Altered Spontaneous Brain Activity in Patients with Hemifacial Spasm: A Resting-State Functional MRI Study

Resting-state functional magnetic resonance imaging (fMRI) has been used to detect the alterations of spontaneous neuronal activity in various neurological and neuropsychiatric diseases, but rarely in hemifacial spasm (HFS), a nervous system disorder. We used resting-state fMRI with regional homogeneity (ReHo) analysis to investigate changes in spontaneous brain activity of patients with HFS and to determine the relationship of these functional changes with clinical features. Thirty patients with HFS and 33 age-, sex-, and education-matched healthy controls were included in this study. Compared with controls, HFS patients had significantly decreased ReHo values in left middle frontal gyrus (MFG), left medial cingulate cortex (MCC), left lingual gyrus, right superior temporal gyrus (STG) and right precuneus; and increased ReHo values in left precentral gyrus, anterior cingulate cortex (ACC), right brainstem, and right cerebellum. Furthermore, the mean ReHo value in brainstem showed a positive correlation with the spasm severity (r = 0.404, p = 0.027), and the mean ReHo value in MFG was inversely related with spasm severity in HFS group (r = -0.398, p = 0.028). This study reveals that HFS is associated with abnormal spontaneous brain activity in brain regions most involved in motor control and blinking movement. The disturbances of spontaneous brain activity reflected by ReHo measurements may provide insights into the neurological pathophysiology of HFS.     

Associative stimulation of the supraorbital nerve fails to induce timing-specific plasticity in the human blink reflex

Background

Associative high-frequency electrical stimulation (HFS) of the supraorbital nerve in five healthy individuals induced long-term potentiation (LTP)-like or depression (LTD)-like changes in the human blink reflex circuit according to the rules of spike timing-dependent plasticity (Mao and Evinger, 2001). HFS given at the onset of the R2 component of the blink reflex (HFS_LTP) produced a lasting facilitation of the R2, whereas HFS given shortly before R2 (HFS_LTD) caused a lasting suppression of the R2. In patients with benign essential blepharospasm (BEB), a focal dystonia affecting the orbicularis oculi muscles, HFS_LTP induced excessive LTP-like associative plasticity relative to healthy controls, which was normalized after botulinum toxin (BTX) injections (Quartarone et al, 2006).

Methodology/Principal Findings

We used HFS conditioning of the supraorbital nerve to study homeostatic metaplasticity of the blink reflex circuit in healthy subjects and dystonic patients. On separate days, we tested the conditioning effects on the R2 response and paired-pulse R2 inhibition after (i) HFS_LTP, (ii) HFS_LTP followed by HFS_LTP, and (iii) HFS_LTP followed by HFS_LTD. Controls also received (iv) HFS_LTD alone and (v) a non-intervention protocol. In BEB patients, HFS_LTP followed by HFS_LTD was given before and after BTX treatment. We were not able to replicate the bidirectional timing-dependent effects of HFS_LTP and HFS_LTD alone. All HFS protocols produced a non-specific reduction of the R2 response and a relative decrease in paired-pulse inhibition. These R2 changes also occurred in controls when no HFS was applied. There was also no trace of a homeostatic response pattern in BEB patients before or after BTX treatment.

Conclusion/Significance

Our data challenge the efficacy of associative HFS to produce bidirectional plasticity in the human blink reflex circuit. The non-specific decrease of the R2 response might indicate habituation of the blink reflex following repeated electrical supraorbital stimulation. The increase of inhibition after paired pulse stimulation might reflect homeostatic behaviour to prevent further down regulation of the R2 response to preserve the protection of this adverse-effects reflex.     

猫听觉脑干诱发电反应中P_(2a)和P_(2b)波的起源

在33例猫将普鲁卡因或海人酸微量注入耳蜗核(CN)和上橄榄复合体(SOC)内,观察ABR的相应改变,以分析P_(2a)和P_(2b)波的来源。猫P_(2a)波的出现率与电极导联有关,颅顶-颈后为90％,颅顶-乳突仅为18％。普普卡因注入CN后,同侧耳短声诱发的ABR仅保留P_1波,对侧耳的则无改变。海人酸注入CN后,P_1和P_(2a)存留,P_(2a)不减小反而增大。普鲁卡因注入双侧SOC,可使P_3、P_4和P_5消失。这些结果提示,P_(2a)波主要起源于CN区域内的第一级听觉传入神经元轴突并受第二级神经元负电位的影响,P_(2b)波主要起源于SOC以下的第二级听觉传入神经元,猫的P_(2a)和P_(2a)波与对侧脑干结构无关。     

Novel Classification of the Posterior Auricular Artery Based on Angiographical Appearance

Purpose

To investigate the length variation of the posterior auricular artery and propose a novel classification of the posterior auricular artery based on angiographical appearance.

Patients and Methods

A series of 234 consecutive patients who had undergone conventional cerebral angiography was analyzed. The posterior auricular artery was examined on the lateral projection of the external carotid or common carotid arteriography. The posterior auricular artery was classified into four groups by length, using the external auditory canal and the top of the helix as radiographical landmarks. Our proposed classification is as follows: Type A, posterior auricular artery terminates between its origin and the center of the external auditory canal; Type B, posterior auricular artery terminates between the center of the external auditory canal and the top of the helix; Type C, posterior auricular artery terminates between the top of the helix and the vertex; and Type D, posterior auricular artery reaches up to the vertex.

Results

A total of 424 (right, 214; left, 210) posterior auricular arteries were analyzed in 111 men and 123 women aged 11 to 91 years (mean, 61.0 years) examined for aneurysms in 78 cases, occlusive vascular diseases in 56, intracranial hemorrhages in 41, tumors in 35, and others in 24. Types A, B, C, and D were found in 15.1%, 34.9%, 48.8%, and 1.2% of the patients, respectively.

Conclusion

A novel classification of the posterior auricular artery identifies four types based on its length on cerebral angiography.     

Deletion of Fmr1 Alters Function and Synaptic Inputs in the Auditory Brainstem

Fragile X Syndrome (FXS), a neurodevelopmental disorder, is the most prevalent single-gene cause of autism spectrum disorder. Autism has been associated with impaired auditory processing, abnormalities in the auditory brainstem response (ABR), and reduced cell number and size in the auditory brainstem nuclei. FXS is characterized by elevated cortical responses to sound stimuli, with some evidence for aberrant ABRs. Here, we assessed ABRs and auditory brainstem anatomy in Fmr1^-/- mice, an animal model of FXS. We found that Fmr1^-/- mice showed elevated response thresholds to both click and tone stimuli. Amplitudes of ABR responses were reduced in Fmr1^-/- mice for early peaks of the ABR. The growth of the peak I response with sound intensity was less steep in mutants that in wild type mice. In contrast, amplitudes and response growth in peaks IV and V did not differ between these groups. We did not observe differences in peak latencies or in interpeak latencies. Cell size was reduced in Fmr1^-/- mice in the ventral cochlear nucleus (VCN) and in the medial nucleus of the trapezoid body (MNTB). We quantified levels of inhibitory and excitatory synaptic inputs in these nuclei using markers for presynaptic proteins. We measured VGAT and VGLUT immunolabeling in VCN, MNTB, and the lateral superior olive (LSO). VGAT expression in MNTB was significantly greater in the Fmr1^-/- mouse than in wild type mice. Together, these observations demonstrate that FXS affects peripheral and central aspects of hearing and alters the balance of excitation and inhibition in the auditory brainstem.     

Approche empirique pour déterminer les générateurs neurophysiologiques sous-jacents des potentiels évoqués auditifs engendrés par des sons de parole (Speech ABR)

Auditory evoked potentials to speech (Speech auditory brainstem response [Speech ABR]) are a non-invasive way to investigate neurophysiological activity, at the level of the brainstem. The Speech ABR precise neurophyiological generators remain poorly defined. However, latencies and low-pass spectrum both suggest that these generators might lie in the upper brainstem (roughly between the cochlear nucleus and the inferior colliculus). Having considered the particular functional pattern of cells along the auditory pathway, specific stimuli have been synthesized to make out the acoustic sensitivity of Speech ABR components. Accordingly, hypotheses have been made on the probable neurophysiological generators, most likely to have elicited both Speech ABR components: onset response and frequency following response. Speech ABR have been recorded to pure tones, harmonic complex tones, /ba/ and /pa/ syllables, and their analogues (calculated as a sum of five weighted sine waves at the formant frequencies and amplitudes, and modulated by the syllables temporal envelopes). In addition, the Auditory Image Model (Patterson et al., 1995 [17]), simulating the neural activity at the auditory periphery, i.e. inferior colliculus input, suggests that both analogues and syllables elicit the same amount of energy, in contrast to the recorded FFR. This contradiction means that the neurophysiological signal processing leading to FFR is made beyond auditory periphery. Indeed, FFR synchronisation on F0 seems to be the result of an overall processing of the whole stimulus spectrum. This behaviour reminds the functional characteristics of disc-shape cells in the inferior colliculus, as described in a previous study of physiological periodicity coding (Periodicity analysis network, Voutsas et al., 2005 [42]).     

婴儿痉挛症脑干信息传导障碍的混沌学研究

婴儿痉挛症（Infantile Spasms,IS）是婴幼儿难治性癫痫。IS的发病机理至今也不清楚,目前比较一致的假说是：脑干是IS的责任结构,但该假说不能用神经生理学的传统方法来证实。从信息学的角度,婴儿弃挛症的发病机制可能是源自脑干神经信息传递障碍的脑干功能失调,为了证实这一论点,用可以反遇脑干传导功能的听觉诱发响应的相关维数,来评估脑干神经信息传导不同的功能状态,经过对IS患者、颞叶癫痫患者和健康人三个组的结果比较分析,表明IS患者脑干听觉诱发响应的相关维数明显低下,而颞叶癫痫患者该相关维数在颞叶病灶处最低。以上结果,证实了IS患者脑干神经信息传导功能障碍的存在。     

No effects of mobile phone electromagnetic field on auditory brainstem response

The present study investigated the possible effects of the electromagnetic field (EMF) emitted by an ordinary GSM mobile phone (902.4 MHz pulsed at 217 Hz) on brainstem auditory processing. Auditory brainstem responses (ABR) were recorded in 17 healthy young adults, without a mobile phone at baseline, and then with a mobile phone on the ear under EMF‐off and EMF‐on conditions. The amplitudes, latencies, and interwave intervals of the main ABR components (waves I, III, V) were compared among the three conditions. ABR waveforms showed no significant differences due to exposure, suggesting that short‐term exposure to mobile phone EMF did not affect the transmission of sensory stimuli from the cochlea up to the midbrain along the auditory nerve and brainstem auditory pathways. Bioelectromagnetics 31:48–55, 2010. © 2009 Wiley‐Liss, Inc.     

微血管减压术治疗面肌痉挛术后相关并发症的临床分析

目的:总结面肌痉挛患者的术后并发症的发生情况并分析其原因。方法:回顾性分析了1548名在我院行微血管减压术治疗面肌痉挛的患者的临床资料,所有患者接受电话随访或者门诊随访,随访时间均超过2年,总结其临床疗效及术后并发症的发生情况。结果:微血管减压术后痊愈率及明显缓解率分别为92.5%及4.2%。249名(16.09%)患者出现不同的并发症,其中最常见的并发症为面瘫及术后手术区域皮肤感觉障碍,无死亡及重大并发症患者。听力损害发生率为3.5%。其他并发症包括脑脊液漏、后组颅神经损伤、外展神经损伤、颅内出血等。结论:微血管减压术是治疗面肌痉挛的安全有效操作,以手术区域感觉障碍及迟发性面瘫是主要的并发症,持久性的或者严重的并发症比较少见。     

瞬目反射对老年人脑干梗死诊断价值的研究

目的：探讨瞬目反射对老年人脑干梗死的诊断价值。方法：采用神经电生理检查方法对100例老年人（50例健康受试者、50例脑干梗死患者）进行BR检测。确定BR正常值,记录各组潜伏期和波幅的变化,与正常对照组比较;并对50例脑干梗死患者行MRI检测,比较MRI与BR对脑干梗死的诊断阳性率。结果：健康对照组BR各波潜伏期的平均值分别是R1为10.9 ms、R2为30.4 ms、R2＇为29.5 ms,波幅的平均值分别是R1为306.3μv、R2为276.7μv、R2＇为257.8μv。脑干梗死组中有44例BR异常,其中6例中脑梗死患者BR正常;36例桥脑梗死患者BR完全异常;8例延髓梗死患者R1正常,结果具有统计学差异（P〈0.01）。BR与MRI检查对脑干梗死的诊断阳性率比较无统计学差异（P〉0.05）。结论：瞬目反射是一种早期诊断脑干梗死的有价值的临床电生理方法,相对于传统MRI检查,其诊断率稍低,但能敏感地反应脑干尤其是脑桥的病变情况,对定位诊断有重要意义。     

Neurodynamics, tonality, and the auditory brainstem response

Tonal relationships are foundational in music, providing the basis upon which musical structures, such as melodies, are constructed and perceived. A recent dynamic theory of musical tonality predicts that networks of auditory neurons resonate nonlinearly to musical stimuli. Nonlinear resonance leads to stability and attraction relationships among neural frequencies, and these neural dynamics give rise to the perception of relationships among tones that we collectively refer to as tonal cognition. Because this model describes the dynamics of neural populations, it makes specific predictions about human auditory neurophysiology. Here, we show how predictions about the auditory brainstem response (ABR) are derived from the model. To illustrate, we derive a prediction about population responses to musical intervals that has been observed in the human brainstem. Our modeled ABR shows qualitative agreement with important features of the human ABR. This provides a source of evidence that fundamental principles of auditory neurodynamics might underlie the perception of tonal relationships, and forces reevaluation of the role of learning and enculturation in tonal cognition.     

A 型肉毒毒素治疗半侧面肌痉挛的临床疗效评价

目的：观察A型肉毒毒素对面肌痉挛患者的痉挛程度、抑郁症状和焦虑症状的改善。方法：对58例面肌痉挛患者进行局部注射A型肉毒毒素。在治疗前后对痉挛程度改善情况进行评定以及用汉密顿焦虑量表（HAMA）、汉密顿抑郁量表（HAMD）对焦虑状态、抑郁状态进行评分,并对药物的副作用进行观察。结果：A型肉毒毒素明显改善面肌痉挛患者的痉挛程度,治疗后2周的HAMA、HA肋评分较治疗前明显下降,且差异具有统计学意义（P〈0．01）。结论：局部注射A型肉毒毒素可迅速缓解或消除面肌痉挛患者肌肉痉挛及相关的抑郁和焦虑状态,提高患者的生活质量。     

脑干缺血对听觉脑干反应影响的实验研究

目的 :探讨脑干缺血模型ABR变化特点及其在脑缺血早期诊断中的应用价值。方法 :阻断猫基底动脉不同部位血流 ,观察记录阻断血流后不同时间ABR变化特点及其规律。结果 :①夹闭基底动脉上、下段或小脑下前动脉 10min左右 ,ABRP3 ,P4振幅明显减小 (P <0 .0 1,P <0 .0 5 ) ,60min恢复夹前水平 ;②夹闭基底动脉上段 10～60minP5明显减小 (P <0 .0 5 ) ,直到 12 0min尚未恢复至夹前状态。结论 :①猫的ABRP3脑区的血供主要来自小脑下前动脉 ,P1,P2产生部位基本不依赖基底动脉供血 ;②轻度暂短性脑缺血时ABR振幅比潜伏期更敏感 ,振幅减小的程度与脑干缺血的程度密切相关 ;③ABR可用于脑缺血定位诊断及脑功能动态观察的电生理检测。     

Impaired auditory-vestibular functions and behavioral abnormalities of Slitrk6-deficient mice

A recent study revealed that Slitrk6, a transmembrane protein containing a leucine-rich repeat domain, has a critical role in the development of the inner ear neural circuit. However, it is still unknown how the absence of Slitrk6 affects auditory and vestibular functions. In addition, the role of Slitrk6 in regions of the central nervous system, including the dorsal thalamus, has not been addressed. To understand the physiological role of Slitrk6, Slitrk6-knockout (KO) mice were subjected to systematic behavioral analyses including auditory and vestibular function tests. Compared to wild-type mice, the auditory brainstem response (ABR) of Slitrk6-KO mice indicated a mid-frequency range (8-16 kHz) hearing loss and reduction of the first ABR wave. The auditory startle response was also reduced. A vestibulo-ocular reflex (VOR) test showed decreased vertical (head movement-induced) VOR gains and normal horizontal VOR. In an open field test, locomotor activity was reduced; the tendency to be in the center region was increased, but only in the first 5 min of the test, indicating altered adaptive responses to a novel environment. Altered adaptive responses were also found in a hole-board test in which head-dip behavior was increased and advanced. Aside from these abnormalities, no clear abnormalities were noted in the mood, anxiety, learning, spatial memory, or fear memory-related behavioral tests. These results indicate that the Slitrk6-KO mouse can serve as a model of hereditary sensorineural deafness. Furthermore, the altered responses of Slitrk6-KO mice to the novel environment suggest a role of Slitrk6 in some cognitive functions.     

Auditory evoked responses in tropical men during sojourn over the arctic region

The influence of an arctic environment on auditory evoked responses, both brainstem and cognitive, were evaluated in 10 Indian soldiers. They were first tested in Delhi and then flown to an arctic region where they were tested in the first week and again in the eighth week of their stay. Two migrants from Moscow, their usual place of residence, and six natives, born and brought up in the arctic, were also tested for comparison. The Indians, on their return to India, were tested again. The auditory evoked responses were recorded using the Nicolet (USA) Compact 4 Instrument. The Indians showed a delay in all the waves of the auditory brainstem response (ABR) during their induction in the arctic and these persisted even on their return to India whereas the migrants and the natives had relatively higher ABR latency values.     

Alterations in Peripheral and Central Components of the Auditory Brainstem Response: A Neural Assay of Tinnitus

Chronic tinnitus, or “ringing of the ears”, affects upwards of 15% of the adult population. Identifying a cost-effective and objective measure of tinnitus is needed due to legal concerns and disability issues, as well as for facilitating the effort to assess neural biomarkers. We developed a modified gap-in-noise (GIN) paradigm to assess tinnitus in mice using the auditory brainstem response (ABR). We then compared the commonly used acoustic startle reflex gap-prepulse inhibition (gap-PPI) and the ABR GIN paradigm in young adult CBA/CaJ mice before and after administrating sodium salicylate (SS), which is known to reliably induce a 16 kHz tinnitus percept in rodents. Post-SS, gap-PPI was significantly reduced at 12 and 16 kHz, consistent with previous studies demonstrating a tinnitus-induced gap-PPI reduction in this frequency range. ABR audiograms indicated thresholds were significantly elevated post-SS, also consistent with previous studies. There was a significant increase in the peak 2 (P2) to peak 1 (P1) and peak 4 (P4) to P1 amplitude ratios in the mid-frequency range, along with decreased latency of P4 at higher intensities. For the ABR GIN, peak amplitudes of the response to the second noise burst were calculated as a percentage of the first noise burst response amplitudes to quantify neural gap processing. A significant decrease in this ratio (i.e. recovery) was seen only at 16 kHz for P1, indicating the presence of tinnitus near this frequency. Thus, this study demonstrates that GIN ABRs can be used as an efficient, non-invasive, and objective method of identifying the approximate pitch and presence of tinnitus in a mouse model. This technique has the potential for application in human subjects and also indicates significant, albeit different, deficits in temporal processing in peripheral and brainstem circuits following drug induced tinnitus.     

Auditory brain-stem responses in Marcus Gunn ptosis

The auditory brain-stem response (ABR) can detect anomalies both in the auditory pathways and in structures adjacent to these pathways. Patients with Duaneś retraction syndrome, associated with hypoplasia of the abducens nerve in the brain-stem, and patients with hemifacial spasm, due to compression of the facial nerve in the brain-stem, have been found to have abnormal ABRs. Marcus Gunn ptosis with ‘jaw winking’ is considered to be due to misconnection of oculomotor, trigeminal and other cranial nerves. Suspecting that perhaps some ‘jaw-winking’ phenomena may be due to detectable brain-stem anomalies we tested 7 patients with Marcus Gunn ptosis. Three of the patients demonstrated abnormal ABRs indicative of pontine pathology.     

Adult Plasticity in the Subcortical Auditory Pathway of the Maternal Mouse

Subcortical auditory nuclei were traditionally viewed as non-plastic in adulthood so that acoustic information could be stably conveyed to higher auditory areas. Studies in a variety of species, including humans, now suggest that prolonged acoustic training can drive long-lasting brainstem plasticity. The neurobiological mechanisms for such changes are not well understood in natural behavioral contexts due to a relative dearth of in vivo animal models in which to study this. Here, we demonstrate in a mouse model that a natural life experience with increased demands on the auditory system – motherhood – is associated with improved temporal processing in the subcortical auditory pathway. We measured the auditory brainstem response to test whether mothers and pup-naïve virgin mice differed in temporal responses to both broadband and tone stimuli, including ultrasonic frequencies found in mouse pup vocalizations. Mothers had shorter latencies for early ABR peaks, indicating plasticity in the auditory nerve and the cochlear nucleus. Shorter interpeak latency between waves IV and V also suggest plasticity in the inferior colliculus. Hormone manipulations revealed that these cannot be explained solely by estrogen levels experienced during pregnancy and parturition in mothers. In contrast, we found that pup-care experience, independent of pregnancy and parturition, contributes to shortening auditory brainstem response latencies. These results suggest that acoustic experience in the maternal context imparts plasticity on early auditory processing that lasts beyond pup weaning. In addition to establishing an animal model for exploring adult auditory brainstem plasticity in a neuroethological context, our results have broader implications for models of perceptual, behavioral and neural changes that arise during maternity, where subcortical sensorineural plasticity has not previously been considered.     

基于小波变换的婴儿痉挛症脑干听觉诱发电位复杂性分析

采用多尺度小波变换计算脑干听觉诱发电位近似熵的方法,对比婴儿痉挛症患儿与正常幼儿的近似熵值,按照脑干听觉诱发电位成份波对应的解剖位置,分段、分尺度计算并统计近似熵值,从神经信息传递角度探讨阻碍婴儿痉挛症患儿智能发育的原因。采集12例正常儿童和13例婴儿痉挛症患儿的脑干听觉诱发电位,将它们进行60尺度小波分解,分段、分尺度计算各尺度近似熵值。发现婴儿痉挛症组患儿脑干听觉诱发电位中代表脑干活动的3~7ms段的分尺度近似熵明显高于正常组(P<0.01),小尺度上表现尤为显著。结果表明婴儿痉挛症患儿脑干传导通路不畅通,其中的随机成份增多,阻碍信息在脑干的传递,进而影响患儿大脑皮层的发育。     

猫耳蜗电图中N_2波起源的分析

在35只猫进行了耳蜗电图、听觉脑干电反应及耳蜗核局部电位的同时描记,将普鲁卡因或海人酸微量注入耳蜗核内,观察电位的变化,以分析耳蜗电图中N_2 波的起源。实验结果表明:猫的 N_2 波来源于外周第一级神经元冲动的成分和耳蜗核电活动的成分。