Detailed mapping of the complex fiber structure and white matter pathways of the chimpanzee brain.

Long-standing questions about human brain evolution may only be resolved through comparisons with close living evolutionary relatives, such as chimpanzees. This applies in particular to structural white matter (WM) connectivity, which continuously expanded throughout evolution. However, due to legal restrictions on chimpanzee research, neuroscience research currently relies largely on data with limited detail or on comparisons with evolutionarily distant monkeys. Here, we present a detailed magnetic resonance imaging resource to study structural WM connectivity in the chimpanzee. This open-access resource contains (1) WM reconstructions of a postmortem chimpanzee brain, using the highest-quality diffusion magnetic resonance imaging data yet acquired from great apes; (2) an optimized and validated method for high-quality fiber orientation reconstructions; and (3) major fiber tract segmentations for cross-species morphological comparisons. This dataset enabled us to identify phylogenetically relevant details of the chimpanzee connectome, and we anticipate that it will substantially contribute to understanding human brain evolution.

Mapping short association fibre connectivity up to V3 in the human brain in vivo.

Short association fibres (SAF) are the most abundant fibre pathways in the human white matter. Until recently, SAF could not be mapped comprehensively in vivo because diffusion weighted magnetic resonance imaging with sufficiently high spatial resolution needed to map these thin and short pathways was not possible. Recent developments in acquisition hardware and sequences allowed us to create a dedicated in vivo method for mapping the SAF based on sub-millimetre spatial resolution diffusion weighted tractography, which we validated in the human primary (V1) and secondary (V2) visual cortex against the expected SAF retinotopic order. Here, we extended our original study to assess the feasibility of the method to map SAF in higher cortical areas by including SAF up to V3. Our results reproduced the expected retinotopic order of SAF in the V2-V3 and V1-V3 stream, demonstrating greater robustness to the shorter V1-V2 and V2-V3 than the longer V1-V3 connections. The demonstrated ability of the method to map higher-order SAF connectivity patterns in vivo is an important step towards its application across the brain.

Improving MR axon radius estimation in human white matter using spiral acquisition and field monitoring.

PURPOSE: To compare MR axon radius estimation in human white matter using a multiband spiral sequence combined with field monitoring to the current state-of-the-art echo-planar imaging (EPI)-based approach. METHODS: A custom multiband spiral sequence was used for diffusion-weighted imaging at ultra-high b $$ b $$ -values. Field monitoring and higher order image reconstruction were employed to greatly reduce artifacts in spiral images. Diffusion weighting parameters were chosen to match a state-of-the art EPI-based axon radius mapping protocol. The spiral approach was compared to the EPI approach by comparing the image signal-to-noise ratio (SNR) and performing a test-retest study to assess the respective variability and repeatability of axon radius mapping. Effective axon radius estimates were compared over white matter voxels and along the left corticospinal tract. RESULTS: Increased SNR and reduced artifacts in spiral images led to reduced variability in resulting axon radius maps, especially in low-SNR regions. Test-retest variability was reduced by a factor of approximately 1.5 using the spiral approach. Reduced repeatability due to significant bias was found for some subjects in both spiral and EPI approaches, and attributed to scanner instability, pointing to a previously unknown limitation of the state-of-the-art approach. CONCLUSION: Combining spiral readouts with field monitoring improved mapping of the effective axon radius compared to the conventional EPI approach.

Longitudinal motor system changes from acute to chronic spinal cord injury.

BACKGROUND AND PURPOSE: In acute spinal cord injury (SCI), magnetic resonance imaging (MRI) reveals tissue bridges and neurodegeneration for 2 years. This 5-year study aims to track initial lesion changes, subsequent neurodegeneration, and their impact on recovery. METHODS: This prospective longitudinal study enrolled acute SCI patients and healthy controls who were assessed clinically-and by MRI-regularly from 3 days postinjury up to 60 months. We employed histologically cross-validated quantitative MRI sequences sensitive to volume, myelin, and iron changes, thereby reflecting indirectly processes of neurodegeneration and neuroinflammation. General linear models tracked lesion and remote changes in volume, myelin- and iron-sensitive magnetic resonance indices over 5 years. Associations between lesion, degeneration, and recovery (using the Spinal Cord Independence Measure [SCIM] questionnaire and the International Standards for Neurological Classification of Spinal Cord Injury total motor score) were assessed. RESULTS: Patients' motor scores improved by an average of 12.86 (95% confidence interval [CI] = 6.70-19.00) points, and SCIM by 26.08 (95% CI = 17.00-35.20) points. Within 3-28 days post-SCI, lesion size decreased by more than two-thirds (3 days: 302.52 ± 185.80 mm2 , 28 days: 76.77 ± 88.62 mm2 ), revealing tissue bridges. Cervical cord and corticospinal tract volumes transiently increased in SCI patients by 5% and 3%, respectively, accompanied by cervical myelin decreases and iron increases. Over time, progressive atrophy was observed in both regions, which was linked to early lesion dynamics. Tissue bridges, reduced swelling, and myelin content decreases were predictive of long-term motor score recovery and improved SCIM score. CONCLUSIONS: Studying acute changes and their impact on longer follow-up provides insights into SCI trajectory, highlighting the importance of acute intervention while indicating the potential to influence outcomes in the later stages.

Characterisation of laminar and vascular spatiotemporal dynamics of CBV and BOLD signals using VASO and ME-GRE at 7T in humans.

Interpretation of cortical laminar functional magnetic resonance imaging (fMRI) activity requires detailed knowledge of the spatiotemporal haemodynamic response across vascular compartments due to the well-known vascular biases (e.g. the draining veins). Further complications arise from the spatiotemporal hemodynamic response that differs depending on the duration of stimulation. This information is crucial for future studies using depth-dependent cerebral blood volume (CBV) measurements, which promise higher specificity for the cortical microvasculature than the blood oxygenation level dependent (BOLD) contrast. To date, direct information about CBV dynamics with respect to stimulus duration, cortical depth and vasculature is missing in humans. Therefore, we characterized the cortical depth-dependent CBV-haemodynamic responses across a wide set of stimulus durations with 0.9 mm isotropic spatial and 0.785 seconds effective temporal resolution in humans using slice-selective slab-inversion vascular space occupancy (SS-SI VASO). Additionally, we investigated signal contributions from macrovascular compartments using fine-scale vascular information from multi-echo gradient-echo (ME-GRE) data at 0.35 mm isotropic resolution. In total, this resulted in >7.5h of scanning per participant (n=5). We have three major findings: (I) While we could demonstrate that 1 second stimulation is viable using VASO, more than 12 seconds stimulation provides better CBV responses in terms of specificity to microvasculature, but durations beyond 24 seconds of stimulation may be wasteful for certain applications. (II) We observe that CBV responses show dilation patterns across the cortex. (III) While we found increasingly strong BOLD signal responses in vessel-dominated voxels with longer stimulation durations, we found increasingly strong CBV signal responses in vessel-dominated voxels only until 4 second stimulation durations. After 4 seconds, only the signal from non-vessel dominated voxels kept increasing. This might explain why CBV responses are more specific to the underlying neuronal activity for long stimulus durations.

Laminar dissociation of feedforward and feedback in high-level ventral visual cortex during imagery and perception.

Visual imagery and perception share neural machinery but rely on different information flow. While perception is driven by the integration of sensory feedforward and internally generated feedback information, imagery relies on feedback only. This suggests that although imagery and perception may activate overlapping brain regions, they do so in informationally distinctive ways. Using lamina-resolved MRI at 7 T, we measured the neural activity during imagery and perception of faces and scenes in high-level ventral visual cortex at the mesoscale of laminar organization that distinguishes feedforward from feedback signals. We found distinctive laminar profiles for imagery and perception of scenes and faces in the parahippocampal place area and the fusiform face area, respectively. Our findings provide insight into the neural basis of the phenomenology of visual imagery versus perception and shed new light into the mesoscale organization of feedforward and feedback information flow in high-level ventral visual cortex.

Functional locus coeruleus imaging to investigate an ageing noradrenergic system.

The locus coeruleus (LC), our main source of norepinephrine (NE) in the brain, declines with age and is a potential epicentre of protein pathologies in neurodegenerative diseases (ND). In vivo measurements of LC integrity and function are potentially important biomarkers for healthy ageing and early ND onset. In the present study, high-resolution functional MRI (fMRI), a reversal reinforcement learning task, and dedicated post-processing approaches were used to visualise age differences in LC function (N = 50). Increased LC responses were observed during emotionally and task-related salient events, with subsequent accelerations and decelerations in reaction times, respectively, indicating context-specific adaptive engagement of the LC. Moreover, older adults exhibited increased LC activation compared to younger adults, indicating possible compensatory overactivation of a structurally declining LC in ageing. Our study shows that assessment of LC function is a promising biomarker of cognitive aging.

Reliability of task-based fMRI in the dorsal horn of the human spinal cord.

The application of functional magnetic resonance imaging (fMRI) to the human spinal cord is still a relatively small field of research and faces many challenges. Here we aimed to probe the limitations of task-based spinal fMRI at 3T by investigating the reliability of spinal cord blood oxygen level dependent (BOLD) responses to repeated nociceptive stimulation across two consecutive days in 40 healthy volunteers. We assessed the test-retest reliability of subjective ratings, autonomic responses, and spinal cord BOLD responses to short heat pain stimuli (1s duration) using the intraclass correlation coefficient (ICC). At the group level, we observed robust autonomic responses as well as spatially specific spinal cord BOLD responses at the expected location, but no spatial overlap in BOLD response patterns across days. While autonomic indicators of pain processing showed good-to-excellent reliability, both ß-estimates and z-scores of task-related BOLD responses showed poor reliability across days in the target region (gray matter of the ipsilateral dorsal horn). When taking into account the sensitivity of gradient-echo echo planar imaging (GE-EPI) to draining vein signals by including the venous plexus in the analysis, we observed BOLD responses with fair reliability across days. Taken together, these results demonstrate that heat pain stimuli as short as one second are able to evoke a robust and spatially specific BOLD response, which is however strongly variable within participants across time, resulting in low reliability in the dorsal horn gray matter. Further improvements in data acquisition and analysis techniques are thus necessary before event-related spinal cord fMRI as used here can be reliably employed in longitudinal designs or clinical settings.

Brain structure and function: a multidisciplinary pipeline to study hominoid brain evolution.

To decipher the evolution of the hominoid brain and its functions, it is essential to conduct comparative studies in primates, including our closest living relatives. However, strong ethical concerns preclude in vivo neuroimaging of great apes. We propose a responsible and multidisciplinary alternative approach that links behavior to brain anatomy in non-human primates from diverse ecological backgrounds. The brains of primates observed in the wild or in captivity are extracted and fixed shortly after natural death, and then studied using advanced MRI neuroimaging and histology to reveal macro- and microstructures. By linking detailed neuroanatomy with observed behavior within and across primate species, our approach provides new perspectives on brain evolution. Combined with endocranial brain imprints extracted from computed tomographic scans of the skulls these data provide a framework for decoding evolutionary changes in hominin fossils. This approach is poised to become a key resource for investigating the evolution and functional differentiation of hominoid brains.