Automatic Localization of Key Structures for Subthalamic Nucleus-Deep Brain Stimulation Surgery via Prior-Enhanced Multi-Object Magnetic Resonance Imaging Segmentation.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established and effective neurosurgical treatment for relieving motor symptoms in Parkinson disease. The localization of key brain structures is critical to the success of DBS surgery. However, in clinical practice, this process is heavily dependent on the radiologist's experience. METHODS: In this study, we propose an automatic localization method of key structures for STN-DBS surgery via prior-enhanced multi-object magnetic resonance imaging segmentation. We use the U-Net architecture for the multi-object segmentation, including STN, red nucleus, brain sulci, gyri, and ventricles. To address the challenge that only half of the brain sulci and gyri locate in the upper area, potentially causing interference in the lower area, we perform region of interest detection and ensemble joint processing to enhance the segmentation performance of brain sulci and gyri. RESULTS: We evaluate the segmentation accuracy by comparing our method with other state-of-the-art machine learning segmentation methods. The experimental results show that our approach outperforms state-of-the-art methods in terms of segmentation performance. Moreover, our method provides effective visualization of key brain structures from a clinical application perspective and can reduce the segmentation time compared with manual delineation. CONCLUSIONS: Our proposed method uses deep learning to achieve accurate segmentation of the key structures more quickly than and with comparable accuracy to human manual segmentation. Our method has the potential to improve the efficiency of surgical planning for STN-DBS.

Automatic localization of target point for subthalamic nucleus-deep brain stimulation via hierarchical attention-UNet based MRI segmentation.

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for patients with advanced Parkinson's disease, the outcome of this surgery is highly dependent on the accurate placement of the electrode in the optimal target of STN. PURPOSE: In this study, we aim to develop a target localization pipeline for DBS surgery, considering that the heart of this matter is to achieve the STN and red nucleus segmentation, a deep learning-based automatic segmentation approach is proposed to tackle this issue. METHODS: To address the problems of ambiguous boundaries and variable shape of the segmentation targets, the hierarchical attention mechanism with two different attention strategies is integrated into an encoder-decoder network for mining both semantics and fine-grained details for segmentation. The hierarchical attention mechanism is utilized to suppress irrelevant regions in magnetic resonance (MR) images while build long-range dependency among segmentation targets. Specifically, the attention gate (AG) is integrated into low-level features to suppress irrelevant regions in an input image while highlighting the salient features useful for segmentation. Besides, the self-attention involved in the transformer block is integrated into high-level features to model the global context. Ninety-nine brain magnetic resonance imaging (MRI) studies were collected from 99 patients with Parkinson's disease undergoing STN-DBS surgery, among which 80 samples were randomly selected as the training datasets for deep learning training, and ground truths (segmentation masks) were manually generated by radiologists. RESULTS: We applied five-fold cross-validation on these data to train our model, the mean results on 19 test samples are used to conduct the comparison experiments, the Dice similarity coefficient (DSC), Jaccard (JA), sensitivity (SEN), and HD95 of the segmentation for STN are 88.20%, 80.32%, 90.13%, and 1.14 mm, respectively, outperforming the state-of-the-art STN segmentation method with 2.82%, 4.52%, 2.56%, and 0.02 mm respectively. The source code and trained models of this work have been released in the URL below: https://github.com/liuruiqiang/HAUNet/tree/master. CONCLUSIONS: In this study, we demonstrate the effectiveness of the hierarchical attention mechanism for building global dependency on high-level semantic features and enhancing the fine-grained details on low-level features, the experimental results show that our method has considerable superiority for STN and red nucleus segmentation, which can provide accurate target localization for STN-DBS.

Serum neurofilament indicates that DBS surgery can cause neuronal damage whereas stimulation itself does not.

Deep brain stimulation (DBS) is a potent symptomatic therapy for Parkinson's disease, but it is debated whether it causes or prevents neurodegeneration. We used serum neurofilament light chain (NFL) as a reporter for neuronal damage and found no difference between 92 patients with chronic STN-DBS and 57 patients on best medical treatment. Serum NFL transiently increased after DBS surgery whereas the initiation of STN stimulation did not affect NFL levels, suggesting that DBS surgery can be associated with neuronal damage whereas stimulation itself is not.

Unraveling the Role of Astrocytes in Subthalamic Nucleus Deep Brain Stimulation in a Parkinson's Disease Rat Model.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective therapeutic strategy for motor symptoms of Parkinson's disease (PD) when L-DOPA therapy induces disabling side effects. Classical inflammatory activation of glial cells is well established in PD, contributing to the progressive neurodegenerative state; however, the role of DBS in regulating the inflammatory response remains largely unknown. To understand the involvement of astrocytes in the mechanisms of action of DBS, we evaluated the effect of STN-DBS in regulating motor symptoms, astrocyte reactivity, and cytokine expression in a 6-OHDA-induced PD rat model. To mimic in vivo DBS, we investigate the effect of high-frequency stimulation (HFS) in cultured astrocytes regulating cytokine induction and NF-κB activation. We found that STN-DBS improved motor impairment, induced astrocytic hyperplasia, and reversed increased IFN-γ and IL-10 levels in the globus pallidus (GP) of lesioned rats. Moreover, HFS activated astrocytes and prevented TNF-α-induced increase of monocyte chemoattractant protein-1 (MCP-1) and NF-κB activation in vitro. Our results indicate that DBS/HFS may act as a regulator of the inflammatory response in PD states, attenuating classical activation of astrocytes and cytokine induction, potentially through its ability to regulate NF-κB activation. These findings may help us understand the role of astrocyte signaling in HFS, highlighting its possible relationship with the effectiveness of DBS in neurodegenerative disorders.

Multistable properties of human subthalamic nucleus neurons in Parkinson's disease.

To understand the function and dysfunction of neural circuits, it is necessary to understand the properties of the neurons participating in the behavior, the connectivity between these neurons, and the neuromodulatory status of the circuits at the time they are producing the behavior. Such knowledge of human neural circuits is difficult, at best, to obtain. Here, we study firing properties of human subthalamic neurons, using microelectrode recordings and microstimulation during awake surgery for Parkinson's disease. We demonstrate that low-amplitude, brief trains of microstimulation can lead to persistent changes in neuronal firing behavior including switching between firing rates, entering silent periods, or firing several bursts then entering a silent period. We suggest that these multistable states reflect properties of finite state machines and could have implications for the function of circuits involving the subthalamic nucleus. Furthermore, understanding these states could lead to therapeutic strategies aimed at regulating the transitions between states.

Significance of N-isopropyl-[123I] p-iodoamphetamine single-photon emission computed tomography in detection of responsible hypoperfusion in hemichorea.

Hemichorea is relatively an uncommon clinical presentation while its known etiology are vascular, metabolic, neoplastic, infectious, autoimmune, and inherited disorders. In the acquired case of hemichorea, the most common cause is the cerebrovascular insult, which is often diagnosed by the magnetic resonance (MR) imaging. An 84-year-old woman reported a one-week history of involuntary movements in the left side of her face and left limbs. Blood tests were normal and brain MR imaging showed no responsible hyperintense lesion on T1-, FLAIR, and diffusion-weighted imaging. N-isopropyl-[123I] p-iodoamphetamine single-photon emission computed tomography (SPECT) detected hypoperfusion in the right thalamus. Further three-dimensional tomography clearly detected the hypoperfusion in the right subthalamic nucleus. The hypoperfused lesion was MR-negative and remained unchanged in SPECT one year after the onset. After the treatment with 0.35 mg of oral haloperidol was initiated, the hemichorea was gradually decreased and completely disappeared in 9 months. Because the three-dimensional analysis performs voxel-by-voxel analysis, it possibly detects the precise hypoperfusion in a specific region. In conclusion, evaluation of cerebral blood flow using SPECT on patients presenting with acute hemichorea can lead to the detection of responsible lesion when the routine examinations are negative.

Dopamine-dependent scaling of subthalamic gamma bursts with movement velocity in patients with Parkinson's disease.

Gamma synchronization increases during movement and scales with kinematic parameters. Here, disease-specific characteristics of this synchronization and the dopamine-dependence of its scaling in Parkinson's disease are investigated. In 16 patients undergoing deep brain stimulation surgery, movements of different velocities revealed that subthalamic gamma power peaked in the sensorimotor part of the subthalamic nucleus, correlated positively with maximal velocity and negatively with symptom severity. These effects relied on movement-related bursts of transient synchrony in the gamma band. The gamma burst rate highly correlated with averaged power, increased gradually with larger movements and correlated with symptom severity. In the dopamine-depleted state, gamma power and burst rate significantly decreased, particularly when peak velocity was slower than ON medication. Burst amplitude and duration were unaffected by the medication state. We propose that insufficient recruitment of fast gamma bursts during movement may underlie bradykinesia as one of the cardinal symptoms in Parkinson's disease.

Neuronal inhibition and synaptic plasticity of basal ganglia neurons in Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson's disease symptoms. The therapeutic benefits of deep brain stimulation are frequency-dependent, but the underlying physiological mechanisms remain unclear. To advance deep brain stimulation therapy an understanding of fundamental mechanisms is critical. The objectives of this study were to (i) compare the frequency-dependent effects on cell firing in subthalamic nucleus and substantia nigra pars reticulata; (ii) quantify frequency-dependent effects on short-term plasticity in substantia nigra pars reticulata; and (iii) investigate effects of continuous long-train high frequency stimulation (comparable to conventional deep brain stimulation) on synaptic plasticity. Two closely spaced (600 µm) microelectrodes were advanced into the subthalamic nucleus (n = 27) and substantia nigra pars reticulata (n = 14) of 22 patients undergoing deep brain stimulation surgery for Parkinson's disease. Cell firing and evoked field potentials were recorded with one microelectrode during stimulation trains from the adjacent microelectrode across a range of frequencies (1-100 Hz, 100 µA, 0.3 ms, 50-60 pulses). Subthalamic firing attenuated with ≥20 Hz (P < 0.01) stimulation (silenced at 100 Hz), while substantia nigra pars reticulata decreased with ≥3 Hz (P < 0.05) (silenced at 50 Hz). Substantia nigra pars reticulata also exhibited a more prominent increase in transient silent period following stimulation. Patients with longer silent periods after 100 Hz stimulation in the subthalamic nucleus tended to have better clinical outcome after deep brain stimulation. At ≥30 Hz the first evoked field potential of the stimulation train in substantia nigra pars reticulata was potentiated (P < 0.05); however, the average amplitude of the subsequent potentials was rapidly attenuated (P < 0.01). This is suggestive of synaptic facilitation followed by rapid depression. Paired pulse ratios calculated at the beginning of the train revealed that 20 Hz (P < 0.05) was the minimum frequency required to induce synaptic depression. Lastly, the average amplitude of evoked field potentials during 1 Hz pulses showed significant inhibitory synaptic potentiation after long-train high frequency stimulation (P < 0.001) and these increases were coupled with increased durations of neuronal inhibition (P < 0.01). The subthalamic nucleus exhibited a higher frequency threshold for stimulation-induced inhibition than the substantia nigra pars reticulata likely due to differing ratios of GABA:glutamate terminals on the soma and/or the nature of their GABAergic inputs (pallidal versus striatal). We suggest that enhancement of inhibitory synaptic plasticity, and frequency-dependent potentiation and depression are putative mechanisms of deep brain stimulation. Furthermore, we foresee that future closed-loop deep brain stimulation systems (with more frequent off stimulation periods) may benefit from inhibitory synaptic potentiation that occurs after high frequency stimulation.

Subthalamic Nucleus Deep Brain Stimulation Does Not Modify the Functional Deficits or Axonopathy Induced by Nigrostriatal α-Synuclein Overexpression.

Subthalamic nucleus deep brain stimulation (STN DBS) protects dopaminergic neurons of the substantia nigra pars compacta (SNpc) against 6-OHDA and MPTP. We evaluated STN DBS in a parkinsonian model that displays α-synuclein pathology using unilateral, intranigral injections of recombinant adeno-associated virus pseudotype 2/5 to overexpress wildtype human α-synuclein (rAAV2/5 α-syn). A low titer of rAAV2/5 α-syn results in progressive forelimb asymmetry, loss of striatal dopaminergic terminal density and modest loss of SNpc dopamine neurons after eight weeks, corresponding to robust human-Snca expression and no effect on rat-Snca, Th, Bdnf or Trk2. α-syn overexpression increased phosphorylation of ribosomal protein S6 (p-rpS6) in SNpc neurons, a readout of trkB activation. Rats received intranigral injections of rAAV2/5 α-syn and three weeks later received four weeks of STN DBS or electrode implantation that remained inactive. STN DBS did not protect against α-syn-mediated deficits in forelimb akinesia, striatal denervation or loss of SNpc neuron, nor did STN DBS elevate p-rpS6 levels further. ON stimulation, forelimb asymmetry was exacerbated, indicating α-syn overexpression-mediated neurotransmission deficits. These results demonstrate that STN DBS does not protect the nigrostriatal system against α-syn overexpression-mediated toxicity. Whether STN DBS can be protective in other models of synucleinopathy is unknown.

Posterolateral Trajectories Favor a Longer Motor Domain in Subthalamic Nucleus Deep Brain Stimulation for Parkinson Disease.

OBJECTIVE: The clinical outcome of patients with Parkinson disease (PD) who undergo subthalamic nucleus (STN) deep brain stimulation (DBS) is, in part, determined by the length of the electrode trajectory through the motor STN domain, the dorsolateral oscillatory region (DLOR). Trajectory length has been found to correlate with the stimulation-related improvement in patients' motor function (estimated by part III of the United Parkinson's Disease Rating Scale [UPDRS]). Therefore, it seems that ideally trajectories should have maximal DLOR length. METHODS: We retrospectively studied the influence of various anatomic aspects of the brains of patients with PD and the geometry of trajectories planned on the length of the DLOR and STN recorded during DBS surgery. We examined 212 trajectories and 424 microelectrode recording tracks in 115 patients operated on in our center between 2010 and 2015. RESULTS: We found a strong correlation between the length of the recorded DLOR and STN. Trajectories that were more lateral and/or posterior in orientation had a longer STN and DLOR pass, although the DLOR/STN fraction length remained constant. The STN target was more lateral when the third ventricle was wider, and the latter correlated with older age and male gender. CONCLUSIONS: Trajectory angles correlate with the recorded STN and DLOR lengths, and should be altered toward a more posterolateral angle in older patients and atrophied brains to compensate for the changes in STN location and geometry. These fine adjustments should yield a longer motor domain pass, thereby improving the patient's predicted outcome.

Reduced Vglut2/Slc17a6 Gene Expression Levels throughout the Mouse Subthalamic Nucleus Cause Cell Loss and Structural Disorganization Followed by Increased Motor Activity and Decreased Sugar Consumption.

The subthalamic nucleus (STN) plays a central role in motor, cognitive, and affective behavior. Deep brain stimulation (DBS) of the STN is the most common surgical intervention for advanced Parkinson's disease (PD), and STN has lately gained attention as target for DBS in neuropsychiatric disorders, including obsessive compulsive disorder, eating disorders, and addiction. Animal studies using STN-DBS, lesioning, or inactivation of STN neurons have been used extensively alongside clinical studies to unravel the structural organization, circuitry, and function of the STN. Recent studies in rodent STN models have exposed different roles for STN neurons in reward-related functions. We have previously shown that the majority of STN neurons express the vesicular glutamate transporter 2 gene (Vglut2/Slc17a6) and that reduction of Vglut2 mRNA levels within the STN of mice [conditional knockout (cKO)] causes reduced postsynaptic activity and behavioral hyperlocomotion. The cKO mice showed less interest in fatty rewards, which motivated analysis of reward-response. The current results demonstrate decreased sugar consumption and strong rearing behavior, whereas biochemical analyses show altered dopaminergic and peptidergic activity in the striatum. The behavioral alterations were in fact correlated with opposite effects in the dorsal versus the ventral striatum. Significant cell loss and disorganization of the STN structure was identified, which likely accounts for the observed alterations. Rare genetic variants of the human VGLUT2 gene exist, and this study shows that reduced Vglut2/Slc17a6 gene expression levels exclusively within the STN of mice is sufficient to cause strong modifications in both the STN and the mesostriatal dopamine system.

Resting-state functional magnetic resonance imaging of the subthalamic microlesion and stimulation effects in Parkinson's disease: Indications of a principal role of the brainstem.

During implantation of deep-brain stimulation (DBS) electrodes in the target structure, neurosurgeons and neurologists commonly observe a "microlesion effect" (MLE), which occurs well before initiating subthalamic DBS. This phenomenon typically leads to a transitory improvement of motor symptoms of patients suffering from Parkinson's disease (PD). Mechanisms behind MLE remain poorly understood. In this work, we exploited the notion of ranking to assess spontaneous brain activity in PD patients examined by resting-state functional magnetic resonance imaging in response to penetration of DBS electrodes in the subthalamic nucleus. In particular, we employed a hypothesis-free method, eigenvector centrality (EC), to reveal motor-communication-hubs of the highest rank and their reorganization following the surgery; providing a unique opportunity to evaluate the direct impact of disrupting the PD motor circuitry in vivo without prior assumptions. Penetration of electrodes was associated with increased EC of functional connectivity in the brainstem. Changes in connectivity were quantitatively related to motor improvement, which further emphasizes the clinical importance of the functional integrity of the brainstem. Surprisingly, MLE and DBS were associated with anatomically different EC maps despite their similar clinical benefit on motor functions. The DBS solely caused an increase in connectivity of the left premotor region suggesting separate pathophysiological mechanisms of both interventions. While the DBS acts at the cortical level suggesting compensatory activation of less affected motor regions, the MLE affects more fundamental circuitry as the dysfunctional brainstem predominates in the beginning of PD. These findings invigorate the overlooked brainstem perspective in the understanding of PD and support the current trend towards its early diagnosis.

Reduced Verbal Fluency following Subthalamic Deep Brain Stimulation: A Frontal-Related Cognitive Deficit?

OBJECTIVE: The decrease in verbal fluency in patients with Parkinson's disease (PD) undergoing subthalamic nucleus deep brain stimulation (STN-DBS) is usually assumed to reflect a frontal lobe-related cognitive dysfunction, although evidence for this is lacking. METHODS: To explore its underlying mechanisms, we combined neuropsychological, psychiatric and motor assessments with an examination of brain metabolism using F-18 fluorodeoxyglucose positron emission tomography, in 26 patients with PD, 3 months before and after surgery. We divided these patients into two groups, depending on whether or not they exhibited a postoperative deterioration in either phonemic (10 patients) or semantic (8 patients) fluency. We then compared the STN-DBS groups with and without verbal deterioration on changes in clinical measures and brain metabolism. RESULTS: We did not find any neuropsychological change supporting the presence of an executive dysfunction in patients with a deficit in either phonemic or semantic fluency. Similarly, a comparison of patients with or without impaired fluency on brain metabolism failed to highlight any frontal areas involved in cognitive functions. However, greater changes in cognitive slowdown and apathy were observed in patients with a postoperative decrease in verbal fluency. CONCLUSIONS: These results suggest that frontal lobe-related cognitive dysfunction could play only a minor role in the postoperative impairment of phonemic or semantic fluency, and that cognitive slowdown and apathy could have a more decisive influence. Furthermore, the phonemic and semantic impairments appeared to result from the disturbance of distinct mechanisms.

The Involvement of Oxytocin in the Subthalamic Nucleus on Relapse to Methamphetamine-Seeking Behaviour.

The psychostimulant methamphetamine (METH) is an addictive drug of abuse. The neuropeptide oxytocin has been shown to modulate METH-related reward and METH-seeking behaviour. Recent findings implicated the subthalamic nucleus (STh) as a key brain region in oxytocin modulation of METH-induced reward. However, it is unclear if oxytocin acts in this region to attenuate relapse to METH-seeking behaviour, and if this action is through the oxytocin receptor. We aimed to determine whether oxytocin pretreatment administered into the STh would reduce reinstatement to METH use in rats experienced at METH self-administration, and if this could be reversed by the co-administration of the oxytocin receptor antagonist desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT. Male Sprague Dawley rats underwent surgery to implant an intravenous jugular vein catheter and bilateral microinjection cannulae into the STh under isoflourane anaesthesia. Rats were then trained to self-administer intravenous METH (0.1 mg/kg/infusion) by lever press during 2-hour sessions under a fixed ratio 1 schedule for 20 days. Following extinction of lever press activity, the effect of microinjecting saline, oxytocin (0.2 pmol, 0.6 pmol, 1.8 pmol, 3.6 pmol) or co-administration of oxytocin (3.6 pmol) and desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT (3 nmol) into the STh (200 nl/side) was examined on METH-primed reinstatement (1 mg/kg; i.p.). We found that local administration of the highest oxytocin dose (3.6 pmol) into the STh decreased METH-induced reinstatement and desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT had a non-specific effect on lever press activity. These findings highlight that oxytocin modulation of the STh is an important modulator of relapse to METH abuse.

A comparison of two surgical approaches in functional neurosurgery: individualized versus conventional stereotactic frames.

OBJECT: The individualized Starfix® miniframe belongs to a new generation of stereotactic systems enabling high-precision electrode placement with considerably better time-efficiency in deep brain stimulation (DBS). We evaluated the usability and reliability of this novel technique in patients with idiopathic Parkinson's disease (IPD) and compared surgical and clinical results with those obtained in a historical group in which a conventional stereotactic frame was employed. METHODS: Sixty patients underwent surgery for implantation of DBS electrodes in the subthalamic nucleus. In 31 of them (group I) a conventional Zamorano-Dujovny frame was used and in 29 of them (group II) a Starfix® miniframe was used. Image fusion of preoperatively acquired 3D T1w and T2w 1.5 T MR-image series was used for the targeting procedure. Placement of the test electrodes and permanent electrodes corresponded to standard functional neurosurgery and included microelectrode recording and macrostimulation. Clinical (L-Dopa equivalent dose, United Parkinson's disease rating scale part III) and time for surgical electrode implantation were evaluated postoperatively in a 3-, 6- and 12-month follow-up. RESULTS: Twelve months postoperatively, L-Dopa dose was significantly reduced from 685.19 to 205.88 mg/day and from 757.92 to 314.42 mg/day in groups I and II, respectively. A comparable reduction of the LED could be observed 1 year after surgery. Motor function has improved in a significant and identical manner with 59% (group I) and 61% (group II). Besides clinical effects by stimulation therapy there was a significantly reduced surgery time required for electrode implantation using the Starfix® miniframe (group I: 234.1 min, group II: 173.6 min; p < 0.001). CONCLUSIONS: Individualized miniframes such as the Starfix® miniframe allow implantation of DBS electrodes in IPD that is equally effective as conventional systems. The time efficiency achieved in surgery using of the Starfix® system helps to minimize patients' discomfort during DBS surgery.

Deep-brain stimulation associates with improved microvascular integrity in the subthalamic nucleus in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an accepted treatment for motor symptoms in a subset of Parkinson's disease (PD) patients. The mechanisms why DBS is effective are incompletely understood, but previous studies show that DBS targeted in brain structures other than the STN may modify the microvasculature. However, this has not been studied in PD subjects who have received STN-DBS. Here we investigated the extent and nature of microvascular changes in post-mortem STN samples from STN-DBS PD patients, compared to aged controls and PD patients who had not been treated with STN-DBS. We used immunohistochemical and immunofluorescent methods to assess serial STN-containing brain sections from PD and STN-DBS PD cases, compared to similar age controls using specific antibodies to detect capillaries, an adherens junction and tight junction-associated proteins as well as activated microglia. Cellular features in stained sections were quantified by confocal fluorescence microscopy and stereological methods in conjunction with in vitro imaging tools. We found significant upregulation of microvessel endothelial cell thickness, length and density but lowered activated microglia density and striking upregulation of all analysed adherens junction and tight junction-associated proteins in STN-DBS PD patients compared to non-DBS PD patients and controls. Moreover, in STN-DBS PD samples, expression of an angiogenic factor, vascular endothelial growth factor (VEGF), was significantly upregulated compared to the other groups. Our findings suggest that overexpressed VEGF and downregulation of inflammatory processes may be critical mechanisms underlying the DBS-induced microvascular changes.

Decline in verbal fluency after subthalamic nucleus deep brain stimulation in Parkinson's disease: a microlesion effect of the electrode trajectory?

BACKGROUND: Decline in verbal fluency (VF) is frequently reported after chronic deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson disease (PD). OBJECTIVE: We investigated whether the trajectory of the implanted electrode correlate with the VF decline 6 months after surgery. METHODS: We retrospectively analysed 59 PD patients (mean age, 61.9 ± 7; mean disease duration, 13 ± 4.6) who underwent bilateral STN-DBS. The percentage of VF decline 6 months after STN-DBS in the on-drug/on-stimulation condition was determined in respect of the preoperative on-drug condition. The patients were categorised into two groups (decline and stable) for each VF. Cortical entry angles, intersection with deep grey nuclei (caudate, thalamic or pallidum), and anatomical extent of the STN affected by the electrode pathway, were compared between groups. RESULTS: A significant decline of both semantic and phonemic VF was found after surgery, respectively 14.9% ± 22.1 (P < 0.05) and 14.2% ± 30.3 (P < 0.05). Patients who declined in semantic VF (n = 44) had a left trajectory with a more anterior cortical entry point (56 ± 53 versus 60 ± 55 degree, P = 0.01) passing less frequently trough the thalamus (P = 0.03). CONCLUSIONS: Microlesion of left brain regions may contribute to subtle cognitive impairment following STN-DBS in 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.

Activity parameters of subthalamic nucleus neurons selectively predict motor symptom severity in Parkinson's disease.

Parkinson's disease (PD) is a heterogeneous disorder that leads to variable expression of several different motor symptoms. While changes in firing rate, pattern, and oscillation of basal ganglia neurons have been observed in PD patients and experimental animals, there is limited evidence linking them to specific motor symptoms. Here we examined this relationship using extracellular recordings of subthalamic nucleus neurons from 19 PD patients undergoing surgery for deep brain stimulation. For each patient, ≥ 10 single units and/or multi-units were recorded in the OFF medication state. We correlated the proportion of neurons displaying different activities with preoperative Unified Parkinson's Disease Rating Scale subscores (OFF medication). The mean spectral power at sub-beta frequencies and percentage of units oscillating at beta frequencies were positively correlated with the axial and limb rigidity scores, respectively. The percentage of units oscillating at gamma frequency was negatively correlated with the bradykinesia scores. The mean intraburst rate was positively correlated with both bradykinesia and axial scores, while the related ratio of interspike intervals below/above 10 ms was positively correlated with these symptoms and limb rigidity. None of the activity parameters correlated with tremor. The grand average of all the significantly correlated subthalamic nucleus activities accounted for >60% of the variance of the combined bradykinetic-rigid and axial scores. Our results demonstrate that the occurrence of alterations in the rate and pattern of basal ganglia neurons could partly underlie the variability in parkinsonian phenotype.