Neurovascular coupling during deep brain stimulation

BackgroundDeep brain stimulation (DBS) is an effective treatment for movement disorders, yet its mechanisms of action remain unclear. One method used to study its circuit-wide neuromodulatory effects is functional magnetic resonance imaging (fMRI) which measures hemodynamics as a proxy of neural activity. To interpret functional imaging data, we must understand the relationship between neural and vascular responses, which has never been studied with the high frequencies used for DBS.ObjectiveTo measure neurovascular coupling in the rat motor cortex during thalamic DBS.MethodSimultaneous intrinsic optical imaging and extracellular electrophysiology was performed in the motor cortex of urethane-anesthetized rats during thalamic DBS at 7 different frequencies. We related Maximum Change in Reflectance (MCR) from the imaging data to Integrated Evoked Potential (IEP) and change in broadband power of multi-unit (MU) activity, computing Spearman’s correlation to determine the strength of these relationships. To determine the source of these effects, we studied the contributions of antidromic versus orthodromic activation in motor cortex perfusion using synaptic blockers.ResultsMCR, IEP and change in MU power increased linearly to 60 Hz and saturated at higher frequencies of stimulation. Blocking orthodromic transmission only reduced the DBS-induced change in optical signal by ∼25%, suggesting that activation of corticofugal fibers have a major contribution in thalamic-induced cortical activation.ConclusionDBS-evoked vascular response is related to both evoked field potentials as well as multi-unit activity.     

Comparison of Transcallosal Inhibition Between Hemispheres and Its Relationship with Motor Behavior in Patients with Severe Upper Extremity Impairment After Subacute Stroke

ObjectiveTo compare corticospinal excitability and transcallosal inhibition between contralesional primary motor cortex (M1) and ipsilesional M1. We also investigated the correlation between transcallosal inhibition and upper extremity motor behavior.Materials and methods19 individuals with unilateral ischemic subacute stroke who had severe upper extremity impairment participated in this study. Corticospinal excitability was assessed by measuring the resting motor threshold, active motor threshold and motor evoked potential amplitude. Transcallosal inhibition was investigated by measuring the duration and depth of the ipsilateral silent period (ISP). The data from the two hemispheres were compared and the relationships of transcallosal inhibition with upper extremity motor impairment, grip strength and pinch strength were analyzed.ResultsResting motor threshold (p = 0.001) and active motor threshold (p = 0.001) were lower and motor evoked potential amplitude was higher (p = 0.001) in the contralesional M1 compared to the ipsilesional M1. However, there were no differences between the two M1s in ISP duration (p = 0.297) or ISP depth (p =0. 229). Transcallosal inhibition from the contralesional M1 was positively associated with motor impairment (ISP duration, p = 0.003; ISP depth, p = 0.017) and grip strength (ISP duration, p = 0.016; ISP depth, p = 0.045).ConclusionsSymmetric transcallosal inhibition between hemispheres and positive association of transcallosal inhibition from contralesional M1 with upper extremity motor behavior indicate that recruitment of contralesional M1 may be necessary for recovery in patients with severe upper extremity impairment after subacute ischemic stroke.     

The influence of obesity on the motor coordination in children between 6 and 9 years of age

ObjectiveObesity is the most common childhood illness in developed countries and its prevalence continues to increase. The objective was to analyze the influence of obesity on the motor coordination of children between 6 and 9 years old.Equipment and methodsA number of 52 pupils of both genders participated for evaluation of the prevalence of obesity using the measurement of the abdominal perimeter and the Body Mass Index (BMI) categorized as Normal-Weighted, Excess Weight and Obesity. The assessment of motor coordination was performed by the KTK test. SPSS (version 19.0) was used for statistical purposes.ResultsGirls had lower levels of performance rather than boys, and the pupils presented worse levels of motor performance as the age progressed. Regarding the prevalence of obesity, the two-gender obtained high mean values for the Normal-weighted category, whereas 25% is overweight. Regarding the level of motor coordination, 57.7% of the pupils had Normal Coordination and 40.4% had coordinative difficulties. Pupils with higher values of BMI and abdominal perimeter obtains lower results of motor coordination.     

Variation of circadian activity rhythm according to body mass index in children

Background/objectivesThis study aimed to examine the variations of circadian activity rhythm of children according to objective body mass index (BMI) values, using a novel statistical framework (ie, Functional Linear Modeling, FLM), separately for school- and weekend days.MethodsA total of 107 participants (60 females; mean age: 10.25 ± 0.48 years) wore an actigraph for seven days during a regular school-week. While valid actigraphic data during school days were available for each of these children, this number decreased to 53 (31 females; mean age: 10.28 ± 0.51 years) during weekend days.ResultsExamining the school days, significantly higher motor activity in participants with higher BMI was observed from around 4:00 a.m. to 6:00 a.m., with a peak about 5:00 a.m. On the contrary, applying the FLM to the weekend days actigraphic data, no significantly different variation of circadian activity rhythm was observed, according to BMI.ConclusionsIn this specific sample of children, during school days, higher BMI is associated with higher activity level in a specific time window in the second half of nocturnal sleep. The lack of significant findings during weekend days could be explained because of higher variability of get-up time and/or the reduced sample size. Future longitudinal studies could explore if the higher motor activity in that specific time window qualifies as a predictive marker of the development of overweight and obesity. If so, early preventive strategies directed towards those at higher risk could be effectively implemented.     

氯氮平片辅助治疗PD合并精神障碍患者的有效性及不良反应研究

目的:对氯氮平片在帕金森病(Parkinson’s disease,PD)合并精神障碍辅助治疗中的应用价值予以探讨。方法:选取50例我院2013年1月1日—2019年6月30日接诊的PD合并精神障碍患者进行研究,按照随机数表法分为对照组和观察组。对照组用多巴丝肼,观察组联合氯氮平片,对比治疗效果。结果:观察组疾病治疗总有效率96.00%(24/25)高于对照组68.00%(17/25),差异有统计学意义(P<0.05),不良反应发生率8.00%(2/25)与对照组20.00%(5/25)差异无统计学意义(P>0.05);观察组UPDRD评分、VGI-S评分和BPRS评分明显低于对照组,差异有统计学意义(P<0.05)。结论:氯氮平片辅助治疗PD合并精神障碍患者,既可提高临床疗效,也不会增加用药后不良反应,安全性高,值得推广。     

Excitability of motor and sensory axons in multifocal motor neuropathy

ObjectiveTo assess excitability differences between motor and sensory axons of affected nerves in patients with multifocal motor neuropathy (MMN).MethodsWe performed motor and sensory excitability tests in affected median nerves of 20 MMN patients and in 20 age-matched normal subjects. CMAPs were recorded from the thenar and SNAPs from the 3rd digit. Clinical tests included assessment of muscle strength, two-point discrimination and joint position.ResultsAll MMN patients had weakness of the thenar muscle and normal sensory tests. Motor excitability testing in MMN showed an increased threshold for a 50% CMAP, increased rheobase, decreased stimulus-response slope, fanning-out of threshold electrotonus, decreased resting I/V slope, shortened refractory period, and more pronounced superexcitability. Sensory excitability testing in MMN revealed decreased accommodation half-time and S2-accommodation and less pronounced subexcitability. Mathematical modeling indicated increased Barrett-Barrett conductance for motor fibers and increase in internodal fast potassium conductance for sensory fibers.ConclusionsExcitability findings in MMN suggest myelin sheath or paranodal seal involvement in motor fibers and, possibly, paranodal detachment in sensory fibers.SignificanceExcitability properties of affected nerves in MMN differ between motor and sensory nerve fibers.     

Altered sensorimotor cortex noradrenergic function in idiopathic REM sleep behaviour disorder – A PET study

IntroductionNoradrenergic denervation is thought to aggravate motor dysfunction in Parkinson's disease (PD). In a previous PET study with the norepinephrine transporter (NART) ligand ¹¹C-MeNER, we detected reduced NART binding in primary sensorimotor cortex (M1S1) of PD patients. Idiopathic rapid-eye-movement sleep behaviour disorder (iRBD) is a phenotype of prodromal PD. Using ¹¹C-MeNER PET, we investigated whether iRBD patients showed similar NART binding reductions in M1S1 cortex as PD patients. Additionally, we investigated whether ¹¹C-MeNER binding and loss of nigrostriatal dopamine storage capacity measured with ¹⁸F-DOPA PET were correlated.Methods17 iRBD patients, 16 PD patients with (PD^RBD+) and 14 without RBD (PD^RBD−), and 25 control subjects underwent ¹¹C-MeNER PET. iRBD patients also had ¹⁸F-DOPA PET. Volume-of-interest analyses and voxel-level statistical parametric mapping were performed.ResultsPartial-volume corrected ¹¹C-MeNER binding potential (BP^ND) values in M1S1 differed across the groups (P = 0.022) with the iRBD and PD^RBD+ groups showing significant reductions (controls vs. iRBD P = 0.007; control vs. PD^RBD+ P = 0.008). Voxel-wise comparisons confirmed reductions of M1S1 ¹¹C-MeNER binding in PD and iRBD patients. Significant correlation was seen between putaminal ¹⁸F-DOPA uptake and thalamic ¹¹C-MeNER binding in iRBD patients (r² = 0.343, P = 0.013).ConclusionsThis study found altered noradrenergic neurotransmission in the M1S1 cortex of iRBD patients. The observed reduction of M1S1 ¹¹C-MeNER binding in iRBD may represent noradrenergic terminal degeneration or physiological down-regulation of NARTs in this prodromal phenotype of PD. The correlation between thalamic ¹¹C-MeNER binding and putaminal ¹⁸F-DOPA binding suggests that these neurotransmitter systems degenerate in parallel in the iRBD phenotype of prodromal PD.     

Direct cortical stimulation with cylindrical depth electrodes in the interhemispheric fissure for leg motor evoked potential monitoring

ObjectiveTo evaluate cylindrical depth electrodes in the interhemispheric fissure as an alternative to subdural strip electrodes for direct cortical stimulation (DCS) leg motor evoked potential (MEP) monitoring.MethodsA cylindrical depth electrode was positioned in the interhemispheric fissure of 37 patients who underwent supratentorial brain surgery. Leg sensory and motor cortices were localized by highest tibial nerve somatosensory evoked potential amplitude and lowest DCS leg MEP threshold; the lowest-threshold electrode was then used for DCS leg MEP monitoring.ResultsIntraoperative leg MEPs were obtained from all the patients in the series. The mean intensity applied for leg MEP monitoring with the cylindrical depth electrode was 15.2 ± 4.0 mA. No complications secondary to neurophysiological monitoring were detected.ConclusionsLower extremity MEPs were consistently recorded using a multi-contact cylindrical depth electrode in the interhemispheric fissure by DCS.SignificanceCylindrical depth electrodes may be a safe and effective alternative for DCS in the interhemispheric fissure, where subdural strips are difficult to place.     

Linking cortical and behavioural inhibition: Testing the parameter specificity of a transcranial magnetic stimulation protocol

Across a series of studies, our laboratory has shown that the efficiency of action stopping is associated with the strength of GABA_A-mediated short-intracortical inhibition (SICI) as measured using transcranial magnetic stimulation (TMS). However, these studies used fixed TMS parameters, which may not optimally probe GABA_A receptor activity for each individual. In the present study, we measured the relationship between stopping efficiency and SICI using a range of TMS parameters. Participants completed a right-hand unimanual stop signal task to obtain a measure of stopping efficiency. Resting-state SICI was measured from the left primary motor cortex using six combinations of interstimulus intervals and conditioning pulse intensities. We also established the parameters which generated the strongest SICI (SICI_max) and weakest SICI (SICI_min) for each individual. We found that stopping efficiency was significantly predicted by SICI using various TMS parameters, including SICI_max. Interestingly, SICI_min accounted for a similar proportion of variance in stopping efficiency as SICI measured using other TMS parameters. The findings suggest that the relationship between stopping efficiency and SICI is robust, reliable, and not influenced by the extent to which SICI is optimally probed.