High-Resolution Tractography Protocol to Investigate the Pathways between Human Mediodorsal Thalamic Nucleus and Prefrontal Cortex.

Animal studies have established that the mediodorsal nucleus (MD) of the thalamus is heavily and reciprocally connected with all areas of the prefrontal cortex (PFC). In humans, however, these connections are difficult to investigate. High-resolution imaging protocols capable of reliably tracing the axonal tracts linking the human MD with each of the PFC areas may thus be key to advance our understanding of the variation, development, and plastic changes of these important circuits, in health and disease. Here, we tested in adult female and male humans the reliability of a new reconstruction protocol based on in vivo diffusion MRI to trace, measure, and characterize the fiber tracts interconnecting the MD with 39 human PFC areas per hemisphere. Our protocol comprised the following three components: (1) defining regions of interest; (2) preprocessing diffusion data; and, (3) modeling white matter tracts and tractometry. This analysis revealed largely separate PFC territories of reciprocal MD-PFC tracts bearing striking resemblance with the topographic layout observed in macaque connection-tracing studies. We then examined whether our protocol could reliably reconstruct each of these MD-PFC tracts and their profiles across test and retest sessions. Results revealed that this protocol was able to trace and measure, in both left and right hemispheres, the trajectories of these 39 area-specific axon bundles with good-to-excellent test-retest reproducibility. This protocol, which has been made publicly available, may be relevant for cognitive neuroscience and clinical studies of normal and abnormal PFC function, development, and plasticity.SIGNIFICANCE STATEMENT Reciprocal MD-PFC interactions are critical for complex human cognition and learning. Reliably tracing, measuring and characterizing MD-PFC white matter tracts using high-resolution noninvasive methods is key to assess individual variation of these systems in humans. Here, we propose a high-resolution tractography protocol that reliably reconstructs 39 area-specific MD-PFC white matter tracts per hemisphere and quantifies structural information from diffusion MRI data. This protocol revealed a detailed mapping of thalamocortical and corticothalamic MD-PFC tracts in four different PFC territories (dorsal, medial, orbital/frontal pole, inferior frontal) showing structural connections resembling those observed in tracing studies with macaques. Furthermore, our automated protocol revealed high test-retest reproducibility and is made publicly available, constituting a step forward in mapping human MD-PFC circuits in clinical and academic research.

Reproducible protocol to obtain and measure first-order relay human thalamic white-matter tracts.

The "primary" or "first-order relay" nuclei of the thalamus feed the cerebral cortex with information about ongoing activity in the environment or the subcortical motor systems. Because of the small size of these nuclei and the high specificity of their input and output pathways, new imaging protocols are required to investigate thalamocortical interactions in human perception, cognition and language. The goal of the present study was twofold: I) to develop a reconstruction protocol based on in vivo diffusion MRI to extract and measure the axonal fiber tracts that originate or terminate specifically in individual first-order relay nuclei; and, II) to test the reliability of this reconstruction protocol. In left and right hemispheres, we investigated the thalamocortical/corticothalamic axon bundles linking each of the first-order relay nuclei and their main cortical target areas, namely, the lateral geniculate nucleus (optic radiation), the medial geniculate nucleus (acoustic radiation), the ventral posterior nucleus (somatosensory radiation) and the ventral lateral nucleus (motor radiation). In addition, we examined the main subcortical input pathway to the ventral lateral posterior nucleus, which originates in the dentate nucleus of the cerebellum. Our protocol comprised three components: defining regions-of-interest; preprocessing diffusion data; and modeling white-matter tracts and tractometry. We then used computation and test-retest methods to check whether our protocol could reliably reconstruct these tracts of interest and their profiles. Our results demonstrated that the protocol had nearly perfect computational reproducibility and good-to-excellent test-retest reproducibility. This new protocol may be of interest for both basic human brain neuroscience and clinical studies and has been made publicly available to the scientific community.

Neural correlates of phonological, orthographic and semantic reading processing in dyslexia.

Developmental dyslexia is one of the most prevalent learning disabilities, thought to be associated with dysfunction in the neural systems underlying typical reading acquisition. Neuroimaging research has shown that readers with dyslexia exhibit regional hypoactivation in left hemisphere reading nodes, relative to control counterparts. This evidence, however, comes from studies that have focused only on isolated aspects of reading. The present study aims to characterize left hemisphere regional hypoactivation in readers with dyslexia for the main processes involved in successful reading: phonological, orthographic and semantic. Forty-one participants performed a demanding reading task during MRI scanning. Results showed that readers with dyslexia exhibited hypoactivation associated with phonological processing in parietal regions; with orthographic processing in parietal regions, Broca's area, ventral occipitotemporal cortex and thalamus; and with semantic processing in angular gyrus and hippocampus. Stronger functional connectivity was observed for readers with dyslexia than for control readers 1) between the thalamus and the inferior parietal cortex/ventral occipitotemporal cortex during pseudoword reading; and, 2) between the hippocampus and the pars opercularis during word reading. These findings constitute the strongest evidence to date for the interplay between regional hypoactivation and functional connectivity in the main processes supporting reading in dyslexia.

Developmental evaluation of atypical auditory sampling in dyslexia: Functional and structural evidence.

Whether phonological deficits in developmental dyslexia are associated with impaired neural sampling of auditory information at either syllabic- or phonemic-rates is still under debate. In addition, whereas neuroanatomical alterations in auditory regions have been documented in dyslexic readers, whether and how these structural anomalies are linked to auditory sampling and reading deficits remains poorly understood. In this study, we measured auditory neural synchronization at different frequencies corresponding to relevant phonological spectral components of speech in children and adults with and without dyslexia, using magnetoencephalography. Furthermore, structural MRI was used to estimate cortical thickness of the auditory cortex of participants. Dyslexics showed atypical brain synchronization at both syllabic (slow) and phonemic (fast) rates. Interestingly, while a left hemispheric asymmetry in cortical thickness was functionally related to a stronger left hemispheric lateralization of neural synchronization to stimuli presented at the phonemic rate in skilled readers, the same anatomical index in dyslexics was related to a stronger right hemispheric dominance for neural synchronization to syllabic-rate auditory stimuli. These data suggest that the acoustic sampling deficit in development dyslexia might be linked to an atypical specialization of the auditory cortex to both low and high frequency amplitude modulations.

Adult eyewitness memory and compliance: effects of post-event misinformation on memory for a negative event.

This study investigated effects of misleading post-event information, delay, and centrality definition on eyewitness memory and suggestibility for a negative event (a vividly filmed murder). Either immediately or 2 weeks after viewing the film, 93 adults read a (misleading or control) narrative about the event and then completed a recognition memory test. Misinformation acceptance was operative, but strong evidence for memory malleability was lacking. Compliance predicted misinformation effects, especially on the delayed test. Although accuracy was generally higher for central than peripheral information, centrality criteria influenced the pattern of results. Self-report of greater distress was associated with better recognition accuracy. The results suggest that use of different centrality definitions may partly explain inconsistencies across studies of memory and suggestibility for central and peripheral information. Moreover, social factors appeared, at least in part, to influence misinformation effects for the highly negative event, especially as memory faded. Implications for eyewitness memory and suggestibility are discussed.

Trauma and memory: effects of post-event misinformation, retrieval order, and retention interval.

The present study concerned effects of misinformation, retrieval order, and retention interval on eyewitness memory for a traumatic event (a vivid murder). Relations between misinformation acceptance and compliance were also examined. The classic three-stage misinformation paradigm (Loftus, 1979) was employed, with a multi-component recognition test added. Either immediately or 2 weeks after viewing a distressing film, 232 adults read a narrative (misleading or control) about the murder and then took a recognition test that tapped memory for central and peripheral details. Test-item order either matched the chronology of the film or was randomly determined. Significant misinformation effects were obtained. Moreover, control participants were more accurate in response to questions about central than peripheral information; however, this was not so for misinformed participants. Sequential but not random retrieval order resulted in a higher proportion of correct responses for central as opposed to peripheral misinformation questions. Compliance was significantly related to misinformation effects. Delay increased participants' suggestibility, impaired memory accuracy, and produced higher confidence ratings for misinformed participants compared to controls. Findings indicate that even for a highly negative event, adults' memory is not immune to inaccuracies and suggestive influences.