A Tracking prior to Localization workflow for Ultrasound Localization Microscopy.

Ultrasound Localization Microscopy (ULM) has proven effective in resolving microvascular structures and local mean velocities at sub-diffraction-limited scales, offering high-resolution imaging capabilities. Dynamic ULM (DULM) enables the creation of angiography or velocity movies throughout cardiac cycles. Currently, these techniques rely on a Localization-and-Tracking (LAT) workflow consisting in detecting microbubbles (MB) in the frames before pairing them to generate tracks. While conventional LAT methods perform well at low concentrations, they suffer from longer acquisition times and degraded localization and tracking accuracy at higher concentrations, leading to biased angiogram reconstruction and velocity estimation. In this study, we propose a novel approach to address these challenges by reversing the current workflow. The proposed method, Tracking-and-Localization (TAL), relies on first tracking the MB and then performing localization. Through comprehensive benchmarking using both in silico and in vivo experiments and employing various metrics to quantify ULM angiography and velocity maps, we demonstrate that the TAL method consistently outperforms the reference LAT workflow. Moreover, when applied to DULM, TAL successfully extracts velocity variations along the cardiac cycle with improved repeatability. The findings of this work highlight the effectiveness of the TAL approach in overcoming the limitations of conventional LAT methods, providing enhanced ULM angiography and velocity imaging.

Equivalent-time-active-cavitation-imaging enables vascular-resolution blood-brain-barrier-opening-therapy planning.

Objective. Linking cavitation and anatomy was found to be important for predictable outcomes in focused-ultrasound blood-brain-barrier-opening and requires high resolution cavitation mapping. However, cavitation mapping techniques for planning and monitoring of therapeutic procedures either (1) do not leverage the full resolution capabilities of ultrasound imaging or (2) place constraints on the length of the therapeutic pulse. This study aimed to develop a high-resolution technique that could resolve vascular anatomy in the cavitation map.Approach. Herein, we develop BandPass-sampled-equivalent-time-active-cavitation-imaging (BP-ETACI), derived from bandpass sampling and dual-frequency contrast imaging at 12.5 MHz to produce cavitation maps prior and during blood-brain barrier opening with long therapeutic bursts using a 1.5 MHz focused transducer in the brain of C57BL/6 mice.Main results. The BP-ETACI cavitation maps were found to correlate with the vascular anatomy in ultrasound localization microscopy vascular maps and in histological sections. Cavitation maps produced from non-blood-brain-barrier disrupting doses showed the same cavitation-bearing vasculature as maps produced over entire blood-brain-barrier opening procedures, allowing use for (1) monitoring focused-ultrasound blood-brain-barrier-opening (FUS-BBBO), but also for (2) therapy planning and target verification.Significance. BP-ETACI is versatile, created high resolution cavitation maps in the mouse brain and is easily translatable to existing FUS-BBBO experiments. As such, it provides a means to further study cavitation phenomena in FUS-BBBO.

Gel nail polish as an alternative to traditional coverslip sealants: A quick solution to a sticky situation.

A widespread protocol to seal coverslips on a microscope slide for histological analysis utilizes air-drying nail polish. Nail polish is applied to glue the coverslip in place and prevent the leakage of mounting media. Air drying takes time, typically overnight, and generates an unpleasant smell. Equally familiar is the waiting game, lightly touching the polish to check its dryness, while being careful not to disrupt the coverslip, often leaving sticky spots on one's fingertips. An advantageous solution to these drawbacks is to use gel nail polish, which rapidly hardens and dries by being cured under a LED/UV lamp. We show that UV-cured gel nail polish provides a rapid, stable, scentless, nontoxic, and cost-effective solution for coverslip sealing. Cured in 10 s, with no impact on fluorescent labels, gel polish hardens completely and the slide is ready to be imaged. Furthermore, we show that gel nail polish can be used to generate 3D ridges and structures to support coverslipping thicker samples. Gel nail polish is purposefully unscented, and the brands used in our study employ environmentally conscious, vegan, and cruelty-free ingredients. UV-cured gel nail polish is a cost-effective alternative that presents an easy, accessible, and inexpensive solution to traditional coverslip sealing methods.•Inexpensive method to rapidly seal coverslips onto a microscope slide to immediately image samples for Histological analyses.•Utilizes LED/UV light to cure gel nail polish in 10 s without bleaching fluorophores.•Can be used to generate 3D ridges and structures to support coverslipping thicker samples.

Reproducibility of cerebellar involvement as quantified by consensus structural MRI biomarkers in advanced essential tremor.

Essential tremor (ET) is the most prevalent movement disorder with poorly understood etiology. Some neuroimaging studies report cerebellar involvement whereas others do not. This discrepancy may stem from underpowered studies, differences in statistical modeling or variation in magnetic resonance imaging (MRI) acquisition and processing. To resolve this, we investigated the cerebellar structural differences using a local advanced ET dataset augmented by matched controls from PPMI and ADNI. We tested the hypothesis of cerebellar involvement using three neuroimaging biomarkers: VBM, gray/white matter volumetry and lobular volumetry. Furthermore, we assessed the impacts of statistical models and segmentation pipelines on results. Results indicate that the detected cerebellar structural changes vary with methodology. Significant reduction of right cerebellar gray matter and increase of the left cerebellar white matter were the only two biomarkers consistently identified by multiple methods. Results also show substantial volumetric overestimation from SUIT-based segmentation-partially explaining previous literature discrepancies. This study suggests that current estimation of cerebellar involvement in ET may be overemphasized in MRI studies and highlights the importance of methods sensitivity analysis on results interpretation. ET datasets with large sample size and replication studies are required to improve our understanding of regional specificity of cerebellum involvement in ET. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 21 March 2022. The protocol, as accepted by the journal, can be found at: https://doi.org/10.6084/m9.figshare.19697776 .

A standardized accelerometry method for characterizing tremor: Application and validation in an ageing population with postural and action tremor.

Background: Ordinal scales based on qualitative observation are the mainstay in the clinical assessment of tremor, but are limited by inter-rater reliability, measurement precision, range, and ceiling effects. Quantitative tremor evaluation is well-developed in research, but clinical application has lagged, in part due to cumbersome mathematical application and lack of established standards. Objectives: To develop a novel method for evaluating tremor that integrates a standardized clinical exam, wrist-watch accelerometers, and a software framework for data analysis that does not require advanced mathematical or computing skills. The utility of the method was tested in a sequential cohort of patients with predominant postural and action tremor presenting to a specialized surgical clinic with the presumptive diagnosis of Essential Tremor (ET). Methods: Wristwatch accelerometry was integrated with a standardized clinical exam. A MATLAB application was developed for automated data analysis and graphical representation of tremor. Measures from the power spectrum of acceleration of tremor in different upper limb postures were derived in 25 consecutive patients. The linear results from accelerometry were correlated with the commonly used non-linear Clinical Rating Scale for Tremor (CRST). Results: The acceleration power spectrum was reliably produced in all consecutive patients. Tremor frequency was stable in different postures and across patients. Both total and peak power of acceleration during postural conditions correlated well with the CRST. The standardized clinical examination with integrated accelerometry measures was therefore effective at characterizing tremor in a population with predominant postural and action tremor. The protocol is also illustrated on repeated measures in an ET patient who underwent Magnetic Resonance-Guided Focused Ultrasound thalamotomy. Conclusion: Quantitative assessment of tremor as a continuous variable using wristwatch accelerometry is readily applicable as a clinical tool when integrated with a standardized clinical exam and a user-friendly software framework for analysis. The method is validated for patients with predominant postural and action tremor, and can be adopted for characterizing tremor of different etiologies with dissemination in a wide variety of clinical and research contexts in ageing populations.

The netrin-1 receptor DCC promotes the survival of a subpopulation of midbrain dopaminergic neurons: Relevance for ageing and Parkinson's disease.

Mechanisms that determine the survival of midbrain dopaminergic (mDA) neurons in the adult central nervous system (CNS) are not fully understood. Netrins are a family of secreted proteins that are essential for normal neural development. In the mature CNS, mDA neurons express particularly high levels of netrin-1 and its receptor Deleted in Colorectal Cancer (DCC). Recent findings indicate that overexpressing netrin-1 protects mDA neurons in animal models of Parkinson's disease (PD), with a proposed pro-apoptotic dependence function for DCC that triggers cell death in the absence of a ligand. Here, we sought to determine if DCC expression influences mDA neuron survival in young adult and ageing mice. To circumvent the perinatal lethality of DCC null mice, we selectively deleted DCC from mDA neurons utilizing DATcre /loxP gene-targeting and examined neuronal survival in adult and aged animals. Reduced numbers of mDA neurons were detected in the substantia nigra pars compacta (SNc) of young adult DATcre /DCCfl/fl mice, with further reduction in aged DATcre /DCCfl/fl animals. In contrast to young adults, aged mice also exhibited a gene dosage effect, with fewer SNc mDA neurons in DCC heterozygotes (DATcre /DCCfl/wt ). Notably, loss of mDA neurons in the SN was not uniform. Neuronal loss in the SN was limited to ventral tier mDA neurons, while mDA neurons in the dorsal tier of the SN, which resist degeneration in PD, were spared from the effect of DCC deletion in both young and aged mice. In the ventral tegmental area (VTA), young adult mice with conditional deletion of DCC had normal mDA neuronal numbers, while significant loss occurred in aged DATcre /DCCfl/fl and DATcre /DCCfl/wt mice compared to age-matched wild-type mice. Our results indicate that expression of DCC is required for the survival of subpopulations of mDA neurons and may be relevant to the degenerative processes in PD.

Pitch and Rhythm Perception and Verbal Short-Term Memory in Acute Traumatic Brain Injury.

Music perception deficits are common following acquired brain injury due to stroke, epilepsy surgeries, and aneurysmal clipping. Few studies have examined these deficits following traumatic brain injury (TBI), resulting in an under-diagnosis in this population. We aimed to (1) compare TBI patients to controls on pitch and rhythm perception during the acute phase; (2) determine whether pitch and rhythm perception disorders co-occur; (3) examine lateralization of injury in the context of pitch and rhythm perception; and (4) determine the relationship between verbal short-term memory (STM) and pitch and rhythm perception. Music perception was examined using the Scale and Rhythm tests of the Montreal Battery of Evaluation of Amusia, in association with CT scans to identify lesion laterality. Verbal short-term memory was examined using Digit Span Forward. TBI patients had greater impairment than controls, with 43% demonstrating deficits in pitch perception, and 40% in rhythm perception. Deficits were greater with right hemisphere damage than left. Pitch and rhythm deficits co-occurred 31% of the time, suggesting partly dissociable networks. There was a dissociation between performance on verbal STM and pitch and rhythm perception 39 to 42% of the time (respectively), with most individuals (92%) demonstrating intact verbal STM, with impaired pitch or rhythm perception. The clinical implications of music perception deficits following TBI are discussed.

Microstructural Abnormalities of the Dentatorubrothalamic Tract in Cervical Dystonia.

BACKGROUND: The dentatorubrothalamic tract (DRTT) remains understudied in idiopathic cervical dystonia (CD), despite evidence that the pathway is relevant in the pathophysiology of the disorder. OBJECTIVE: The aim of this study was to examine the DRTT in patients with CD using diffusion tensor imaging (DTI)-based tractography. METHODS: Magnetic resonance imaging scans from 67 participants were collected to calculate diffusion tractography metrics using a binary tractography-based DRTT template. Fractional anisotropy and diffusivity measures of left and right DRTT were computed and compared between 32 subjects with CD and 35 age-matched healthy volunteers. RESULTS: Fractional anisotropy of right DRTT and mean and axial diffusivity of left DRTT were significantly reduced in patients with CD. Similar abnormalities were observed in patients with focal CD and patients with CD without tremor. DTI metrics did not correlate with disease duration or severity. CONCLUSIONS: Significant reductions in DTI measures suggest microstructural abnormalities within the DRTT in CD, characterized by a tractography pattern consistent with decreased axonal integrity. © 2021 International Parkinson and Movement Disorder Society.

The Role of the Subthalamic Nucleus in Inhibitory Control of Oculomotor Behavior in Parkinson's Disease.

Inhibiting inappropriate actions in a context is an important part of the human cognitive repertoire, and deficiencies in this ability are common in neurological and psychiatric disorders. An anti-saccade is a simple oculomotor task that tests this ability by requiring inhibition of saccades to peripheral targets (pro-saccade) and producing voluntary eye movements toward the mirror position (anti-saccades). Previous studies provide evidence for a possible contribution from the basal ganglia in anti-saccade behavior, but the precise role of different components is still unclear. Parkinson's disease patients with implanted deep brain stimulators (DBS) in subthalamic nucleus (STN) provide a unique opportunity to investigate the role of the STN in anti-saccade behavior. Previous attempts to show the effect of STN DBS on anti-saccades have produced conflicting observations. For example, the effect of STN DBS on anti-saccade error rate is not yet clear. Part of this inconsistency may be related to differences in dopaminergic states in different studies. Here, we tested Parkinson's disease patients on anti- and pro-saccade tasks ON and OFF STN DBS, in ON and OFF dopaminergic medication states. First, STN DBS increases anti-saccade error rate while patients are OFF dopamine replacement therapy. Second, dopamine replacement therapy and STN DBS interact: L-dopa reduces the effect of STN DBS on anti-saccade error rate. Third, STN DBS induces different effects on pro- and anti-saccades in different patients. These observations provide evidence for an important role for the STN in the circuitry underlying context-dependent modulation of visuomotor action selection.

Thalamostriatal degeneration contributes to dystonia and cholinergic interneuron dysfunction in a mouse model of Huntington's disease.

Huntington's disease (HD) is an autosomal dominant trinucleotide repeat disorder characterized by choreiform movements, dystonia and striatal neuronal loss. Amongst multiple cellular processes, abnormal neurotransmitter signalling and decreased trophic support from glutamatergic cortical afferents are major mechanisms underlying striatal degeneration. Recent work suggests that the thalamostriatal (TS) system, another major source of glutamatergic input, is abnormal in HD although its phenotypical significance is unknown. We hypothesized that TS dysfunction plays an important role in generating motor symptoms and contributes to degeneration of striatal neuronal subtypes. Our results using the R6/2 mouse model of HD indicate that neurons of the parafascicular nucleus (PF), the main source of TS afferents, degenerate at an early stage. PF lesions performed prior to motor dysfunction or striatal degeneration result in an accelerated dystonic phenotype and are associated with premature loss of cholinergic interneurons. The progressive loss of striatal medium spiny neurons and parvalbumin-positive interneurons observed in R6/2 mice is unaltered by PF lesions. Early striatal cholinergic ablation using a mitochondrial immunotoxin provides evidence for increased cholinergic vulnerability to cellular energy failure in R6/2 mice, and worsens the dystonic phenotype. The TS system therefore contributes to trophic support of striatal interneuron subtypes in the presence of neurodegenerative stress, and TS deafferentation may be a novel cell non-autonomous mechanism contributing to the pathogenesis of HD. Furthermore, behavioural experiments demonstrate that the TS system and striatal cholinergic interneurons are key motor-network structures involved in the pathogenesis of dystonia. This work suggests that treatments aimed at rescuing the TS system may preserve important elements of striatal structure and function and provide symptomatic relief in HD.

BAG3P215L/KO Mice as a Model of BAG3P209L Myofibrillar Myopathy.

BCL-2-associated athanogene 3 (BAG3) is a co-chaperone to heat shock proteins important in degrading misfolded proteins through chaperone-assisted selective autophagy. The recurrent dominant BAG3-P209L mutation results in a severe childhood-onset myofibrillar myopathy (MFM) associated with progressive muscle weakness, cardiomyopathy, and respiratory failure. Because a homozygous knock-in (KI) strain for the mP215L mutation homologous to the human P209L mutation did not have a gross phenotype, compound heterozygote knockout (KO) and KI mP215L mice were generated to establish whether further reduction in BAG3 expression would lead to a phenotype. The KI/KO mice have a significant decrease in voluntary movement compared with wild-type and KI/KI mice in the open field starting at 7 months. The KI/KI and KI/KO mice both have significantly smaller muscle fiber cross-sectional area. However, only the KI/KO mice have clear skeletal muscle histologic changes in MFM. As in patient muscle, there are increased levels of BAG3-interacting proteins, such as p62, heat shock protein B8, and αB-crystallin. The KI/KO mP215L strain is the first murine model of BAG3 myopathy that resembles the human skeletal muscle pathologic features. The results support the hypothesis that the pathologic development of MFM requires a significant decrease in BAG3 protein level and not only a gain of function caused by the dominant missense mutation.

The noradrenergic system is necessary for survival of vulnerable midbrain dopaminergic neurons: implications for development and Parkinson's disease.

The cause of midbrain dopaminergic (mDA) neuron loss in sporadic Parkinson's disease (PD) is multifactorial, involving cell autonomous factors, cell-cell interactions, and the effects of environmental toxins. Early loss of neurons in the locus coeruleus (LC), the main source of ascending noradrenergic (NA) projections, is an important feature of PD and other neurodegenerative disorders. We hypothesized that NA afferents provide trophic support for vulnerable mDA neurons. We demonstrate that depriving mDA neurons of NA input increases postnatal apoptosis and decreases cell survival in young adult rodents, with relative sparing of calbindin-positive subpopulations known to be resistant to degeneration in PD. As a mechanism, we propose that the neurotrophin brain-derived neurotrophic factor (BDNF) modulates anterograde survival effects of LC inputs to mDA neurons. We demonstrate that the LC is rich in BDNF mRNA in postnatal and young adult brains. Early postnatal NA denervation reduces both BDNF protein and activation of TrkB receptors in the ventral midbrain. Furthermore, overexpression of BDNF in NA afferents in transgenic mice increases mDA neuronal survival. Finally, increasing NA activity in primary cultures of mDA neurons improves survival, an effect that is additive or synergistic in the presence of different concentrations of BDNF. Taken together, our results point to a novel mechanism whereby LC afferents couple BDNF effects and NA activity to provide anterograde trophic support for vulnerable mDA neurons. Early loss of NA activity and anterograde neurotrophin support may contribute to degeneration of vulnerable neurons in PD and other neurodegenerative disorders.

IBIS: an OR ready open-source platform for image-guided neurosurgery.

PURPOSE: Navigation systems commonly used in neurosurgery suffer from two main drawbacks: (1) their accuracy degrades over the course of the operation and (2) they require the surgeon to mentally map images from the monitor to the patient. In this paper, we introduce the Intraoperative Brain Imaging System (IBIS), an open-source image-guided neurosurgery research platform that implements a novel workflow where navigation accuracy is improved using tracked intraoperative ultrasound (iUS) and the visualization of navigation information is facilitated through the use of augmented reality (AR). METHODS: The IBIS platform allows a surgeon to capture tracked iUS images and use them to automatically update preoperative patient models and plans through fast GPU-based reconstruction and registration methods. Navigation, resection and iUS-based brain shift correction can all be performed using an AR view. IBIS has an intuitive graphical user interface for the calibration of a US probe, a surgical pointer as well as video devices used for AR (e.g., a surgical microscope). RESULTS: The components of IBIS have been validated in the laboratory and evaluated in the operating room. Image-to-patient registration accuracy is on the order of [Formula: see text] and can be improved with iUS to a median target registration error of 2.54 mm. The accuracy of the US probe calibration is between 0.49 and 0.82 mm. The average reprojection error of the AR system is [Formula: see text]. The system has been used in the operating room for various types of surgery, including brain tumor resection, vascular neurosurgery, spine surgery and DBS electrode implantation. CONCLUSIONS: The IBIS platform is a validated system that allows researchers to quickly bring the results of their work into the operating room for evaluation. It is the first open-source navigation system to provide a complete solution for AR visualization.

Subthalamic deep brain stimulation and dopaminergic medication in Parkinson's disease: Impact on inter-limb coupling.

Patients with Parkinson's disease (PD) often present with bimanual coordination deficits whose exact origins remain unclear. One aspect of bimanual coordination is inter-limb coupling. This is characterized by the harmonization of movement parameters between limbs. We assessed different aspects of bimanual coordination in patients with PD, including inter-limb coupling, and determined whether they are altered by subthalamic (STN) deep brain stimulation (DBS) or dopaminergic medication. Twenty PD patients were tested before STN DBS surgery; with and without medication. Post- surgery, patients were tested with their stimulators on and off as well as with and without medication. Patients were asked to perform a unimanual and bimanual rapid repetitive diadochokinesis task. The difference in mean amplitude and mean duration of cycles between hands was computed in order to assess inter-limb coupling. Also, mean angular velocity of both hands and structural coupling were computed for the bimanual task. There was a positive effect of medication and stimulation on mean angular velocity, which relates to clinical improvement. PD patients exhibited temporal inter-limb coupling that was not altered by either medication or STN stimulation. However, PD patients did not exhibit spatial inter-limb coupling. Again, this was not altered by medication or stimulation. Collectively, the results suggest that structures independent of the dopaminergic system and basal ganglia may mediate temporal and spatial inter-limb coupling.

Impaired TrkB Signaling Underlies Reduced BDNF-Mediated Trophic Support of Striatal Neurons in the R6/2 Mouse Model of Huntington's Disease.

The principal projection neurons of the striatum are critically dependent on an afferent supply of brain derived neurotrophic factor (BDNF) for neurotrophic support. These neurons express TrkB, the cognate receptor for BDNF, which activates signaling pathways associated with neuronal survival and phenotypic maintenance. Impairment of the BDNF-TrkB pathway is suspected to underlie the early dysfunction and prominent degeneration of striatal neurons in Huntington disease (HD). Some studies in HD models indicate that BDNF supply is reduced, while others suggest that TrkB signaling is impaired earlier in disease progression. It remains important to determine whether a primary defect in TrkB signaling underlies reduced neurotrophic support and the early vulnerability of striatal neurons in HD. Using the transgenic R6/2 mouse model of HD we found that prior to striatal degeneration there are early deficits in striatal protein levels of activated phospho-TrkB and the downstream-regulated protein DARPP-32. In contrast, total-TrkB and BDNF protein levels remained normal. Primary neurons cultured from R6/2 striatum exhibited reduced survival in response to exogenous BDNF applications. Moreover, BDNF activation of phospho-TrkB and downstream signal transduction was attenuated in R6/2 striatal cultures. These results suggest that neurotrophic support of striatal neurons is attenuated early in disease progression due to defects in TrkB signal transduction in the R6/2 model of HD.

Metacognitive knowledge of olfactory dysfunction in Parkinson's disease.

It is well known that patients with Parkinson's Disease (PD) suffer from olfactory impairments, but it is not clear whether patients are aware of their level of deficit in olfactory functioning. Since PD is a neurodegenerative disorder and its progression may be correlated with olfactory loss (Ansari & Johnson, 1975; but see also Doty, Deems, & Stellar, 1988), it is possible that these patients would be subject to metacognitive errors of over-estimation of olfactory ability (White & Kurtz, 2003). Nineteen non-demented PD patients and 19 age-matched controls were each given an objective measure of olfactory identification (the UPSIT, Doty, Shaman, Kimmelman, & Dann, 1984) and a subjective measure involving a questionnaire that asked them to self-rate both their olfactory function generally and their ability to smell each of 20 odors, 12 of which were assessed on the UPSIT. All of the PD patients showed impaired olfactory ability, as did 7 of the controls, according to the UPSIT norms. Self-rated and performance-based olfactory ability scores were significantly correlated in controls (r=.49, p=.03) but not in patients with PD (r=.20, p=.39). When the 12 odors common to both the self-rated questionnaire and UPSIT were compared, PD patients were less accurate than controls (t(36)=-4.96, p<.01) at estimating their own ability and the number of over-estimation errors was significantly higher (tone-tailed(29)=1.80, p=.04) in PD patients than in the control group, showing less metacognitive awareness of their ability than controls. These results support the idea that olfactory metacognition is often impaired in PD, as well as in controls recruited for normosmic ability (Wehling, Nordin, Espeseth, Reinvang, & Lundervold, 2011), and indicate that people with PD generally exhibit over-estimation of their olfactory ability at a rate that is higher than controls. These findings imply that PD patients, unaware of their olfactory deficit, are at greater risk of harm normally detected through olfaction, such as smoke or spoiled foods.

A brain network model explaining tremor in Parkinson's disease.

This paper presents a novel model of tremor in Parkinson's disease (PD) based on extensive literature review as well as novel results stemming from functional stereotactic neurosurgery for the alleviation of tremor in PD. Specifically, evidence that suggests the basal ganglia induces PD tremor via excessive inhibitory output to the thalamus and altered firing patterns which in turn generate rhythmic bursting activity of thalamic cells is presented. Then, evidence that the thalamus generates PD tremor by facilitating the generation and consolidation of rhythmic bursting activity of neurons within its nuclei is also offered. Finally, evidence that the cerebellum may modulate characteristics of PD tremor by treating it as if it was a voluntary motor behavior is presented. Accordingly, the current paper proposes that PD tremor is induced by abnormal basal ganglia activity; it is generated by the thalamus, and modulated or reinforced by the cerebellum.

Inter-limb coupling during diadochokinesis in Parkinson's and Huntington's disease.

Patients with neurodegenerative diseases often exhibit deficits in bimanual coordination. One characteristic of bimanual movements is inter-limb coupling. It is the property of motor performance harmonization between hands during a bimanual task. The objective of this study was to identify whether spatial and temporal inter-limb coupling occurred in Parkinson's disease (PD) and Huntington's disease (HD) patients. Twenty-three PD patients and 15 healthy controls were tested. Data from 12 choreic HD patients were also taken from a databank. Participants were asked to perform a unimanual and bimanual rapid repetitive diadochokinesis task. The difference between hands in mean amplitude and mean duration of cycles was computed in the unimanual and bimanual tasks for each group. Results show that healthy controls exhibited temporal and spatial inter-limb coupling during the bimanual diadochokinesis task. Conversely, PD and HD patients exhibited temporal inter-limb coupling; but failed to exhibit spatial inter-limb coupling during the bimanual diadochokinesis task. Furthermore, HD patients exhibited reduced levels of structural coupling compared to controls and PD patients. These results suggest that alterations in basal ganglia-thalamo-cortical networks due to PD and HD do not affect temporal inter-limb coupling. However, common pathophysiological changes related to PD and HD may cause altered spatial inter-limb coupling during a rapid repetitive bimanual diadochokinesis task.

Multi-contrast unbiased MRI atlas of a Parkinson's disease population.

PURPOSE: Parkinson's disease (PD) is the second leading neurodegenerative disease after Alzheimer's disease. In PD research and its surgical treatment, such as deep brain stimulation (DBS), anatomical structural identification and references for spatial normalization are essential, and human brain atlases/templates are proven highly instrumental. However, two shortcomings affect current templates used for PD. First, many templates are derived from a single healthy subject that is not sufficiently representative of the PD-population anatomy. This may result in suboptimal surgical plans for DBS surgery and biased analysis for morphological studies. Second, commonly used mono-contrast templates lack sufficient image contrast for some subcortical structures (i.e., subthalamic nucleus) and biochemical information (i.e., iron content), a valuable feature in current PD research. METHODS: We employed a novel T1-T2* fusion MRI that visualizes both cortical and subcortical structures to drive groupwise registration to create co-registered multi-contrast (T1w, T2*w, T1-T2* fusion, phase, and an R2* map) unbiased templates from 15 PD patients, and a high-resolution histology-derived 3D atlas is co-registered. For validation, these templates are compared against the Colin27 template for landmark registration and midbrain nuclei segmentation. RESULTS: While the T1w, T2*w, and T1-T2* fusion templates provide excellent anatomical details for both cortical and subcortical structures, the phase and R2* map contain the biochemical features. By one-way ANOVA tests, our templates significantly ([Formula: see text]) outperform the Colin27 template in the registration-based tasks. CONCLUSION: The proposed unbiased templates are more representative of the population of interest and can benefit both the surgical planning and research of PD.

Patch-based label fusion segmentation of brainstem structures with dual-contrast MRI for Parkinson's disease.

PURPOSE: Parkinson's disease (PD) is a neurodegenerative disorder that impairs the motor functions. Both surgical treatment and study of PD require delineation of basal ganglia nuclei morphology. While many automatic volumetric segmentation methods have been proposed for the lentiform nucleus, few have attempted to identify the key brainstem substructures including the subthalamic nucleus (STN), substantia nigra (SN), and red nucleus (RN) due to their small size and poor contrast in conventional T1W MRI. METHODS: A dual-contrast patch-based label fusion method was developed to segment the SN, STN, and RN using multivariate cross-correlation. Two different MRI contrasts (T2*w and phase) are produced from a multi-contrast multi-echo FLASH MRI sequence, enabling visualization of these nuclei. T1-T2* fusion MRI was used to resolve the issue of poor nuclei (i.e., the STN, SN, and RN) contrast on T1w MRI, and to mitigate susceptibility artifacts that may hinder accurate nonlinear registration on T2*w MRI. Unbiased group-wise registration was used for anatomical normalization between the atlas library and the target subject. The performance of the proposed method was compared with a state-of-the-art single-contrast label fusion technique. RESULTS: The proposed method outperformed a state-of-the-art single-contrast patch-based method in segmenting the STN, RN and SN, and the results were better than those reported in previous literature. CONCLUSION: Our dual-contrast patch-based label fusion method was superior to a single-contrast method for segmenting brainstem nuclei using a multi-contrast multi-echo FLASH MRI sequence. The method is promising for the treatment and research of Parkinson's disease. This method can be extended for multiple alternative image contrasts and other fields of applications.