothesis that this network includes functionally distinct subregions (Andrews-Hanna et al., 2010).”

• cites Andrews-Hanna et al., 2010 sourceNot checked yet

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The striking functional connectivity differences for nearby seed locations reflect high data quality and amount, topology-respecting preprocessing, and advanced noise and artifact reduction.

“These striking differences in functional connectivity for nearby locations reflect several factors, including the high quality (and large amount) of data acquired from each subject; the use of preprocessing and analysis steps that respect the topology of the cortical sheet; and the advanced methods used to reduce noise and artifacts.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Subcortical gray matter excluding cerebellar cortex constitutes about 8% of brain volume, and its vital roles are achieved with fewer than 1% of total brain neurons.

“Subcortical gray matter (excluding cerebellar cortex) constitutes about 8% of brain volume; remarkably, the many vital roles of subcortical nuclei in brain function are achieved with fewer than 1% of the total number of brain neurons (Azevedo et al., 2009).”

• cites Azevedo et al., 2009 sourceNot checked yet

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Data from any individual diffusion shell can be used with standard fiber reconstruction, but methods using all three shells get the largest benefit.

“Data from any individual shell (b = 1000, 2000, and 3000 s/mm2) can be used with standard fiber reconstruction techniques, but methods that make use of all three shells will get the largest benefit.”

Probably not a substantial claim: may not pass S3 (load-bearing).

If each time point could carry 2 bits of independent information, the theoretical maximum would be about one gigabit per subject.

“If, hypothetically, each time point could encode just 2 bits of information that was statistically independent of other time points and other grayordinates, then the theoretical upper bound would be about one gigabit (109 bits) of information per subject.”

Probably not a substantial claim: may not pass S4 (based).

Accurate source reconstruction is a critical prerequisite for comparing electrophysiological results with those from other imaging modalities.

“Accurate source reconstruction is a critical prerequisite for comparing electrophysiological results to those obtained from other imaging modalities.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Linear constrained minimum variance beamformers reconstruct source-space data in the time domain and are useful for inferring connectivity in oscillatory brain activity.

“Linear constrained minimum variance beamformers (LCMV) reconstruct source space data in the time domain and are useful for inferring connectivity in oscillatory brain activity (Schoffelen and Gross, 2009; Brookes et al., 2011).”

• cites Schoffelen and Gross, 2009Not checked yet

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• cites Brookes et al., 2011 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Dynamic imaging of coherent source reconstructs source-space data in the frequency domain.

“Dynamic imaging of coherent source (DICS) reconstructs source-space data in the frequency domain (Van Veen et al., 1997; Gross et al., 2001).”

• cites Van Veen et al., 1997 sourceNot checked yet

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• cites Gross et al., 2001 sourceNot checked yet

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May combine two claims.

Other refinements were individually modest, but combining many small gains produced large aggregate benefits.

“Many other refinements represent incremental improvements individually, but the concatenation of many small increments has led to large gains in the aggregate.”

Probably not a substantial claim: may not pass S3 (load-bearing).

A second approach using the covariance matrix of the fMRI time series gives a similar estimate.

“An alternative assessment that yields a similar estimate comes from considering the covariance matrix of the fMRI timeseries, which presumably should be more reproducible across different scan sessions than the timeseries itself.”

May combine two claims.

MRI-based connectivity analyses could distinguish connectivity 'brainprints' among many individuals, though not uniquely for everyone on Earth.

“It suggests that MRI-based connectivity analyses have the potential to discriminate connectivity ‘brainprints’ among large numbers of individuals, albeit not unique for every individual on the planet.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Under that assumption, resting-state fMRI would supply roughly 10^7 bits of information about brain circuits per HCP subject.

“If so, the amount of information about brain circuits provided by rfMRI would be in the range of 107 bits per HCP subject.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Macaque evidence indicates that connection strength between any two cortical areas can vary by one or two orders of magnitude.

“and evidence from the macaque monkey suggests that the strength of pathways between any pair of cortical areas can vary by one or two orders of magnitude (Markov et al., 2011).”

• cites Markov et al., 2011 sourceNot checked yet

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May combine two claims.

For 7T scans, the smaller voxels (about 1 mm^3) increase spatial elements about eightfold, while lower temporal resolution by two- to threefold, suggesting total information may be about twice as large.

“For the 7T HCP scans, the smaller voxel size attainable (~1 mm3) will increase the number of spatial elements about 8-fold, but the anticipated temporal resolution will be lower by 2- or 3-fold, suggesting that the total amount of information may be about 2-fold greater.”

May combine two claims.

Human brain connectivity can be measured much less accurately than genome sequencing, but its individual variability is much greater.

“In contrast, the accuracy with which human brain connectivity can be quantitatively assessed is much lower than for genome sequencing, but the degree of individual variability is far greater.”