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The European Journal of Neuroscience Aug 2017Drug addiction is a chronic disease that is shaped by alterations in neuronal function within the cortical-basal ganglia-thalamic circuit. However, our understanding of...
Drug addiction is a chronic disease that is shaped by alterations in neuronal function within the cortical-basal ganglia-thalamic circuit. However, our understanding of how this circuit regulates drug-seeking remains incomplete, and relapse rates remain high. The midline thalamic nuclei are an integral component of the cortical-basal ganglia-thalamic circuit and are poised to mediate addiction behaviors, including relapse. It is surprising that little research has examined the contribution of midline thalamic nuclei and their efferent projections in relapse. To address this, we expressed inhibitory, G -coupled DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) in a subset of the midline thalamic nuclei or in midline thalamic nuclei neurons projecting to either the nucleus accumbens or the amygdala. We examined the effect of transiently decreasing activity of these neuronal populations on cue-induced and cocaine-primed reinstatement of cocaine-seeking. Reducing activity of midline thalamic nuclei neurons attenuated both cue-induced and cocaine-primed reinstatement, but had no effect on cue-induced reinstatement of sucrose-seeking or locomotor activity. Interestingly, attenuating activity of efferent projections from the anterior portion of midline thalamic nuclei to the nucleus accumbens blocked cocaine-primed reinstatement but enhanced cue-induced reinstatement. Decreasing activity of efferent projections from either the posterior midline thalamic nuclei to the nucleus accumbens or the midline thalamic nuclei to amygdala had no effect. These results reveal a novel contribution of subsets of midline thalamic nuclei neurons in drug-seeking behaviors and suggest that modulation of midline thalamic nuclei activity may be a promising therapeutic target for preventing relapse.
Topics: Animals; Clozapine; Cocaine-Related Disorders; Cues; Designer Drugs; Drug-Seeking Behavior; Efferent Pathways; Male; Neurons; Nucleus Accumbens; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled; Repetition Priming; Thalamic Nuclei
PubMed: 28664636
DOI: 10.1111/ejn.13631 -
NeuroImage Nov 2022The "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...
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.
Topics: Geniculate Bodies; Humans; Neural Pathways; Reproducibility of Results; Thalamic Nuclei; Thalamus; Ventral Thalamic Nuclei; White Matter
PubMed: 35973564
DOI: 10.1016/j.neuroimage.2022.119558 -
Molecular Pain 2022The anterior cingulate cortex (ACC) is located in the frontal part of the cingulate cortex, and plays important roles in pain perception and emotion. The thalamocortical...
The anterior cingulate cortex (ACC) is located in the frontal part of the cingulate cortex, and plays important roles in pain perception and emotion. The thalamocortical pathway is the major sensory input to the ACC. Previous studies have show that several different thalamic nuclei receive projection fibers from spinothalamic tract, that in turn send efferents to the ACC by using neural tracers and optical imaging methods. Most of these studies were performed in monkeys, cats, and rats, few studies were reported systematically in adult mice. Adult mice, especially genetically modified mice, have provided molecular and synaptic mechanisms for cortical plasticity and modulation in the ACC. In the present study, we utilized rabies virus-based retrograde tracing system to map thalamic-anterior cingulate monosynaptic inputs in adult mice. We also combined with a new high-throughput VISoR imaging technique to generate a three-dimensional whole-brain reconstruction, especially the thalamus. We found that cortical neurons in the ACC received direct projections from different sub-nuclei in the thalamus, including the anterior, ventral, medial, lateral, midline, and intralaminar thalamic nuclei. These findings provide key anatomic evidences for the connection between the thalamus and ACC.
Topics: Animals; Gyrus Cinguli; Mice; Neural Pathways; Neurons; Rats; Thalamic Nuclei; Thalamus
PubMed: 35240879
DOI: 10.1177/17448069221087034 -
Multiple Sclerosis (Houndmills,... Jul 2020Investigating the degeneration of specific thalamic nuclei in multiple sclerosis (MS) remains challenging.
BACKGROUND
Investigating the degeneration of specific thalamic nuclei in multiple sclerosis (MS) remains challenging.
METHODS
White-matter-nulled (WMn) MPRAGE, MP-FLAIR, and standard T1-weighted magnetic resonance imaging (MRI) were performed on MS patients ( = 15) and matched controls ( = 12). Thalamic lesions were counted in individual sequences and lesion contrast-to-noise ratio (CNR) was measured. Volumes of 12 thalamic nuclei were measured using an automatic segmentation pipeline specifically developed for WMn-MPRAGE.
RESULTS
WMn-MPRAGE showed more thalamic MS lesions ( = 35 in 9 out of 15 patients) than MP-FLAIR ( = 25) and standard T1 ( = 23), which was associated with significant improvement of CNR ( < 0.0001). MS patients had whole thalamus atrophy ( = 0.003) with lower volumes found for the anteroventral ( < 0.001), the pulvinar ( < 0.0001), and the habenular ( = 0.004) nuclei.
CONCLUSION
WMn-MPRAGE and automatic thalamic segmentation can highlight thalamic MS lesions and measure patterns of focal thalamic atrophy.
Topics: Adult; Atlases as Topic; Atrophy; Female; Humans; Image Interpretation, Computer-Assisted; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Multiple Sclerosis; Neuroimaging; Thalamic Nuclei; White Matter
PubMed: 30730233
DOI: 10.1177/1352458519828297 -
ENeuro 2021Both nucleus reuniens and the anterior thalamic nuclei are densely interconnected with medial cortical and hippocampal areas, connections that reflect their respective...
Both nucleus reuniens and the anterior thalamic nuclei are densely interconnected with medial cortical and hippocampal areas, connections that reflect their respective contributions to learning and memory. To better appreciate their comparative roles, pairs of different retrograde tracers were placed in these two thalamic sites in adult rats. Both thalamic sites receive modest cortical inputs from layer V that contrasted with much denser projections from layer VI. Despite frequent overlap in layer VI, ventral prefrontal and anterior cingulate inputs to nucleus reuniens were concentrated in the deepest sublayer (VIb). Meanwhile, inputs to the anterior thalamic nuclei originated more evenly from both sublayers VIa and VIb, with the result that they were often located more superficially than the projections to nucleus reuniens. Again, while the many hippocampal (subiculum) neurons projecting to nucleus reuniens and the anterior thalamic nuclei were partially intermingled within the deep cellular parts of the subiculum, cells projecting to nucleus reuniens consistently tended to lie even deeper (i.e., immediately adjacent to the alveus). Variable numbers of double-labeled cells were present in those cortical and subicular portions where the two cell populations intermingled, though they remained in a minority. Our data also show how projections to these two thalamic sites are organized in opposing dorsal/ventral and rostral/caudal gradients across both the cortex and hippocampal formation. While the anterior thalamic nuclei are preferentially innervated by dorsal cortical sites, more ventral frontal sites preferentially reach nucleus reuniens. These anatomic differences may underpin the complementary cognitive functions of these two thalamic areas.
Topics: Animals; Anterior Thalamic Nuclei; Hippocampus; Limbic System; Midline Thalamic Nuclei; Neural Pathways; Rats
PubMed: 34301721
DOI: 10.1523/ENEURO.0103-20.2021 -
The European Journal of Neuroscience Nov 2022As the functional properties of a cortical area partly reflect its thalamic inputs, the present study compared collateral projections arising from various rostral...
As the functional properties of a cortical area partly reflect its thalamic inputs, the present study compared collateral projections arising from various rostral thalamic nuclei that terminate across prefrontal (including anterior cingulate) and retrosplenial areas in the rat brain. Two retrograde tracers, fast blue and cholera toxin B, were injected in pairs to different combinations of cortical areas. The research focused on the individual anterior thalamic nuclei, including the interanteromedial nucleus, nucleus reuniens and the laterodorsal nucleus. Of the principal anterior thalamic nuclei, only the anteromedial nucleus contained neurons reaching both the anterior cingulate cortex and adjacent cortical areas (prefrontal or retrosplenial), though the numbers were modest. For these same cortical pairings (medial prefrontal/anterior cingulate and anterior cingulate/retrosplenial), the interanteromedial nucleus and nucleus reuniens contained slightly higher proportions of bifurcating neurons (up to 11% of labelled cells). A contrasting picture was seen for collaterals reaching different areas within retrosplenial cortex. Here, the anterodorsal nucleus, typically provided the greatest proportion of bifurcating neurons (up to 15% of labelled cells). While individual neurons that terminate in different retrosplenial areas were also found in the other thalamic nuclei, they were infrequent. Consequently, these thalamo-cortical projections predominantly arise from separate populations of neurons with discrete cortical termination zones, consistent with the transmission of segregated information and influence. Overall, two contrasting medial-lateral patterns of collateral projections emerged, with more midline nuclei, for example, nucleus reuniens and the interoanteromedial nucleus innervating prefrontal areas, while more dorsal and lateral anterior thalamic collaterals innervated retrosplenial cortex.
Topics: Rats; Animals; Gyrus Cinguli; Thalamic Nuclei; Thalamus; Cerebral Cortex; Midline Thalamic Nuclei; Neural Pathways
PubMed: 36089888
DOI: 10.1111/ejn.15819 -
NeuroImage Sep 2020The human thalamus is an integrative hub richly connected with cortical networks, involving diverse cognitive functions. Emerging evidence suggests that multiscale...
The human thalamus is an integrative hub richly connected with cortical networks, involving diverse cognitive functions. Emerging evidence suggests that multiscale structural and functional gradients integrate various information across modalities into an abstract representation. However, the presence of functional gradients in the thalamus and its relationship to structural properties and cognitive functions remain unknown. We estimated the functional gradients of the thalamus in two independent normal cohorts using a novel diffusion embedding analysis. We identified two main axes of the functional connectivity patterns, and examined associations with thalamic anatomy, morphology, intrinsic geometry, and specific behavioral relevance. We found that the dominant gradient indicated a lateral/medial axis across the thalamus and captured associations with anatomical nuclei and gray matter volume. The second gradient was an anterior/posterior axis and provided a behavioral characterization from lower level perception to higher level cognition. Furthermore, these two gradients strongly correlated with spatial distance, indicating the prominence of intrinsic geometry in functional hierarchies. These findings were replicated in an independent dataset. Overall, our findings suggested that macroscale gradients showed a coordination of structural and functional interactions, with hierarchical organization contributing to behavior characterization.
Topics: Adult; Behavior; Brain Mapping; Cerebral Cortex; Cognition; Connectome; Female; Gray Matter; Humans; Magnetic Resonance Imaging; Male; Neural Pathways; Perception; Reference Values; Thalamic Nuclei; Thalamus; Young Adult
PubMed: 32454205
DOI: 10.1016/j.neuroimage.2020.116960 -
Human Brain Mapping Feb 2023Specific thalamic nuclei are implicated in healthy aging and age-related neurodegenerative diseases. However, few methods are available for robust automated segmentation...
Specific thalamic nuclei are implicated in healthy aging and age-related neurodegenerative diseases. However, few methods are available for robust automated segmentation of thalamic nuclei. The threefold aims of this study were to validate the use of a modified thalamic nuclei segmentation method on standard T1 MRI data, to apply this method to quantify age-related volume declines, and to test functional meaningfulness by predicting performance on motor testing. A modified version of THalamus Optimized Multi-Atlas Segmentation (THOMAS) generated 22 unilateral thalamic nuclei. For validation, we compared nuclear volumes obtained from THOMAS parcellation of white-matter-nulled (WMn) MRI data to T1 MRI data in 45 participants. To examine the effects of age/sex on thalamic nuclear volumes, T1 MRI available from a second data set of 121 men and 117 women, ages 20-86 years, were segmented using THOMAS. To test for functional ramifications, composite regions and constituent nuclei were correlated with Grooved Pegboard test scores. THOMAS on standard T1 data showed significant quantitative agreement with THOMAS from WMn data, especially for larger nuclei. Sex differences revealing larger volumes in men than women were accounted for by adjustment with supratentorial intracranial volume (sICV). Significant sICV-adjusted correlations between age and thalamic nuclear volumes were detected in 20 of the 22 unilateral nuclei and whole thalamus. Composite Posterior and Ventral regions and Ventral Anterior/Pulvinar nuclei correlated selectively with higher scores from the eye-hand coordination task. These results support the use of THOMAS for standard T1-weighted data as adequately robust for thalamic nuclear parcellation.
Topics: Humans; Male; Female; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Thalamic Nuclei; Thalamus; Aging; White Matter; Magnetic Resonance Imaging
PubMed: 36181510
DOI: 10.1002/hbm.26088 -
Brain Stimulation 2023MRI-guided transcranial focused ultrasound (MRgFUS) as a next-generation neuromodulation tool can precisely target and stimulate deep brain regions with high spatial...
BACKGROUND
MRI-guided transcranial focused ultrasound (MRgFUS) as a next-generation neuromodulation tool can precisely target and stimulate deep brain regions with high spatial selectivity. Combined with MR-ARFI (acoustic radiation force imaging) and using fMRI BOLD signal as functional readouts, our previous studies have shown that low-intensity FUS can excite or suppress neural activity in the somatosensory cortex.
OBJECTIVE
To investigate whether low-intensity FUS can suppress nociceptive heat stimulation-induced responses in thalamic nuclei during hand stimulation, and to determine how this suppression influences the information processing flow within nociception networks.
FINDINGS
BOLD fMRI activations evoked by 47.5 °C heat stimulation of hand were detected in 24 cortical regions, which belong to sensory, affective, and cognitive nociceptive networks. Concurrent delivery of low-intensity FUS pulses (650 kHz, 550 kPa) to the predefined heat nociceptive stimulus-responsive thalamic centromedial_parafascicular (CM_para), mediodorsal (MD), ventral_lateral (VL_ and ventral_lateral_posteroventral (VLpv) nuclei suppressed their heat responses. Off-target cortical areas exhibited reduced, enhanced, or no significant fMRI signal changes, depending on the specific areas. Differentiable thalamocortical information flow during the processing of nociceptive heat input was observed, as indicated by the time to reach 10% or 30% of the heat-evoked BOLD signal peak. Suppression of thalamic heat responses significantly altered nociceptive processing flow and direction between the thalamus and cortical areas. Modulation of contralateral versus ipsilateral areas by unilateral thalamic activity differed. Signals detected in high-order cortical areas, such as dorsal frontal (DFC) and ventrolateral prefrontal (vlPFC) cortices, exhibited faster response latencies than sensory areas.
CONCLUSIONS
The concurrent delivery of FUS suppressed nociceptive heat response in thalamic nuclei and disrupted the nociceptive network. This study offers new insights into the causal functional connections within the thalamocortical networks and demonstrates the modulatory effects of low-intensity FUS on nociceptive information processing.
Topics: Nociception; Thalamic Nuclei; Thalamus; Brain; Cognition
PubMed: 37741439
DOI: 10.1016/j.brs.2023.09.013 -
Neuroinformatics Jul 2022Thalamic nuclei have been implicated in several neurological diseases. Thalamic nuclei parcellation from structural MRI is challenging due to poor intra-thalamic nuclear...
Thalamic nuclei have been implicated in several neurological diseases. Thalamic nuclei parcellation from structural MRI is challenging due to poor intra-thalamic nuclear contrast while methods based on diffusion and functional MRI are affected by limited spatial resolution and image distortion. Existing multi-atlas based techniques are often computationally intensive and time-consuming. In this work, we propose a 3D convolutional neural network (CNN) based framework for thalamic nuclei parcellation using T1-weighted Magnetization Prepared Rapid Gradient Echo (MPRAGE) images. Transformation of images to an efficient representation has been proposed to improve the performance of subsequent classification tasks especially when working with limited labeled data. We investigate this by transforming the MPRAGE images to White-Matter-nulled MPRAGE (WMn-MPRAGE) contrast, previously shown to exhibit good intra-thalamic nuclear contrast, prior to the segmentation step. We trained two 3D segmentation frameworks using MPRAGE images (n = 35 subjects): (a) a native contrast segmentation (NCS) on MPRAGE images and (b) a synthesized contrast segmentation (SCS) where synthesized WMn-MPRAGE representation generated by a contrast synthesis CNN were used. Thalamic nuclei labels were generated using THOMAS, a multi-atlas segmentation technique proposed for WMn-MPRAGE images. The segmentation accuracy and clinical utility were evaluated on a healthy cohort (n = 12) and a cohort (n = 45) comprising of healthy subjects and patients with alcohol use disorder (AUD), respectively. Both the segmentation CNNs yielded comparable performances on most thalamic nuclei with Dice scores greater than 0.84 for larger nuclei and at least 0.7 for smaller nuclei. However, for some nuclei, the SCS CNN yielded significant improvements in Dice scores (medial geniculate nucleus, P = 0.003, centromedian nucleus, P = 0.01) and percent volume difference (ventral anterior, P = 0.001, ventral posterior lateral, P = 0.01) over NCS. In the AUD cohort, the SCS CNN demonstrated a significant atrophy in ventral lateral posterior nucleus in AUD patients compared to healthy age-matched controls (P = 0.01), agreeing with previous studies on thalamic atrophy in alcoholism, whereas the NCS CNN showed spurious atrophy of the ventral posterior lateral nucleus. CNN-based segmentation of thalamic nuclei provides a fast and automated technique for thalamic nuclei prediction in MPRAGE images. The transformation of images to an efficient representation, such as WMn-MPRAGE, can provide further improvements in segmentation performance.
Topics: Atrophy; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Neural Networks, Computer; Thalamic Nuclei; White Matter
PubMed: 34626333
DOI: 10.1007/s12021-021-09544-5