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High-resolution MRI and diffusion-weighted imaging of the human habenula at 7T

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To investigate the feasibility of discriminating the habenula in human brain using high-resolution structural MRI and diffusion-weighted imaging at 7 Tesla (T). MRI experiments included a MP2RAGE and GRE sequence to acquire quantitative parameter maps of T1, T2*, and a calculated proton density map and the combined approach of zoomed and parallel imaging (ZOOPPA) to obtain dw images. Probabilistic tractography algorithms were used to identify multiple fiber orientations in submillimetre voxels, and constrained spherical deconvolution to resolve orientations in regions where fibers cross. Maps of T1, T2*, and proton density showed high contrast of the human habenula. The lateral habenula and its commissure can be distinguished from medial habenula and adjacent tissue. DWI data with 0.7 mm isotropic resolution revealed that fiber populations differ in medial and lateral habenula and two major fiber bundles that connect habenular nuclei with forebrain structures and brainstem. High resolution 7T MR imaging of the human habenula provides sufficient signal-to-noise and contrast to enable identification of the lateral and medial nuclei. In vivo high resolution DWI at 7T is able to distinguish between lateral and medial habenula, and to detect major fiber tracts that connect the habenula with other brain areas.J. Magn. Reson. Imaging 2013. © 2013 Wiley Periodicals, Inc.

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... SM and its termination, the habenula, are inconsistently seen on standard T1/T2 MRI due to being ''missed'' between slices (Strotmann et al., 2014;Kochanski et al., 2016). ...
... We believe our approach more accurately describes the trajectory of the SM and could be useful in conjunction with standard structural imaging in perioperative stereotactic localization of the SM for DBS. Furthermore, the habenula is a small structure of approximately 30-36 mm 3 (Savitz et al., 2011;Lawson et al., 2013) and may not be accurately identified on standard MRI especially at 3T (Strotmann et al., 2014). We felt it more appropriate to use an imaging fixed point at the pineal to optimize consistency and reliability. ...
... Changes in afferent habenula inputs may be reflected in diffusion metric changes, focusing attention on regions upstream to the DCCS such as the septal pleasure areas. Future research using higher resolution imaging may also reveal the lateral and medial habenular components (Strotmann et al., 2014) and their discrete afferents via the SM using diffusion connectomics, furthering our understanding of the complex and distinct connections between the forebrain and midbrain. ...
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The Stria medullaris (SM) Thalami is a discrete white matter tract that directly connects frontolimbic areas to the habenula, allowing the forebrain to influence midbrain monoaminergic output. Habenular dysfunction has been shown in various neuropsychiatric conditions. However, there exists a paucity of research into the habenula's principal afferent tract, the SM. Diffusion-weighted tractography may provide insights into the properties of the SM in vivo, opening up investigation of this tract in conditions of monoamine dysregulation such as depression, schizophrenia, addiction and pain. We present a reliable method for reconstructing the SM using diffusion-weighted imaging, and examine the effects of age and gender on tract diffusion metrics. We also investigate reproducibility of the method through inter-rater comparisons. In consultation with neuroanatomists, a Boolean logic gate protocol was developed for use in ExploreDTI to extract the SM from constrained spherical deconvolution based whole brain tractography. Particular emphasis was placed on the reproducibility of the tract, attention to crossing white matter tract proximity and anatomical consistency of anterior and posterior boundaries. The anterior commissure, pineal gland and mid point of the thalamus were defined as anatomical fixed points used for reconstruction. Fifty subjects were scanned using High Angular Resolution Diffusion Imaging (HARDI; 61 directions, b-value 1500 mm 3). Following constrained spherical deconvolution whole brain tractography, two independent raters isolated the SM. Each output was checked, examined and cleaned for extraneous streamlines inconsistent with known anatomy of the tract by the rater and a neuroanatomist. A second neuroanatomist assessed tracts for face validity. The SM was reconstructed with excellent inter-rater reliability for dimensions and diffusion metrics. Gender had no effect on the dimensions or diffusion metrics, however radial diffusivity (RD) showed a positive correlation with age. Reliable identification and quantification of diffusion metrics of the SM invites further exploration Frontiers in Neuroanatomy | www.frontiersin.org 1 May 2018 | Volume 12 | Article 39 Roddy et al. Diffusion Imaging Tractography of the Stria Medullaris of this key habenula linked structure in neuropsychiatric disorders such as depression, anxiety, chronic pain and addiction. The accurate anatomical localization of the SM may also aid preoperative stereotactic localization of the tract for deep brain stimulation (DBS) treatment.
... These terminate in the contralateral habenula (Buchanan and Frazer 1937;Naidich and Duvernoy 2009;Diaz et al. 2011). This decussation is known as the habenular commissure (Strotmann et al. 2014). Note that the nearby posterior commissure found in the inferior part of the pineal stalk is not anatomically or functionally part of the DDCS. ...
... Note that the nearby posterior commissure found in the inferior part of the pineal stalk is not anatomically or functionally part of the DDCS. The habenular commissure lying across the superior part of the pineal stalk together with the SM and habenulae form what is anatomically known as the habenular trigone (Strotmann et al. 2014). The lateral habenula also contributes to the habenular commissure in rats (Kim 2009); however, in humans, it is unclear what proportion of these commissural fibers derive from the SM, medial or lateral habenulae. ...
... Regional microscopic differences in cellular distribution, however, allow the habenula to be distinguished from the white matter fibers of the SM and the multipolar cells of the adjacent thalamus (Marburg 1944;Díaz et al. 2011). The habenular width is approximately 5-9 mm across (Strotmann et al. 2014), as such the structure is difficult to visualize accurately using standard clinical MRI. However, using high-resolution magnetic resonance imaging (resolution < 1.5mm 3 ), it has recently been possible to determine the mean habenular volumes in a number of studies (Table 2a). ...
Article
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The often-overlooked dorsal diencephalic conduction system (DDCS) is a highly conserved pathway linking the basal forebrain and the monoaminergic brainstem. It consists of three key structures; the stria medullaris, the habenula and the fasciculus retroflexus. The first component of the DDCS, the stria medullaris, is a discrete bilateral tract composed of fibers from the basal forebrain that terminate in the triangular eminence of the stalk of the pineal gland, known as the habenula. The habenula acts as a relay hub where incoming signals from the stria medullaris are processed and subsequently relayed to the midbrain and hindbrain monoaminergic nuclei through the fasciculus retroflexus. As a result of its wide-ranging connections, the DDCS has recently been implicated in a wide range of behaviors related to reward processing, aversion and motivation. As such, an understanding of the structure and connections of the DDCS may help illuminate the pathophysiology of neuropsychiatric disorders such as depression, addiction and pain. This is the first review of all three components of the DDCS, the stria medullaris, the habenula and the fasciculus retroflexus, with particular focus on their anatomy, function and development.
... Recent case reports from two treatment-resistant MDD patients describe symptom improvements following deep brain stimulation (DBS) targeting the Hb (Kiening and Sartorius, 2013;Sartorius et al., 2010), supporting the proposed link between Hb dysfunction and MDD. Given its functional importance and potential role in psychiatric disorders, accurate localization and segmentation of the Hb in neuroimaging studies is important for morphological evaluation, DBS targeting (Sartorius and Henn, 2007), and seed region selection in both functional magnetic resonance imaging (fMRI) (Lawson et al., 2014;Hennigan et al., 2015;Erpelding et al., 2014;Ely et al., under revision) and diffusion magnetic resonance imaging (dMRI) (Shelton et al., 2012;Strotmann et al., 2014). ...
... Recently, pioneering high-resolution quantitative in vivo and ex vivo 7 T imaging studies of the Hb have showed lower T1 and T2* values in the Hb than the surrounding thalamic tissue (Strotmann et al., 2014). Attempt has also been made to use ultra-high-resolution (60 μm) ex vivo T1 and T2* maps to classify Hb subdivisions (Strotmann et al., 2013). ...
... Moreover, the variation in center of mass (n = 49) was less than two anatomical voxels (b 1.4 mm), making it sufficiently small to have little or no effect on placement of seed voxels in fMRI or dMRI studies (typically ≥ 1.5 mm isotropic resolution at 3 T). Hence, our segmentation scheme provides a robust, objective, and anatomically grounded approach for selecting Hb seed voxels for fMRI and dMRI application (Shelton et al., 2012;Strotmann et al., 2014;Lawson et al., 2014;Hennigan et al., 2015;Erpelding et al., 2014;Ely et al., under revision). For Hb morphological studies, the choice of the optimal α value may depend on image resolution and/or image contrast, which will need to be explored further. ...
Article
The habenula consists of a pair of small epithalamic nuclei located adjacent to the dorsomedial thalamus. In spite of increasing interest in imaging the habenula due to its critical role in mediating subcortical reward circuitry, in vivo neuroimaging research targeting the human habenula has been limited by its small size and low anatomical contrast. In this work, we have developed an objective semi-automated habenula segmentation scheme consisting of histogram-based thresholding, region growing, geometric constraints, and partial volume estimation steps. This segmentation scheme was designed around in vivo 3 T myelin sensitive images, generated by taking the ratio of high resolution T1w over T2w images. Due to the high myelin content of the habenula, the contrast-to-noise ratio with the thalamus in the in vivo 3 T myelin sensitive images was significantly higher than the T1w or T2w images alone. In addition, in vivo 7 T myelin sensitive images (T1w over T2*w ratio images) and ex vivo proton density weighted images, along with histological evidence from the literature, strongly corroborated the in vivo 3 T habenula myelin contrast used in the proposed segmentation scheme. The proposed segmentation scheme represents a step towards a scalable approach for objective segmentation of the habenula suitable for both morphological evaluation and habenula seed region selection in functional and diffusion MRI applications.
... SM and its termination, the habenula, are inconsistently seen on standard T1/T2 MRI due to being ''missed'' between slices (Strotmann et al., 2014;Kochanski et al., 2016). ...
... We believe our approach more accurately describes the trajectory of the SM and could be useful in conjunction with standard structural imaging in perioperative stereotactic localization of the SM for DBS. Furthermore, the habenula is a small structure of approximately 30-36 mm 3 (Savitz et al., 2011;Lawson et al., 2013) and may not be accurately identified on standard MRI especially at 3T (Strotmann et al., 2014). We felt it more appropriate to use an imaging fixed point at the pineal to optimize consistency and reliability. ...
... Changes in afferent habenula inputs may be reflected in diffusion metric changes, focusing attention on regions upstream to the DCCS such as the septal pleasure areas. Future research using higher resolution imaging may also reveal the lateral and medial habenular components (Strotmann et al., 2014) and their discrete afferents via the SM using diffusion connectomics, furthering our understanding of the complex and distinct connections between the forebrain and midbrain. ...
Article
Full-text available
Background Clinical histological studies demonstrate that the distribution of natural killer (NK) cells, other immune cells and μ-opioid receptors (MOR) within cancer tissue can predict cancer prognosis. No clinical study has evaluated whether anesthetic technique influences immune cell and MOR expression within human breast cancer. Methods Excised preoperative biopsies and intraoperative breast cancer specimens from 20 patients randomly chosen from patients previously enrolled in an ongoing, prospective, randomized trial (NCT00418457) investigating the effect of anesthetic technique on long-term breast cancer outcome were immunohistochemically stained and microscopically examined by two independent investigators, masked to randomization, to quantify MOR and immune cell infiltration: CD56, CD57 (NK cells), CD4 (T helper cells), CD8 (cytotoxic T cells) and CD68 (macrophages). Patients had been randomized to receive either a propofol–paravertebral anesthetic with continuing analgesia (PPA, n = 10) or balanced general anesthetic with opioid analgesia (GA, n = 10). ResultsThere were no differences between the groups in staining intensity in preoperative biopsy specimens. Expression intensity values (median 25–75%) for MOR in intraoperative resected biopsy were higher in GA 8.5 (3–17) versus PPA 1 (0–10), p = 0.04. The numbers of MOR-positive cells were also higher in GA patients. Expression and absolute numbers of CD56, CD57, CD4 and CD68 were similar in resected tumor in both groups. Conclusion General anesthesia with opioid analgesia increased resected tumor MOR expression compared with propofol–paravertebral anesthetic technique, but the anesthetic technique did not significantly influence the expression of immune cell markers.
... SM and its termination, the habenula, are inconsistently seen on standard T1/T2 MRI due to being ''missed'' between slices (Strotmann et al., 2014;Kochanski et al., 2016). ...
... We believe our approach more accurately describes the trajectory of the SM and could be useful in conjunction with standard structural imaging in perioperative stereotactic localization of the SM for DBS. Furthermore, the habenula is a small structure of approximately 30-36 mm 3 (Savitz et al., 2011;Lawson et al., 2013) and may not be accurately identified on standard MRI especially at 3T (Strotmann et al., 2014). We felt it more appropriate to use an imaging fixed point at the pineal to optimize consistency and reliability. ...
... Changes in afferent habenula inputs may be reflected in diffusion metric changes, focusing attention on regions upstream to the DCCS such as the septal pleasure areas. Future research using higher resolution imaging may also reveal the lateral and medial habenular components (Strotmann et al., 2014) and their discrete afferents via the SM using diffusion connectomics, furthering our understanding of the complex and distinct connections between the forebrain and midbrain. ...
Article
Chronic pain may be modulated by descending pathways, resulting in monoaminergic changes in the midbrain. One such pathway, the dorsal diencephalic conduction system, integrates frontolimbic inputs through the stria medullaris (SM) and habenula to directly influence midbrain dopamine serotonin and noradrenaline. A role for the habenula has already been suggested in chronic pain; however, it has been impossible to investigate the SM in vivo until now. We present an anatomically validated and reliable protocol diffusion-weighted magnetic resonance protocol for tractographic identification and quantification of the SM. Fifty subjects were scanned using advanced diffusion imaging (61 directions, b-value 1500 mm3, 3T) combined with a higher-order tractography algorithm as part of the ongoing REDEEM study. Two independent raters and a neuroanatomist isolated the SM using a novel tractography protocol. The SM was reconstructed with excellent inter-rater reliability (P = 0.88 between raters) and consistent tract diffusion metrics (P = 0.92). Diffusion-rendered tracts were compared with cadaveric anatomical measurements, suggesting satisfactory face validity. As such, we present the first investigation showing reliable diffusion tractography reconstruction of the SM in vivo. Analyzing diffusion metrics may allow investigation of this structure’s role in the descending neuromodulation of pain pathways in chronic pain states. Additionally, accurate stereotactic localization of the SM through this technique may allow deep brain stimulation of this structure as a treatment for chronic pain. References: 1) Shelton L, Becerra L, Borsook D. Unmasking the mysteries of the habenula in pain and analgesia. Prog Neurobiol 2012;96(2):208–19. 2) Erpelding N, Sava S, Simons LE, et al. Habenula functional resting-state connectivity in pediatric CRPS. J Neurophysiol 2014;111(2):239–47. 3) Gardon O, Faget L, Chu Sin Chung P, Matifas A, Massotte D, Kieffer BL. Expression of mu opioid receptor in dorsal diencephalic conduction system: New insights for the medial habenula. Neuroscience 2014;277:595
... Contrast in MR images depends on tissue properties such as proton spin density, T1, T2* and susceptibility, for example. To date, research on measuring the tissue properties of the habenula is limited and mapping susceptibility in the habenula is scant [14,15]. ...
... Schmidt et al. created T1 maps [14] and used coronal landmarks to locate the habenula. However, in their work they were unable to separate the habenula into medial and lateral divisions as was shown ex vivo in another study [15]. They also note that the high myelin content of the habenula appears to differentiate it from the surrounding gray matter tissues in high-resolution images at 7 T and as seen in our study. ...
... They also note that the high myelin content of the habenula appears to differentiate it from the surrounding gray matter tissues in high-resolution images at 7 T and as seen in our study. Another paper used T1, spin density and T2* to visualize the Lhb and they state: "Probably due to a concomitant high iron content, the habenula also shows reduced T2* compared with neighboring regions" [15]. No description of why white matter would show high iron content was presented. ...
Article
The habenulae consist of a pair of small nuclei which bridge the limbic forebrain and midbrain monoaminergic centers. They are implicated in major depressive disorders due to abnormal phasic response when provoked by a conditioned stimulus. The lateral habenula (Lhb) is believed to be involved in dopamine metabolism and is now a target for deep brain stimulation, a treatment which has shown promising anti-depression effects. We imaged the habenulae with susceptibility weighted imaging (SWI) and quantitative susceptibility mapping (QSM) in order to localize the lateral habenula. Fifty-six healthy controls were recruited for this study. For the quantitative assessment, we traced the structure to compute volume from magnitude images and mean susceptibility bilaterally for the habenula on QSM. Thresholding methods were used to delineate the Lhb habenula on QSM. SWI, tSWI, and QSM data were subjectively reviewed for increased Lhb contrast. SWI, QSM, and true SWI showed bilateral signal changes in the posterior location of the habenulae relative to the anterior location, which may indicate increased putative iron content within the Lhb. This signal behavior was shown in 41/44 (93%) subjects. In summary, it is possible to localize the lateral component of the habenula using SWI and QSM at 3 T.
... Furthermore, it is imbedded deep within brain tissue, so it is not easy to isolate from the surrounding white matter structures. The SM and its termination, the Hb, are inconsistently seen in standard T1/T2 MRI as a result of being "missed" between slices [33,34]. ...
... The Hb receives its main input from different brain regions through the SM, so it was hypothesized to be an opportune seed region for the application of probabilistic tractography. On three consecutive 1.2-mm slices of axial T1-weighted MPRAGE images, the Hb was identified by its morphological features, in which it appears as a triangular ridge extending into the third ventricle on the medial surface of the thalamus [33], [39,40]. This visibility facilitated manual drawing of a twodimensional seed region within the central axial slice of the Hb on high-resolution MPRAGE images. ...
... There was a positive correlation of the Radial Diffusivity (RD) with age, but there was no effect of gender on the diffusion or dimension metrics (Fig. 3). Strotmann et al. [33] investigated the feasibility of discriminating the habenula in human brain using highresolution structural MRI and diffusion-weighted imaging at 7 Tesla (T). To allow precise localization of the region of interest, they first acquired a 3D T1-weighted data set using the MP2RAGE sequence (TR = 6000 ms, TI1 = 900 ms, TI2 = 2750 ms, TE = 3.11 ms, 0.7 mm isotropic resolution, flip angle 1 and 2 = 4° and 3°). ...
Article
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The Stria Medullaris (SM) is a white-matter tract that contains afferent fibres that connect the cognitive-emotional areas in the forebrain to the Habenula (Hb). The Hb plays an important role in behavioral responses to reward, stress, anxiety, pain, and sleep through its action on neuromodulator systems. The Fasciculus Retroflexus (FR) forms the primary output of the Hb to the midbrain. The SM, Hb, and FR are part of a special pathway between the forebrain and the midbrain known as the Dorsal Diencephalic Conduction system (DDC). Hb dysfunction is accompanied by different types of neuropsychiatric disorders, such as schizophrenia, depression, and Treatment-Resistant Depression (TRD). Due to difficulties in the imaging assessment of the SM and HB in vivo , they had not been a focus of clinical studies until the invention of Diffusion Tensor Imaging (DTI), which has revolutionized the imaging and investigation of the SM and Hb. DTI has facilitated the imaging of the SM and Hb and has provided insights into their properties through the investigation of their monoamine dysregulation. DTI is a well-established technique for mapping brain microstructure and white matter tracts; it provides indirect information about the microstructural architecture and integrity of white matter in vivo , based on water diffusion properties in the intra- and extracellular space, such as Axial Diffusivity (AD), Radial Diffusivity (RD), mean diffusivity, and Fractional Anisotropy (FA). Neurosurgeons have recognized the potential value of DTI in the direct anatomical targeting of the SM and Hb prior to Deep Brain Stimulation (DBS) surgery for the treatment of certain neuropsychiatric conditions, such as TRD. DTI is the only non-invasive method that offers the possibility of visualization in vivo of the white-matter tracts and nuclei in the human brain. This review study summarizes the use of DTI as a promising new imaging method for accurate identification of the SM and Hb, with special emphasis on direct anatomical targeting of the SM and Hb prior to DBS surgery.
... To better understand pathological changes, first or recurrent disease episode as well as psychotropic medication has to be taken into account. But most important, given the small size of this structure, an increase in spatial resolution by using recent ultra-high field methods is essential [25]. ...
... The size of the present sample and subgroups may have led to type II errors with an under-recognition of possible subtle differences in habenula volumes between groups. We have to acknowledge that by using the present approach, even on high-resolution 7T MR, it was not possible to separate the habenula into medial and lateral divisions as it has been shown ex vivo [25]. Since both components appear to have some independent functions, the combined measurement may not therefore fully account for distinct changes in habenula volumes. ...
Article
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The habenula is a paired epithalamic structure involved in the pathogenesis of major depressive disorder (MDD). Evidence comes from its impact on the regulation of serotonergic and dopaminergic neurons, the role in emotional processing and studies on animal models of depression. The present study investigated habenula volumes in 20 unmedicated and 20 medicated MDD patients and 20 healthy controls for the first time by applying a triplanar segmentation algorithm on 7 Tesla magnetic resonance (MR) whole-brain T1 maps. The hypothesis of a right-side decrease of habenula volumes in the MDD patients was tested, and the relationship between volumetric abnormalities and disease severity was exploratively investigated. Absolute and relative total and hemispheric habenula volumes did not differ significantly between the three groups. In the patients with short duration of disease for which medication effects could be ruled out, significant correlations were found between bilateral habenula volumes and HAMD-17- and BDI-II-related severities. In the medicated patients, this positive relationship disappeared. Our findings suggest an involvement of habenula pathology in the beginning of MDD, while general effects independent of severity or stage of disease did not occur. Our findings warrant future combined tractographic and functional investigation using ultra-high-resolution in vivo MR imaging.
... Subcortically, the habenula is functionally coupled with thalamus, hippocampus, para-hippocampus, septofimbria nucleus, and striatum (caudate and putamen). Strong structural connections throughout the thalamus, for example, has been shown using probabilistic diffusion tractography of the habenula (figure 8 of Strotmann et al. (2014)). These authors were able to additionally confirm the presence of the stria medullaris connecting the habenula with forebrain regions and the fasciculus retroflexus descending ventrally into the midbrain. ...
... Furthermore, our incomplete brain coverage, determined from a common temporal/spatial tradeoff, prevented us from detecting connectivity with superior cortical regions, such as the sensorimotor cortex, which has previously been observed to functionally connect with the habenula (Ely et al., 2016). In addition, although we acquired data with high spatial resolution, lateral and medial habenula subdivisions could not be distinguished, in contrast to recent in vivo and ex vivo studies at 7 T of habenula structure (Strotmann et al., 2014(Strotmann et al., , 2013. Therefore, this inability to resolve medial and lateral subdivisions of the habenula means that our results likely reflect connectivity with both subdivisions. ...
Article
The habenula, a portion of the epithalamus, is implicated in the pathophysiology of depression, anxiety and addiction disorders. Its small size and connection to other small regions prevent standard human imaging from delineating its structure and connectivity with confidence. Resting state functional connectivity is an established method for mapping connections across the brain from a seed region of interest. The present study takes advantage of 7 T fMRI to map, for the first time, the habenula resting state network with very high spatial resolution in 32 healthy human participants. Results show novel functional connections in humans, including functional connectivity with the septum and bed nucleus of the stria terminalis (BNST). Results also show many habenula connections previously described only in animal research, such as with the nucleus basalis of Meynert, dorsal raphe, ventral tegmental area (VTA), and periaqueductal grey (PAG). Connectivity with caudate, thalamus and cortical regions such as the anterior cingulate, retrosplenial cortex and auditory cortex are also reported. This work, which demonstrates the power of ultra-high field for mapping human functional connections, is a valuable step toward elucidating subcortical and cortical regions of the habenula network.
... [1][2][3] The human habenula is quite small, approximately 5-9 mm in diameter (volume 15-36 mm 3 ). [4][5][6][7] It protrudes slightly into the third ventricle on either side of the midsagittal plane between the medial dorsal thalamus and the pineal gland ( Figure 1). Extensive white matter fibers make this structure appear bright on T1-weighted magnetic resonance imaging (MRI). ...
... [1][2][3][8][9][10][11][12][13] Although the small size of the habenula makes it challenging to study in humans, methodological advances (e.g., higher field [7 Tesla] and higher resolution [smaller voxel] MRI, myelin sensitive imaging [ratio of T1-weighted MRI to T2-weighted MRI], diffusion tensor imaging [DTI]) are improving delineation. [4][5][6] A few studies have assessed either structural connectivity (DTI tractography) or functional connectivity (resting state functional MRI) in healthy individuals. In general, both types of connectivity studies have reported results in humans consistent with the brainstem and subcortical connections of the habenula identified in other mammals. ...
... However, we found habenular connectivity with cerebellum instead of the motor cortex which inconsistent with previous studies (Ely et al. 2016;Erpelding et al. 2014;Hetu et al. 2016). Notably, habenula may serve as a link between the midbrain and forebrain during reward processing These connections are primarily responsible for establishing and maintaining emotional/motivational states of negative emotional processing, such as anxiety (Hikosaka 2010), as evidenced by strong structural connections with midbrain and forebrain in humans using diffusion-weighted tractography (Strotmann et al. 2014). Specifically, VTA in midbrain, which is predominantly composed of dopaminergic neurons involved in the reward system and goal-directed actions, inhibited both reward-responsive and aversive stimuli (Benarroch 2015;Fiorillo 2013;Hong et al. 2011). ...
... Our study has several limitations. First, although it is important to distinguish medial and lateral habenulae as well we acquired data with high spatial resolution, the habenular (about 32 mm 3 ) is too small to distinguish lateral and medial habenula subdivisions at 3 T, in contrast to recent in vivo studies at 7 T of habenula structure and FC (Strotmann et al. 2014;Strotmann et al. 2013;Torrisi et al. 2017). Thus, we would like to recover medial and lateral subdivisions of the habenula using 7 T MRI scanners in the future, but wish to balance this with reducing cost, in keeping with our ultimate goal of translating our methodologies to the clinic. ...
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Studies identify the habenula as a key subcortical component in anxiety, with a role in predicting error coding within the evaluative system. However, no clinical reports of generalized anxiety disorder (GAD) describe resting state functional connectivity of habenular circuits. We hypothesized that resting-state functional connectivities of habenula would show differences in neuroanatomical correlates of the evaluative system (prefrontal cortex, habenula) of patients with GAD. We obtained 22 patients with GAD and 21 HCs, matched for gender, age, and years of education. Resting-state functional connectivity of the habenula was assessed using a seed-based template imposed on whole brain MRI, which provided an objective and semi-automated segmentation algorithm in MNI space. Patients with GAD demonstrated enhanced connectivities in the bilateral premotor cortex, right ventrolateral prefrontal cortex, medial frontal cortex, as well as the left orbitofrontal cortex, and reduced connectivities in the left posterior cingulate cortex, and right pulvinar. Moreover, striking differences of abnormal connectivities between groups were observed via analysis of receiver operating characteristic curves (ROC) of statistically significant. These results including ROC curves suggest the potential importance of the habenula in evaluating and deciding to personally relevant reward-related information.
... To characterize these fiber tracts in human subjects, we utilized diffusion magnetic resonance imaging (dMRI). Prior studies have reconstructed the SM with dMRI using the LHb as a seed region for probabilistic tractography (Strotmann et al., 2014;Kochanski et al., 2016Kochanski et al., , 2018Grodd et al., 2020). While effective, this strategy does not allow for selection of specific input and output tracts that may be associated with depressive symptomatology. ...
... In this study, we describe a novel method for reconstruction of the human afferent (SM) and efferent (FR) tracts of the LHb using dMRI data. Prior studies used the LHb itself as a seed region to generate the putative afferent and efferent tracts of this epithalamic nucleus (Strotmann et al., 2014;Kochanski et al., 2016Kochanski et al., , 2018Grodd et al., 2020). The LHb is a very small brain region; therefore, manual selection is difficult and may lead to operator dependent variability and inconsistencies in tractography results (Schilling et al., 2021). ...
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IntroductionThe lateral habenula (LHb) is an epithalamic nucleus associated with negative valence and affective disorders. It receives input via the stria medullaris (SM) and sends output via the fasciculus retroflexus (FR). Here, we use tractography to reconstruct and characterize this pathway.Methods Multi-shell human diffusion magnetic resonance imaging (dMRI) data was obtained from the human connectome project (HCP) (n = 20, 10 males) and from healthy controls (n = 10, 6 males) scanned at our institution. We generated LHb afferents and efferents using probabilistic tractography by selecting the pallidum as the seed region and the ventral tegmental area as the output target.ResultsWe were able to reconstruct the intended streamlines in all individuals from the HCP dataset and our dataset. Our technique also aided in identification of the LHb. In right-handed individuals, the streamlines were significantly more numerous in the left hemisphere (mean ratio 1.59 ± 0.09, p = 0.04). In left-handed individuals, there was no hemispheric asymmetry on average (mean ratio 1.00 ± 0.09, p = 1.0). Additionally, these streamlines were significantly more numerous in females than in males (619.9 ± 159.7 vs. 225.9 ± 66.03, p = 0.04).Conclusion We developed a method to reconstruct the SM and FR without manual identification of the LHb. This technique enables targeting of these fiber tracts as well as the LHb. Furthermore, we have demonstrated that there are sex and hemispheric differences in streamline number. These findings may have therapeutic implications and warrant further investigation.
... The achievable SNR is intricately linked with the implemented pulse sequence, field strength, maximum gradient amplitude and diffusion weighting (higher b-value = more signal attenuation and thus lower SNR). With state-of-the-art MRI hardware (7-Tesla) and advanced (time consuming) pulse sequences, the resolution of DWI has been pushed to 0.8 mm 3 [139]. However, for standard 3-Tesla hardware acquiring ss-EPI within a clinically time-frame, a maximum resolution of 1.5-2 mm 3 is achievable [117]. ...
Thesis
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Deep Brain Stimulation (DBS) in the Subthalamic Nucleus (STN) is an effective, albeit poorly understood, treatment option for advanced stage Parkinson’s Disease Parkinson’s Disease (PD). While DBS can significantly improve motor symptoms, patient quality of life and reduce the use of medication, it can be associated with non-motor side effects and impaired cognitive function. In DBS for PD, electrodes are typically placed bilaterally in the STN from where they modulate the activity of surrounding neuronal tissue through electrical impulses. Preoperative planning is traditionally based on direct visualisation of the STN using conventional Magnetic Resonance Imaging (MRI) acquisitions (T2-weighted (T2w) or Susceptibility Weighted Imaging (SWI)). Diffusion Weighted Imaging (DWI) is a valuable tool that allows in vivo investigation of tissue microstructure. One promising extension of DWI is tractography, a technique that can delineate major white matter pathways in the brain. Recent advances in both DWI acquisition and data analysis allow investigation of structural connections in the human brain at resolutions previously unattainable. Taking advantage of these advances for preoperative delineation of STN connectivity could play a pivotal role in future DBS targeting procedures and postoperative patient management. This PhD work has focused on implementing and evaluating an advanced high-resolution readout-segmented echo planar imaging acquisition technique, together with probabilistic tractography in PD patients. The major aim was to consider how future DBS treatment pro- cedures might be optimised with such methodological approaches. In addition, delineating structural pathways of clinical relevance might improve our understanding of the DBS mechanisms which lead to positive treatment outcomes. In this thesis, I present a number of studies exploring the feasibil- ity and practical limitations of tractography-informed-targeting and optimising postoperative DBS stimulation management. In part 1, I provide an overview of stereotactic DBS surgery (Chap- ter 1), PD (Chapter 2), the STN (Chapter 3) and DWI acquisition and analysis (Chapter 4). In Part 2, I describe the clinical data acquired for this study and an overview of the analysis tools implemented. (Chapter 5. In the following empirical chapters, I present studies aiming to inform (i) pre- processing procedures (Chapter 6) (ii) preoperative targeting (Chapter 7) (iii) postoperative stimulation management (Chapter 8). The final chapter offers a summary of key results and their interpretation and a discussion of potential avenues for future work Chapter 9.
... The primary challenges include motion sensitivity and the reduced SNR at high spatial resolution, in which the latter is particularly problematic for diffusion MRI due to its low intrinsic SNR, which often means imaging near the noise floor. To improve the SNR of in vivo high-resolution diffusion MRI without substantially increasing the scan time, the two dominant approaches are the use of ultra-high field (7T and up) scanners (Heidemann et al., 2012;Eichner et al., 2014;Strotmann et al., 2014;Vu et al., 2015) and acquisition schemes with higher SNR per unit time compared to the current standard, two dimensional (2D) single-shot echo planar imaging (EPI) (Van et al., 2011;Setsompop et al., 2012a;Engstrom and Skare, 2013;Uğurbil et al., 2013;Frost et al., 2014;Chang et al., 2015). ...
Article
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High-resolution diffusion MRI can provide the ability to resolve small brain structures, enabling investigations of detailed white matter architecture. A major challenge for in vivo high-resolution diffusion MRI is the low signal-to-noise ratio. In this work, we combine two highly compatible methods, ultra-high field and three-dimensional multi-slab acquisition to improve the SNR of high-resolution diffusion MRI. As each kz plane is encoded using a single-shot echo planar readout, scan speeds of the proposed technique are similar to the commonly used two-dimensional diffusion MRI. In-plane parallel acceleration is applied to reduce image distortions. To reduce the sensitivity of auto-calibration signal data to subject motion and respiration, several new adaptions of the fast low angle excitation echo-planar technique (FLEET) that are suitable for 3D multi-slab echo planar imaging are proposed and evaluated. A modified reconstruction scheme is proposed for auto-calibration with the most robust method, Slice-FLEET acquisition, to make it compatible with navigator correction of motion induced phase errors. Slab boundary artefacts are corrected using the nonlinear slab profile encoding method recently proposed by our group. In vivo results demonstrate that using 7T and three-dimensional multi-slab acquisition with improved auto-calibration signal acquisition and nonlinear slab boundary artefacts correction, high-quality diffusion MRI data with ~1mm isotropic resolution can be achieved.
... habenula can be reliably identified by its morphology on typically three consecutive 1.2-mm axial slices of the T 1 -weighted MPRAGE, in which it appears as a triangular ridge extending into the third ventricle on the medial surface of the thalamus [19][20][21] . This visibility enabled us to manually draw a two-dimensional seed region within the habenula on its most central axial slice of the original, high-resolution MPRAGE images (Figure 1). ...
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Background Deep brain stimulation (DBS) via anatomical targeting of white matter tracts defined by diffusion tensor imaging (DTI) may be a useful tool in the treatment of pathologic neurophysiologic circuits implicated in certain disease states like treatment resistant depression (TRD). We sought to determine if DTI could be used to define the stria medullaris thalami (SM), the major afferent white matter pathway to the lateral habenula (LHb), a thalamic nucleus implicated in the pathophysiology of TRD. Methods Probabilistic DTI was performed on ten cerebral hemispheres in five patients who underwent preoperative MRI for DBS surgery. Manual identification of the LHb on axial T1 weighted MRI was used for the initial seed region for tractography. Variations in tractography depending on chosen axial slice of the LHb and chosen voxel within the LHb were also assessed. Results In all hemispheres the SM was reliably visualized. Variations in chosen axial seed slice as well as variations in single seed placement did not lead to significant changes in SM tractography. Conclusions Probabilistic DTI can be used to visualize the SM which may ultimately provide utility for direct anatomic targeting in DBS surgery.
... UHF diffusion-weighted imaging (DWI) MRI has been conducted in both post-mortem and in vivo studies to visualize white matter pathways between different grey matter areas [42][43][44] . High-resolution DWI enables the visualisation and quantification of highly interconnected structural networks (for examples, see REF. 45) and can be used to inform and constrain the architecture of computational models. ...
Article
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The human subcortex is a densely populated part of the brain, of which only 7% of the individual structures are depicted in standard MRI atlases. In vivo MRI of the subcortex is challenging owing to its anatomical complexity and its deep location in the brain. The technical advances that are needed to reliably uncover this ‘terra incognita’ call for an interdisciplinary human neuroanatomical approach. We discuss the emerging methods that could be used in such an approach and the incorporation of the data that are generated from these methods into model-based cognitive neuroscience frameworks.
... UHF diffusion-weighted imaging (DWI) MRI has been conducted in both post-mortem and in vivo studies to visualize white matter pathways between different grey matter areas [42][43][44] . High-resolution DWI enables the visualisation and quantification of highly interconnected structural networks (for examples, see REF. 45) and can be used to inform and constrain the architecture of computational models. ...
Article
The human subcortex is a densely populated part of the brain, of which only 7% of the individual structures are depicted in standard MRI atlases. In vivo MRI of the subcortex is challenging owing to its anatomical complexity and its deep location in the brain. The technical advances that are needed to reliably uncover this 'terra incognita' call for an interdisciplinary human neuroanatomical approach. We discuss the emerging methods that could be used in such an approach and the incorporation of the data that are generated from these methods into model-based cognitive neuroscience frameworks.
... Future studies are needed to evaluate the reproducibility of such segmentation scheme under various acquisition and contrast conditions both in healthy controls and psychiatric patients, including patients suffering from substance use and mood disorders. High-resolution and high contrast 7T Hb imaging (Strotmann et al., 2014) and associated segmentation schemes represent a promising future research direction for more accurate Hb morphological and functional evaluation. Such techniques could shed light on the functional activity of the LHb and MHb in humans. ...
Article
The habenula (Hb) is an evolutionary well-conserved structure located in the epithalamus. The Hb receives inputs from the septum, basal ganglia, hypothalamus, anterior cingulate and medial prefrontal cortex, and projects to several midbrain centers, most importantly the inhibitory rostromedial tegmental nucleus (RMTg) and the excitatory interpeduncular nucleus (IPN), which regulate the activity of midbrain monoaminergic nuclei. The Hb is postulated to play a key role in reward and aversion processing across species, including humans, and to be implicated in the different stages of transition from recreational drug intake to addiction and co-morbid mood disorders. The Hb is divided into two anatomically and functionally distinct nuclei, the lateral (LHb) and the medial (MHb), which are primarily involved in reward-seeking (LHb) and misery-fleeing (MHb) behavior by controlling the RMTg and IPN, respectively. This review provides a neuroanatomical description of the Hb, discusses preclinical and human findings regarding its role in the development of addiction and co-morbid mood disorders, and addresses future directions in this area.
... In addition to mapping myelin noninvasively, MRI is also a powerful means of mapping brain iron (Drayer et al., 1986). The putamen, the substantia nigra, and the habenula (Strotmann et al., 2014) are rich in iron and are distinguished using MRI sequences which use a gradient echo to prepare the signal for acquisition. Such sequences deliver maps of the MRI parameter T2*, which describes the speed of the free induction decay, and also quantitative maps of magnetic susceptibility (QSM) (Marques and Bowtell, 2005) each of which provides interpretable information regarding the concentration and the spatial distribution of iron atoms within brain tissue. ...
Chapter
The volume of published research at the levels of systems and cellular neuroscience continues to increase at an accelerating rate. At the same time, progress in psychiatric medicine has stagnated and scientific confidence in cognitive psychology research is under threat due to careless analysis methods and underpowered experiments. With the advent of ultra-high field MRI, with submillimeter image voxels, imaging neuroscience holds the potential to bridge the cellular and systems levels. Use of these accurate and precisely localized quantitative measures of brain activity may go far in providing more secure foundations for psychology, and hence for more appropriate treatment and management of psychiatric illness. However, fundamental issues regarding the construction of testable mechanistic models using imaging data require careful consideration. This chapter summarizes the characteristics of acceptable models of brain function and provides concise descriptions of the relevant types of neuroimaging data that have recently become available. Approaches to data-driven experiments and analyses are described that may lead to more realistic conceptions of the competences of neural assemblages, as they vary across the brain's complex neuroanatomy.
... Here, we analyzed multi-shell high-angular resolution dMRI (HARDI) data acquired on a 7-Tesla MRI scanner, to evaluate the DOC-related shape deformation of thalamic nuclei and the microstructural changes within thalamic nuclei and along the thalamocortical pathways in patients with DOC. Compared with the 3T MR, the 7T MR improves the spatial resolution and the signal-to-noise ratio (SNR; Vu et al. 2015), which is important for subnuclei segmentation and accurate and reliable reconstruction of the parameter maps (Luetzkendorf et al. 2012), for example, the habenula of thalamus could be better differentiated given the high contrast at 7T than 3T (Strotmann et al. 2014). With the advantage of high-spatial and angular resolutions, we computed the thalamic parcellation for each individual by using the FODbased thalamic nuclei segmentation approach and estimated the shape distortion of each nucleus in DOC patients relative to the HCs. ...
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The thalamus plays crucial roles in consciousness generation and information processing. Previous evidence suggests that disorder of consciousness (DOC) caused by severe brain injury, is potentially related to thalamic abnormalities. However, how the morphology and microstructure change in thalamic subfields and thalamocortical fiber pathways in patients with DOC, and the relationships between these changes and the consciousness status remain unclear. Here, we generated the individual-specific thalamic parcellation in 10 DOC patients and 10 healthy controls (HC) via a novel thalamic segmentation framework based on the fiber orientation distribution (FOD) derived from 7-Tesla diffusion MRI, and investigated the shape deformation of thalamic nuclei as well as the microstructural changes associated with thalamic nuclei and thalamocortical pathways in patients with DOC. Enlargement of dorsal posterior nucleus and atrophy of anterior nucleus in the right thalamus were observed in DOC cohort relative to the HCs, and the former was closely linked to the consciousness level of the patients. We also found significant reductions of fiber density, but not fiber bundle cross-section, within several thalamic nuclei and most of the thalamocortical fiber pathways, suggesting that loss of axons might take primary responsibility for the impaired thalamocortical connections in patients with DOC rather than the change in fiber-bundle morphology. Furthermore, the individual-specific thalamic parcellation achieved 80% accuracy in classifying patients at the minimally conscious state from the vegetative state, compared to around 60% accuracy based on group-level parcellations. Our findings provide the first evidence for the shape deformation of thalamic nuclei in DOC patients and the microstructural basis of the disrupted thalamocortical connections.
... UHF diffusion-weighted imaging (DWI) MRI has been conducted in both post mortem and in vivo studies to visualize the white matter pathways between different grey matter areas (Strotmann et al., 2013;Wargo and Gore, 2013;Dyvorne et al., 2015). High-resolution DWI allows the visualisation and quantification of highly interconnected structural networks and can be used to inform and constrain the architecture of computational models. ...
Thesis
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In my PhD thesis I used Ultra-High Field 7 Tesla MRI to better understand the functional neuroanatomy of the human subthalamic nucleus.
... Because the size of the individual thalamus differs between subjects, it is not easy to identify the exact same slice and anatomic localisation by distance to the AC-PC line. The habenulae, an easily-identifiable structure in MRI [11,25], could be identified in all subjects. Nevertheless, a slightly different anatomical organisation might be the reason that some structures, such as the Voa, were only visible in some subjects. ...
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Objective: Deep brain stimulation has received increasing attention in recent years as a treatment option for many neurological diseases. The thalamic nuclei in particular are widely used as targets. The goal of the present work was to evaluate whether the combination of two known MRI techniques can lead to identification of thalamic substructures at 3 T. Methods: In nine healthy subjects, an optimized 3D magnetization prepared rapid acquisition GRE (MPRAGE) protocol and phase data from a 3D GRE sequence were combined to form a new contrast (MPRAGE*). The depiction of 13 thalamic substructures was rated by two independent raters in the MPRAGE, phase and MPRAGE* image on a five-point scale. Inter-rater reliability was scored with a weighted Cohen's kappa. Results: Inter-rater reliability was good, with the average weighted κ = 0.68. No significant difference between the depiction of the thalamic substructures between phase and MPRAGE images could be found. MPRAGE* showed a significantly better depiction of thalamic substructures in comparison to MPRAGE and phase (p < 0.001 for both cases). Conclusion: The combination of an optimized MPRAGE protocol with phase data to form an MPRAGE* image leads to a further improvement in the depiction of thalamic substructures, which enables the depiction of thalamic nuclei at 3 T.
... At high magnetic fields (C7T), MP2RAGE provided proton density-, T 2 * contrast-and B 1 inhomogeneitycorrected 3D T 1 -weighted images of the human brain with increased T 1 contrast. Moreover, T 1 mapping could be performed with no need for additional acquisitions providing simultaneous quantitative investigation of various interesting human brain structures (Marques and Gruetter 2013;Strotmann et al. 2014;Gizewski et al. 2014). Here the potential of MP2RAGE for imaging the mouse brain with regards to SNR, CNR and T 1 accuracy are discussed. ...
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With the increasing development of transgenic mouse models of neurodegenerative diseases allowing improved understanding of the underlying mechanisms of these disorders, robust quantitative mapping techniques are also needed in rodents. MP2RAGE has shown great potential for structural imaging in humans at high fields. In the present work, MP2RAGE was successfully implemented at 9.4T and 14.1T. Following fractionated injections of MnCl2, MP2RAGE images were acquired allowing simultaneous depiction and T1 mapping of structures in the mouse brain at both fields. In addition, T1 maps demonstrated significant T1 shortenings in different structures of the mouse brain (p < 0.0008 at 9.4T, p < 0.000001 at 14.1T). T1 values recovered to the levels of saline-injected animals 1 month after the last injection except in the pituitary gland. We believe that MP2RAGE represents an important prospective translational tool for further structural MRI.
... The 7T UNI image and T1 map from MP2RAGE showed much higher habenula contrast than the 3T myelin-sensitive images ( Figure 3), as has been previously suggested by others (Strotmann et al., 2014;Schmidt et al., 2016). We chose to use UNI image for our manual segmentation because of its similar contrast to T1w images (i.e., habenula as hyperintense). ...
Article
In vivo morphological study of the human habenula, a pair of small epithalamic nuclei adjacent to the dorsomedial thalamus, has recently gained significant interest for its role in reward and aversion processing. However, segmenting the habenula from in vivo magnetic resonance imaging (MRI) is challenging due to the habenula's small size and low anatomical contrast. Although manual and semi‐automated habenula segmentation methods have been reported, the test‐retest reproducibility of the segmented habenula volume and the consistency of the boundaries of habenula segmentation have not been investigated. In this study, we evaluated the intra‐ and inter‐site reproducibility of in vivo human habenula segmentation from 3T MRI (0.7–0.8 mm isotropic resolution) using our previously proposed semi‐automated myelin contrast‐based method and its fully‐automated version, as well as a previously published manual geometry‐based method. The habenula segmentation using our semi‐automated method showed consistent boundary definition (high Dice coefficient, low mean distance, and moderate Hausdorff distance) and reproducible volume measurement (low coefficient of variation). Furthermore, the habenula boundary in our semi‐automated segmentation from 3T MRI agreed well with that in the manual segmentation from 7T MRI (0.5 mm isotropic resolution) of the same subjects. Overall, our proposed semi‐automated habenula segmentation showed reliable and reproducible habenula localization, while its fully‐automated version offers an efficient way for large sample analysis.
... While the LHb and MHb have been distinguished both in radiological and histological studies, differences in their connectivity with other regions have not been rigorously established in human studies (Torrisi et al., 2017). In general, it appears that the LHb seems to be mostly connected with the forebrain and limbic system, while the MHb is mainly connected to the brainstem and habenular commissure (Strotmann et al., 2014;Fakhoury, 2017). ...
Article
Background: The habenula is a small, mostly underrated structure in the pineal region. Multidisciplinary findings demonstrate an underlying complex connectivity of the habenula with the rest of the brain, subserving its major role in normal behavior and the pathophysiology of depression. These findings suggest the potential application of "habenular psychosurgery" in the treatment of mental disorders. Objective/hypothesis: The remission of two patients with treatment-resistant major depression treated with deep brain stimulation of the habenula supported the hypothesis that the habenula is an effective target for deep brain stimulation and initiated a surge of basic science research. This review aims to assess the viability of the deep brain stimulation of the habenula as a treatment option for treatment resistant depression. Methods: PubMed and the Cochrane Library databases were searched with no chronological restrictions for the identification of relevant articles. Results: The results of this review are presented in a narrative form describing the functional neuroanatomy of the human habenula, its implications in major depression, findings of electrode implantation of this region and findings of deep brain stimulation of the habenula for the treatment of depression. Conclusion: Data assessing the hypothesis are scarce. Nonetheless, findings highlight the major role of the habenula in normal, as well as in pathological brain function, particularly in depression disorders. Moreover, findings of studies utilizing electrode implantation in the region of the habenula underscore our growing realization that research in neuroscience and deep brain stimulation complement each other in a reciprocal relationship; they are as self-reliant, as much as they depend on each other.
... These extracted values were used to perform a three-way, 3 (affect) × 2 (masking) × 10 (ROI) RM-ANOVA to address our hypotheses. The main effects of masking (F [1,40] 77,190.60] = 51.84, ...
Article
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Knowledge of the neural underpinnings of processing sad information and how it differs in people with depression could elucidate the neural mechanisms perpetuating sad mood in depression. Here, we conduct a 7 T fMRI study to delineate the neural correlates involved only in processing sad information, including pons, amygdala, and corticolimbic regions. We then conduct a 3 T fMRI study to examine the resting-state connectivity in another sample of people with and without depression. Only clinically depressed people demonstrate hyperactive amygdala–pons connectivity. Furthermore, this connectivity is related to depression symptom severity and is a significant indicator of depression. We speculate that visual sad information reinforces depressed mood and stimulates the pons, strengthening the amygdala–pons connectivity. The relationship between this connectivity and depressive symptom severity suggests that guiding one’s visual attention and processing of sad information may benefit mood regulation.
... ; https://doi.org/10.1101/2022.01.10.475656 doi: bioRxiv preprint tract estimation by reducing the potential for contamination from medial Hb fibers (48). Nevertheless, PFC input to the Hb terminates exclusively in the lateral nucleus (49), which supports our decision to emphasize functions attributed to the LHb. ...
Preprint
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Drug addiction is characterized by neuroadaptations in mesocorticolimbic networks regulating reward and inhibitory control. The habenula (Hb) is central to adaptive reward and aversion-driven behaviors, serving as a hub connecting emotion/cognitive processing regions including the prefrontal cortex (PFC). However, its role in human drug addiction has not been fully explored. Using diffusion tractography, we detailed PFC structural connectivity with three regions, namely the Hb, ventral tegmental area (VTA), and anterior thalamus (AT), and quantified the tract-specific microstructural integrity using diffusion tensor imaging within the anterior limb of the internal capsule (ALIC) in healthy and cocaine-addicted individuals. White matter microstructure in cocaine-addicted individuals was uniquely impaired in PFC-Hb projections in the ALIC, distinguishable from adjacent PFC-VTA and PFC-AT projections, with more pronounced abnormalities in short-term abstinence. These findings extend preclinical evidence of PFC-Hb circuit impairments in addiction and contextualize the plausible existence of a similar PFC-Hb connection in the human brain.
... ; https://doi.org/10.1101/2022.01.10.475656 doi: bioRxiv preprint tract estimation by reducing the potential for contamination from medial Hb fibers (48). Nevertheless, PFC input to the Hb terminates exclusively in the lateral nucleus (49), which supports our decision to emphasize functions attributed to the LHb. ...
... Pain and itch share similar processing pathways (reviewed in Liu and Ji, 2013) and it is of interest to look into existing data about pain processing and analgesia in the CNS. In humans, fMRI and PET studies support a role of the habenula in analgesia and pain processing (Shelton et al., 2012a), but further analysis of the medial habenula has not been possible yet due to the lack of resolution in current MRI techniques (Strotmann et al., 2014(Strotmann et al., , 2013. A limitation of our study is that we cannot exclude the activation of the medial habenula as consequence of emotion, physical activity or effects secondary to itch. ...
Article
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Background: Strategies to efficiently control itch require a deep understanding of the underlying mechanisms. Several areas in the brain involved in itch and scratching responses have been postulated, but the central mechanisms that drive pruritic responses are still unknown. Histamine is recognized as a major mediator of itch in humans, and has been the most frequently used stimulus as an experimental pruritogen for brain imaging of itch. Objective: Histaminergic itch via histamine and the selective histamine H4 receptor (H4R) agonist, ST-1006, recruit brain nuclei through c-fos activation and activate specific areas in the brain. Methods: An acute itch model was established in c-fos-EGFP transgenic mice using ST-1006 and histamine. Coronal brain sections were stained for c-fos immunoreactivity and the forebrain was mapped for density of c-fos + nuclei. Results: Histamine and ST-1006 significantly increased scratching response in c-fos-EGFP mice compared to vehicle controls. Mapping c-fos immunostained brain sections revealed neuronal activity in the cortex, striatum, hypothalamus, thalamus, amygdala, and the midbrain. Conclusions: Histaminergic itch and selective H4R activation significantly increased the density of c-fos + nuclei in the medial habenula (MHb). Thus, the MHb may be a new target to investigate and subsequently develop novel mechanism-based strategies to treat itch and possibly provide a locus for pharmacological control of pruritus.
... This is particularly true for subcortical structures such as the ventral tegmental area (source of dopaminergic reward signals) and the habenula (inhibits dopamine signals in response to negative outcomes). These and other key reward-related structures have limited anatomical tissue contrast and have proven difficult to reliably segment, with the most accepted methods rely on heuristic anatomical landmarks (93)(94)(95)(96). These issues are compounded in fMRI studies, where the combination of low spatial resolution, signal contamination from poorly delineated tissue boundaries, and high physiological noise make subcortical reward structures especially challenging to study (93,97). ...
Article
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Depression is a highly prevalent condition with devastating personal and public health consequences that often first manifests during adolescence. Though extensively studied, the pathogenesis of depression remains poorly understood, and efforts to stratify risks and identify optimal interventions have proceeded slowly. A major impediment has been the reliance on an all-or-nothing categorical diagnostic scheme based solely on whether a patient endorses an arbitrary number of common symptoms for a sufficiently long period. This approach masks the well-documented heterogeneity of depression, a disorder that is highly variable in presentation, severity, and course between individuals and is frequently comorbid with other psychiatric conditions. In this targeted review, we outline the limitations of traditional diagnosis-based research and instead advocate an alternative approach centered around symptoms as unique dimensions of clinical dysfunction that span across disorders and more closely reflect underlying neurobiological abnormalities. In particular, we highlight anhedonia—the reduced ability to anticipate and experience pleasure—as a specific, quantifiable index of reward dysfunction and an ideal candidate for dimensional investigation. Anhedonia is a core symptom of depression but also a salient feature of numerous other conditions, and its severity varies widely within clinical and even healthy populations. Similarly, reward dysfunction is a hallmark of depression but is evident across many psychiatric conditions. Reward function is especially relevant in adolescence, a period characterized by exaggerated reward-seeking behaviors and rapid maturation of neural reward circuitry. We detail extensive work by our research group and others to investigate the neural and systemic factors contributing to reward dysfunction in youth, including our cumulative findings using multiple neuroimaging and immunological measures to study depressed adolescents but also trans-diagnostic cohorts with diverse psychiatric symptoms. We describe convergent evidence that reward dysfunction: (a) predicts worse clinical outcomes, (b) is associated with functional and chemical abnormalities within and beyond the neural reward circuitry, (c) is linked to elevated peripheral levels of inflammatory biomarkers, and (d) manifests early in the course of illness. Emphasis is placed on high-resolution neuroimaging techniques, comprehensive immunological assays, and data-driven analyses to fully capture and characterize the complex, interconnected nature of these systems and their contributions to adolescent reward dysfunction.
... We have also highlighted evidence that ketamine produces its antidepressant effects through action on the habenular complex and frontomesolimbic networks. As we are entering the third decade of human research into the antidepressant effects of NMDA receptor antagonists, future studies could harness existing computational modelling, functional connectivity, novel neuroimaging analysis methods and imaging modalities with higher spatial and temporal resolution (e.g., scan human participants at higher magnetic field strengths [81,82] or with MEG and pupillometry). So far only a small number of studies have focused on the human habenula in healthy and clinical populations. ...
Article
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Anhedonia, a pronounced reduction in interest or pleasure in any of life’s daily activities, is a cardinal symptom of major depression. In this Perspective article, we synthesise the recent evidence from rodent, monkey and human neuroimaging literature to highlight how the habenula, a small evolutionarily conserved subcortical structure located in the midbrain, may orchestrate the behavioural expression of anhedonia across fronto-mesolimbic networks. We then review how this circuitry can be modulated by ketamine, an NMDA receptor antagonist with rapid antidepressant properties. We propose that experimental paradigms founded in reinforcement learning and value-based decision-making can usefully probe this network and thereby help elucidate the mechanisms underlying ketamine’s rapid antidepressant action.
... As judged from the fact that the LHbM and LHbL act on the activity in the midbrain dopaminergic neurons in a distinctive manner as an example, it would be of great importance to examine how those subcomponents of the habenula contribute to the net changes of the signal in the human habenula with the help of ultra-high-field magnetic resonance imaging. 67,68 To validate the hypothesis that the hyperactivated habenula induces depression as supported by animal studies, the results of recent imaging studies are controversial. One showed reduction of habenular response during aversive conditioning in unmedicated depression, 69 while the other showed that punishment prediction error in the habenula was correlated positively with the number of depressive episodes. ...
Article
Habenula is an evolutionarily conserved structure in vertebrate brain. Lesion and electrophysiological studies in animals have suggested that it is involved in the regulation of the monoaminergic activity through projection to the brain stem nuclei. Since the studies in animal models of depression and human functional imaging have indicated that increased activity of the habenula was associated with the depressive phenotypes, this structure has attracted a surge of interest in neuroscience research. According to the pathway‐ and cell type‐specific dissection of the habenular function in the animals, we begin to understand how the heterogeneity of the habenula accounts for alteration of the diverse physiological functions in depression. Indeed, recent studies have revealed that the subnuclei embedded in the habenula showed a wide variety of molecular profiles not only in neurons but also in glial cells implementing the multifaceted regulatory mechanism for output from the habenula. In this review, we overview the known facts on mediolateral subdivision in the habenular structure, then discuss heterogeneity of the habenular structure from the anatomical and functional viewpoint to understand its emerging role in diverse neural functions relevant to the depressive phenotypes. Despite the prevalent use of antidepressants acting on the monoamine metabolisms, ~30% of patients with major depression are reported to be treatment‐resistant. Thus, cellular mechanisms deciphering such diversity in depressive symptoms would be a promising candidate for the development of new antidepressants. This article is protected by copyright. All rights reserved.
... Until recently, one problem with imaging the habenula was due to its small size which makes functional imaging a challenge (Lawson et al., 2013). Recently, using magnetic resonance imaging (MRI) with better resolution has made it possible to functionally image the human habenula (Strotmann et al., 2013(Strotmann et al., , 2014. However, it is still not possible to reliably distinguish between the medial and lateral divisions in humans. ...
Article
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Adverse events and childhood trauma increase the susceptibility towards developing psychiatric disorders (substance use disorder, anxiety, depression, etc.) in adulthood. Although there are treatment strategies that have utility in combating these psychiatric disorders, little attention is placed on how to therapeutically intervene in children exposed to early life stress (ELS) to prevent the development of later psychopathology. The lateral habenula (LHb) has been a topic of extensive investigation in mental health disorders due to its prominent role in emotion and mood regulation through modulation of brain reward and motivational neural circuits. Importantly, rodent models of ELS have been shown to promote LHb dysfunction. Moreover, one of the potential mechanisms contributing to LHb neuronal and synaptic dysfunction involves endocannabinoid (eCB) signaling, which has been observed to critically regulate emotion/mood and motivation. Many pre-clinical studies targeting eCB signaling suggest that this neuromodulatory system could be exploited as an intervention therapy to halt maladaptive processes that promote dysfunction in reward and motivational neural circuits involving the LHb. In this perspective article, we report what is currently known about the role of eCB signaling in LHb function and discuss our opinions on new research directions to determine whether the eCB system is a potentially attractive therapeutic intervention for the prevention and/or treatment of ELS-associated psychiatric illnesses.
... These studies demonstrate that the habenula plays a prominent role in the neural pathway through which aversive motivation interacts with cognitive control . However, a significant limitation for investigating the LHb in humans is its relatively small size, which is around 30 mm 3 in volume (Boulos et al., 2017;Lawson et al., 2013;Strotmann et al., 2014). While some early fMRI studies suggest that the human habenula is activated for negative outcomes and negative reward prediction errors (Salas et al., 2010;Shepard et al., 2006;Ullsperger & Cramon, 2003), a potential limitation of this early work may be the lack of spatial specificity due to the available MRI methods at the time. ...
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Aversive motivation plays a prominent role in motivating individuals to exert cognitive control. However, a significant obstacle has been the complexity of behavioral responses attributed to aversive incentives. In this review, we posit that incorporating motivational context and mixed motivation will enhance our current understanding of the neural and computational mechanisms underpinning these interactions. We highlight how delineating whether aversive incentives facilitate negative reinforcement or punishment can inform dissociable neural pathways and computational mechanisms for cognitive control allocation. Additionally, we demonstrate how including multiple bundled incentives in experimental paradigms enables precise measurement of aversive influences on cognitive control. The lateral habenula and dorsal anterior cingulate cortex are featured as part of a broader neural circuit for aversive motivational value, and dopaminergic and serotonergic projections may guide dissociable strategies for cognitive control allocation. Finally, these motivational dimensions help generate normative predictions for divergent strategies for control allocation. In sum, incorporating these motivational dimensions will facilitate more sophisticated understanding of the neural, monoaminergic, and computational mechanisms of aversive motivation and cognitive control.
... Ultra-high field MRI with excellent spatial resolution is gradually finding its way into the clinic and increasingly specific diagnostic challenges are required to drive its implementation and development. Indeed, using a 7 T clinical MRI scanner combined with multi-array coils, a r Mesoscopic MRI of Epileptic Hippocampus r r 13 r resolution of 700 lm is achievable [Strotmann et al., 2014] and with postprocessing a "super-resolution" of 200lm isotropic resolution becomes a realistic target in human subjects [Calamante et al., 2013]. Although the array of applications will remain far more limited than at lower field strengths, specific indications, such as uncovering aberrant hippocampal connections, might be on the clinical horizon pending further developments on ex vivo samples. ...
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... While He et al. identified the hyperintense voxels in the habenula with the lateral habenula (in the context of deep brain stimulation) 12 , in our opinion such association would require further investigation. In a 2014 report 33 Strotmann et al. have used 1 mm isotropic-resolution diffusion tractography to demonstrate distinct fiber orientations for the lateral and the medial habenula. In an ex vivo study 34 , high-resolution (0.06-0.3 mm isotropic) T1 and T2* maps have revealed further differentiation of the lateral habenula into lateral and medial subcomponents consistent with histological results. ...
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Recently there has been renewed interest in the habenula; a pair of small, highly evolutionarily conserved epithalamic nuclei adjacent to the medial dorsal (MD) nucleus of the thalamus. The habenula has been has been implicated in a range of behaviours including sleep, stress and pain, and studies in non-human primates have suggested a potentially important role in reinforcement processing, putatively via its effects on monoaminergic neurotransmission. Over the last decade, an increasing number of neuroimaging studies have reported functional responses in the human habenula using functional magnetic resonance imaging (fMRI). However, standard fMRI analysis approaches face several challenges in isolating signal from this structure because of its relatively small size, around 30mm(3) in volume. In this paper we offer a set of guidelines for locating and manually tracing the habenula in humans using high-resolution T1-weighted structural images. We also offer recommendations for appropriate pre-processing and analysis of high-resolution functional magnetic resonance imaging (fMRI) data such that signal from the habenula can be accurately resolved from that in surrounding structures.
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Although positive reward prediction error, a key element in learning that is signaled by dopamine cells, has been extensively studied, little is known about negative reward prediction errors in humans. Detailed animal electrophysiology shows that the habenula, an integrative region involved in many processes including learning, reproduction, and stress responses, also encodes negative reward-related events such as negative reward prediction error signals. In humans, however, the habenula's extremely small size has prevented direct assessments of its function. We developed a method to functionally locate and study the habenula in humans using fMRI, based on the expected reward-dependent response phenomenology of habenula and striatum and, we provide conclusive evidence for activation in human habenula to negative reward prediction errors.
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There is a growing awareness that emotion, motivation, and reward values are important determinants of our behavior. The habenula is uniquely positioned both anatomically and functionally to participate in the circuit mediating some forms of emotive decision making. In the last few years there has been a surge of interest in this structure, especially the lateral habenula (LHb). The new studies suggest that the LHb plays a pivotal role in controlling motor and cognitive behaviors by influencing the activity of dopamine and serotonin neurons. Further, dysfunctions of the LHb have also been implicated in psychiatric disorders, such as depression, schizophrenia, and drug-induced psychosis.
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The efferent connections of the medial (MHb) and lateral (LHb) habenular nuclei in the rat were demonstrated autoradiographically following small injections of tritiated amino acids localized within various parts of the habenular complex. Comparison of individual cases led to the following conclusions. MHb efferents form the core portion of the fasciculus retroflexus and pass to the interpeduncular nucleus (IP) in which they terminate in a topographic pattern that reflects 90° rotations such that dorsal MHb projects to lateral IP, medial MHb to ventral, and lateral MHb to dorsal IP. Most MHb fibers cross in the interpeduncular nucleus in the “figure 8” pattern described by Cajal, and terminate throughout the width of IP with only moderate preference for the ip-silateral side. However, the most dorsal part of MHb projects almost exclusively to the most lateral IP zone in a cluster pattern that is particularly dense on the ipsilateral side. The MHb appears to have no other significant projections, but very sparse MHb fibers may pass to the supracommissural septum and to the median raphe nucleus. Except for some fibers passing ventrally into the mediodorsal nucleus, all of the LHb efferents enter the fasciculus retroflexus and compose the mantle portion of the bundle. No LHb projections follow the stria medullaris. In the ventral tegmental area LHb efferents become organized into groups that disperse in several directions: (a) Rostrally directed fibers follow the medial forebrain bundle to the lateral, posterior and dorsomedial hypothalamic nuclei, ventromedial thalamic nucleus, lateral preoptic area, substantia innominata and ventrolateral septum, (b) Fibers turning laterally distribute to the substantia nigra, pars compacta (SNC); a small number continue through SNC to adjacent tegmentum, (c) The largest contingent of LHb efferents passes dorsocaudally into paramedian midbrain regions including median and dorsal raphe nuclei, and to adjacent tegmental reticular formation. Sparse additional LHb projections pass to the pretectal area, superior colliculus, nucleus reticularis tegmen-ti pontis, parabrachial nuclei and locus coeruleus. No LHb projections appear to involve the interpeduncular nucleus. All of these connections are in varying degree bilateral, with decussations in the supramammillary region, ventral tegmental area and median raphe nucleus. On the basis of differential afferent and efferent connections, the LHb can be divided into a medial (M-LHb) and a lateral (L-LHb) portion. The M-LHb, receiving most of its afferents from limbic regions and only few from globus pallidus, projects mainly to the raphe nuclei, while L-LHb, afferented mainly by globus pallidus and in lesser degree by the limbic forebrain, projects predominantly to a large region of reticular formation alongside the median raphe nucleus. Both M-LHb and L-LHb, however, project to SNC. The reported data are discussed in correlation with recent histochemical findings.
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To overcome the problems of gradient strength, large receiver bandwidth and computing time in nuclear magnetic resonance real-time echo-planar imaging (EPI) with large pixel arrays, the concept of zonal image magnification or zoomed EPI (ZEPI) is introduced. The image zone is defined by two selective RF pulses and the receiver bandwidth. For a fixed image array size it is shown that zooming requires less gradient strength to achieve a given spatial resolution than in an equivalent unzoomed image. Two different zoom techniques are described, ZEPI-1 and ZEPI-2, which employ a single and a double pulse sequence respectively. Experimental results obtained with these sequences on a phantom and a live piglet are presented.
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Calculations of the radiofrequency magnetic (B1) field, SAR, and SNR as functions of frequency between 64 and 345 MHz for a surface coil against an anatomically-accurate human chest are presented. Calculated B1 field distributions are in good agreement with previously-published experimental results up to 175 MHz, especially considering the dependence of field behavior on subject anatomy. Calculated SNR in the heart agrees well with theory for low frequencies (nearly linear increase with B0 field strength). Above 175 MHz, the trend in SNR with frequency begins to depend largely on location in the heart. At all frequencies, present limits on local (1 g) SAR levels are exceeded before limits on whole-body average limits. At frequencies above 175 MHz, limits on SAR begin to be an issue in some common imaging sequences. These results are relevant for coils and subjects similar to those modeled here. Magn Reson Med 45:692–699, 2001. © 2001 Wiley-Liss, Inc.
Article
The afferent connections of the habenular complex in the rat were examined by injecting horseradish peroxidase (HRP) into discrete portions of the habenular nuclei by microelectrophoresis. 1. HRP deposits confined to the lateral half of the lateral habenular nucleus labeled a multitude of cells in the entopeduncular nucleus. Numerous labeled cells also appeared in such cases in the lateral hypothalamus, indicating that the lateral habenular nucleus is a major convergence point of projections from these otherwise. 2. HRP injected into the medial part of the lateral habenular nucleus labeled cells in the same regions, but more in the diagonal band and fewer in the entopeduncular nucleus than were labeled by more lateral injections. The contrast suggests that the projections from the basal forebrain and entopeduncular nucleus to the lateral habenular nucleus are somewhat topographically organized. 3. Injections of the medial habenular nucleus labeled an abundance of cells in the posterior parts of the supracommissural septum, but also a small number of cells in the diagonal band and mesencephalic raphe. 4. HRP injected into the stria medullaris labeled cells in all of the afore-mentioned areas and, in addition, cells in several olfactory structures, confirming that HRP may be taken up by fibers of passage and label their cells of origin, and suggesting that olfactory structures contribute fibers to the stria medullaris that do not terminate in the habenula.
Article
A single-shot echo-planar diffusion imaging sequence (IVIM-EPI: intra-voxel incoherent motion echo-planar imaging) is presented, which is immune from the motion artifacts which may seriously impair images obtained using other diffusion imaging sequences. For a static water phantom, the measured value of diffusion constant (D = 2.30 × 10−9 m2 s−1 at T = 298 K) shows excellent agreement with that obtained using a multipulse spin-echo technique and with literature values. Single-shot diffusion imaging can now be used reliably to make dynamic time-course studies with excellent time resolution.
Article
Echo-planar imaging is the most widely used imaging sequence for functional magnetic resonance imaging (fMRI) due to its fast acquisition. However, it is prone to local distortions, image blurring, and signal voids. As these effects scale with echo train length and field strength, it is essential for high-resolution echo-planar imaging at ultrahigh field to address these problems. Partially parallel acquisition methods can be used to improve the image quality of echo-planar imaging. However, partially parallel acquisition can be affected by aliasing artifacts and noise enhancement. Another way to shorten the echo train length is to reduce the field-of-view (FOV) while maintaining the same spatial resolution. However, to achieve significant acceleration, the resulting FOV becomes very small. Another problem occurs when FOV selection is incomplete such that there is remaining signal aliased from the region outside the reduced FOV. In this article, a novel approach, a combination of reduced FOV imaging with partially parallel acquisition, is presented. This approach can address the problems described above of each individual method, enabling high-quality single-shot echo-planar imaging acquisition, with submillimeter isotropic resolution and good signal-to-noise ratio, for fMRI at ultrahigh field strength. This is demonstrated in fMRI of human brain at 7T with an isotropic resolution of 650 μm. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
Article
The corticoreticular pathway (CRP) is involved in postural control and locomotor function. No study has been conducted for identification of the CRP in the human brain. In the current study, we attempted to identify the CRP in the human brain, using diffusion tensor tractography (DTT). We recruited 24 healthy volunteers for this study. Diffusion tensor images were scanned using 1.5-T. For reconstruction of the CRP, a seed region of interest (ROI) was placed on the reticular formation of the medulla. The first target ROI was placed on the midbrain tegmentum and the second target ROI was placed on the premotor cortex (Brodmann area 6). Values of fractional anisotropy, mean diffusivity, and tract volume of the CRP were measured. The CRP, which originated from the premotor cortex, descended through the corona radiata and the posterior limb of the internal capsule anterior to the corticospinal tract. In the midbrain and pons, it passed through the tegmentum and terminated at the pontomedullary reticular formation. No differences in terms of fractional anisotropy, mean diffusivity, and tract volume were observed between hemispheres (P>0.05). We identified the CRP in the human brain using DTT. These methods and results would be helpful to both clinicians and researchers in the neuroscience field.
Article
The rubrospinal tract (RST) is an extrapyramidal motor pathway in the human brain. In this study, using diffusion tensor tractography (DTT), we attempted to identify the RST in the normal human brain. Twenty-one healthy volunteers were recruited for this study. A 1.5-T scanner was used for scanning of diffusion tensor images, and the RSTs were isolated by DTT using FMRIB software. Values of fractional anisotropy (FA), mean diffusivity (MD), and tract volume of the RSTs were measured. Among 42 hemispheres of 21 subjects, RSTs were isolated in 27 hemispheres (64.28%) of 15 subjects. All identified tracts originated from the red nucleus and crossed the midline via ventral tegmental decussation. Then, they passed through the area between the inferior olivary nucleus and the inferior cerebellar peduncle in the contralateral medulla. The tracts finally descended through the lateral funiculus of the upper spinal cord. Mean values of FA, MD, and tract volume did not differ significantly between the left and right hemispheres (P>0.05). We believe that the methodologies used and the results of this study would be helpful to researchers interested in the function of the human RST and its clinical implications.
Article
A good spatial resolution is essential for high precision segmentations of small structures in magnetic resonance images. However, any increase in the spatial resolution results in a decrease of the signal-to-noise ratio (SNR). In this article, this problem is addressed by a new image restoration technique that is used to partly compensate for the loss in SNR. Specifically, a two-stage hybrid image restoration procedure is proposed where the first stage is a Wiener wavelet filter for an initial denoising. The artifacts that will inevitably be produced by this step are subsequently reduced using a recent variant of anisotropic diffusion. The method is applied to magnetic resonance imaging data acquired on a 7-T magnetic resonance imaging scanner and compared with averaged multiple measurements of the same subject. It was found that the effect of image restoration procedure roughly corresponds to averaging across three repeated measurements.
Article
We have discovered a simple and highly robust method for removal of chemical shift artifact in spin-echo MR images, which simultaneously decreases the radiofrequency power deposition (specific absorption rate). The method is demonstrated in spin-echo echo-planar imaging brain images acquired at 7 T, with complete suppression of scalp fat signal. When excitation and refocusing pulses are sufficiently different in duration, and thus also different in the amplitude of their slice-select gradients, a spatial mismatch is produced between the fat slices excited and refocused, with no overlap. Because no additional radiofrequency pulse is used to suppress fat, the specific absorption rate is significantly reduced compared with conventional approaches. This enables greater volume coverage per unit time, well suited for functional and diffusion studies using spin-echo echo-planar imaging. Moreover, the method can be generally applied to any sequence involving slice-selective excitation and at least one slice-selective refocusing pulse at high magnetic field strengths. The method is more efficient than gradient reversal methods and more robust against inhomogeneities of the static (polarizing) field (B(0)).
Article
Surviving in a world with hidden rewards and dangers requires choosing the appropriate behaviours. Recent discoveries indicate that the habenula plays a prominent part in such behavioural choice through its effects on neuromodulator systems, in particular the dopamine and serotonin systems. By inhibiting dopamine-releasing neurons, habenula activation leads to the suppression of motor behaviour when an animal fails to obtain a reward or anticipates an aversive outcome. Moreover, the habenula is involved in behavioural responses to pain, stress, anxiety, sleep and reward, and its dysfunction is associated with depression, schizophrenia and drug-induced psychosis. As a highly conserved structure in the brain, the habenula provides a fundamental mechanism for both survival and decision-making.