Internal Capsule

The fMRI analysis was based around the timeseries of model-free and
model-based RPEs as generated from the simulation of the model over each
subject’s experiences. We defined two parametric regressors –
the model-free RPE, and the difference between the model-free and model-based
RPEs. The latter regressor characterizes how net BOLD activity would differ if
it were correlated with model-based RPEs or any weighted mixture of both. For
each trial, the RPE timeseries were entered as parametric regressors modulating
impulse events at the second-stage onset and reward receipt. To test the
correspondence between behavioral and neural estimates of the model-based
effect, we also included the per-subject estimate of the model-based effect
(w, above) from the behavioral fits as a second-level
covariate for the difference regressor. A full description of the analysis is
given in Supplemental
Experimental Procedures.
For display purposes, we render activations at an uncorrected threshold
of p<.001 (except relaxing this in one case to p<.005), overlaid on the
average of subjects’ normalized structural images. For all reported
statistics, we subjected these uncorrected maps to cluster-level correction for
family-wise error due to multiple comparisons over the whole brain, or, in a few
cases (noted specifically) over a small volume defined by an anatomical mask of
bilateral nucleus accumbens. This mask was hand-drawn on the subject-averaged
structural image, according to the guidelines of Breiter et al. (Ballmaier et al., 2004 (link); Breiter et al., 1997 (link); Schonberg et al., 2010 (link)), notably, defining the nucleus’
superior border by a line connecting the most ventral point of the lateral
ventricle to the most ventral point of the internal capsule at the level of the
putamen. Conjunction inference was by the minimum t-statistic
(Nichols et al., 2005 (link)) using the
conjunction null hypothesis. The difference regressor was orthogonalized against
the RPE regressor, so that up to minor correlation that can be reintroduced by
whitening and filtering, it captured only residual variation in BOLD activity
not otherwise explained by the model-free RPE. However, note that conjunction
inference via the minimum t-statistic is valid even when the
conjoined contrasts are not independent (Nichols
et al., 2005).

Authorizations for reporting these three cases were granted by the Eastern Ontario Regional Forensic Unit and the Laboratoire de Sciences Judiciaires et de Médecine Légale du Québec.
The sampling followed a relatively standardized protocol for all TBI cases: samples were collected from the cortex and underlying white matter of the pre-frontal gyrus, superior and middle frontal gyri, temporal pole, parietal and occipital lobes, deep frontal white matter, hippocampus, anterior and posterior corpus callosum with the cingula, lenticular nucleus, thalamus with the posterior limb of the internal capsule, midbrain, pons, medulla, cerebellar cortex and dentate nucleus. In some cases, gross pathology (e.g. contusions) mandated further sampling along with the dura and spinal cord if available. The number of available sections for these three cases was 26 for case1, and 24 for cases 2 and 3.
For the detection of ballooned neurons, all HE or HPS sections, including contusions, were screened at 200×.
Representative sections were stained with either hematoxylin–eosin (HE) or hematoxylin-phloxin-saffron (HPS). The following histochemical stains were used: iron, Luxol-periodic acid Schiff (Luxol-PAS) and Bielschowsky. The following antibodies were used for immunohistochemistry: glial fibrillary acidic protein (GFAP) (Leica, PA0026,ready to use), CD-68 (Leica, PA0073, ready to use), neurofilament 200 (NF200) (Leica, PA371, ready to use), beta-amyloid precursor-protein (β-APP) (Chemicon/Millipore, MAB348, 1/5000), αB-crystallin (EMD Millipore, MABN2552 1/1000), ubiquitin (Vector, 1/400), β-amyloid (Dako/Agilent, 1/100), tau protein (Thermo/Fisher, MN1020 1/2500), synaptophysin (Dako/Agilent, ready to use), TAR DNA binding protein 43 (TDP-43) ((Protein Tech, 10,782-2AP, 1/50), fused in sarcoma binding protein (FUS) (Protein tech, 60,160–1-1 g, 1/100), and p62 (BD Transduc, 1/25). In our index cases, the following were used for the evaluation of TAI: β-APP, GFAP, CD68 and NF200; for the neurodegenerative changes: αB-crystallin, NF200, ubiquitin, tau protein, synaptophysin, TDP-43, FUS were used.
For the characterization of the ballooned neurons only, two cases of fronto-temporal lobar degeneration, FTLD-Tau, were used as controls. One was a female aged 72 who presented with speech difficulties followed by neurocognitive decline and eye movement abnormalities raising the possibility of Richardson’s disorder. The other was a male aged 67 who presented with a primary non-fluent aphasia progressing to fronto-temporal demαentia. In both cases, the morphological findings were characteristic of a corticobasal degeneration.

An ASPECTS atlas (Fig. 2) was created using the JHU_SS_MNI template^{20 (link)}, by selecting regions of interest (ROIs) from our previously published atlas^{21 (link)–23 (link)}. The ASPECTS atlas defines the 10 areas considered in the ASPECTS system: the caudate, the lentiform, the internal capsule (IC), the insula, and the cortical / subcortical regions from M1-M6^{24 (link)}. This proposed ASPECTS deformable 3D atlas is publicly available in ADS¹³ . The visual ASPECTS rating was done by two evaluators, and finally defined by consensus with a neuroradiologist. The evaluation was done on the DWI and ADC images in MNI space, having access to the overlapped ASPECTS map. Raters used the typical clinical scoring system (1 if the given region is considered affected by the infarct, 0 if not. For the total ASPECTS, each point was subtracted from 10, which is the normal). The consensus visual ASPECTS are considered as "ground truth" scores in this study. The frequency of ASPECTS per score classes and per region is summarized in Supplementary Table 1.

High-pressure and high-temperature experiments were conducted using Kawai-type 2000-ton multi-anvil apparatus (Orange-2000) and Kawai-type 3000-ton multi-anvil apparatus (Orange-3000) installed at Geodynamics Research Center, Ehime University (GRC), Japan. The Orange-2000 was used only for Run No. OS3083, whereas all other experiments were conducted using the Orange-3000. All experiments were conducted at 28 GPa and temperatures were 1400 °C, 1500 °C, 1620 °C and 1700 °C, respectively (see also Supplementary Table 2). The relationship between the pressure and load was calibrated in advance. The heating duration for all experiments was 2 h. Tungsten carbide anvils (Fujilloy F08) with 4 mm truncated edge length (TEL) were used. The cell assembly used in this study is shown in Fig. 7. A platinum sample capsule was surrounded by an Fe-FeO buffer (iron wüstite buffer) to reproduce the oxygen fugacity corresponding to the lower mantle condition^{30 (link),42 (link),43 (link)}. We used 150 mesh iron powder and iron oxide (FeO) powders with 8 μm or 200 mesh for the Fe-FeO buffer [Fe:FeO = 2:1 (wt. %)]. Then, 20–50 μl of water was added to 0.5 g of Fe–FeO buffer. The platinum capsule was enclosed in an outer gold capsule. The two gold capsules were insulated from the Re heater with a thickness of 25 μm using a magnesia sleeve. The temperature was measured with a precision of ± 5 °C using a W–Re (W3%Re–W25%Re) thermocouple inserted into the octahedron and attached to the gold capsules. The hydrogen fugacity in the inner and outer capsules was assumed to be equal because of the high hydrogen permeability of platinum compared with that of gold. ¹⁵NH₄¹⁵NO₃ decomposes into ¹⁵N₂O and H₂O at high temperatures, and ¹⁵NH₃ is expected to be formed in the ¹⁵N–H–O fluid under reduced conditions buffered by Fe–FeO in an inner platinum capsule.Figure 7

Schematic illustrating the cell assembly that was used in high-pressure and high-temperature experiments using multi-anvil apparatus. A LaCrO₃ (brown) sleeve served as a thermal insulator. A platinum (light gray) sample capsule was made by combining two platinum tubes with 0.1 mm wall thickness, and outer diameters of 1.3 mm and 1.5 mm, respectively, by welding each end of the capsules. A gold capsule (yellow) was made from a gold tube with 0.1 mm wall thickness and 2.5 mm outer diameter.