Medial Lemniscus Research Articles

Technical Feasibility of Delineating the Thalamic Gustatory Tract Using Tractography.

Magnetic resonance-guided focused ultrasound (MRgFUS) has been increasingly performed in recent years as a minimally invasive treatment of essential tremor and tremor-dominant Parkinson disease. One of the side effects after treatment is dysgeusia. Some centers use tractography to facilitate the treatment planning. However, there have been no reports of identifying gustatory tracts so far. Our aim was to investigate the technical feasibility of isolating and visualizing the gustatory tracts, as well as to explore the relationship between the gustatory tract and the MRgFUS lesion using actual patient data. We used 20 randomly selected individuals from the Human Connectome Project database to perform tractography of the gustatory tracts. We defined region of interest as the dorsal region of the brainstem, Brodmann area 43 associated with taste perception, and a sphere with a 3-mm radius centered around the ventral intermediate nucleus in the anterior commissure-posterior commissure plane. We also examined the position of the gustatory tract in relation with other tracts, including the medial lemniscus, the pyramidal tract, and the dentatorubrothalamic tract. In addition, using the data of real patients with essential tremor, we investigated the distance between MRgFUS lesions and the gustatory tract and its association with the development of dysgeusia. We delineated a mean of 15 streamlines of the gustatory tracts per subject in each hemisphere. There was no statistical difference in the localization of the gustatory tracts between the left and right cerebral hemispheres. The gustatory tract was located anteromedial to the medial lemniscus and posteromedial to the dentatorubrothalamic tract in the anterior commissure-posterior commissure plane. The distance from the MRgFUS lesion to the gustatory tract was significantly shorter in the case where dysgeusia occurred compared with nondysgeusia cases (P-value: .0068). The thalamic gustatory tracts can be reliably visualized using tractography.

In Vivo visualization of white matter fiber tracts in the brainstem using low flip angle double echo 3D gradient echo imaging at 3T

BackgroundWhite matter (WM) fiber tracts in the brainstem communicate with various regions in the cerebrum, cerebellum, and spinal cord. Clinically, small lesions, malformations, or histopathological changes in the brainstem can cause severe neurological disorders. A direct and non-invasive assessment approach could bring valuable information about the intricate anatomical variations of the white matter fiber tracts and nuclei. Although tractography from diffusion tensor imaging has been commonly used to map the WM fiber tracts connectivity, it is difficult to differentiate the complex WM tracts anatomically. Both high field MRI methods and ultrahigh-field MRI methods at 7T and 11.7 T have been used to enhance the contrast of WM fiber tracts. Despite their promising results, it is still challenging to achieve wide clinical adoption at 3T. In this study, we explored a clinically feasible method using a proton density weighted (PDW) 3D gradient echo (GRE) sequence to directly image the WM fiber tracts in the brainstem at 3T in vivo. MethodsWe optimized a 3D high resolution, double echo, short TR, PDW GRE sequence on 5 healthy volunteers using a clinical 3T scanner to visualize the complicated anatomy of WM fiber tracts in the brain stem. Tissue properties including T1, proton density and T2* from in vivo quantitative MRI data were used for simulations to determine the optimal flip angle for the sequence. The visualization of multiple WM fiber tracts in the brainstem was assessed qualitatively and quantitatively using relative contrast and contrast-to-noise ratio (CNR). To improve the CNR, the final images were created by averaging over all echoes from two consecutive scans at the optimal flip angle. The results were compared to anatomical atlases and histology sections to identify the major fiber tracts. All the identified major fiber tracts were labeled on axial, sagittal and coronal slices. ResultsThe WM fiber tracts were found to have distinct hypointense signal throughout the brainstem and most of the major WM fiber tracts, such as the corticospinal tract, medial lemniscus, medial longitudinal fasciculus, and central tegmental tract, in the brainstem up to and including the thalamus were identified in all subjects. Both qualitative and quantitative evaluations showed that the 3° scan offered the best contrast for WM fiber tracts for a TR of 20 ms. The average over the first two echo times and two consecutive 3° scans gave a CNR of 47.8 ± 6.2 for the pyramidal tracts in particular and CNRs values greater than 6.5 ± 2.4 for the rest of the fiber tracts. ConclusionsAll the major fiber tracts in the brainstem could be visualized. Given the reasonably short scan time of 10 min at 3T, double echo PDW GRE sequence is a very practical approach for clinical adoption.

The effect of subthalamic nucleus deep brain stimulation on speech performance: a prospective clinical and tractography study.

Speech changes significantly impact the quality of life for Parkinson's disease (PD) patients. Deep Brain Stimulation (DBS) of the Subthalamic Nucleus (STN) is a standard treatment for advanced PD, but its effects on speech remain unclear. This study aimed to investigate the relationship between STN-DBS and speech changes in PD patients using comprehensive clinical assessments and tractography. Forty-seven PD patients underwent STN-DBS, with preoperative and 3-month postoperative assessments. Speech analyses included acoustic measurements, auditory-perceptual evaluations, and fluency-intelligibility tests. On the other hand, structures within the volume tissue activated (VTA) were identified using MRI and DTI. The clinical and demographic data and structures associated with VTA (Corticospinal tract, Internal capsule, Dentato-rubro-thalamic tract, Medial forebrain bundle, Medial lemniscus, Substantia nigra, Red nucleus) were compared with speech analyses. The majority of patients (36.2-55.4% good, 29.7-53.1% same) exhibited either improved or unchanged speech quality following STN-DBS. Only a small percentage (8.5-14.9%) experienced deterioration. Older patients and those with worsened motor symptoms postoperatively were more likely to experience negative speech changes (p < 0.05). Interestingly, stimulation of the right Substantia Nigra correlated with improved speech quality (p < 0.05). No significant relationship was found between other structures affected by VTA and speech changes. This study suggests that STN-DBS does not predominantly negatively impact speech in PD patients, with potential benefits observed, especially in younger patients. These findings underscore the importance of individualized treatment approaches and highlight the need for further long-term studies to optimize therapeutic outcomes and better understand the effects of STN-DBS on speech.

Exploring cognitive related microstructural alterations in normal appearing white matter and deep grey matter for small vessel disease: A quantitative susceptibility mapping study

Brain microstructural alterations possibly occur in the normal-appearing white matter (NAWM) and grey matter of small vessel disease (SVD) patients, and may contribute to cognitive impairment. The aim of this study was to explore cognitive related microstructural alterations in white matter and deep grey matter nuclei in SVD patients using magnetic resonance (MR) quantitative susceptibility mapping (QSM). 170 SVD patients, including 103 vascular mild cognitive impairment (VaMCI) and 67 no cognitive impairment (NCI), and 21 healthy control (HC) subjects were included, all underwent a whole-brain QSM scanning. Using a white matter and a deep grey matter atlas, subregion-based QSM analysis was conducted to identify and characterize microstructural alterations occurring within white matter and subcortical nuclei. Significantly different susceptibility values were revealed in NAWM and in several specific white matter tracts including anterior limb of internal capsule, corticospinal tract, medial lemniscus, middle frontal blade, superior corona radiata and tapetum among VaMCI, NCI and HC groups. However, no difference was found in white matter hyperintensities between VaMCI and NCI. A trend toward higher susceptibility in the caudate nucleus and globus pallidus of VaMCI patients compared to HC, indicating elevated iron deposition in these areas. Interestingly, some of these QSM parameters were closely correlated with both global and specific cognitive function scores, controlling age, gender and education level. Our study suggested that QSM may serve as a useful imaging tool for monitoring cognitive related microstructural alterations in brain. This is especially meaningful for white matter which previously lacks of attention.

Neural Mechanisms Associated With Postural Control in Collegiate Soccer and Non-Soccer Athletes.

Sport-specific training may improve postural control, while repetitive head acceleration events (RHAEs) may compromise it. Understanding the neural mechanisms underlying postural control may contextualize changes due to training and RHAE. The goal of this study was to determine whether postural sway during the Balance Error Scoring System (BESS) is related to white matter organization (WMO) in collegiate athletes. Collegiate soccer ( N =33) and non-soccer athletes ( N =44) completed BESS and diffusion tensor imaging. Postural sway during each BESS stance, fractional anisotropy (FA), and mean diffusivity (MD) were extracted for each participant. Partial least squares analyses determined group differences in postural sway and WMO and the relationship between postural sway and WMO in soccer and non-soccer athletes separately. Soccer athletes displayed better performance during BESS 6, with lower FA and higher MD in the medial lemniscus (ML) and inferior cerebellar peduncle (ICP), compared to non-soccer athletes. In soccer athletes, lower sway during BESS 2, 5, and 6 was associated with higher FA and lower MD in the corticospinal tract, ML, and ICP. In non-soccer athletes, lower sway during BESS 2 and 4 was associated with higher FA and lower MD in the ML and ICP. BESS 1 was associated with higher FA, and BESS 3 was associated with lower MD in the same tracts in non-soccer athletes. Soccer and non-soccer athletes showed unique relationships between sway and WMO, suggesting that sport-specific exposures are partly responsible for changes in neurological structure and accompanying postural control performance and should be considered when evaluating postural control after injury.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content, available at: http://links.lww.com/JNPT/A472 ).

Correlation of diffusion tensor tractography with obstructive sleep apnea severity.

Using correlation tractography, this study aimed to find statistically significant correlations between white matter (WM) tracts in participants with obstructive sleep apnea (OSA) and OSA severity. We hypothesized that changes in certain WM tracts could be related to OSA severity. We enrolled 40 participants with OSA who underwent diffusion tensor imaging (DTI) using a 3.0 Tesla MRI scanner. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and quantitative anisotropy (QA)-values were used in the connectometry analysis. The apnea-hypopnea index (AHI) is a representative measure of the severity of OSA. Diffusion MRI connectometry that was used to derive correlational tractography revealed changes in the values of FA, MD, AD, RD, and QA when correlated with the AHI. A false-discovery rate threshold of 0.05 was used to select tracts to conduct multiple corrections. Connectometry analysis revealed that the AHI in participants with OSA was negatively correlated with FA values in WM tracts that included the cingulum, corpus callosum, cerebellum, inferior longitudinal fasciculus, fornices, thalamic radiations, inferior fronto-occipital fasciculus, superior and posterior corticostriatal tracts, medial lemnisci, and arcuate fasciculus. However, there were no statistically significant results in the WM tracts, in which FA values were positively correlated with the AHI. In addition, connectometry analysis did not reveal statistically significant results in WM tracts, in which MD, AD, RD, and QA values were positively or negatively correlated with the AHI. Several WM tract changes were correlated with OSA severity. However, WM changes in OSA likely involve tissue edema and not neuronal changes, such as axonal loss. Connectometry analyses are valuable tools for detecting WM changes in sleep disorders.

Connectomic deep brain stimulators in Parkinson`s sub cortical functional zones

Shaking palsy is a brain disease involving motor and non motor zones affecting circa 1 to 2%of humans&amp;#62;60 years age. To date there has been no invention for curing this chronic disease and to stop its progression. But existing therapeutic procedures can offer symptomatic relief to Parkinson patients. DBS is most successful therapy for the Parkinson`s yet depends on the accuracy of electrode implantation and location within the anatomical subcortical neural-structures. This study examines the likelihood of net-work-based induced stimuli and the application of connectomic DBS in Parkinson`s. The subthalamic nucleus is divided into3 sub zones, namely, limbic (anterior), associative (middle) and motor (posterior) as well as diffusion weighted imaging (D W I). The surgical targets are tiny (few millimeters) and good enough to neuroanatomical-structures within the b r a i n. STN (size:12×5×3mm3) and lies nearby internal capsule, medial lemniscus, corticospinal tract, plus red-nucleus. Through sub optimal lead insertion and over stimuli, flow of electrons can spread to these adjoining sucortics, thereby developing dyskinesias ( ). With time, DW-MRI plus f-MRI is used to study the anatomical-structural functional connectivity in advanced idiopathic Parkinson`s. Contrasting conventional lesion based stimulus hypothesis, the novel net stimulus hypothesis advocated that induced stimulus of exact circuits of b r a i n can modulate pathophysiological net-work, reinstate near the tissue region, thus producing stabilization-of human-brain-connectome within Parkinson`s. The DBS connectomes makes use of circuit based stimulus procedure instead of lesion-based stimulus, has transformed neuromodulation. Connectomes via DBS can be tailor made for every Parkinson plus enhance the operation. It`s just a sketch for human-brain-connectivity (HMC) transversely compound longitudinal-scales. Yet, it won`t yield cell information plus cotacts with cells at the level of micro scale.

Deep Brain Stimulation for Orthostatic Tremor: An Observational Study.

Primary orthostatic tremor (OT) can affect patients' life. Treatment of OT with deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (Vim) is described in a limited number of patients. The Vim and posterior subthalamic area (PSA) can be targeted in a single trajectory, allowing both stimulation of the Vim and/or dentatorubrothalamic tract (DRT). In essential tremor this is currently often used with positive effects. To evaluate the efficacy of Vim/DRT-DBS in OT-patients, based on standing time and Quality of Life (QoL), also on the long-term. Furthermore, to relate stimulation of the Vim and DRT, medial lemniscus (ML) and pyramidal tract (PT) to beneficial clinical and side-effects. Nine severely affected OT-patients received bilateral Vim/DRT-DBS. Primary outcome measure was standing time; secondary measures included self-reported measures, neurophysiological measures, structural analyses, surgical complications, stimulation-induced side-effects, and QoL up to 56 months. Stimulation of volume of tissue activated (VTA) were related to outcome measures. Average maximum standing time increased from 41.0 s ± 51.0 s to 109.3 s ± 65.0 s after 18 months, with improvements measured in seven of nine patients. VTA (n = 7) overlapped with the DRT in six patients and with the ML and/or PT in six patients. All patients experienced side-effects and QoL worsened during the first year after surgery, which improved again during long-term follow-up, although remaining below age-related normal values. Most patients reported a positive effect of DBS. Vim/DRT-DBS improved standing time in patients with severe OT. Observed side-effects are possibly related to stimulation of the ML and PT.

Topographical anatomy of the subthalamic region with special interest in the human medial forebrain bundle.

The medial forebrain bundle (MFB) is a novel promising deep brain stimulation (DBS) target in severe affective disorders that courses through the subthalamic region according to tractography studies. Its potential therapeutic role arose in connection with the development of hypomania during stimulation of the subthalamic nucleus (STN) in Parkinson's disease, offering an alternative explanation for the occurrence of this side effect. However, until now its course exclusively described by tractography had not yet been confirmed by any anatomical method. The aim of this study was to fill this gap as well as to provide a detailed description of the fiber tracts surrounding the STN to facilitate a better understanding of the background of side effects occurring during STN DBS. Ten human cadaveric brains (20 hemispheres) and 100 healthy subjects (200 hemispheres) from the S500 Release of the Human Connectome Project were involved in this study. Nineteen hemispheres were dissected according to Klingler's method. One additional hemisphere was prepared for histological examinations to validate the macroscopical results and stained with neurofibril silver impregnation according to Krutsay. The authors also aimed to reconstruct the MFB using tractography and correlated the results with their dissections and histological findings. The white matter connections coursing through the subthalamic region were successfully dissected. The ansa lenticularis, lenticular fasciculus, thalamic fasciculus, ipsi- and contralateral cerebellar fibers, and medial lemniscus were revealed as closely related fiber tracts to the STN. However, the existence of a distinct fiber bundle corresponding to the MFB described by tractography could not be identified. Using tractography, the authors showed that the depiction of the streamlines representing the MFB was also strongly dependent on the threshold parameters. According to this study's findings, the streamlines of the MFB described by tractography arise from the limitations of the diffusion-weighted MRI fiber tracking method and actually correspond to subthalamic fiber bundles, especially the ansa lenticularis and lenticular fasciculus, which erroneously continue in the anterior limb of the internal capsule, toward the prefrontal cortex.

Poststroke Executive Function in Relation to White Matter Damage on Clinically Acquired CT Brain Imaging.

Executive function (EF) impairments are prevalent post stroke and are associated with white matter (WM) damage on MRI. However, less is known about the relationship between poststroke EF and WM damage on CT imaging. To investigate the relationship between poststroke EF and WM damage associated with stroke lesions and WM hypointensities (WMHs) on clinically acquired CT imaging. This study analyzed data from the Oxford Cognitive Screening Program, which recruited individuals aged ≥18 years with a confirmed stroke from an acute stroke unit. The individuals completed a follow-up assessment 6 months post stroke. We included individuals with a CT scan showing a visible stroke who completed follow-up EF assessment using the Oxford Cognitive Screen-Plus rule-finding task. We manually delineated stroke lesions and quantified then dichotomized WM damage caused by the stroke using the HCP-842 atlas. We visually rated then dichotomized WMHs using the Age-Related White Matter Changes Scale. Among 87 stroke survivors (M age = 73.60 ± 11.75; 41 female; 61 ischemic stroke), multivariable linear regression showed that stroke damage to the medial lemniscus ( B = -8.86, P < 0.001) and the presence of WMHs ( B = -5.42, P = 0.005) were associated with poorer EF 6 months post stroke after adjusting for covariates including age and education. Poorer EF was associated with WM damage caused by stroke lesions and WMHs on CT. These results confirm the importance of WM integrity for EF post stroke and demonstrate the prognostic utility of CT-derived imaging markers for poststroke cognitive outcomes.

White matter microstructure of children with sensory over-responsivity is associated with affective behavior.

Sensory processing dysfunction (SPD) is linked to altered white matter (WM) microstructure in school-age children. Sensory over-responsivity (SOR), a form of SPD, affects at least 2.5% of all children and has substantial deleterious impact on learning and mental health. However, SOR has not been well studied using microstructural imaging such as diffusion MRI (dMRI). Since SOR involves hypersensitivity to external stimuli, we test the hypothesis that children with SOR require compensatory neuroplasticity in the form of superior WM microstructural integrity to protect against internalizing behavior, leaving those with impaired WM microstructure vulnerable to somatization and depression. Children ages 8-12years old with neurodevelopmental concerns were assessed for SOR using a comprehensive structured clinical evaluation, the Sensory Processing 3 Dimensions Assessment, and underwent 3 Tesla MRI with multishell multiband dMRI. Tract-based spatial statistics was used to measure diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) metrics from global WM and nineteen selected WM tracts. Correlations of DTI and NODDI measures with measures of somatization and emotional disturbance from the Behavioral Assessment System for Children, 3rd edition (BASC-3), were computed in the SOR group and in matched children with neurodevelopmental concerns but not SOR. Global WM fractional anisotropy (FA) is negatively correlated with somatization and with emotional disturbance in the SOR group but not the non-SOR group. Also observed in children with SOR are positive correlations of radial diffusivity (RD) and free water fraction (FISO) with somatization and, in most cases, emotional disturbance. These effects are significant in boys with SOR, whereas the study is underpowered for girls. The most affected white matter are medial lemniscus and internal capsule sensory tracts, although effects of SOR are observed in many cerebral, cerebellar, and brainstem tracts. White matter microstructure is related to affective behavior in children with SOR.

Medial Pontine Area: A Safe Entry to the Brainstem as a Cut Above the Rest.

To examine the fiber-based anatomy of the medial pontine area (MPA), one of the most commonly used brainstem (BS) safe entry zones in neurosurgery. According to the protocol of Klingler and Ludwig, six BSs were kept in 10% formalin solution for at least 2 months. After removing the arachnoid mater, pia mater, and vascular structures, the samples were frozen at -16°C for at least 2 weeks. White matter (WM) pathways of the BS were gradually examined using fiber dissections under a surgical microscope. Safe entry zones of the BS were defined and investigated, focusing on the ventral pontine region and pontomesencephalic junction. Because of the lack of fibers on the anterior surface of the pons, the MPA formed a safe surgical area. The MPA, strategically positioned between the descending corticospinal tracts and extending securely to the anterior limit of the medial lemniscus, serves as a protective pathway, creating a secure environment for accessing safe entry zones within the BS during surgery. The position of the MPA has the potential to provide a combined surgical path with superiorly located BS entry zones, resulting in a larger surgical area. Entry to the BS via the MPA increases the accessible surface area in the ventral pons and can be combined with the other perioculomotor safe regions outlined. Our findings might lead to safer endoscopic endonasal transclival interventions for intrinsic pontine lesions.

Associations between white matter integrity and postural control in adults with traumatic brain injury.

Abnormalities of postural sway have been extensively reported in traumatic brain injury (TBI). However, the underlying neural correlates of balance disturbances in TBI remain to be elucidated. Studies in children with TBI have reported associations between the Sensory Organization Test (SOT) and measures of white matter (WM) integrity with diffusion tensor imaging (DTI) in brain areas responsible for multisensory integration. This study seeks to replicate those associations in adults as well as explore relationships between DTI and the Limits of Stability (LOS) Test. Fifty-six participants (43±17 years old) with a history of TBI were tested 30 days to 5 years post-TBI. This study confirmed results in children for associations between the SOT and the medial lemniscus as well as middle cerebellar peduncle, and revealed additional associations with the posterior thalamic radiation. Additionally, this study found significant correlations between abnormal LOS scores and impaired WM integrity in the cingulum, corpus callosum, corticopontine and corticospinal tracts, fronto-occipital fasciculi, longitudinal fasciculi, medial lemniscus, optic tracts and thalamic radiations. Our findings indicate the involvement of a broad range of WM tracts in the control of posture, and demonstrate the impact of TBI on balance via disruptions to WM integrity.

Brainstem anatomy with 7-T MRI: in vivo assessment and ex vivo comparison

Background The brainstem contains grey matter nuclei and white matter tracts to be identified in clinical practice. The small size and the low contrast among them make their in vivo visualisation challenging using conventional magnetic resonance imaging (MRI) sequences at high magnetic field strengths. Combining higher spatial resolution, signal- and contrast-to-noise ratio and sensitivity to magnetic susceptibility (χ), susceptibility-weighted 7-T imaging could improve the assessment of brainstem anatomy.MethodsWe acquired high-resolution 7-T MRI of the brainstem in a 46-year-old female healthy volunteer (using a three-dimensional multi-echo gradient-recalled-echo sequence; spatial resolution 0.3 × 0.3 × 1.2 mm3) and in a brainstem sample from a 48-year-old female body donor that was sectioned and stained. Images were visually assessed; nuclei and tracts were labelled and named according to the official nomenclature.ResultsThis in vivo imaging revealed structures usually evaluated through light microscopy, such as the accessory olivary nuclei, oculomotor nucleus and the medial longitudinal fasciculus. Some fibre tracts, such as the medial lemniscus, were visible for most of their course. Overall, in in vivo acquisitions, χ and frequency maps performed better than T2*-weighted imaging and allowed for the evaluation of a greater number of anatomical structures. All the structures identified in vivo were confirmed by the ex vivo imaging and histology.ConclusionsThe use of multi-echo GRE sequences at 7 T allowed the visualisation of brainstem structures that are not visible in detail at conventional magnetic field and opens new perspectives in the diagnostic and therapeutical approach to brain disorders.Relevance statementIn vivo MR imaging at UHF provides detailed anatomy of CNS substructures comparable to that obtained with histology. Anatomical details are fundamentals for diagnostic purposes but also to plan a direct targeting for a minimally invasive brain stimulation or ablation.Key points• The in vivo brainstem anatomy was explored with ultrahigh field MRI (7 T).• In vivo T2*-weighted magnitude, χ, and frequency images revealed many brainstem structures.• Ex vivo imaging and histology confirmed all the structures identified in vivo.• χ and frequency imaging revealed more brainstem structures than magnitude imaging.Graphical

Evaluation of cellular activity in response to sleep deprivation by a comprehensive analysis of the whole mouse brain.

Sleep deprivation (SD) causes several adverse functional outcomes, and understanding the associated processes can improve quality of life. Although the effects of SD on neuronal activity in several brain regions have been identified, a comprehensive evaluation of the whole brain is still lacking. Hence, we performed SD using two different methods, gentle handling and a dedicated chamber, in targeted recombination in active populations 2 (TRAP2) mice crossed with Rosa-ZsGreen reporter mice and visualized cellular activity in the whole brain. Using the semi-automated post-imaging analysis tool Slice Histology Alignment, Registration, and Cell Quantification (SHARCQ), the number of activated cells was quantified. From the analysis of 14 brain regions, cellular activity was significantly increased in the olfactory areas and decreased in the medulla by the two SD methods. From the analysis of the further subdivided 348 regions, cellular activity was significantly increased in the vascular organ of the lamina terminalis, lateral hypothalamic area, parabigeminal nucleus, ventral tegmental area, and magnocellular reticular nucleus, and decreased in the anterior part of the basolateral amygdalar nucleus, nucleus accumbens, septohippocampal nucleus, reticular nucleus of the thalamus, preoptic part of the periventricular hypothalamic nucleus, ventromedial preoptic nucleus, rostral linear nucleus raphe, facial motor nucleus, vestibular nuclei, and some fiber tracts (oculomotor nerve, genu of corpus callosum, and rubrospinal tract) by the two SD methods. Two subdivided regions of the striatum (caudoputamen and other striatum), epithalamus, vascular organ of the lamina terminalis, anteroventral preoptic nucleus, superior colliculus optic layer, medial terminal nucleus of the accessory optic tract, pontine gray, and fiber tracts (medial lemniscus, columns of the fornix, brachium of the inferior colliculus, and mammillary peduncle) were differentially affected by the two SD methods. Most brain regions detected from these analyses have been reported to be involved in regulating sleep/wake regulatory circuits. Moreover, the results from the connectivity analysis indicated that the connectivity of cellular activity among brain regions was altered by SD. Together, such a comprehensive analysis of the whole brain is useful for understanding the mechanisms by which SD and/or sleep disruption affects brain function.

Role of white matter in cognitive impairment among relapsing remitting multiple sclerosis patients

BackgroundMultiple Sclerosis (MS) associated cognitive impairment is believed to be mostly connected with damage to gray matter. The contribution of white matter is still poorly understood. We aim to examine the relationship between cognition and white matter tracts among relapsing remitting MS (RRMS) patients. MethodsThirty RRMS patients were selected undergo the (3-seconds-interstimulus-interval paced auditory serial addition test) PASAT-3, the (symbol digit modalities test (SDMT) and full-brain MRI scans on a SIEMENS 3 Tesla Verio scanner. Diffusion Tensor Imaging (DTI) parameters, such as fractional anisotropy (FA) and mean diffusivity (MD) were examined in 37 white matter (WM) tracts. WM tracts were selected from the association pathways, projection pathways, commissural pathways by applying Human Connectome project (HCP)842 tractography atlas after DTI data reconstruction and registration to HCP1065 diffusion template in DSI Studio (version March 2021) In SPSS v26, Spearman's rank correlation analysis was used to examine the connection between DTI WM tracts and cognitive scores. The power of the study was increased by using false discovery rate (FDR) software. ResultsThe mean scores on the PASAT-3 and SDMT were 31.5 ± 12.8 and 46.9 ± 16.7 respectively. Better cognitive performance was correlated to higher FA values, while lower cognitive function was correlated to higher MD values. There was a positive correlation between FA values in the right medial lemniscus and superior cerebellar peduncle and SDMT scores (p 0.05). Additionally, there was a trend for significance between the FA values in the left corticothalamic tract and SDMT scores. MD values in the superior cerebellar peduncle, left arcuate Fasciculus and left extreme capsule were negatively correlated with SDMT scores (p<0.05). PASAT-3 scores were negatively correlated with MD values in the right cerebellum, however, there was no significant correlation between PASAT-3 and FA values. ConclusionsWhite matter tracts, particularly the superior cerebellar peduncle, contribute to the cognitive impairment in RRMS. Larger sample sizes for longitudinal research are necessary.

Identifying the white matter pathways involved in multiple sclerosis-related tremor using diffusion tensor imaging.

Tremor affects up to 45% of patients with Multiple Sclerosis (PwMS). Current understanding is based on insights from other neurological disorders, thus, not fully addressing the distinctive aspects of MS pathology. To characterize the brain white matter (WM) correlates of MS-related tremor using diffusion tensor imaging (DTI). In a prospective case-control study, PwMS with tremor were assessed for tremor severity and underwent MRI scans including DTI. PwMS without tremor served as matched controls. After tract selection and segmentation, the resulting diffusivity measures were used to calculate group differences and correlations with tremor severity. This study included 72 PwMS. The tremor group (n = 36) exhibited significant changes in several pathways, notably in the right inferior longitudinal fasciculus (Cohen's d = 1.53, q < 0.001) and left corticospinal tract (d = 1.32, q < 0.001), compared to controls (n = 36). Furthermore, specific tracts showed a significant correlation with tremor severity, notably in the left medial lemniscus (Spearman's coefficient [rsp] = -0.56, p < 0.001), and forceps minor of corpus callosum (rsp = -0.45, p < 0.01). MS-related tremor is associated with widespread diffusivity changes in WM pathways and its severity correlates with commissural and sensory projection pathways, which suggests a role for proprioception or involvement of the dentato-rubro-olivary circuit.

Multishell diffusion MRI reveals whole-brain white matter changes in HIV.

Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) have been previously used to explore white matter related to human immunodeficiency virus (HIV) infection. While DTI and DKI suffer from low specificity, the Combined Hindered and Restricted Model of Diffusion (CHARMED) provides additional microstructural specificity. We used these three models to evaluate microstructural differences between 35 HIV-positive patients without neurological impairment and 20 healthy controls who underwent diffusion-weighted imaging using three b-values. While significant group effects were found in all diffusion metrics, CHARMED and DKI analyses uncovered wider involvement (80% vs. 20%) of all white matter tracts in HIV infection compared with DTI. In restricted fraction (FR) analysis, we found significant differences in the left corticospinal tract, middle cerebellar peduncle, right inferior cerebellar peduncle, right corticospinal tract, splenium of the corpus callosum, left superior cerebellar peduncle, left superior cerebellar peduncle, pontine crossing tract, left posterior limb of the internal capsule, and left/right medial lemniscus. These are involved in language, motor, equilibrium, behavior, and proprioception, supporting the functional integration that is frequently impaired in HIV-positivity. Additionally, we employed a machine learning algorithm (XGBoost) to discriminate HIV-positive patients from healthy controls using DTI and CHARMED metrics on an ROIwise basis, and unique contributions to this discrimination were examined using Shapley Explanation values. The CHARMED and DKI estimates produced the best performance. Our results suggest that biophysical multishell imaging, combining additional sensitivity and built-in specificity, provides further information about the brain microstructural changes in multimodal areas involved in attentive, emotional and memory networks often impaired in HIV patients.

Cognitive function in primary and secondary progressive multiple sclerosis: a multiparametric MRI study.

The differences in cognitive function between primary progressive (PP) and secondary progressive (SP) multiple sclerosis (MS) remain unclear. We compared cognitive performance between PPMS and SPMS, and explored the structural and functional MRI correlates of their cognitive functions. Seventy-five healthy controls and 183 MS patients (60 PPMS and 123 SPMS) underwent 3.0T MRI. MS patients were administered the Brief Repeatable Battery of Neuropsychological Tests; cognitive domain z-scores were calculated and then averaged to obtain a measure of global cognition. Using hierarchical linear regression analysis, the contribution of lesion volumes, normalized brain volumes, white matter fractional anisotropy (FA) and mean diffusivity abnormalities, and resting state (RS) functional connectivity (FC) alterations to global cognition in PPMS and SPMS was investigated. PPMS and SPMS had similar z-scores in all investigated cognitive domains. Poor global cognitive function resulted associated with decreased FA of the medial lemniscus (ΔR2 =0.11; p=0.011) and lower normalized gray matter volume (ΔR2 =0.29; p<0.001) in PPMS, and with decreased FA of the fornix (ΔR2 =0.35; p<0.001) and lower normalized white matter volume (ΔR2 =0.05; p=0.034) in SPMS. PPMS and SPMS had similar neuropsychological performance. Cognitive dysfunction in PPMS and SPMS was related to distinct patterns of structural MRI abnormalities and involvement of different white matter tracts, while RS FC alterations did not contribute to explain their global cognitive functioning.

Improving tremor response to focused ultrasound thalamotomy.

MRI-guided high-intensity focused ultrasound thalamotomy is an incisionless therapy for essential tremor. To reduce adverse effects, the field has migrated to treating at 2 mm above the anterior commissure-posterior commissure plane. We perform MRI-guided high-intensity focused ultrasound with an advanced imaging targeting technique, four-tract tractography. Four-tract tractography uses diffusion tensor imaging to identify the critical white matter targets for tremor control, the decussating and non-decussating dentatorubrothalamic tracts, while the corticospinal tract and medial lemniscus are identified to be avoided. In some patients, four-tract tractography identified a risk of damaging the medial lemniscus or corticospinal tract if treated at 2 mm superior to the anterior commissure-posterior commissure plane. In these patients, we chose to target 1.2-1.5 mm superior to the anterior commissure-posterior commissure plane. In these patients, post-operative imaging revealed that the focused ultrasound lesion extended into the posterior subthalamic area. This study sought to determine if patients with focused ultrasound lesions that extend into the posterior subthalamic area have a differnce in tremor improvement than those without. Twenty essential tremor patients underwent MRI-guided high-intensity focused ultrasound and were retrospectively classified into two groups. Group 1 included patients with an extension of the thalamic-focused ultrasound lesion into the posterior subthalamic area. Group 2 included patients without extension of the thalamic-focused ultrasound lesion into the posterior subthalamic area. For each patient, the percent change in postural tremor, kinetic tremor and Archimedes spiral scores were calculated between baseline and a 3-month follow-up. Two-tailed Wilcoxon rank-sum tests were used to compare the improvement in tremor scores, the total number of sonications, thermal dose to achieve initial tremor response, and skull density ratio between groups. Group 1 had significantly greater postural, kinetic, and Archimedes spiral score percent improvement than Group 2 (P values: 5.41 × 10-5, 4.87 × 10-4, and 5.41 × 10-5, respectively). Group 1 also required significantly fewer total sonications to control the tremor and a significantly lower thermal dose to achieve tremor response (P values: 6.60 × 10-4 and 1.08 × 10-5, respectively). No significant group differences in skull density ratio were observed (P = 1.0). We do not advocate directly targeting the posterior subthalamic area with MRI-guided high-intensity focused ultrasound because the shape of the focused ultrasound lesion can result in a high risk of adverse effects. However, when focused ultrasound lesions naturally extend from the thalamus into the posterior subthalamic area, they provide greater tremor control than those that only involve the thalamus.