Equilibrium Line Altitude fluctuations at HualcaHualca volcano (southern Peru).

NASA Astrophysics Data System (ADS)

Alcalá, Jesus; Palacios, David; Juan Zamorano, Jose

2015-04-01

Interest in Andean glaciers has substantially increased during the last decades, due to its high sensitivity to climate fluctuations. In this sense, Equilibrium Line Altitude (ELA) is a reliable indicator of climate variability that has been frequently used to reconstruct palaeoenvironmental conditions at different temporal and spatial scales. However, the number of sites with ELA reconstructions is still insufficient to determine patterns in tropical climate or estimations of atmospheric cooling since the Last Glacial Maximum. The main purpose of this study is to contribute in resolving tropical climate evolution through ELA calculations on HualcaHualca (15° 43' S; 71° 52' W; 6,025 masl), a large andesitic stratovolcano located in the south-western Peruvian Andes approximately 70 km north-west of Arequipa. We applied Terminus Headwall Altitude Ratio (THAR) with 0.2; 0.4; 0.5; 0.57 ratios, Accumulation Area Ratio (AAR) and Accumulation Area Balance Ratio (AABR) methods in four valleys of HualcaHualca volcano: Huayuray (north side), Pujro Huayjo (southwest side), Mollebaya (east side) and Mucurca (west side). To estimate ELA depression, we calculated the difference between the ELA on 1955 with its position in the Maximum Glacier Extent (MGE), Tardiglacial phases, little Ice Age (LIA) and 2000. Paleotemperature reconstructions derived from vertical temperature gradient 6.5° C / 1 km, based on GODDARD global observation system considered the most appropriate model for arid Andes. During MGE, the ELA was located between 5,005 (AABR) and 5,215 (AAR 0.67) masl. But in 1955, ELA rose to 5,685 (AABR) - 5,775 (AAR 0.67) masl. The ELA depression between those two phases is 560 - 680 m that implies a temperature decrease of 3.5° - 4.4° C. The experimental process based in the use and contrast of different ELA reconstruction techniques applied in this study suggests that THAR (0.57), AAR (0.67) or AABR are the most consistent procedures for HualcaHualca glaciers, while THAR with ratios 0.2; 0.4 and 0.5 tend to underestimate it's position. Research funded by Cryocrisis project (CGL2012-35858), Government of Spain.

The human auditory brainstem response to running speech reveals a subcortical mechanism for selective attention.

PubMed

Forte, Antonio Elia; Etard, Octave; Reichenbach, Tobias

2017-10-10

Humans excel at selectively listening to a target speaker in background noise such as competing voices. While the encoding of speech in the auditory cortex is modulated by selective attention, it remains debated whether such modulation occurs already in subcortical auditory structures. Investigating the contribution of the human brainstem to attention has, in particular, been hindered by the tiny amplitude of the brainstem response. Its measurement normally requires a large number of repetitions of the same short sound stimuli, which may lead to a loss of attention and to neural adaptation. Here we develop a mathematical method to measure the auditory brainstem response to running speech, an acoustic stimulus that does not repeat and that has a high ecological validity. We employ this method to assess the brainstem's activity when a subject listens to one of two competing speakers, and show that the brainstem response is consistently modulated by attention.

Stimulation of the cochlea using green laser light

NASA Astrophysics Data System (ADS)

Wenzel, G. I.; Balster, S.; Lim, H. H.; Zhang, K.; Reich, U.; Lubatschowski, H.; Ertmer, W.; Lenarz, T.; Reuter, G.

2009-02-01

The success of conventional hearing aids and electrical cochlear implants have generally been limited to hearing in quiet situations, in part due to a lack of localized (i.e., frequency specificity) sensorineural activation and subsequent impaired speech discrimination in noise. Laser light is a source of energy that can be focused in a controlled manner and may provide more localized activation of the inner ear, the cochlea. Compound action potentials have been elicited using 2.12 µm laser pulses through activation of auditory nerve fibers (Izzo et al. 2006). Laser stimulation (813 nm) of the cochlea has shown to induce basilar membrane motion and cochlear microphonic potentials (Fridberger et al. 2006). We sought to assess if visible light (green, 532 nm, 10 ns pulses) could be used to consistently activate the cochlea. The laser parameters were selected based on our initial attempt to induce an optoacoustic effect as the energy transfer mechanism to the cochlea. Click evoked auditory brainstem responses (AABRs) were recorded preoperatively in ketamine-anesthetized guinea pigs to confirm normal hearing. The bulla and then the cochlea were exposed. Optically evoked ABRs (OABR) were recorded in response to laser stimulation with a 50 µm optical fiber (532 nm, 10 ns pulses, 500 repetitions, 10 pulses/s; Nd:YAG laser) at the round window (RW) directed towards the basilar membrane (BM). OABRs similar in morphology to acoustically evoked ABRs, except for shorter latencies, were obtained for stimulation through the RW with energy levels between 1.7-30 µJ/pulse. The OABRs increased with increasing energy level reaching a saturation level around 13-15 µJ/pulse. Furthermore the responses remained consistent across stimulation over time, including stimulation at 13 µJ/pulse for over 30 minutes, indicating minimal or no damage within the cochlea with this type of laser stimulation. Overall we have demonstrated that laser light stimulation with 532 nm has potential for a new type of auditory prosthesis that can activate the cochlea without any apparent functional damage. Further studies are needed to determine the optimal laser parameters and fiber placement locations for localized and tonotopic activation.

Brainstem Encoding of Aided Speech in Hearing Aid Users with Cochlear Dead Region(s).

PubMed

Hassaan, Mohammad Ramadan; Ibraheem, Ola Abdallah; Galhom, Dalia Helal

2016-07-01

Neural encoding of speech begins with the analysis of the signal as a whole broken down into its sinusoidal components in the cochlea, which has to be conserved up to the higher auditory centers. Some of these components target the dead regions of the cochlea causing little or no excitation. Measuring aided speech-evoked auditory brainstem response elicited by speech stimuli with different spectral maxima can give insight into the brainstem encoding of aided speech with spectral maxima at these dead regions. This research aims to study the impact of dead regions of the cochlea on speech processing at the brainstem level after a long period of hearing aid use. This study comprised 30 ears without dead regions and 46 ears with dead regions at low, mid, or high frequencies. For all ears, we measured the aided speech-evoked auditory brainstem response using speech stimuli of low, mid, and high spectral maxima. Aided speech-evoked auditory brainstem response was producible in all subjects. Responses evoked by stimuli with spectral maxima at dead regions had longer latencies and smaller amplitudes when compared with the control group or the responses of other stimuli. The presence of cochlear dead regions affects brainstem encoding of speech with spectral maxima perpendicular to these regions. Brainstem neuroplasticity and the extrinsic redundancy of speech can minimize the impact of dead regions in chronic hearing aid users.

Gender differences in binaural speech-evoked auditory brainstem response: are they clinically significant?

PubMed

Jalaei, Bahram; Azmi, Mohd Hafiz Afifi Mohd; Zakaria, Mohd Normani

2018-05-17

Binaurally evoked auditory evoked potentials have good diagnostic values when testing subjects with central auditory deficits. The literature on speech-evoked auditory brainstem response evoked by binaural stimulation is in fact limited. Gender disparities in speech-evoked auditory brainstem response results have been consistently noted but the magnitude of gender difference has not been reported. The present study aimed to compare the magnitude of gender difference in speech-evoked auditory brainstem response results between monaural and binaural stimulations. A total of 34 healthy Asian adults aged 19-30 years participated in this comparative study. Eighteen of them were females (mean age=23.6±2.3 years) and the remaining sixteen were males (mean age=22.0±2.3 years). For each subject, speech-evoked auditory brainstem response was recorded with the synthesized syllable /da/ presented monaurally and binaurally. While latencies were not affected (p>0.05), the binaural stimulation produced statistically higher speech-evoked auditory brainstem response amplitudes than the monaural stimulation (p<0.05). As revealed by large effect sizes (d>0.80), substantive gender differences were noted in most of speech-evoked auditory brainstem response peaks for both stimulation modes. The magnitude of gender difference between the two stimulation modes revealed some distinct patterns. Based on these clinically significant results, gender-specific normative data are highly recommended when using speech-evoked auditory brainstem response for clinical and future applications. The preliminary normative data provided in the present study can serve as the reference for future studies on this test among Asian adults. Copyright © 2018 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Auditory Brainstem Responses in Childhood Psychosis.

ERIC Educational Resources Information Center

Gillberg, Christopher; And Others

1983-01-01

Auditory brainstem responses (ABR) were compared in 24 autistic children, seven children with other childhood psychoses, and 31 normal children. One-third of the autistic Ss showed abnormal ABR indicating brainstem dysfunction and correlating with muscular hypotonia and severe language impairment. Ss with other psychoses and normal Ss showed…

Brainstem Encoding of Aided Speech in Hearing Aid Users with Cochlear Dead Region(s)

PubMed Central

Hassaan, Mohammad Ramadan; Ibraheem, Ola Abdallah; Galhom, Dalia Helal

2016-01-01

Introduction  Neural encoding of speech begins with the analysis of the signal as a whole broken down into its sinusoidal components in the cochlea, which has to be conserved up to the higher auditory centers. Some of these components target the dead regions of the cochlea causing little or no excitation. Measuring aided speech-evoked auditory brainstem response elicited by speech stimuli with different spectral maxima can give insight into the brainstem encoding of aided speech with spectral maxima at these dead regions. Objective  This research aims to study the impact of dead regions of the cochlea on speech processing at the brainstem level after a long period of hearing aid use. Methods  This study comprised 30 ears without dead regions and 46 ears with dead regions at low, mid, or high frequencies. For all ears, we measured the aided speech-evoked auditory brainstem response using speech stimuli of low, mid, and high spectral maxima. Results  Aided speech-evoked auditory brainstem response was producible in all subjects. Responses evoked by stimuli with spectral maxima at dead regions had longer latencies and smaller amplitudes when compared with the control group or the responses of other stimuli. Conclusion  The presence of cochlear dead regions affects brainstem encoding of speech with spectral maxima perpendicular to these regions. Brainstem neuroplasticity and the extrinsic redundancy of speech can minimize the impact of dead regions in chronic hearing aid users. PMID:27413404

Improved outcomes in auditory brainstem implantation with the use of near-field electrical compound action potentials.

PubMed

Mandalà, Marco; Colletti, Liliana; Colletti, Giacomo; Colletti, Vittorio

2014-12-01

To compare the outcomes (auditory threshold and open-set speech perception at 48-month follow-up) of a new near-field monitoring procedure, electrical compound action potential, on positioning the auditory brainstem implant electrode array on the surface of the cochlear nuclei versus the traditional far-field electrical auditory brainstem response. Retrospective study. Tertiary referral center. Among the 202 patients with auditory brainstem implants fitted and monitored with electrical auditory brainstem response during implant fitting, 9 also underwent electrical compound action potential recording. These subjects were matched retrospectively with a control group of 9 patients in whom only the electrical auditory brainstem response was recorded. Electrical compound action potentials were obtained using a cotton-wick recording electrode located near the surface of the cochlear nuclei and on several cranial nerves. Significantly lower potential thresholds were observed with the recording electrode located on the cochlear nuclei surface compared with the electrical auditory brainstem response (104.4 ± 32.5 vs 158.9 ± 24.2, P = .0030). Electrical brainstem response and compound action potentials identified effects on the neighboring cranial nerves on 3.2 ± 2.4 and 7.8 ± 3.2 electrodes, respectively (P = .0034). Open-set speech perception outcomes at 48-month follow-up had improved significantly in the near- versus far-field recording groups (78.9% versus 56.7%; P = .0051). Electrical compound action potentials during auditory brainstem implantation significantly improved the definition of the potential threshold and the number of auditory and extra-auditory waves generated. It led to the best coupling between the electrode array and cochlear nuclei, significantly improving the overall open-set speech perception. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

Relationship between brainstem, cortical and behavioral measures relevant to pitch salience in humans.

PubMed

Krishnan, Ananthanarayan; Bidelman, Gavin M; Smalt, Christopher J; Ananthakrishnan, Saradha; Gandour, Jackson T

2012-10-01

Neural representation of pitch-relevant information at both the brainstem and cortical levels of processing is influenced by language or music experience. However, the functional roles of brainstem and cortical neural mechanisms in the hierarchical network for language processing, and how they drive and maintain experience-dependent reorganization are not known. In an effort to evaluate the possible interplay between these two levels of pitch processing, we introduce a novel electrophysiological approach to evaluate pitch-relevant neural activity at the brainstem and auditory cortex concurrently. Brainstem frequency-following responses and cortical pitch responses were recorded from participants in response to iterated rippled noise stimuli that varied in stimulus periodicity (pitch salience). A control condition using iterated rippled noise devoid of pitch was employed to ensure pitch specificity of the cortical pitch response. Neural data were compared with behavioral pitch discrimination thresholds. Results showed that magnitudes of neural responses increase systematically and that behavioral pitch discrimination improves with increasing stimulus periodicity, indicating more robust encoding for salient pitch. Absence of cortical pitch response in the control condition confirms that the cortical pitch response is specific to pitch. Behavioral pitch discrimination was better predicted by brainstem and cortical responses together as compared to each separately. The close correspondence between neural and behavioral data suggest that neural correlates of pitch salience that emerge in early, preattentive stages of processing in the brainstem may drive and maintain with high fidelity the early cortical representations of pitch. These neural representations together contain adequate information for the development of perceptual pitch salience. Copyright © 2012 Elsevier Ltd. All rights reserved.

Tracing the neural basis of auditory entrainment.

PubMed

Lehmann, Alexandre; Arias, Diana Jimena; Schönwiesner, Marc

2016-11-19

Neurons in the auditory cortex synchronize their responses to temporal regularities in sound input. This coupling or "entrainment" is thought to facilitate beat extraction and rhythm perception in temporally structured sounds, such as music. As a consequence of such entrainment, the auditory cortex responds to an omitted (silent) sound in a regular sequence. Although previous studies suggest that the auditory brainstem frequency-following response (FFR) exhibits some of the beat-related effects found in the cortex, it is unknown whether omissions of sounds evoke a brainstem response. We simultaneously recorded cortical and brainstem responses to isochronous and irregular sequences of consonant-vowel syllable /da/ that contained sporadic omissions. The auditory cortex responded strongly to omissions, but we found no evidence of evoked responses to omitted stimuli from the auditory brainstem. However, auditory brainstem responses in the isochronous sound sequence were more consistent across trials than in the irregular sequence. These results indicate that the auditory brainstem faithfully encodes short-term acoustic properties of a stimulus and is sensitive to sequence regularity, but does not entrain to isochronous sequences sufficiently to generate overt omission responses, even for sequences that evoke such responses in the cortex. These findings add to our understanding of the processing of sound regularities, which is an important aspect of human cognitive abilities like rhythm, music and speech perception. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Neurophysiological aspects of brainstem processing of speech stimuli in audiometric-normal geriatric population.

PubMed

Ansari, M S; Rangasayee, R; Ansari, M A H

2017-03-01

Poor auditory speech perception in geriatrics is attributable to neural de-synchronisation due to structural and degenerative changes of ageing auditory pathways. The speech-evoked auditory brainstem response may be useful for detecting alterations that cause loss of speech discrimination. Therefore, this study aimed to compare the speech-evoked auditory brainstem response in adult and geriatric populations with normal hearing. The auditory brainstem responses to click sounds and to a 40 ms speech sound (the Hindi phoneme |da|) were compared in 25 young adults and 25 geriatric people with normal hearing. The latencies and amplitudes of transient peaks representing neural responses to the onset, offset and sustained portions of the speech stimulus in quiet and noisy conditions were recorded. The older group had significantly smaller amplitudes and longer latencies for the onset and offset responses to |da| in noisy conditions. Stimulus-to-response times were longer and the spectral amplitude of the sustained portion of the stimulus was reduced. The overall stimulus level caused significant shifts in latency across the entire speech-evoked auditory brainstem response in the older group. The reduction in neural speech processing in older adults suggests diminished subcortical responsiveness to acoustically dynamic spectral cues. However, further investigations are needed to encode temporal cues at the brainstem level and determine their relationship to speech perception for developing a routine tool for clinical decision-making.

Auditory brainstem activity and development evoked by apical versus basal cochlear implant electrode stimulation in children.

PubMed

Gordon, K A; Papsin, B C; Harrison, R V

2007-08-01

The role of apical versus basal cochlear implant electrode stimulation on central auditory development was examined. We hypothesized that, in children with early onset deafness, auditory development evoked by basal electrode stimulation would differ from that evoked more apically. Responses of the auditory nerve and brainstem, evoked by an apical and a basal implant electrode, were measured over the first year of cochlear implant use in 50 children with early onset severe to profound deafness who used hearing aids prior to implantation. Responses at initial stimulation were of larger amplitude and shorter latency when evoked by the apical electrode. No significant effects of residual hearing or age were found on initial response amplitudes or latencies. With implant use, responses evoked by both electrodes showed decreases in wave and interwave latencies reflecting decreased neural conduction time through the brainstem. Apical versus basal differences persisted with implant experience with one exception; eIII-eV interlatency differences decreased with implant use. Acute stimulation shows prolongation of basally versus apically evoked auditory nerve and brainstem responses in children with severe to profound deafness. Interwave latencies reflecting neural conduction along the caudal and rostral portions of the brainstem decreased over the first year of implant use. Differences in neural conduction times evoked by apical versus basal electrode stimulation persisted in the caudal but not rostral brainstem. Activity-dependent changes of the auditory brainstem occur in response to both apical and basal cochlear implant electrode stimulation.

Impact of early hearing screening and treatment on language development and education level: evaluation of 6 years of universal newborn hearing screening (ALGO) in Flanders, Belgium.

PubMed

Verhaert, N; Willems, M; Van Kerschaver, E; Desloovere, C

2008-05-01

Early intervention in hearing-impaired children may improve language outcomes and subsequent school and occupational performance. The objective of this study was to retrospectively analyze over 6 years the educational outcome and language development of a first cohort of children, detected by the Flemish universal newborn hearing screening (UNHS) program based on automated auditory brainstem response (AABR), with the oldest children being in primary school. We studied 229 hearing-impaired children from 1998 till 2003. The following variables were considered: the age during the school year 2005-2006, the degree of hearing loss, additional impairments including presence of intellectual disability, school placement and early intervention. Analysis showed that 85.4% of the children with moderate, severe or profound hearing loss and no additional disability, older than 5.5 years, reach mainstream education. Further detailed description was provided for the outcomes of children with uni- and bilateral cochlear implants. Overall results stress that 46% of all children with a cochlear implant obtain mainstream education. Of all cochlear implant (CI) children above 5.5 years, without additional handicaps, 78.9% of children attend primary mainstream school. Data on language development show that up to 45% of the children with unilateral cochlear implant and no additional disabilities had normal to slight delay on language development. These data are fulfilling the goals stated by the JCIH and the American Academy of Pediatrics (AAP) in 2000. The role and impact of additional handicaps is discussed. The importance of early hearing loss identification and hearing therapy for appropriate language development is highlighted. Finally our preliminary results on children with bilateral cochlear implants without additional handicaps present an improved language development in comparison to unilateral CI-children. A vast majority of the children detected by the UNHS program, with moderate, severe or profound hearing loss and no additional disability, older than 5.5 years, reach mainstream education. Additional disabilities have a major influence.

Brainstem transcription of speech is disrupted in children with autism spectrum disorders

PubMed Central

Russo, Nicole; Nicol, Trent; Trommer, Barbara; Zecker, Steve; Kraus, Nina

2009-01-01

Language impairment is a hallmark of autism spectrum disorders (ASD). The origin of the deficit is poorly understood although deficiencies in auditory processing have been detected in both perception and cortical encoding of speech sounds. Little is known about the processing and transcription of speech sounds at earlier (brainstem) levels or about how background noise may impact this transcription process. Unlike cortical encoding of sounds, brainstem representation preserves stimulus features with a degree of fidelity that enables a direct link between acoustic components of the speech syllable (e.g., onsets) to specific aspects of neural encoding (e.g., waves V and A). We measured brainstem responses to the syllable /da/, in quiet and background noise, in children with and without ASD. Children with ASD exhibited deficits in both the neural synchrony (timing) and phase locking (frequency encoding) of speech sounds, despite normal click-evoked brainstem responses. They also exhibited reduced magnitude and fidelity of speech-evoked responses and inordinate degradation of responses by background noise in comparison to typically developing controls. Neural synchrony in noise was significantly related to measures of core and receptive language ability. These data support the idea that abnormalities in the brainstem processing of speech contribute to the language impairment in ASD. Because it is both passively-elicited and malleable, the speech-evoked brainstem response may serve as a clinical tool to assess auditory processing as well as the effects of auditory training in the ASD population. PMID:19635083

Dyslexia risk gene relates to representation of sound in the auditory brainstem.

PubMed

Neef, Nicole E; Müller, Bent; Liebig, Johanna; Schaadt, Gesa; Grigutsch, Maren; Gunter, Thomas C; Wilcke, Arndt; Kirsten, Holger; Skeide, Michael A; Kraft, Indra; Kraus, Nina; Emmrich, Frank; Brauer, Jens; Boltze, Johannes; Friederici, Angela D

2017-04-01

Dyslexia is a reading disorder with strong associations with KIAA0319 and DCDC2. Both genes play a functional role in spike time precision of neurons. Strikingly, poor readers show an imprecise encoding of fast transients of speech in the auditory brainstem. Whether dyslexia risk genes are related to the quality of sound encoding in the auditory brainstem remains to be investigated. Here, we quantified the response consistency of speech-evoked brainstem responses to the acoustically presented syllable [da] in 159 genotyped, literate and preliterate children. When controlling for age, sex, familial risk and intelligence, partial correlation analyses associated a higher dyslexia risk loading with KIAA0319 with noisier responses. In contrast, a higher risk loading with DCDC2 was associated with a trend towards more stable responses. These results suggest that unstable representation of sound, and thus, reduced neural discrimination ability of stop consonants, occurred in genotypes carrying a higher amount of KIAA0319 risk alleles. Current data provide the first evidence that the dyslexia-associated gene KIAA0319 can alter brainstem responses and impair phoneme processing in the auditory brainstem. This brain-gene relationship provides insight into the complex relationships between phenotype and genotype thereby improving the understanding of the dyslexia-inherent complex multifactorial condition. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Auditory-Brainstem Response to Continuous, Non-repetitive Speech Is Modulated by the Speech Envelope and Reflects Speech Processing

PubMed Central

Reichenbach, Chagit S.; Braiman, Chananel; Schiff, Nicholas D.; Hudspeth, A. J.; Reichenbach, Tobias

2016-01-01

The auditory-brainstem response (ABR) to short and simple acoustical signals is an important clinical tool used to diagnose the integrity of the brainstem. The ABR is also employed to investigate the auditory brainstem in a multitude of tasks related to hearing, such as processing speech or selectively focusing on one speaker in a noisy environment. Such research measures the response of the brainstem to short speech signals such as vowels or words. Because the voltage signal of the ABR has a tiny amplitude, several hundred to a thousand repetitions of the acoustic signal are needed to obtain a reliable response. The large number of repetitions poses a challenge to assessing cognitive functions due to neural adaptation. Here we show that continuous, non-repetitive speech, lasting several minutes, may be employed to measure the ABR. Because the speech is not repeated during the experiment, the precise temporal form of the ABR cannot be determined. We show, however, that important structural features of the ABR can nevertheless be inferred. In particular, the brainstem responds at the fundamental frequency of the speech signal, and this response is modulated by the envelope of the voiced parts of speech. We accordingly introduce a novel measure that assesses the ABR as modulated by the speech envelope, at the fundamental frequency of speech and at the characteristic latency of the response. This measure has a high signal-to-noise ratio and can hence be employed effectively to measure the ABR to continuous speech. We use this novel measure to show that the ABR is weaker to intelligible speech than to unintelligible, time-reversed speech. The methods presented here can be employed for further research on speech processing in the auditory brainstem and can lead to the development of future clinical diagnosis of brainstem function. PMID:27303286

Nonlinear Processing of Auditory Brainstem Response

DTIC Science & Technology

2001-10-25

Kraków, Poland Abstract: - Auditory brainstem response potentials (ABR) are signals calculated from the EEG signals registered as responses to an...acoustic activation of the auditory system. The ABR signals provide an objective, diagnostic method, widely applied in examinations of hearing organs

Exploring the Relationship between Physiological Measures of Cochlear and Brainstem Function

PubMed Central

Dhar, S.; Abel, R.; Hornickel, J.; Nicol, T.; Skoe, E.; Zhao, W.; Kraus, N.

2009-01-01

Objective Otoacoustic emissions and the speech-evoked auditory brainstem response are objective indices of peripheral auditory physiology and are used clinically for assessing hearing function. While each measure has been extensively explored, their interdependence and the relationships between them remain relatively unexplored. Methods Distortion product otoacoustic emissions (DPOAE) and speech-evoked auditory brainstem responses (sABR) were recorded from 28 normal-hearing adults. Through correlational analyses, DPOAE characteristics were compared to measures of sABR timing and frequency encoding. Data were organized into two DPOAE (Strength and Structure) and five brainstem (Onset, Spectrotemporal, Harmonics, Envelope Boundary, Pitch) composite measures. Results DPOAE Strength shows significant relationships with sABR Spectrotemporal and Harmonics measures. DPOAE Structure shows significant relationships with sABR Envelope Boundary. Neither DPOAE Strength nor Structure is related to sABR Pitch. Conclusions The results of the present study show that certain aspects of the speech-evoked auditory brainstem responses are related to, or covary with, cochlear function as measured by distortion product otoacoustic emissions. Significance These results form a foundation for future work in clinical populations. Analyzing cochlear and brainstem function in parallel in different clinical populations will provide a more sensitive clinical battery for identifying the locus of different disorders (e.g., language based learning impairments, hearing impairment). PMID:19346159

Auditory Brainstem Responses in Young Adults with Down Syndrome.

ERIC Educational Resources Information Center

Widen, Judith E.; And Others

1987-01-01

In a study of 15 individuals (ages 15-21) with Down Syndrome, auditory brainstem response (ABR) detection levels were elevated, response amplitude reduced, and latency-intensity functions were significantly steeper than for a matched control group. Findings were associated with an impairment in hearing sensitivity at 8000 Hz for the experimental…

Hyper-excitability of brainstem pathways in cerebral palsy.

PubMed

Smith, Allison Teresa; Gorassini, Monica Ann

2018-06-27

Individuals with cerebral palsy (CP) experience impairments in the control of head and neck movements, suggesting dysfunction in brainstem circuitry. To examine if brainstem circuitry is altered in CP we compared reflexes evoked in the sternocleidomastoid (SCM) muscle by trigeminal nerve stimulation in adults with CP and age/sex-matched controls. Increasing the intensity of trigeminal nerve stimulation produced progressive increases in the long-latency suppression of ongoing SCM EMG in controls. In contrast, participants with CP showed progressively increased facilitation around the same reflex window, suggesting heightened excitability of brainstem pathways. We also examined if there was altered activation of cortico-brainstem pathways in response to pre-natal injury of the brain. Motor-evoked potentials (MEPs) in the SCM that were conditioned by a prior trigeminal afferent stimulation were more facilitated in CP compared to controls, especially in ipsilateral MEPs that are likely mediated by cortico-reticulospinal pathways. In some participants with CP, but not in controls, a combined trigeminal nerve and cortical stimulation near threshold intensities produced large, long-lasting responses in both the SCM and biceps brachii muscles. We propose that the enhanced excitatory responses evoked from trigeminal and cortical inputs in CP are produced by heightened excitability of brainstem circuits, resulting in the augmented activation of reticulospinal pathways. Enhanced activation of reticulospinal pathways in response to early injury of the corticospinal tract may provide a compensated activation of the spinal cord, or alternatively, contribute to impairments in the precise control of head and neck functions.

Auditory Brainstem Responses from Children Three Months to Three Years of Age: Normal Patterns of Response II.

ERIC Educational Resources Information Center

Gorga, Michael P.; And Others

1989-01-01

Auditory brainstem responses (ABR) were measured in 535 children from 3 months to 3 years of age. Results suggested that changes in wave V latency with age are due to central (neural) factors and that age-appropriate norms should be used in evaluations of ABR latencies in children. (Author/DB)

Aberrant Lateralization of Brainstem Auditory Evoked Responses by Individuals with Down Syndrome.

ERIC Educational Resources Information Center

Miezejeski, Charles M.; And Others

1994-01-01

Brainstem auditory evoked response latencies were studied in 80 males (13 with Down's syndrome). Latencies for waves P3 and P5 were shorter for Down's syndrome subjects, who also showed a different pattern of left versus right ear responses. Results suggest decreased lateralization and receptive and expressive language ability among people with…

Auditory Detection of the Human Brainstem Auditory Evoked Response.

ERIC Educational Resources Information Center

Kidd, Gerald, Jr.; And Others

1993-01-01

This study evaluated whether listeners can distinguish human brainstem auditory evoked responses elicited by acoustic clicks from control waveforms obtained with no acoustic stimulus when the waveforms are presented auditorily. Detection performance for stimuli presented visually was slightly, but consistently, superior to that which occurred for…

Functional Ear (A)Symmetry in Brainstem Neural Activity Relevant to Encoding of Voice Pitch: A Precursor for Hemispheric Specialization?

ERIC Educational Resources Information Center

Krishnan, Ananthanarayan; Gandour, Jackson T.; Ananthakrishnan, Saradha; Bidelman, Gavin M.; Smalt, Christopher J.

2011-01-01

Pitch processing is lateralized to the right hemisphere; linguistic pitch is further mediated by left cortical areas. This experiment investigates whether ear asymmetries vary in brainstem representation of pitch depending on linguistic status. Brainstem frequency-following responses (FFRs) were elicited by monaural stimulation of the left and…

Comparison between chloral hydrate and propofol-ketamine as sedation regimens for pediatric auditory brainstem response testing.

PubMed

Abulebda, Kamal; Patel, Vinit J; Ahmed, Sheikh S; Tori, Alvaro J; Lutfi, Riad; Abu-Sultaneh, Samer

2017-10-28

The use of diagnostic auditory brainstem response testing under sedation is currently the "gold standard" in infants and young children who are not developmentally capable of completing the test. The aim of the study is to compare a propofol-ketamine regimen to an oral chloral hydrate regimen for sedating children undergoing auditory brainstem response testing. Patients between 4 months and 6 years who required sedation for auditory brainstem response testing were included in this retrospective study. Drugs doses, adverse effects, sedation times, and the effectiveness of the sedative regimens were reviewed. 73 patients underwent oral chloral hydrate sedation, while 117 received propofol-ketamine sedation. 12% of the patients in the chloral hydrate group failed to achieve desired sedation level. The average procedure, recovery and total nursing times were significantly lower in the propofol-ketamine group. Propofol-ketamine group experienced higher incidence of transient hypoxemia. Both sedation regimens can be successfully used for sedating children undergoing auditory brainstem response testing. While deep sedation using propofol-ketamine regimen offers more efficiency than moderate sedation using chloral hydrate, it does carry a higher incidence of transient hypoxemia, which warrants the use of a highly skilled team trained in pediatric cardio-respiratory monitoring and airway management. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Speech-evoked Brainstem Auditory Responses and Auditory Processing Skills: A Correlation in Adults with Hearing Loss

PubMed Central

Sanguebuche, Taissane Rodrigues; Peixe, Bruna Pias; Bruno, Rúbia Soares; Biaggio, Eliara Pinto Vieira; Garcia, Michele Vargas

2018-01-01

Introduction  The auditory system consists of sensory structures and central connections. The evaluation of the auditory pathway at a central level can be performed through behavioral and electrophysiological tests, because they are complementary to each other and provide important information about comprehension. Objective  To correlate the findings of speech brainstem-evoked response audiometry with the behavioral tests Random Gap Detection Test and Masking Level Difference in adults with hearing loss. Methods  All patients were submitted to a basic audiological evaluation, to the aforementioned behavioral tests, and to an electrophysiological assessment, by means of click-evoked and speech-evoked brainstem response audiometry. Results  There were no statistically significant values among the electrophysiological test and the behavioral tests. However, there was a significant correlation between the V and A waves, as well as the D and F waves, of the speech-evoked brainstem response audiometry peaks. Such correlations are positive, indicating that the increase of a variable implies an increase in another and vice versa. Conclusion  It was possible to correlate the findings of the speech-evoked brainstem response audiometry with those of the behavioral tests Random Gap Detection and Masking Level Difference. However, there was no statistically significant correlation between them. This shows that the electrophysiological evaluation does not depend uniquely on the behavioral skills of temporal resolution and selective attention. PMID:29379574

Speech-evoked brainstem frequency-following responses during verbal transformations due to word repetition.

PubMed

Galbraith, G C; Jhaveri, S P; Kuo, J

1997-01-01

Speech-evoked brainstem frequency-following responses (FFRs) were recorded to repeated presentations of the same stimulus word. Word repetition results in illusory verbal transformations (VTs) in which word perceptions can differ markedly from the actual stimulus. Previous behavioral studies support an explanation of VTs based on changes in arousal or attention. Horizontal and vertical dipole FFRs were recorded to assess responses with putative origins in the auditory nerve and central brainstem, respectively. FFRs were recorded from 18 subjects when they correctly heard the stimulus and when they reported VTs. Although horizontal and vertical dipole FFRs showed different frequency response patterns, dipoles did not differentiate between perceptual conditions. However, when subjects were divided into low- and high-VT groups (based on percentage of VT trials), a significant Condition x Group interaction resulted. This interaction showed the largest difference in FFR amplitudes during VT trials, with the low-VT group showing increased amplitudes, and the high-VT group showing decreased amplitudes, relative to trials in which the stimulus was correctly perceived. These results demonstrate measurable subject differences in the early processing of complex signals, due to possible effects of attention on the brainstem FFR. The present research shows that the FFR is useful in understanding human language as it is coded and processed in the brainstem auditory pathway.

Brainstem response patterns in deeply-sedated critically-ill patients predict 28-day mortality.

PubMed

Rohaut, Benjamin; Porcher, Raphael; Hissem, Tarik; Heming, Nicholas; Chillet, Patrick; Djedaini, Kamel; Moneger, Guy; Kandelman, Stanislas; Allary, Jeremy; Cariou, Alain; Sonneville, Romain; Polito, Andréa; Antona, Marion; Azabou, Eric; Annane, Djillali; Siami, Shidasp; Chrétien, Fabrice; Mantz, Jean; Sharshar, Tarek

2017-01-01

Deep sedation is associated with acute brain dysfunction and increased mortality. We had previously shown that early-assessed brainstem reflexes may predict outcome in deeply sedated patients. The primary objective was to determine whether patterns of brainstem reflexes might predict mortality in deeply sedated patients. The secondary objective was to generate a score predicting mortality in these patients. Observational prospective multicenter cohort study of 148 non-brain injured deeply sedated patients, defined by a Richmond Assessment sedation Scale (RASS) <-3. Brainstem reflexes and Glasgow Coma Scale were assessed within 24 hours of sedation and categorized using latent class analysis. The Full Outline Of Unresponsiveness score (FOUR) was also assessed. Primary outcome measure was 28-day mortality. A "Brainstem Responses Assessment Sedation Score" (BRASS) was generated. Two distinct sub-phenotypes referred as homogeneous and heterogeneous brainstem reactivity were identified (accounting for respectively 54.6% and 45.4% of patients). Homogeneous brainstem reactivity was characterized by preserved reactivity to nociceptive stimuli and a partial and topographically homogenous depression of brainstem reflexes. Heterogeneous brainstem reactivity was characterized by a loss of reactivity to nociceptive stimuli associated with heterogeneous brainstem reflexes depression. Heterogeneous sub-phenotype was a predictor of increased risk of 28-day mortality after adjustment to Simplified Acute Physiology Score-II (SAPS-II) and RASS (Odds Ratio [95% confidence interval] = 6.44 [2.63-15.8]; p<0.0001) or Sequential Organ Failure Assessment (SOFA) and RASS (OR [95%CI] = 5.02 [2.01-12.5]; p = 0.0005). The BRASS (and marginally the FOUR) predicted 28-day mortality (c-index [95%CI] = 0.69 [0.54-0.84] and 0.65 [0.49-0.80] respectively). In this prospective cohort study, around half of all deeply sedated critically ill patients displayed an early particular neurological sub-phenotype predicting 28-day mortality, which may reflect a dysfunction of the brainstem.

Neonatal Auditory Brainstem Responses Recorded from Four Electrode Montages.

ERIC Educational Resources Information Center

Stuart, Andrew; And Others

1996-01-01

Simultaneous auditory brainstem responses (ABRs) to click stimuli at 30 and 60 decibels were recorded from 16 full-term neonates with 4 different electrode arrays. Results indicated that ABR waveforms were morphologically similar to those recorded in adults. Waveform expression was variable with different electrode recording montages. (Author/DB)

Quantitative proteomic analysis of the brainstem following lethal sarin exposure.

PubMed

Meade, Mitchell L; Hoffmann, Andrea; Makley, Meghan K; Snider, Thomas H; Schlager, John J; Gearhart, Jeffery M

2015-06-22

The brainstem represents a major tissue area affected by sarin organophosphate poisoning due to its function in respiratory and cardiovascular control. While the acute toxic effects of sarin on brainstem-related responses are relatively unknown, other brain areas e.g., cortex or cerebellum, have been studied more extensively. The study objective was to analyze the guinea pig brainstem toxicology response following sarin (2×LD50) exposure by proteome pathway analysis to gain insight into the complex regulatory mechanisms that lead to impairment of respiratory and cardiovascular control. Guinea pig exposure to sarin resulted in the typical acute behavior/physiology outcomes with death between 15 and 25min. In addition, brain and blood acetylcholinesterase activity was significantly reduced in the presence of sarin to 95%, and 89%, respectively, of control values. Isobaric-tagged (iTRAQ) liquid chromatography tandem mass spectrometry (LC-MS/MS) identified 198 total proteins of which 23% were upregulated, and 18% were downregulated following sarin exposure. Direct gene ontology (GO) analysis revealed a sarin-specific broad-spectrum proteomic profile including glutamate-mediated excitotoxicity, calcium overload, energy depletion responses, and compensatory carbohydrate metabolism, increases in ROS defense, DNA damage and chromatin remodeling, HSP response, targeted protein degradation (ubiquitination) and cell death response. With regards to the sarin-dependent effect on respiration, our study supports the potential interference of sarin with CO2/H(+) sensitive chemoreceptor neurons of the brainstem retrotrapezoid nucleus (RTN) that send excitatory glutamergic projections to the respiratory centers. In conclusion, this study gives insight into the brainstem broad-spectrum proteome following acute sarin exposure and the gained information will assist in the development of novel countermeasures. Published by Elsevier B.V.

Inferior colliculus contributions to phase encoding of stop consonants in an animal model

PubMed Central

Warrier, Catherine M; Abrams, Daniel A; Nicol, Trent G; Kraus, Nina

2011-01-01

The human auditory brainstem is known to be exquisitely sensitive to fine-grained spectro-temporal differences between speech sound contrasts, and the ability of the brainstem to discriminate between these contrasts is important for speech perception. Recent work has described a novel method for translating brainstem timing differences in response to speech contrasts into frequency-specific phase differentials. Results from this method have shown that the human brainstem response is surprisingly sensitive to phase-differences inherent to the stimuli across a wide extent of the spectrum. Here we use an animal model of the auditory brainstem to examine whether the stimulus-specific phase signatures measured in human brainstem responses represent an epiphenomenon associated with far field (i.e., scalp-recorded) measurement of neural activity, or alternatively whether these specific activity patterns are also evident in auditory nuclei that contribute to the scalp-recorded response, thereby representing a more fundamental temporal processing phenomenon. Responses in anaesthetized guinea pigs to three minimally-contrasting consonant-vowel stimuli were collected simultaneously from the cortical surface vertex and directly from central nucleus of the inferior colliculus (ICc), measuring volume conducted neural activity and multiunit, near-field activity, respectively. Guinea pig surface responses were similar to human scalp-recorded responses to identical stimuli in gross morphology as well as phase characteristics. Moreover, surface recorded potentials shared many phase characteristics with near-field ICc activity. Response phase differences were prominent during formant transition periods, reflecting spectro-temporal differences between syllables, and showed more subtle differences during the identical steady-state periods. ICc encoded stimulus distinctions over a broader frequency range, with differences apparent in the highest frequency ranges analyzed, up to 3000 Hz. Based on the similarity of phase encoding across sites, and the consistency and sensitivity of response phase measured within ICc, results suggest that a general property of the auditory system is a high degree of sensitivity to fine-grained phase information inherent to complex acoustical stimuli. Furthermore, results suggest that temporal encoding in ICc contributes to temporal features measured in speech-evoked scalp-recorded responses. PMID:21945200

Electrophysiological Evidence for the Sources of the Masking Level Difference.

PubMed

Fowler, Cynthia G

2017-08-16

The purpose of this review article is to review evidence from auditory evoked potential studies to describe the contributions of the auditory brainstem and cortex to the generation of the masking level difference (MLD). A literature review was performed, focusing on the auditory brainstem, middle, and late latency responses used in protocols similar to those used to generate the behavioral MLD. Temporal coding of the signals necessary for generating the MLD occurs in the auditory periphery and brainstem. Brainstem disorders up to wave III of the auditory brainstem response (ABR) can disrupt the MLD. The full MLD requires input to the generators of the auditory late latency potentials to produce all characteristics of the MLD; these characteristics include threshold differences for various binaural signal and noise conditions. Studies using central auditory lesions are beginning to identify the cortical effects on the MLD. The MLD requires auditory processing from the periphery to cortical areas. A healthy auditory periphery and brainstem codes temporal synchrony, which is essential for the ABR. Threshold differences require engaging cortical function beyond the primary auditory cortex. More studies using cortical lesions and evoked potentials or imaging should clarify the specific cortical areas involved in the MLD.

Newborn Auditory Brainstem Evoked Responses (ABRs): Longitudinal Correlates in the First Year.

ERIC Educational Resources Information Center

Murray, Ann D.

1988-01-01

Aimed to determine to what degree newborns' auditory brainstem evoked responses (ABRs) predict delayed or impaired development during the first year. When 93 infants' ABRs were evaluated at three, six, and nine months, newborn ABR was moderately sensitive for detecting hearing impairment and more sensitive than other indicators in detecting…

Evidence from Auditory Nerve and Brainstem Evoked Responses for an Organic Brain Lesion in Children with Autistic Traits

ERIC Educational Resources Information Center

Student, M.; Sohmer, H.

1978-01-01

In an attempt to resolve the question as to whether children with autistic traits have an organic nervous system lesion, auditory nerve and brainstem evoked responses were recorded in a group of 15 children (4 to 12 years old) with autistic traits. (Author)

Newborn Auditory Brainstem Evoked Responses (ABRs): Prenatal and Contemporary Correlates.

ERIC Educational Resources Information Center

Murray, Ann D.

1988-01-01

Presented are a literature review and new data on correlates of newborn auditory brainstem evoked responses (ABRs). Concludes that disorders of the central components of the ABR may be more of prenatal than of postnatal origin. The I-V interval had low but reliable correlations with four of 11 Brazelton scale variables. (RH)

Hearing Loss in Middle-Age Persons with Down Syndrome.

ERIC Educational Resources Information Center

Evenhuis, H. M.; And Others

1992-01-01

This study assessed the hearing function of 35 middle-aged adults with Down's syndrome by means of otoscopy, impedance audiometry, brainstem evoked response audiometry, and pure tone audiometry. The study found brainstem evoked response audiometry useful for routine audiological assessment, as it identified hearing losses of 20 to 90 decibels in…

Neurophysiological responses to music and vibroacoustic stimuli in Rett syndrome.

PubMed

Bergström-Isacsson, Märith; Lagerkvist, Bengt; Holck, Ulla; Gold, Christian

2014-06-01

People with Rett syndrome (RTT) have severe communicative difficulties. They have as well an immature brainstem that implies dysfunction of the autonomic nervous system. Music plays an important role in their life, is often used as a motivating tool in a variety of situations and activities, and caregivers are often clear about people with RTTs favourites. The aim of this study was to investigate physiological and emotional responses related to six different musical stimuli in people with RTT. The study included 29 participants with RTT who were referred to the Swedish Rett Center for medical brainstem assessment during the period 2006-2007. 11 children with a typical developmental pattern were used as comparison. A repeated measures design was used, and physiological data were collected from a neurophysiological brainstem assessment. The continuous dependent variables measured were Cardiac Vagal Tone (CVT), Cardiac Sensitivity to Baroreflex (CSB), Mean Arterial Blood Pressure (MAP) and the Coefficient of Variation of Mean Arterial Blood Pressure (MAP-CV). These parameters were used to categorise brainstem responses as parasympathetic (calming) response, sympathetic (activating) response, arousal (alerting) response and unclear response. The results showed that all participants responded to the musical stimuli, but not always in the expected way. It was noticeable that both people with and without RTT responded with an arousal to all musical stimuli to begin with. Even though the initial expressions sometimes changed after some time due to poor control functions of their brainstem, the present results are consistent with the possibility that the RTT participants' normal responses to music are intact. These findings may explain why music is so important for individuals with RTT throughout life. Copyright © 2014 Elsevier Ltd. All rights reserved.

Brainstem processing following unilateral and bilateral hearing-aid amplification.

PubMed

Dawes, Piers; Munro, Kevin J; Kalluri, Sridhar; Edwards, Brent

2013-04-17

Following previous research suggesting hearing-aid experience may induce functional plasticity at the peripheral level of the auditory system, click-evoked auditory brainstem response was recorded at first fitting and 12 weeks after hearing-aid use by unilateral and bilateral hearing-aid users. A control group of experienced hearing-aid users was tested over a similar time scale. No significant alterations in auditory brainstem response latency or amplitude were identified in any group. This does not support the hypothesis of plastic changes in the peripheral auditory system induced by hearing-aid use for 12 weeks.

Far-field brainstem responses evoked by vestibular and auditory stimuli exhibit increases in interpeak latency as brain temperature is decreased

NASA Technical Reports Server (NTRS)

Hoffman, L. F.; Horowitz, J. M.

1984-01-01

The effect of decreasing of brain temperature on the brainstem auditory evoked response (BAER) in rats was investigated. Voltage pulses, applied to a piezoelectric crystal attached to the skull, were used to evoke stimuli in the auditory system by means of bone-conducted vibrations. The responses were recorded at 37 C and 34 C brain temperatures. The peaks of the BAER recorded at 34 C were delayed in comparison with the peaks from the 37 C wave, and the later peaks were more delayed than the earlier peaks. These results indicate that an increase in the interpeak latency occurs as the brain temperature is decreased. Preliminary experiments, in which responses to brief angular acceleration were used to measure the brainstem vestibular evoked response (BVER), have also indicated increases in the interpeak latency in response to the lowering of brain temperature.

A comparison of the brainstem auditory evoked response in healthy ears of unilaterally deaf dogs and bilaterally hearing dogs.

PubMed

Plonek, M; Nicpoń, J; Kubiak, K; Wrzosek, M

2017-03-01

Auditory plasticity in response to unilateral deafness has been reported in various animal species. Subcortical changes occurring in unilaterally deaf young dogs using the brainstem auditory evoked response have not been evaluated yet. The aim of this study was to assess the brainstem auditory evoked response findings in dogs with unilateral hearing loss, and compare them with recordings obtained from healthy dogs. Brainstem auditory evoked responses (amplitudes and latencies of waves I, II, III, V, the V/I wave amplitude ratio, wave I-V, I-III and III-V interpeak intervals) were studied retrospectively in forty-six privately owned dogs, which were either unilaterally deaf or had bilateral hearing. The data obtained from the hearing ears in unilaterally deaf dogs were compared to values obtained from their healthy littermates. Statistically significant differences in the amplitude of wave III and the V/I wave amplitude ratio at 75 dB nHL were found between the group of unilaterally deaf puppies and the control group. The recordings of dogs with single-sided deafness were compared, and the results showed no statistically significant differences in the latencies and amplitudes of the waves between left- (AL) and right-sided (AR) deafness. The recordings of the brainstem auditory evoked response in canines with unilateral inborn deafness in this study varied compared to recordings from healthy dogs. Future studies looking into electrophysiological assessment of hearing in conjunction with imaging modalities to determine subcortical auditory plasticity and auditory lateralization in unilaterally deaf dogs are warranted.

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

PubMed Central

Rotschafer, Sarah E.; Marshak, Sonya; Cramer, Karina S.

2015-01-01

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. PMID:25679778

Altered auditory function in rats exposed to hypergravic fields

NASA Technical Reports Server (NTRS)

Jones, T. A.; Hoffman, L.; Horowitz, J. M.

1982-01-01

The effect of an orthodynamic hypergravic field of 6 G on the brainstem auditory projections was studied in rats. The brain temperature and EEG activity were recorded in the rats during 6 G orthodynamic acceleration and auditory brainstem responses were used to monitor auditory function. Results show that all animals exhibited auditory brainstem responses which indicated impaired conduction and transmission of brainstem auditory signals during the exposure to the 6 G acceleration field. Significant increases in central conduction time were observed for peaks 3N, 4P, 4N, and 5P (N = negative, P = positive), while the absolute latency values for these same peaks were also significantly increased. It is concluded that these results, along with those for fields below 4 G (Jones and Horowitz, 1981), indicate that impaired function proceeds in a rostro-caudal progression as field strength is increased.

The Impact of Clinical History on the Threshold Estimation of Auditory Brainstem Response Results for Infants

ERIC Educational Resources Information Center

Zaitoun, Maha; Cumming, Steven; Purcell, Alison; O'Brien, Katie

2017-01-01

Purpose: This study assesses the impact of patient clinical history on audiologists' performance when interpreting auditory brainstem response (ABR) results. Method: Fourteen audiologists' accuracy in estimating hearing threshold for 16 infants through interpretation of ABR traces was compared on 2 occasions at least 5 months apart. On the 1st…

Effect of High-Pass Filtering on the Neonatal Auditory Brainstem Response to Air- and Bone-Conducted Clicks.

ERIC Educational Resources Information Center

Stuart, Andrew; Yang, Edward Y.

1994-01-01

Simultaneous 3- channel recorded auditory brainstem responses (ABR) were obtained from 20 neonates with various high-pass filter settings and low intensity levels. Results support the advocacy of less restrictive high-pass filtering for neonatal and infant ABR screening to air-conducted and bone-conducted clicks. (Author/JDD)

The Relationship between Brainstem Temporal Processing and Performance on Tests of Central Auditory Function in Children with Reading Disorders

ERIC Educational Resources Information Center

Billiet, Cassandra R.; Bellis, Teri James

2011-01-01

Purpose: Studies using speech stimuli to elicit electrophysiologic responses have found approximately 30% of children with language-based learning problems demonstrate abnormal brainstem timing. Research is needed regarding how these responses relate to performance on behavioral tests of central auditory function. The purpose of the study was to…

Auditory Brainstem Evoked Responses in Newborns with Down Syndrome

ERIC Educational Resources Information Center

Kittler, Phyllis M.; Phan, Ha T. T.; Gardner, Judith M.; Miroshnichenko, Inna; Gordon, Anne; Karmel, Bernard Z.

2009-01-01

Auditory brainstem evoked responses (ABRs) were compared in 15 newborns with Down syndrome and 15 sex-, age-, and weight-matched control newborns. Participants had normal ABRs based upon values specific to 32- to 42-weeks postconceptional age. Although Wave III and Wave V component latencies and the Wave I-III interpeak latency (IPL) were shorter…

Infant Temperament and the Brainstem Auditory Evoked Response in Later Childhood.

ERIC Educational Resources Information Center

Woodward, Sue A.; McManis, Mark H.; Kagan, Jerome; Deldin, Patricia; Snidman, Nancy; Lewis, Melissa; Kahn, Vali

2001-01-01

Evaluated brainstem auditory evoked responses (BAERs) on 10- to 12-year-olds who had been classified as high or low reactive to unfamiliar stimuli at 4 months of age. Found that children previously classified as high reactive at 4 months had larger wave V components than did low reactive children, possibly suggesting greater excitability in…

Auditory Brainstem Response to Complex Sounds Predicts Self-Reported Speech-in-Noise Performance

ERIC Educational Resources Information Center

Anderson, Samira; Parbery-Clark, Alexandra; White-Schwoch, Travis; Kraus, Nina

2013-01-01

Purpose: To compare the ability of the auditory brainstem response to complex sounds (cABR) to predict subjective ratings of speech understanding in noise on the Speech, Spatial, and Qualities of Hearing Scale (SSQ; Gatehouse & Noble, 2004) relative to the predictive ability of the Quick Speech-in-Noise test (QuickSIN; Killion, Niquette,…

Screening the High-Risk Newborn for Hearing Loss: The Crib-O-Gram v the Auditory Brainstem Response.

ERIC Educational Resources Information Center

Cox, L. Clarke

1988-01-01

Presented are a rationale for identifying hearing loss in infancy and a history of screening procedures. The Crib-O-Gram and auditory brainstem response (ABR) tests are evaluated for reliability, validity, and cost-effectiveness. The ABR is recommended, and fully automated ABR instrumentation, which lowers expenses for trained personnel and…

Vestibular evoked myogenic potentials and MRI in early multiple sclerosis: Validation of the VEMP score.

PubMed

Crnošija, Luka; Krbot Skorić, Magdalena; Gabelić, Tereza; Adamec, Ivan; Habek, Mario

2017-01-15

To validate the VEMP score as a measure of brainstem dysfunction in patients with the first symptom of multiple sclerosis (MS) (clinically isolated syndrome (CIS)) and to investigate the correlation between VEMP and brainstem MRI results. 121 consecutive CIS patients were enrolled and brainstem functional system score (BSFS) was determined. Ocular VEMP (oVEMP) and cervical VEMP (cVEMP) were analyzed for latencies, conduction block and amplitude asymmetry ratio and the VEMP score was calculated. MRI was analyzed for the presence of brainstem lesions as a whole and separately for the presence of pontine, midbrain and medulla oblongata lesions. Patients with signs of brainstem involvement during the neurological examination (with BSFS ≥1) had a higher oVEMP score compared to patients with no signs of brainstem involvement. A binary logistic regression model showed that patients with brainstem lesion on the MRI are 6.780 times more likely to have BSFS ≥1 (p=0.001); and also, a higher VEMP score is associated with BSFS ≥1 (p=0.042). Furthermore, significant correlations were found between clinical brainstem involvement and brainstem and pontine MRI lesions, and prolonged latencies and/or absent VEMP responses. The VEMP score is a valuable tool in evaluation of brainstem involvement in patients with early MS. Copyright © 2016 Elsevier B.V. All rights reserved.

Enhanced brainstem and cortical evoked response amplitudes: single-trial covariance analysis.

PubMed

Galbraith, G C

2001-06-01

The purpose of the present study was to develop analytic procedures that improve the definition of sensory evoked response components. Such procedures could benefit all recordings but would especially benefit difficult recordings where many trials are contaminated by muscle and movement artifacts. First, cross-correlation and latency adjustment analyses were applied to the human brainstem frequency-following response and cortical auditory evoked response recorded on the same trials. Lagged cross-correlation functions were computed, for each of 17 subjects, between single-trial data and templates consisting of the sinusoid stimulus waveform for the brainstem response and the subject's own smoothed averaged evoked response P2 component for the cortical response. Trials were considered in the analysis only if the maximum correlation-squared (r2) exceeded .5 (negatively correlated trials were thus included). Identical correlation coefficients may be based on signals with quite different amplitudes, but it is possible to assess amplitude by the nonnormalized covariance function. Next, an algorithm is applied in which each trial with negative covariance is matched to a trial with similar, but positive, covariance and these matched-trial pairs are deleted. When an evoked response signal is present in the data, the majority of trials positively correlate with the template. Thus, a residual of positively correlated trials remains after matched covariance trials are deleted. When these residual trials are averaged, the resulting brainstem and cortical responses show greatly enhanced amplitudes. This result supports the utility of this analysis technique in clarifying and assessing evoked response signals.

Repetitive Diving in Trained Rats Still Increases Fos Production in Brainstem Neurons after Bilateral Sectioning of the Anterior Ethmoidal Nerve

PubMed Central

McCulloch, Paul F.; Warren, Erik A.; DiNovo, Karyn M.

2016-01-01

This research was designed to investigate the role of the anterior ethmoidal nerve (AEN) during repetitive trained diving in rats, with specific attention to activation of afferent and efferent brainstem nuclei that are part of this reflexive response. The AEN innervates the nose and nasal passages and is thought to be an important component of the afferent limb of the diving response. Male Sprague-Dawley rats (N = 24) were trained to swim and dive through a 5 m underwater maze. Some rats (N = 12) had bilateral sectioning of the AEN, others a Sham surgery (N = 12). Twelve rats (6 AEN cut and 6 Sham) had 24 post-surgical dive trials over 2 h to activate brainstem neurons to produce Fos, a neuronal activation marker. Remaining rats were non-diving controls. Diving animals had significantly more Fos-positive neurons than non-diving animals in the caudal pressor area, ventral medullary dorsal horn, ventral paratrigeminal nucleus, nucleus tractus solitarius, rostral ventrolateral medulla, Raphe nuclei, A5, Locus Coeruleus, and Kölliker-Fuse area. There were no significant differences in brainstem Fos labeling in rats diving with and without intact AENs. Thus, the AENs are not required for initiation of the diving response. Other nerve(s) that innervate the nose and nasal passages, and/or suprabulbar activation of brainstem neurons, may be responsible for the pattern of neuronal activation observed during repetitive trained diving in rats. These results help define the central neuronal circuitry of the mammalian diving response. PMID:27148082

Time-variant fMRI activity in the brainstem and higher structures in response to acupuncture.

PubMed

Napadow, Vitaly; Dhond, Rupali; Park, Kyungmo; Kim, Jieun; Makris, Nikos; Kwong, Kenneth K; Harris, Richard E; Purdon, Patrick L; Kettner, Norman; Hui, Kathleen K S

2009-08-01

Acupuncture modulation of activity in the human brainstem is not well known. This structure is plagued by physiological artifact in neuroimaging experiments. In addition, most studies have used short (<15 min) block designs, which miss delayed responses following longer duration stimulation. We used brainstem-focused cardiac-gated fMRI and evaluated time-variant brain response to longer duration (>30 min) stimulation with verum (VA, electro-stimulation at acupoint ST-36) or sham point (SPA, non-acupoint electro-stimulation) acupuncture. Our results provide evidence that acupuncture modulates brainstem nuclei important to endogenous monoaminergic and opioidergic systems. Specifically, VA modulated activity in the substantia nigra (SN), nucleus raphe magnus, locus ceruleus, nucleus cuneiformis, and periaqueductal gray (PAG). Activation in the ventrolateral PAG was greater for VA compared to SPA. Linearly decreasing time-variant activation, suggesting classical habituation, was found in response to both VA and SPA in sensorimotor (SII, posterior insula, premotor cortex) brain regions. However, VA also produced linearly time-variant activity in limbic regions (amygdala, hippocampus, and SN), which was bimodal and not likely habituation--consisting of activation in early blocks, and deactivation by the end of the run. Thus, acupuncture induces different brain response early, compared to 20-30 min after stimulation. We attribute the fMRI differences between VA and SPA to more varied and stronger psychophysical response induced by VA. Our study demonstrates that acupuncture modulation of brainstem structures can be studied non-invasively in humans, allowing for comparison to animal studies. Our protocol also demonstrates a fMRI approach to study habituation and other time-variant phenomena over longer time durations.

Auditory Brainstem Response Thresholds to Air- and Bone-Conducted CE-Chirps in Neonates and Adults

ERIC Educational Resources Information Center

Cobb, Kensi M.; Stuart, Andrew

2016-01-01

Purpose The purpose of this study was to compare auditory brainstem response (ABR) thresholds to air- and bone-conducted CE-Chirps in neonates and adults. Method Thirty-two neonates with no physical or neurologic challenges and 20 adults with normal hearing participated. ABRs were acquired with a starting intensity of 30 dB normal hearing level…

Brainstem auditory evoked responses and ophthalmic findings in llamas and alpacas in eastern Canada

PubMed Central

Cullen, Cheryl L.; Lamont, Leigh A.

2006-01-01

Abstract Seventeen llamas and 23 alpacas of various coat and iris colors were evaluated for: 1) deafness by using brainstem auditory evoked response testing; and 2) for ocular abnormalities via complete ophthalmic examination. No animals were deaf. The most common ocular abnormalities noted were iris-to-iris persistent pupillary membranes and incipient cataracts. PMID:16536233

Language-experience plasticity in neural representation of changes in pitch salience

PubMed Central

Krishnan, Ananthanarayan; Gandour, Jackson T.; Suresh, Chandan H.

2016-01-01

Neural representation of pitch-relevant information at the brainstem and cortical levels of processing is influenced by language experience. A well-known attribute of pitch is its salience. Brainstem frequency following responses and cortical pitch specific responses, recorded concurrently, were elicited by a pitch salience continuum spanning weak to strong pitch of a dynamic, iterated rippled noise pitch contour—homolog of a Mandarin tone. Our aims were to assess how language experience (Chinese, English) affects i) enhancement of neural activity associated with pitch salience at brainstem and cortical levels, ii) the presence of asymmetry in cortical pitch representation, and iii) patterns of relative changes in magnitude along the pitch salience continuum. Peak latency (Fz: Na, Pb, Nb) was shorter in the Chinese than the English group across the continuum. Peak-to-peak amplitude (Fz: Na-Pb, Pb-Nb) of the Chinese group grew larger with increasing pitch salience, but an experience-dependent advantage was limited to the Na-Pb component. At temporal sites (T7/T8), the larger amplitude of the Chinese group across the continuum was both limited to the Na-Pb component and the right temporal site. At the brainstem level, F0 magnitude gets larger as you increase pitch salience, and it too reveals Chinese superiority. A direct comparison of cortical and brainstem responses for the Chinese group reveals different patterns of relative changes in magnitude along the pitch salience continuum. Such differences may point to a transformation in pitch processing at the cortical level presumably mediated by local sensory and/or extrasensory influence overlaid on the brainstem output. PMID:26903418

Learning Disability Assessed through Audiologic and Physiologic Measures: A Case Study.

ERIC Educational Resources Information Center

Greenblatt, Edward R.; And Others

1983-01-01

The report describes a child with central auditory dysfunction, the first reported case where brain-stem dysfunction on audiologic tests were associated with specific electrophysiologic changes in the brain-stem auditory-evoked responses. (Author/CL)

The auditory brain-stem response to complex sounds: a potential biomarker for guiding treatment of psychosis.

PubMed

Tarasenko, Melissa A; Swerdlow, Neal R; Makeig, Scott; Braff, David L; Light, Gregory A

2014-01-01

Cognitive deficits limit psychosocial functioning in schizophrenia. For many patients, cognitive remediation approaches have yielded encouraging results. Nevertheless, therapeutic response is variable, and outcome studies consistently identify individuals who respond minimally to these interventions. Biomarkers that can assist in identifying patients likely to benefit from particular forms of cognitive remediation are needed. Here, we describe an event-related potential (ERP) biomarker - the auditory brain-stem response (ABR) to complex sounds (cABR) - that appears to be particularly well-suited for predicting response to at least one form of cognitive remediation that targets auditory information processing. Uniquely, the cABR quantifies the fidelity of sound encoded at the level of the brainstem and midbrain. This ERP biomarker has revealed auditory processing abnormalities in various neurodevelopmental disorders, correlates with functioning across several cognitive domains, and appears to be responsive to targeted auditory training. We present preliminary cABR data from 18 schizophrenia patients and propose further investigation of this biomarker for predicting and tracking response to cognitive interventions.

Audiological and electrophysiological evaluation of children with acquired immunodeficiency syndrome (AIDS).

PubMed

Matas, Carla Gentile; Leite, Renata Aparecida; Magliaro, Fernanda Cristina Leite; Gonçalves, Isabela Crivellaro

2006-08-01

We examined the peripheral auditory system and the auditory brainstem pathway of children with Acquired Immunodeficiency Syndrome (AIDS). One hundred and one children, 51 with AIDS diagnosis and 50 normal children were evaluated. Audiological assessment included immittance measures, pure tone and speech audiometry and auditory brainstem response (ABR). The children with AIDS more frequently had abnormal results than did their matched controls, presenting either peripheral or auditory brainstem impairment. We suggest that AIDS be considered a risk factor for peripheral and/or auditory brainstem disorders. Further research should be carried out to investigate the auditory effects of HIV infection along the auditory pathway.

Clinical applications of the human brainstem responses to auditory stimuli

NASA Technical Reports Server (NTRS)

Galambos, R.; Hecox, K.

1975-01-01

A technique utilizing the frequency following response (FFR) (obtained by auditory stimulation, whereby the stimulus frequency and duration are mirror-imaged in the resulting brainwaves) as a clinical tool for hearing disorders in humans of all ages is presented. Various medical studies are discussed to support the clinical value of the technique. The discovery and origin of the FFR and another significant brainstem auditory response involved in studying the eighth nerve is also discussed.

Evidence for Atypical Auditory Brainstem Responses in Young Children with Suspected Autism Spectrum Disorders

ERIC Educational Resources Information Center

Roth, Daphne Ari-Even; Muchnik, Chava; Shabtai, Esther; Hildesheimer, Minka; Henkin, Yael

2012-01-01

Aim: The aim of this study was to characterize the auditory brainstem responses (ABRs) of young children with suspected autism spectrum disorders (ASDs) and compare them with the ABRs of children with language delay and with clinical norms. Method: The ABRs of 26 children with suspected ASDs (21 males, five females; mean age 32.5 mo) and an age-…

Sensory Processing of Backward-Masking Signals in Children with Language-Learning Impairment as Assessed with the Auditory Brainstem Response.

ERIC Educational Resources Information Center

Marler, Jeffrey A.; Champlin, Craig A.

2005-01-01

The purpose of this study was to examine the possible contribution of sensory mechanisms to an auditory processing deficit shown by some children with language-learning impairment (LLI). Auditory brainstem responses (ABRs) were measured from 2 groups of school-aged (8-10 years) children. One group consisted of 10 children with LLI, and the other…

Mechanisms of spectral and temporal integration in the mustached bat inferior colliculus

PubMed Central

Wenstrup, Jeffrey James; Nataraj, Kiran; Sanchez, Jason Tait

2012-01-01

This review describes mechanisms and circuitry underlying combination-sensitive response properties in the auditory brainstem and midbrain. Combination-sensitive neurons, performing a type of auditory spectro-temporal integration, respond to specific, properly timed combinations of spectral elements in vocal signals and other acoustic stimuli. While these neurons are known to occur in the auditory forebrain of many vertebrate species, the work described here establishes their origin in the auditory brainstem and midbrain. Focusing on the mustached bat, we review several major findings: (1) Combination-sensitive responses involve facilitatory interactions, inhibitory interactions, or both when activated by distinct spectral elements in complex sounds. (2) Combination-sensitive responses are created in distinct stages: inhibition arises mainly in lateral lemniscal nuclei of the auditory brainstem, while facilitation arises in the inferior colliculus (IC) of the midbrain. (3) Spectral integration underlying combination-sensitive responses requires a low-frequency input tuned well below a neuron's characteristic frequency (ChF). Low-ChF neurons in the auditory brainstem project to high-ChF regions in brainstem or IC to create combination sensitivity. (4) At their sites of origin, both facilitatory and inhibitory combination-sensitive interactions depend on glycinergic inputs and are eliminated by glycine receptor blockade. Surprisingly, facilitatory interactions in IC depend almost exclusively on glycinergic inputs and are largely independent of glutamatergic and GABAergic inputs. (5) The medial nucleus of the trapezoid body (MNTB), the lateral lemniscal nuclei, and the IC play critical roles in creating combination-sensitive responses. We propose that these mechanisms, based on work in the mustached bat, apply to a broad range of mammals and other vertebrates that depend on temporally sensitive integration of information across the audible spectrum. PMID:23109917

Auditory responses to electric and infrared neural stimulation of the rat cochlear nucleus.

PubMed

Verma, Rohit U; Guex, Amélie A; Hancock, Kenneth E; Durakovic, Nedim; McKay, Colette M; Slama, Michaël C C; Brown, M Christian; Lee, Daniel J

2014-04-01

In an effort to improve the auditory brainstem implant, a prosthesis in which user outcomes are modest, we applied electric and infrared neural stimulation (INS) to the cochlear nucleus in a rat animal model. Electric stimulation evoked regions of neural activation in the inferior colliculus and short-latency, multipeaked auditory brainstem responses (ABRs). Pulsed INS, delivered to the surface of the cochlear nucleus via an optical fiber, evoked broad neural activation in the inferior colliculus. Strongest responses were recorded when the fiber was placed at lateral positions on the cochlear nucleus, close to the temporal bone. INS-evoked ABRs were multipeaked but longer in latency than those for electric stimulation; they resembled the responses to acoustic stimulation. After deafening, responses to electric stimulation persisted, whereas those to INS disappeared, consistent with a reported "optophonic" effect, a laser-induced acoustic artifact. Thus, for deaf individuals who use the auditory brainstem implant, INS alone did not appear promising as a new approach. Copyright © 2014 Elsevier B.V. All rights reserved.

Auditory Responses to Electric and Infrared Neural Stimulation of the Rat Cochlear Nucleus

PubMed Central

Verma, Rohit; Guex, Amelie A.; Hancock, Kenneth E.; Durakovic, Nedim; McKay, Colette M.; Slama, Michaël C. C.; Brown, M. Christian; Lee, Daniel J.

2014-01-01

In an effort to improve the auditory brainstem implant, a prosthesis in which user outcomes are modest, we applied electric and infrared neural stimulation (INS) to the cochlear nucleus in a rat animal model. Electric stimulation evoked regions of neural activation in the inferior colliculus and short-latency, multipeaked auditory brainstem responses (ABRs). Pulsed INS, delivered to the surface of the cochlear nucleus via an optical fiber, evoked broad neural activation in the inferior colliculus. Strongest responses were recorded when the fiber was placed at lateral positions on the cochlear nucleus, close to the temporal bone. INS-evoked ABRs were multipeaked but longer in latency than those for electric stimulation; they resembled the responses to acoustic stimulation. After deafening, responses to electric stimulation persisted, whereas those to INS disappeared, consistent with a reported “optophonic” effect, a laser-induced acoustic artifact. Thus, for deaf individuals who use the auditory brainstem implant, INS alone did not appear promising as a new approach. PMID:24508368

Evaluation of peripheral auditory pathways and brainstem in obstructive sleep apnea.

PubMed

Matsumura, Erika; Matas, Carla Gentile; Magliaro, Fernanda Cristina Leite; Pedreño, Raquel Meirelles; Lorenzi-Filho, Geraldo; Sanches, Seisse Gabriela Gandolfi; Carvallo, Renata Mota Mamede

2016-11-25

Obstructive sleep apnea causes changes in normal sleep architecture, fragmenting it chronically with intermittent hypoxia, leading to serious health consequences in the long term. It is believed that the occurrence of respiratory events during sleep, such as apnea and hypopnea, can impair the transmission of nerve impulses along the auditory pathway that are highly dependent on the supply of oxygen. However, this association is not well established in the literature. To compare the evaluation of peripheral auditory pathway and brainstem among individuals with and without obstructive sleep apnea. The sample consisted of 38 adult males, mean age of 35.8 (±7.2), divided into four groups matched for age and Body Mass Index. The groups were classified based on polysomnography in: control (n=10), mild obstructive sleep apnea (n=11) moderate obstructive sleep apnea (n=8) and severe obstructive sleep apnea (n=9). All study subjects denied a history of risk for hearing loss and underwent audiometry, tympanometry, acoustic reflex and Brainstem Auditory Evoked Response. Statistical analyses were performed using three-factor ANOVA, 2-factor ANOVA, chi-square test, and Fisher's exact test. The significance level for all tests was 5%. There was no difference between the groups for hearing thresholds, tympanometry and evaluated Brainstem Auditory Evoked Response parameters. An association was observed between the presence of obstructive sleep apnea and changes in absolute latency of wave V (p=0.03). There was an association between moderate obstructive sleep apnea and change of the latency of wave V (p=0.01). The presence of obstructive sleep apnea is associated with changes in nerve conduction of acoustic stimuli in the auditory pathway in the brainstem. The increase in obstructive sleep apnea severity does not promote worsening of responses assessed by audiometry, tympanometry and Brainstem Auditory Evoked Response. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Inhalational exposure to carbonyl sulfide produces altered brainstem auditory and somatosensory-evoked potentials in Fischer 344N rats.

PubMed

Herr, David W; Graff, Jaimie E; Moser, Virginia C; Crofton, Kevin M; Little, Peter B; Morgan, Daniel L; Sills, Robert C

2007-01-01

Carbonyl sulfide (COS), a chemical listed by the original Clean Air Act, was tested for neurotoxicity by a National Institute of Environmental Health Sciences/National Toxicology Program and U.S. Environmental Protection Agency collaborative investigation. Previous studies demonstrated that COS produced cortical and brainstem lesions and altered auditory neurophysiological responses to click stimuli. This paper reports the results of expanded neurophysiological examinations that were an integral part of the previously published experiments (Morgan et al., 2004, Toxicol. Appl. Pharmacol. 200, 131-145; Sills et al., 2004, Toxicol. Pathol. 32, 1-10). Fisher 334N rats were exposed to 0, 200, 300, or 400 ppm COS for 6 h/day, 5 days/week for 12 weeks, or to 0, 300, or 400 ppm COS for 2 weeks using whole-body inhalation chambers. After treatment, the animals were studied using neurophysiological tests to examine: peripheral nerve function, somatosensory-evoked potentials (SEPs) (tail/hindlimb and facial cortical regions), brainstem auditory-evoked responses (BAERs), and visual flash-evoked potentials (2-week study). Additionally, the animals exposed for 2 weeks were examined using a functional observational battery (FOB) and response modification audiometry (RMA). Peripheral nerve function was not altered for any exposure scenario. Likewise, amplitudes of SEPs recorded from the cerebellum were not altered by treatment with COS. In contrast, amplitudes and latencies of SEPs recorded from cortical areas were altered after 12-week exposure to 400 ppm COS. The SEP waveforms were changed to a greater extent after forelimb stimulation than tail stimulation in the 2-week study. The most consistent findings were decreased amplitudes of BAER peaks associated with brainstem regions after exposure to 400 ppm COS. Additional BAER peaks were affected after 12 weeks, compared to 2 weeks of treatment, indicating that additional regions of the brainstem were damaged with longer exposures. The changes in BAERs were observed in the absence of altered auditory responsiveness in FOB or RMA. This series of experiments demonstrates that COS produces changes in brainstem auditory and cortical somatosensory neurophysiological responses that correlate with previously described histopathological damage.

The Auditory Brain-Stem Response to Complex Sounds: A Potential Biomarker for Guiding Treatment of Psychosis

PubMed Central

Tarasenko, Melissa A.; Swerdlow, Neal R.; Makeig, Scott; Braff, David L.; Light, Gregory A.

2014-01-01

Cognitive deficits limit psychosocial functioning in schizophrenia. For many patients, cognitive remediation approaches have yielded encouraging results. Nevertheless, therapeutic response is variable, and outcome studies consistently identify individuals who respond minimally to these interventions. Biomarkers that can assist in identifying patients likely to benefit from particular forms of cognitive remediation are needed. Here, we describe an event-related potential (ERP) biomarker – the auditory brain-stem response (ABR) to complex sounds (cABR) – that appears to be particularly well-suited for predicting response to at least one form of cognitive remediation that targets auditory information processing. Uniquely, the cABR quantifies the fidelity of sound encoded at the level of the brainstem and midbrain. This ERP biomarker has revealed auditory processing abnormalities in various neurodevelopmental disorders, correlates with functioning across several cognitive domains, and appears to be responsive to targeted auditory training. We present preliminary cABR data from 18 schizophrenia patients and propose further investigation of this biomarker for predicting and tracking response to cognitive interventions. PMID:25352811

Dynamic modulation of decision biases by brainstem arousal systems.

PubMed

de Gee, Jan Willem; Colizoli, Olympia; Kloosterman, Niels A; Knapen, Tomas; Nieuwenhuis, Sander; Donner, Tobias H

2017-04-11

Decision-makers often arrive at different choices when faced with repeated presentations of the same evidence. Variability of behavior is commonly attributed to noise in the brain's decision-making machinery. We hypothesized that phasic responses of brainstem arousal systems are a significant source of this variability. We tracked pupil responses (a proxy of phasic arousal) during sensory-motor decisions in humans, across different sensory modalities and task protocols. Large pupil responses generally predicted a reduction in decision bias. Using fMRI, we showed that the pupil-linked bias reduction was (i) accompanied by a modulation of choice-encoding pattern signals in parietal and prefrontal cortex and (ii) predicted by phasic, pupil-linked responses of a number of neuromodulatory brainstem centers involved in the control of cortical arousal state, including the noradrenergic locus coeruleus. We conclude that phasic arousal suppresses decision bias on a trial-by-trial basis, thus accounting for a significant component of the variability of choice behavior.

Dynamic modulation of decision biases by brainstem arousal systems

PubMed Central

de Gee, Jan Willem; Colizoli, Olympia; Kloosterman, Niels A; Knapen, Tomas; Nieuwenhuis, Sander; Donner, Tobias H

2017-01-01

Decision-makers often arrive at different choices when faced with repeated presentations of the same evidence. Variability of behavior is commonly attributed to noise in the brain’s decision-making machinery. We hypothesized that phasic responses of brainstem arousal systems are a significant source of this variability. We tracked pupil responses (a proxy of phasic arousal) during sensory-motor decisions in humans, across different sensory modalities and task protocols. Large pupil responses generally predicted a reduction in decision bias. Using fMRI, we showed that the pupil-linked bias reduction was (i) accompanied by a modulation of choice-encoding pattern signals in parietal and prefrontal cortex and (ii) predicted by phasic, pupil-linked responses of a number of neuromodulatory brainstem centers involved in the control of cortical arousal state, including the noradrenergic locus coeruleus. We conclude that phasic arousal suppresses decision bias on a trial-by-trial basis, thus accounting for a significant component of the variability of choice behavior. DOI: http://dx.doi.org/10.7554/eLife.23232.001 PMID:28383284

Brainstem Correlates of Temporal Auditory Processing in Children with Specific Language Impairment

ERIC Educational Resources Information Center

Basu, Madhavi; Krishnan, Ananthanarayan; Weber-Fox, Christine

2010-01-01

Deficits in identification and discrimination of sounds with short inter-stimulus intervals or short formant transitions in children with specific language impairment (SLI) have been taken to reflect an underlying temporal auditory processing deficit. Using the sustained frequency following response (FFR) and the onset auditory brainstem responses…

Positron Emission Tomography in Cochlear Implant and Auditory Brainstem Implant Recipients.

ERIC Educational Resources Information Center

Miyamoto, Richard T.; Wong, Donald

2001-01-01

Positron emission tomography imaging was used to evaluate the brain's response to auditory stimulation, including speech, in deaf adults (five with cochlear implants and one with an auditory brainstem implant). Functional speech processing was associated with activation in areas classically associated with speech processing. (Contains five…

CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FAILS TO ALTER BRAINSTEM AUDITORY EVOKED RESPONSE (BAERS) IN RATS.

EPA Science Inventory

Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Cholinergic transmission is involved in auditory structures in the periphery and the brainstem and is altered following chlorpyrifos exposure. This study e...

Age-Related Changes in Binaural Interaction at Brainstem Level.

PubMed

Van Yper, Lindsey N; Vermeire, Katrien; De Vel, Eddy F J; Beynon, Andy J; Dhooge, Ingeborg J M

2016-01-01

Age-related hearing loss hampers the ability to understand speech in adverse listening conditions. This is attributed to a complex interaction of changes in the peripheral and central auditory system. One aspect that may deteriorate across the lifespan is binaural interaction. The present study investigates binaural interaction at the level of the auditory brainstem. It is hypothesized that brainstem binaural interaction deteriorates with advancing age. Forty-two subjects of various age participated in the study. Auditory brainstem responses (ABRs) were recorded using clicks and 500 Hz tone-bursts. ABRs were elicited by monaural right, monaural left, and binaural stimulation. Binaural interaction was investigated in two ways. First, grand averages of the binaural interaction component were computed for each age group. Second, wave V characteristics of the binaural ABR were compared with those of the summed left and right ABRs. Binaural interaction in the click ABR was demonstrated by shorter latencies and smaller amplitudes in the binaural compared with the summed monaural responses. For 500 Hz tone-burst ABR, no latency differences were found. However, amplitudes were significantly smaller in the binaural than summed monaural condition. An age-effect was found for 500 Hz tone-burst, but not for click ABR. Brainstem binaural interaction seems to decline with age. Interestingly, these changes seem to be stimulus-dependent.

Exposures to fine particulate matter (PM2.5) and ozone above USA standards are associated with auditory brainstem dysmorphology and abnormal auditory brainstem evoked potentials in healthy young dogs.

PubMed

Calderón-Garcidueñas, Lilian; González-González, Luis O; Kulesza, Randy J; Fech, Tatiana M; Pérez-Guillé, Gabriela; Luna, Miguel Angel Jiménez-Bravo; Soriano-Rosales, Rosa Eugenia; Solorio, Edelmira; Miramontes-Higuera, José de Jesús; Gómez-Maqueo Chew, Aline; Bernal-Morúa, Alexia F; Mukherjee, Partha S; Torres-Jardón, Ricardo; Mills, Paul C; Wilson, Wayne J; Pérez-Guillé, Beatriz; D'Angiulli, Amedeo

2017-10-01

Delayed central conduction times in the auditory brainstem have been observed in Mexico City (MC) healthy children exposed to fine particulate matter (PM 2.5 ) and ozone (O 3 ) above the current United States Environmental Protection Agency (US-EPA) standards. MC children have α synuclein brainstem accumulation and medial superior olivary complex (MSO) dysmorphology. The present study used a dog model to investigate the potential effects of air pollution on the function and morphology of the auditory brainstem. Twenty-four dogs living in clean air v MC, average age 37.1 ± 26.3 months, underwent brainstem auditory evoked potential (BAEP) measurements. Eight dogs (4 MC, 4 Controls) were analysed for auditory brainstem morphology and histopathology. MC dogs showed ventral cochlear nuclei hypotrophy and MSO dysmorphology with a significant decrease in cell body size, decreased neuronal packing density with regions in the nucleus devoid of neurons and marked gliosis. MC dogs showed significant delayed BAEP absolute wave I, III and V latencies compared to controls. MC dogs show auditory nuclei dysmorphology and BAEPs consistent with an alteration of the generator sites of the auditory brainstem response waveform. This study puts forward the usefulness of BAEPs to study auditory brainstem neurodegenerative changes associated with air pollution in dogs. Recognition of the role of non-invasive BAEPs in urban dogs is warranted to elucidate novel neurodegenerative pathways link to air pollution and a promising early diagnostic strategy for Alzheimer's Disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Piracetam-induced changes on the brainstem auditory response in anesthetized juvenile rhesus monkeys (Macaca mulatta). Report of two clinical cases.

PubMed

Durand-Rivera, A; Gonzalez-Pina, R; Hernandez-Godinez, B; Ibanez-Contreras, A; Bueno-Nava, A; Alfaro-Rodriguez, A

2012-10-01

We describe two clinical cases and examine the effects of piracetam on the brainstem auditory response in infantile female rhesus monkeys (Macaca mulatta). We found that the interwave intervals show a greater reduction in a 3-year-old rhesus monkey compared to a 1-year-old rhesus monkey. In this report, we discuss the significance of these observations. © 2012 John Wiley & Sons A/S.

The Effect of Otitis Media with Effusion on the Masking-Level Difference and the Auditory Brainstem Response.

ERIC Educational Resources Information Center

Hall, Joseph W.; Grose, John H.

1993-01-01

This study of 14 children (ages 5-9) with a history of otitis media with effusion found that subjects had significantly reduced masking-level differences (MLD) compared to controls. Results suggest that the reduction in MLD may be related to abnormal brainstem processing. (Author/JDD)

Electrophysiological Evidence for the Sources of the Masking Level Difference

ERIC Educational Resources Information Center

Fowler, Cynthia G.

2017-01-01

Purpose: The purpose of this review article is to review evidence from auditory evoked potential studies to describe the contributions of the auditory brainstem and cortex to the generation of the masking level difference (MLD). Method: A literature review was performed, focusing on the auditory brainstem, middle, and late latency responses used…

CO2-evoked release of PGE2 modulates sighs and inspiration as demonstrated in brainstem organotypic culture

PubMed Central

Forsberg, David; Horn, Zachi; Tserga, Evangelia; Smedler, Erik; Silberberg, Gilad; Shvarev, Yuri; Kaila, Kai; Uhlén, Per; Herlenius, Eric

2016-01-01

Inflammation-induced release of prostaglandin E2 (PGE2) changes breathing patterns and the response to CO2 levels. This may have fatal consequences in newborn babies and result in sudden infant death. To elucidate the underlying mechanisms, we present a novel breathing brainstem organotypic culture that generates rhythmic neural network and motor activity for 3 weeks. We show that increased CO2 elicits a gap junction-dependent release of PGE2. This alters neural network activity in the preBötzinger rhythm-generating complex and in the chemosensitive brainstem respiratory regions, thereby increasing sigh frequency and the depth of inspiration. We used mice lacking eicosanoid prostanoid 3 receptors (EP3R), breathing brainstem organotypic slices and optogenetic inhibition of EP3R+/+ cells to demonstrate that the EP3R is important for the ventilatory response to hypercapnia. Our study identifies a novel pathway linking the inflammatory and respiratory systems, with implications for inspiration and sighs throughout life, and the ability to autoresuscitate when breathing fails. DOI: http://dx.doi.org/10.7554/eLife.14170.001 PMID:27377173

Block-Dependent Sedation during Epidural Anaesthesia is Associated with Delayed Brainstem Conduction

PubMed Central

Wadhwa, Anupama; Shah, Yunus M.; Lin, Chum-Ming; Haugh, Gilbert S.; Sessler, Daniel I.

2005-01-01

Neuraxial anaesthesia produces a sedative and anesthetic-sparing effect. Recent evidence suggests that spinal cord anaesthesia modifies reticulo-thalamo-cortical arousal by decreasing afferent sensory transmission. We hypothesized that epidural anaesthesia produces sensory deafferentation-dependent sedation that is associated with impairment of brainstem transmission. We used brainstem auditory evoked potentials (BAEP) to evaluate reticular function in 11 volunteers. Epidural anaesthesia was induced with 2% 2-chloroprocaine. Hemodynamic and respiratory responses, sensory block level, sedation depth and BAEP were assessed throughout induction and resolution of epidural anaesthesia. Sedation was evaluated using verbal rating score (VRS), observer's assessment alertness/sedation (OAA/S) score, and bispectral index (BIS). Prediction probability (PK) was used to associate sensory block with sedation, as well as BIS with other sedation measures. Spearman rank order correlation was used to associate block level and sedation with the absolute and interpeak BAEP latencies. Sensory block level significantly predicted VRS (PK = 0.747), OAA/S score (PK = 0.748) and BIS. Bispectral index predicted VRS and OAA/S score (PK = 0.728). The latency of wave III of BAEP significantly correlated with sedation level (rho = 0.335, P < 0.01) and sensory block (rho = 0.394, P < 0.01). The other BAEP parameters did not change during epidural anaesthesia. Hemodynamic and respiratory responses remained stable throughout the study. Sedation during epidural anaesthesia depends on sensory block level and is associated with detectable block-dependent alterations in the brainstem auditory evoked responses. Sensory deafferentation may reduce CNS alertness through mechanisms related to brainstem neural activity. PMID:15220178

Ear asymmetries in middle-ear, cochlear, and brainstem responses in human infants

PubMed Central

Keefe, Douglas H.; Gorga, Michael P.; Jesteadt, Walt; Smith, Lynette M.

2008-01-01

In 2004, Sininger and Cone-Wesson examined asymmetries in the signal-to-noise ratio (SNR) of otoacoustic emissions (OAE) in infants, reporting that distortion-product (DP)OAE SNR was larger in the left ear, whereas transient-evoked (TE)OAE SNR was larger in the right. They proposed that cochlear and brainstem asymmetries facilitate development of brain-hemispheric specialization for sound processing. Similarly, in 2006 Sininger and Cone-Wesson described ear asymmetries mainly favoring the right ear in infant auditory brainstem responses (ABRs). The present study analyzed 2640 infant responses to further explore these effects. Ear differences in OAE SNR, signal, and noise were evaluated separately and across frequencies (1.5, 2, 3, and 4 kHz), and ABR asymmetries were compared with cochlear asymmetries. Analyses of ear-canal reflectance and admittance showed that asymmetries in middle-ear functioning did not explain cochlear and brainstem asymmetries. Current results are consistent with earlier studies showing right-ear dominance for TEOAE and ABR. Noise levels were higher in the right ear for OAEs and ABRs, causing ear asymmetries in SNR to differ from those in signal level. No left-ear dominance for DPOAE signal was observed. These results do not support a theory that ear asymmetries in cochlear processing mimic hemispheric brain specialization for auditory processing. PMID:18345839

Cortical auditory evoked potentials in the assessment of auditory neuropathy: two case studies.

PubMed

Pearce, Wendy; Golding, Maryanne; Dillon, Harvey

2007-05-01

Infants with auditory neuropathy and possible hearing impairment are being identified at very young ages through the implementation of hearing screening programs. The diagnosis is commonly based on evidence of normal cochlear function but abnormal brainstem function. This lack of normal brainstem function is highly problematic when prescribing amplification in young infants because prescriptive formulae require the input of hearing thresholds that are normally estimated from auditory brainstem responses to tonal stimuli. Without this information, there is great uncertainty surrounding the final fitting. Cortical auditory evoked potentials may, however, still be evident and reliably recorded to speech stimuli presented at conversational levels. The case studies of two infants are presented that demonstrate how these higher order electrophysiological responses may be utilized in the audiological management of some infants with auditory neuropathy.

TEN DAY EXPOSURES TO CARBONYL SULFIDE PRODUCE BRAINSTEM LESIONS AND CHANGES IN BRAINSTEM AUDITORY EVOKED RESPONSES IN FISCHER 344N RATS.

EPA Science Inventory

Carbonyl sulfide (COS) is a chemical intermediate in the production of pesticides and herbicides, a metabolite of carbon disulfide, a byproduct of the combustion of organic material, and a naturally occurring compound. COS was included in a Toxic Substances Control Act request fo...

Musicians and Tone-Language Speakers Share Enhanced Brainstem Encoding but Not Perceptual Benefits for Musical Pitch

ERIC Educational Resources Information Center

Bidelman, Gavin M.; Gandour, Jackson T.; Krishnan, Ananthanarayan

2011-01-01

Behavioral and neurophysiological transfer effects from music experience to language processing are well-established but it is currently unclear whether or not linguistic expertise (e.g., speaking a tone language) benefits music-related processing and its perception. Here, we compare brainstem responses of English-speaking musicians/non-musicians…

Effects of acute brainstem compression on auditory brainstem response in the guinea pig.

PubMed

Tu, T Y; Yu, L H; Chiu, J H; Shu, C H; Shiao, A S; Lien, C F

1998-11-01

The purpose of this study was to establish the norm for parameters of auditory brainstem response (ABR) in the guinea pig and to investigate if acute brainstem compression results in significant changes to these parameters. Thirty-six guinea pigs with positive Preyer's reflex were anesthetized. A craniectomy was performed to remove the right occipital bone and the dura mater was opened to expose the brain, cerebellum and cerebellopontine angle (CPA). A small inflatable balloon was placed into the CPA precisely and slowly. ABR was recorded before incision of the skin as a baseline value, after placement and after inflation of the balloon with water at 0.1-ml intervals. Five stable peaks were recorded in 27 experimental animals. When the balloon was inflated with 0.1 ml water, the absolute latency (AL) of peaks IV and V and the interpeak latency (IPL) of peaks III and IV, and IV and V were prolonged. The amplitude ratios (AR) of peaks II, III, IV and V to peak I decreased. Inflation of the balloon with 0.2 ml of water caused further elongation of ALs of peaks IV and V and decreases in each AR. When the balloon volume increased to 0.3 ml, peak V became unrecognizable and peaks III and IV showed significant elongation of AL; peaks I and II did not show significant change in ALs. Further increase of the balloon volume to 0.4 ml resulted in disappearance of peaks III, IV and V; AL of peak II was also elongated. However, the amplitude and AL of peak I remained unchanged. Similar changes were observed in IPLs. This study establishes the norm of parameters of ABR in guinea pigs and demonstrates that acute brainstem compression causes elongation of ALs and IPLs of peaks II, III, IV and V. This suggests that peaks II, III, IV and V come from the brainstem and that peak I is not generated from the brainstem in the guinea pig.

Encoding of speech sounds at auditory brainstem level in good and poor hearing aid performers.

PubMed

Shetty, Hemanth Narayan; Puttabasappa, Manjula

Hearing aids are prescribed to alleviate loss of audibility. It has been reported that about 31% of hearing aid users reject their own hearing aid because of annoyance towards background noise. The reason for dissatisfaction can be located anywhere from the hearing aid microphone till the integrity of neurons along the auditory pathway. To measure spectra from the output of hearing aid at the ear canal level and frequency following response recorded at the auditory brainstem from individuals with hearing impairment. A total of sixty participants having moderate sensorineural hearing impairment with age range from 15 to 65 years were involved. Each participant was classified as either Good or Poor Hearing aid Performers based on acceptable noise level measure. Stimuli /da/ and /si/ were presented through loudspeaker at 65dB SPL. At the ear canal, the spectra were measured in the unaided and aided conditions. At auditory brainstem, frequency following response were recorded to the same stimuli from the participants. Spectrum measured in each condition at ear canal was same in good hearing aid performers and poor hearing aid performers. At brainstem level, better F 0 encoding; F 0 and F 1 energies were significantly higher in good hearing aid performers than in poor hearing aid performers. Though the hearing aid spectra were almost same between good hearing aid performers and poor hearing aid performers, subtle physiological variations exist at the auditory brainstem. The result of the present study suggests that neural encoding of speech sound at the brainstem level might be mediated distinctly in good hearing aid performers from that of poor hearing aid performers. Thus, it can be inferred that subtle physiological changes are evident at the auditory brainstem in a person who is willing to accept noise from those who are not willing to accept noise. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Speech Evoked Auditory Brainstem Response in Stuttering

PubMed Central

Tahaei, Ali Akbar; Ashayeri, Hassan; Pourbakht, Akram; Kamali, Mohammad

2014-01-01

Auditory processing deficits have been hypothesized as an underlying mechanism for stuttering. Previous studies have demonstrated abnormal responses in subjects with persistent developmental stuttering (PDS) at the higher level of the central auditory system using speech stimuli. Recently, the potential usefulness of speech evoked auditory brainstem responses in central auditory processing disorders has been emphasized. The current study used the speech evoked ABR to investigate the hypothesis that subjects with PDS have specific auditory perceptual dysfunction. Objectives. To determine whether brainstem responses to speech stimuli differ between PDS subjects and normal fluent speakers. Methods. Twenty-five subjects with PDS participated in this study. The speech-ABRs were elicited by the 5-formant synthesized syllable/da/, with duration of 40 ms. Results. There were significant group differences for the onset and offset transient peaks. Subjects with PDS had longer latencies for the onset and offset peaks relative to the control group. Conclusions. Subjects with PDS showed a deficient neural timing in the early stages of the auditory pathway consistent with temporal processing deficits and their abnormal timing may underlie to their disfluency. PMID:25215262

The c-FOS Protein Immunohistological Detection: A Useful Tool As a Marker of Central Pathways Involved in Specific Physiological Responses In Vivo and Ex Vivo

PubMed Central

Perrin-Terrin, Anne-Sophie; Jeton, Florine; Pichon, Aurelien; Frugière, Alain; Richalet, Jean-Paul; Bodineau, Laurence; Voituron, Nicolas

2016-01-01

Many studies seek to identify and map the brain regions involved in specific physiological regulations. The proto-oncogene c-fos, an immediate early gene, is expressed in neurons in response to various stimuli. The protein product can be readily detected with immunohistochemical techniques leading to the use of c-FOS detection to map groups of neurons that display changes in their activity. In this article, we focused on the identification of brainstem neuronal populations involved in the ventilatory adaptation to hypoxia or hypercapnia. Two approaches were described to identify involved neuronal populations in vivo in animals and ex vivo in deafferented brainstem preparations. In vivo, animals were exposed to hypercapnic or hypoxic gas mixtures. Ex vivo, deafferented preparations were superfused with hypoxic or hypercapnic artificial cerebrospinal fluid. In both cases, either control in vivo animals or ex vivo preparations were maintained under normoxic and normocapnic conditions. The comparison of these two approaches allows the determination of the origin of the neuronal activation i.e., peripheral and/or central. In vivo and ex vivo, brainstems were collected, fixed, and sliced into sections. Once sections were prepared, immunohistochemical detection of the c-FOS protein was made in order to identify the brainstem groups of cells activated by hypoxic or hypercapnic stimulations. Labeled cells were counted in brainstem respiratory structures. In comparison to the control condition, hypoxia or hypercapnia increased the number of c-FOS labeled cells in several specific brainstem sites that are thus constitutive of the neuronal pathways involved in the adaptation of the central respiratory drive. PMID:27167092

Brainstem auditory evoked responses in man. 1: Effect of stimulus rise-fall time and duration

NASA Technical Reports Server (NTRS)

Hecox, K.; Squires, N.; Galambos, R.

1975-01-01

Short latency (under 10 msec) evoked responses elicited by bursts of white noise were recorded from the scalp of human subjects. Response alterations produced by changes in the noise burst duration (on-time) inter-burst interval (off-time), and onset and offset shapes are reported and evaluated. The latency of the most prominent response component, wave V, was markedly delayed with increases in stimulus rise-time but was unaffected by changes in fall-time. The amplitude of wave V was insensitive to changes in signal rise-and-fall times, while increasing signal on-time produced smaller amplitude responses only for sufficiently short off-times. It is concluded that wave V of the human auditory brainstem evoked response is solely an onset response.

Changes in pitch height elicit both language universal and language dependent changes in neural representation of pitch in the brainstem and auditory cortex

PubMed Central

Krishnan, Ananthanarayan; Suresh, Chandan H.; Gandour, Jackson T.

2017-01-01

Language experience shapes encoding of pitch-relevant information at both brainstem and cortical levels of processing. Pitch height is a salient dimension that orders pitch from low to high. Herein we investigate the effects of language experience (Chinese, English) in the brainstem and cortex on i) neural responses to variations in pitch height, ii) presence of asymmetry in cortical pitch representation, and iii) patterns of relative changes in magnitude of pitch height between these two levels of brain structure. Stimuli were three nonspeech homologs of Mandarin Tone 2 varying in pitch height only. The frequency-following response (FFR) and the cortical pitch-specific response (CPR) were recorded concurrently. At the Fz-linked T7/T8 site, peak latency of Na, Pb, and Nb decreased with increasing pitch height for both groups. Peak-to-peak amplitude of Na–Pb and Pb–Nb increased with increasing pitch height across groups. A language-dependent effect was restricted to Na-Pb; the Chinese had larger amplitude than the English group. At temporal sites (T7/T8), the Chinese group had larger amplitude, as compared to English, across stimuli, but also limited to the Na-Pb component and right temporal site. In the brainstem, F0 magnitude decreased with increasing pitch height; Chinese had larger magnitude across stimuli. A comparison of CPR and FFR responses revealed distinct patterns of relative changes in magnitude common to both groups. CPR amplitude increased and FFR amplitude decreased with increasing pitch height. Experience-dependent effects on CPR components vary as a function of neural sensitivity to pitch height within a particular temporal window (Na–Pb). Differences between the auditory brainstem and cortex imply distinct neural mechanisms for pitch extraction at both levels of brain structure. PMID:28108254

Changes in pitch height elicit both language-universal and language-dependent changes in neural representation of pitch in the brainstem and auditory cortex.

PubMed

Krishnan, Ananthanarayan; Suresh, Chandan H; Gandour, Jackson T

2017-03-27

Language experience shapes encoding of pitch-relevant information at both brainstem and cortical levels of processing. Pitch height is a salient dimension that orders pitch from low to high. Herein we investigate the effects of language experience (Chinese, English) in the brainstem and cortex on (i) neural responses to variations in pitch height, (ii) presence of asymmetry in cortical pitch representation, and (iii) patterns of relative changes in magnitude of pitch height between these two levels of brain structure. Stimuli were three nonspeech homologs of Mandarin Tone 2 varying in pitch height only. The frequency-following response (FFR) and the cortical pitch-specific response (CPR) were recorded concurrently. At the Fz-linked T7/T8 site, peak latency of Na, Pb, and Nb decreased with increasing pitch height for both groups. Peak-to-peak amplitude of Na-Pb and Pb-Nb increased with increasing pitch height across groups. A language-dependent effect was restricted to Na-Pb; the Chinese had larger amplitude than the English group. At temporal sites (T7/T8), the Chinese group had larger amplitude, as compared to English, across stimuli, but also limited to the Na-Pb component and right temporal site. In the brainstem, F0 magnitude decreased with increasing pitch height; Chinese had larger magnitude across stimuli. A comparison of CPR and FFR responses revealed distinct patterns of relative changes in magnitude common to both groups. CPR amplitude increased and FFR amplitude decreased with increasing pitch height. Experience-dependent effects on CPR components vary as a function of neural sensitivity to pitch height within a particular temporal window (Na-Pb). Differences between the auditory brainstem and cortex imply distinct neural mechanisms for pitch extraction at both levels of brain structure. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Development of N-Methyl-D-Aspartate Receptor Subunits in Avian Auditory Brainstem

PubMed Central

TANG, YE-ZHONG; CARR, CATHERINE E.

2012-01-01

N-methyl-D-aspartate (NMDA) receptor subunit-specific probes were used to characterize developmental changes in the distribution of excitatory amino acid receptors in the chicken’s auditory brainstem nuclei. Although NR1 subunit expression does not change greatly during the development of the cochlear nuclei in the chicken (Tang and Carr [2004] Hear. Res 191:79 – 89), there are significant developmental changes in NR2 subunit expression. We used in situ hybridization against NR1, NR2A, NR2B, NR2C, and NR2D to compare NR1 and NR2 expression during development. All five NMDA subunits were expressed in the auditory brainstem before embryonic day (E) 10, when electrical activity and synaptic responses appear in the nucleus magnocellularis (NM) and the nucleus laminaris (NL). At this time, the dominant form of the receptor appeared to contain NR1 and NR2B. NR2A appeared to replace NR2B by E14, a time that coincides with synaptic refinement and evoked auditory responses. NR2C did not change greatly during auditory development, whereas NR2D increased from E10 and remained at fairly high levels into adulthood. Thus changes in NMDA NR2 receptor subunits may contribute to the development of auditory brainstem responses in the chick. PMID:17366608

Auditory- and visual-evoked potentials in Mexican infants are not affected by maternal supplementation with 400 mg/d docosahexaenoic acid in the second half of pregnancy.

PubMed

Stein, Aryeh D; Wang, Meng; Rivera, Juan A; Martorell, Reynaldo; Ramakrishnan, Usha

2012-08-01

The evidence relating prenatal supplementation with DHA to offspring neurological development is limited. We investigated the effect of prenatal DHA supplementation on infant brainstem auditory-evoked responses and visual- evoked potentials in a double-blind, randomized controlled trial in Cuernavaca, Mexico. Pregnant women were supplemented daily with 400 mg DHA or placebo from gestation wk 18-22 through delivery. DHA and placebo groups did not differ in maternal characteristics at randomization or infant characteristics at birth. Brainstem auditory-evoked responses were measured at 1 and 3 mo in 749 and 664 infants, respectively, and visual-evoked potentials were measured at 3 and 6 mo in 679 and 817 infants, respectively. Left-right brainstem auditory-evoked potentials were moderately correlated (range, 0.26-0.43; all P < 0.001) and left-right visual-evoked potentials were strongly correlated (range, 0.79-0.94; all P < 0.001) within any assessment. Correlations across visits were modest to moderate (range, 0.09-0.38; all P < 0.01). The offspring of DHA-supplemented women did not differ from those of control women with respect to any outcome measure (all comparisons P > 0.10). We conclude that DHA supplementation during pregnancy did not influence brainstem auditory-evoked responses at 1 and 3 mo or visual-evoked potentials at 3 and 6 mo.

Neonatal brainstem dysfunction risks infant social engagement

PubMed Central

Sopher, Koreen; Kurtzman, Lea; Galili, Giora; Feldman, Ruth; Kuint, Jacob

2013-01-01

The role of the brainstem in mediating social signaling in phylogenetic ancestral organisms has been demonstrated. Evidence for its involvement in social engagement in human infants may deepen the understanding of the evolutionary pathway of humans as social beings. In this longitudinal study, neonatal brainstem functioning was measured by auditory brainstem-evoked responses (ABRs) in 125 healthy neonates born prematurely before 35 weeks’ gestational age. At 4 months, infants were tested in a set of structured vignettes that required varying levels of social engagement and cardiac vagal tone was assessed. Data show that neonates with a disrupted I–V waveform, evident mostly by delayed wave V, exhibit shorter latencies to gaze averts in episodes involving direct face-to-face interactions but engage gaze as controls when interacting with masked agents or with agents whose faces are partly veiled by toys. Analysis of variance of infants’ social engagement with ABR, neonatal risk, maternal stress and cardiac vagal tone showed a main effect for ABR and an ABR by gestational age interaction. The integrity of brainstem transmission of sensory information during the final weeks of gestation may scaffold the development of social disengagement, thereby attesting to the brainstem's preserved evolutionary role in developing humans as social organisms prior to engaging in social encounters. PMID:22146141

Curcumin restores diabetes induced neurochemical changes in the brain stem of Wistar rats.

PubMed

Kumar, Peeyush T; George, Naijil; Antony, Sherin; Paulose, Cheramadathikudiyil Skaria

2013-02-28

Diabetes mellitus, when poorly controlled, leads to debilitating central nervous system (CNS) complications including cognitive deficits, somatosensory and motor dysfunction. The present study investigated curcumin's potential in modulating diabetes induced neurochemical changes in brainstem. Expression analysis of cholinergic, insulin receptor and GLUT-3 in the brainstem of streptozotocin (STZ) induced diabetic rats were studied. Radioreceptor binding assays, gene expression studies and immunohistochemical analysis were done in the brainstem of male Wistar rats. Our result showed that Bmax of total muscarinic and muscarinic M3 receptors were increased and muscarinic M1 receptor was decreased in diabetic rats compared to control. mRNA level of muscarinic M3, α7-nicotinic acetylcholine, insulin receptors, acetylcholine esterase, choline acetyltransferase and GLUT-3 significantly increased and M1 receptor decreased in the brainstem of diabetic rats. Curcumin and insulin treatment restored the alterations and maintained all parameters to near control. The results show that diabetes is associated with significant reduction in brainstem function coupled with altered cholinergic, insulin receptor and GLUT-3 gene expression. The present study indicates beneficial effect of curcumin in diabetic rats by regulating the cholinergic, insulin receptor and GLUT-3 in the brainstem similar to the responses obtained with insulin therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

Brainstem dysfunction protects against syncope in multiple sclerosis.

PubMed

Habek, Mario; Krbot Skorić, Magdalena; Crnošija, Luka; Adamec, Ivan

2015-10-15

The aim of this study was to investigate the correlation between autonomic dysfunction in multiple sclerosis (MS) and brainstem dysfunction evaluated with the vestibular evoked myogenic potentials (VEMP) score and conventional MRI. Forty-five patients with the diagnosis of clinically isolated syndrome (CIS) suggestive of MS were enrolled. VEMP, heart rate, and blood pressure responses to the Valsalva maneuver, heart rate response to deep breathing, and pain provoked head-up tilt table test, as well as brain and spinal cord MRI were performed. There was no difference in the VEMP score between patients with and without signs of sympathetic or parasympathetic dysfunction. However, patients with syncope had significantly lower VEMP score compared to patients without syncope (p<0.01). Patients with orthostatic hypotension (OH) showed a trend of higher VEMP score compared to patients without OH (p=0.06). There was no difference in the presence of lesions in the brainstem or cervical spinal cord between patients with or without any of the studied autonomic parameters. The model consisting of a VEMP score of ≤5 and normal MRI of the midbrain and cervical spinal cord has sensitivity and specificity of 83% for the possibility that the patient with MS can develop syncope. Pathophysiological mechanisms underlying functional and structural disorders of autonomic nervous system in MS differ significantly. While preserved brainstem function is needed for development of syncope, structural disorders like OH could be associated with brainstem dysfunction. Copyright © 2015 Elsevier B.V. All rights reserved.

Auditory evoked potentials: predicting speech therapy outcomes in children with phonological disorders.

PubMed

Leite, Renata Aparecida; Wertzner, Haydée Fiszbein; Gonçalves, Isabela Crivellaro; Magliaro, Fernanda Cristina Leite; Matas, Carla Gentile

2014-03-01

This study investigated whether neurophysiologic responses (auditory evoked potentials) differ between typically developed children and children with phonological disorders and whether these responses are modified in children with phonological disorders after speech therapy. The participants included 24 typically developing children (Control Group, mean age: eight years and ten months) and 23 children clinically diagnosed with phonological disorders (Study Group, mean age: eight years and eleven months). Additionally, 12 study group children were enrolled in speech therapy (Study Group 1), and 11 were not enrolled in speech therapy (Study Group 2). The subjects were submitted to the following procedures: conventional audiological, auditory brainstem response, auditory middle-latency response, and P300 assessments. All participants presented with normal hearing thresholds. The study group 1 subjects were reassessed after 12 speech therapy sessions, and the study group 2 subjects were reassessed 3 months after the initial assessment. Electrophysiological results were compared between the groups. Latency differences were observed between the groups (the control and study groups) regarding the auditory brainstem response and the P300 tests. Additionally, the P300 responses improved in the study group 1 children after speech therapy. The findings suggest that children with phonological disorders have impaired auditory brainstem and cortical region pathways that may benefit from speech therapy.

Auditory- and Vestibular-Evoked Potentials Correlate with Motor and Non-Motor Features of Parkinson’s Disease

PubMed Central

Shalash, Ali Soliman; Hassan, Dalia Mohamed; Elrassas, Hanan Hani; Salama, Mohamed Mosaad; Méndez-Hernández, Edna; Salas-Pacheco, José M.; Arias-Carrión, Oscar

2017-01-01

Degeneration of several brainstem nuclei has been long related to motor and non-motor symptoms (NMSs) of Parkinson’s disease (PD). Nevertheless, due to technical issues, there are only a few studies that correlate that association. Brainstem auditory-evoked potential (BAEP) and vestibular-evoked myogenic potential (VEMP) responses represent a valuable tool for brainstem assessment. Here, we investigated the abnormalities of BAEPs, ocular VEMPs (oVEMPs), and cervical VEMPs (cVEMPs) in patients with PD and its correlation to the motor and NMSs. Fifteen patients diagnosed as idiopathic PD were evaluated by Unified Parkinson’s Disease Rating Scale and its subscores, Hoehn and Yahr scale, Schwab and England scale, and Non-Motor Symptoms Scale. PD patients underwent pure-tone, speech audiometry, tympanometry, BAEP, oVEMPs, and cVEMPs, and compared to 15 age-matched control subjects. PD subjects showed abnormal BAEP wave morphology, prolonged absolute latencies of wave V and I–V interpeak latencies. Absent responses were the marked abnormality seen in oVEMP. Prolonged latencies with reduced amplitudes were seen in cVEMP responses. Rigidity and bradykinesia were correlated to the BAEP and cVEMP responses contralateral to the clinically more affected side. Contralateral and ipsilateral cVEMPs were significantly correlated to sleep (p = 0.03 and 0.001), perception (p = 0.03), memory/cognition (p = 0.025), and urinary scores (p = 0.03). The oVEMP responses showed significant correlations to cardiovascular (p = 0.01) and sexual dysfunctions (p = 0.013). PD is associated with BAEP and VEMP abnormalities that are correlated to the motor and some non-motor clinical characteristics. These abnormalities could be considered as potential electrophysiological biomarkers for brainstem dysfunction and its associated motor and non-motor features. PMID:28289399

Cortical influences on brainstem circuitry responsible for conditioned pain modulation in humans.

PubMed

Youssef, Andrew M; Macefield, Vaughan G; Henderson, Luke A

2016-07-01

Conditioned pain modulation (CPM) is a powerful endogenous analgesic mechanism which can completely inhibit incoming nociceptor signals at the primary synapse. The circuitry responsible for CPM lies within the brainstem and involves the subnucleus reticularis dorsalis (SRD). While the brainstem is critical for CPM, the cortex can significantly modulate its expression, likely via the brainstem circuitry critical for CPM. Since higher cortical regions such as the anterior, mid-cingulate, and dorsolateral prefrontal cortices are activated by noxious stimuli and show reduced activations during other analgesic responses, we hypothesized that these regions would display reduced responses during CPM analgesia. Furthermore, we hypothesized that functional connectivity strength between these cortical regions and the SRD would be stronger in those that express CPM analgesia compared with those that do not. We used functional magnetic resonance imaging to determine sites recruited during CPM expression and their influence on the SRD. A lack of CPM analgesia was associated with greater signal intensity increases during each test stimulus in the presence of the conditioning stimulus compared to test stimuli alone in the mid-cingulate and dorsolateral prefrontal cortices and increased functional connectivity with the SRD. In contrast, those subjects exhibiting CPM analgesia showed no change in the magnitude of signal intensity increases in these cortical regions or strength of functional connectivity with the SRD. These data suggest that during multiple or widespread painful stimuli, engagement of the prefrontal and cingulate cortices prevents the generation of CPM analgesia, raising the possibility altered responsiveness in these cortical regions underlie the reduced CPM observed in individuals with chronic pain. Hum Brain Mapp 37:2630-2644, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Convergent input from brainstem coincidence detectors onto delay-sensitive neurons in the inferior colliculus.

PubMed

McAlpine, D; Jiang, D; Shackleton, T M; Palmer, A R

1998-08-01

Responses of low-frequency neurons in the inferior colliculus (IC) of anesthetized guinea pigs were studied with binaural beats to assess their mean best interaural phase (BP) to a range of stimulating frequencies. Phase plots (stimulating frequency vs BP) were produced, from which measures of characteristic delay (CD) and characteristic phase (CP) for each neuron were obtained. The CD provides an estimate of the difference in travel time from each ear to coincidence-detector neurons in the brainstem. The CP indicates the mechanism underpinning the coincidence detector responses. A linear phase plot indicates a single, constant delay between the coincidence-detector inputs from the two ears. In more than half (54 of 90) of the neurons, the phase plot was not linear. We hypothesized that neurons with nonlinear phase plots received convergent input from brainstem coincidence detectors with different CDs. Presentation of a second tone with a fixed, unfavorable delay suppressed the response of one input, linearizing the phase plot and revealing other inputs to be relatively simple coincidence detectors. For some neurons with highly complex phase plots, the suppressor tone altered BP values, but did not resolve the nature of the inputs. For neurons with linear phase plots, the suppressor tone either completely abolished their responses or reduced their discharge rate with no change in BP. By selectively suppressing inputs with a second tone, we are able to reveal the nature of underlying binaural inputs to IC neurons, confirming the hypothesis that the complex phase plots of many IC neurons are a result of convergence from simple brainstem coincidence detectors.

Central nervous versus total body thermosensitivity of the duck

NASA Astrophysics Data System (ADS)

Simon, E.; Martin, R.; Simon-Oppermann, Ch.

1981-09-01

Ducks were chronically implanted with thermodes in the POAH region, the lower brainstem or the vertebral canal. At thermoneutral conditions, lowering the temperature of the spinal cord (Tvc) or the lower brainstem (Tmb) stimulated metabolic heat production (M) with a subsequent rise of core temperature (Tc). Lowering the temperature of the POAH region (Thy) induced a fall of Tc due to paradoxical activation of heat defence and, thus, induced slight to moderate general hypothermia depending on the cooling intensity. When Thy was normalized, the hypothermia temporarily stimulated metabolic heat production until Tc was normalized. Cold sensitivity of the entire body, as revealed by the metabolic response to the hypothermia induced by preceding POAH cooling, and cold sensitivity of the spinal cord and the lower brainstem, as revealed by the metabolic response to local cooling, were quantified by calculating the quotient δM/δT from the maximum metabolic response and the experimentally induced drop of Tc, Tmb and Tvc. With lower brainstem cooling δM/δTmbdid not exceed -0.4 W/(kg · ‡C). With spinal cord cooling, δM/δTvc did not exceed -0.6 W/(kg · ‡C). The mean value of δM/δTc after hypothermia induced by POAH cooling was -4.02 W/(kg · ‡C). The results indicate that the cold sensitivity residing in the CNS of ducks represents only a small fraction of the entire cold sensitivity of the body.

Auditory- and Visual-Evoked Potentials in Mexican Infants Are Not Affected by Maternal Supplementation with 400 mg/d Docosahexaenoic Acid in the Second Half of Pregnancy1234

PubMed Central

Stein, Aryeh D.; Wang, Meng; Rivera, Juan A.; Martorell, Reynaldo; Ramakrishnan, Usha

2012-01-01

The evidence relating prenatal supplementation with DHA to offspring neurological development is limited. We investigated the effect of prenatal DHA supplementation on infant brainstem auditory-evoked responses and visual- evoked potentials in a double-blind, randomized controlled trial in Cuernavaca, Mexico. Pregnant women were supplemented daily with 400 mg DHA or placebo from gestation wk 18–22 through delivery. DHA and placebo groups did not differ in maternal characteristics at randomization or infant characteristics at birth. Brainstem auditory-evoked responses were measured at 1 and 3 mo in 749 and 664 infants, respectively, and visual-evoked potentials were measured at 3 and 6 mo in 679 and 817 infants, respectively. Left-right brainstem auditory-evoked potentials were moderately correlated (range, 0.26–0.43; all P < 0.001) and left-right visual-evoked potentials were strongly correlated (range, 0.79–0.94; all P < 0.001) within any assessment. Correlations across visits were modest to moderate (range, 0.09–0.38; all P < 0.01). The offspring of DHA-supplemented women did not differ from those of control women with respect to any outcome measure (all comparisons P > 0.10). We conclude that DHA supplementation during pregnancy did not influence brainstem auditory-evoked responses at 1 and 3 mo or visual-evoked potentials at 3 and 6 mo. PMID:22739364

Impact of monaural frequency compression on binaural fusion at the brainstem level.

PubMed

Klauke, Isabelle; Kohl, Manuel C; Hannemann, Ronny; Kornagel, Ulrich; Strauss, Daniel J; Corona-Strauss, Farah I

2015-08-01

A classical objective measure for binaural fusion at the brainstem level is the so-called β-wave of the binaural interaction component (BIC) in the auditory brainstem response (ABR). However, in some cases it appeared that a reliable detection of this component still remains a challenge. In this study, we investigate the wavelet phase synchronization stability (WPSS) of ABR data for the analysis of binaural fusion and compare it to the BIC. In particular, we examine the impact of monaural nonlinear frequency compression on binaural fusion. As the auditory system is tonotopically organized, an interaural frequency mismatch caused by monaural frequency compression could negatively effect binaural fusion. In this study, only few subjects showed a detectable β-wave and in most cases only for low ITDs. However, we present a novel objective measure for binaural fusion that outperforms the current state-of-the-art technique (BIC): the WPSS analysis showed a significant difference between the phase stability of the sum of the monaurally evoked responses and the phase stability of the binaurally evoked ABR. This difference could be an indicator for binaural fusion in the brainstem. Furthermore, we observed that monaural frequency compression could indeed effect binaural fusion, as the WPSS results for this condition vary strongly from the results obtained without frequency compression.

Cerebral and brainstem electrophysiologic activity during euthanasia with pentobarbital sodium in horses.

PubMed

Aleman, M; Williams, D C; Guedes, A; Madigan, J E

2015-01-01

An overdose of pentobarbital sodium administered i.v. is the most commonly used method of euthanasia in veterinary medicine. Determining death after the infusion relies on the observation of physical variables. However, it is unknown when cortical electrical activity and brainstem function are lost in a sequence of events before death. To examine changes in the electrical activity of the cerebral cortex and brainstem during an overdose of pentobarbital sodium solution for euthanasia. Our testing hypothesis is that isoelectric pattern of the brain in support of brain death occurs before absence of electrocardiogram (ECG) activity. Fifteen horses requiring euthanasia. Prospective observational study. Horses with neurologic, orthopedic, and cardiac illnesses were selected and instrumented for recording of electroencephalogram, electrooculogram, brainstem auditory evoked response (BAER), and ECG. Physical and neurologic (brainstem reflexes) variables were monitored. Loss of cortical electrical activity occurred during or within 52 seconds after the infusion of euthanasia solution. Cessation of brainstem function as evidenced by a lack of brainstem reflexes and disappearance of the BAER happened subsequently. Despite undetectable heart sounds, palpable arterial pulse, and mean arterial pressure, recordable ECG was the last variable to be lost after the infusion (5.5-16 minutes after end of the infusion). Overdose of pentobarbital sodium solution administered i.v. is an effective, fast, and humane method of euthanasia. Brain death occurs within 73-261 seconds of the infusion. Although absence of ECG activity takes longer to occur, brain death has already occurred. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Diffusion tensor imaging demonstrates brainstem and cerebellar abnormalities in congenital central hypoventilation syndrome.

PubMed

Kumar, Rajesh; Macey, Paul M; Woo, Mary A; Alger, Jeffry R; Harper, Ronald M

2008-09-01

Congenital central hypoventilation syndrome (CCHS) patients show reduced breathing drive during sleep, decreased hypoxic and hypercapnic ventilatory responses, and autonomic and affective deficits, suggesting both brainstem and forebrain injuries. Forebrain damage was previously described in CCHS, but methodological limitations precluded detection of brainstem injury, a concern because genetic mutations in CCHS target brainstem autonomic nuclei. To assess brainstem and cerebellar areas, we used diffusion tensor imaging-based measures, namely axial diffusivity, reflecting water diffusion parallel to fibers, and sensitive to axonal injury, and radial diffusivity, measuring diffusion perpendicular to fibers, and indicative of myelin injury. Diffusion tensor imaging was performed in 12 CCHS and 26 controls, and axial and radial diffusivity maps were compared between groups using analysis of covariance (covariates; age and gender). Increased axial diffusivity in CCHS appeared within the lateral medulla and clusters with injury extended from the dorsal midbrain through the periaqueductal gray, raphé, and superior cerebellar decussation, ventrally to the basal-pons. Cerebellar cortex and deep nuclei, and the superior and inferior cerebellar peduncles showed increased radial diffusivity. Midbrain, pontine, and lateral medullary structures, and the cerebellum and its fiber systems are injured in CCHS, likely contributing to the characteristics found in the syndrome.

Working memory capacity and visual-verbal cognitive load modulate auditory-sensory gating in the brainstem: toward a unified view of attention.

PubMed

Sörqvist, Patrik; Stenfelt, Stefan; Rönnberg, Jerker

2012-11-01

Two fundamental research questions have driven attention research in the past: One concerns whether selection of relevant information among competing, irrelevant, information takes place at an early or at a late processing stage; the other concerns whether the capacity of attention is limited by a central, domain-general pool of resources or by independent, modality-specific pools. In this article, we contribute to these debates by showing that the auditory-evoked brainstem response (an early stage of auditory processing) to task-irrelevant sound decreases as a function of central working memory load (manipulated with a visual-verbal version of the n-back task). Furthermore, individual differences in central/domain-general working memory capacity modulated the magnitude of the auditory-evoked brainstem response, but only in the high working memory load condition. The results support a unified view of attention whereby the capacity of a late/central mechanism (working memory) modulates early precortical sensory processing.

Pontine hyperperfusion in sporadic hyperekplexia

PubMed Central

Vetrugno, Roberto; Mascalchi, Mario; Vella, Alessandra; Nave, Riccardo Della; Guerrini, Laura; Vattimo, Angelo; del Giudice, Emanuele Miraglia; Plazzi, Giuseppe; D'Angelo, Roberto; Greco, Giovanni; Montagna, Pasquale

2007-01-01

Objective To explore with neuroimaging techniques the anatomical and functional correlates of sporadic hyperekplexia. Methods Two elderly women with sporadic hyperekplexia underwent neurophysiological assessment, MRI of the brain and proton magnetic resonance spectroscopy (1H‐MRS) of the brainstem and frontal lobes. Regional cerebral blood flow was investigated with single photon emission tomography (SPECT) during evoked startles and at rest. Results Both patients showed excessively large and non‐habituating startle responses. In both patients, MRI showed impingement of the brainstem by the vertebrobasilar artery, lack of frontal or brainstem abnormalities on 1H‐MRS and hyperperfusion in the dorsal pons and cingulate cortex, and superior frontal gyrus at SPECT during evoked startles. Conclusions In our patients with hyperekplexia, the vertebrobasilar arteries were found to impinge on the brainstem. Neurophysiological findings and neurofunctional imaging of evoked startles indicated a pontine origin of the movement disorder modulated by activation in cortical, especially frontal, areas. The neurofunctional correlates of evoked startles in human sporadic hyperekplexia are similar to those observed for the startle circuit in animals. PMID:17702784

Pontine hyperperfusion in sporadic hyperekplexia.

PubMed

Vetrugno, Roberto; Mascalchi, Mario; Vella, Alessandra; Della Nave, Riccardo; Guerrini, Laura; Vattimo, Angelo; del Giudice, Emanuele Miraglia; Plazzi, Giuseppe; D'Angelo, Roberto; Greco, Giovanni; Montagna, Pasquale

2007-09-01

To explore with neuroimaging techniques the anatomical and functional correlates of sporadic hyperekplexia. Two elderly women with sporadic hyperekplexia underwent neurophysiological assessment, MRI of the brain and proton magnetic resonance spectroscopy (1H-MRS) of the brainstem and frontal lobes. Regional cerebral blood flow was investigated with single photon emission tomography (SPECT) during evoked startles and at rest. Both patients showed excessively large and non-habituating startle responses. In both patients, MRI showed impingement of the brainstem by the vertebrobasilar artery, lack of frontal or brainstem abnormalities on 1H-MRS and hyperperfusion in the dorsal pons and cingulate cortex, and superior frontal gyrus at SPECT during evoked startles. In our patients with hyperekplexia, the vertebrobasilar arteries were found to impinge on the brainstem. Neurophysiological findings and neurofunctional imaging of evoked startles indicated a pontine origin of the movement disorder modulated by activation in cortical, especially frontal, areas. The neurofunctional correlates of evoked startles in human sporadic hyperekplexia are similar to those observed for the startle circuit in animals.

The auditory enhancement effect is not reflected in the 80-Hz auditory steady-state response.

PubMed

Carcagno, Samuele; Plack, Christopher J; Portron, Arthur; Semal, Catherine; Demany, Laurent

2014-08-01

The perceptual salience of a target tone presented in a multitone background is increased by the presentation of a precursor sound consisting of the multitone background alone. It has been proposed that this "enhancement" phenomenon results from an effective amplification of the neural response to the target tone. In this study, we tested this hypothesis in humans, by comparing the auditory steady-state response (ASSR) to a target tone that was enhanced by a precursor sound with the ASSR to a target tone that was not enhanced. In order to record neural responses originating in the brainstem, the ASSR was elicited by amplitude modulating the target tone at a frequency close to 80 Hz. The results did not show evidence of an amplified neural response to enhanced tones. In a control condition, we measured the ASSR to a target tone that, instead of being perceptually enhanced by a precursor sound, was acoustically increased in level. This level increase matched the magnitude of enhancement estimated psychophysically with a forward masking paradigm in a previous experimental phase. We found that the ASSR to the tone acoustically increased in level was significantly greater than the ASSR to the tone enhanced by the precursor sound. Overall, our results suggest that the enhancement effect cannot be explained by an amplified neural response at the level of the brainstem. However, an alternative possibility is that brainstem neurons with enhanced responses do not contribute to the scalp-recorded ASSR.

Systematic Morphometry of Catecholamine Nuclei in the Brainstem.

PubMed

Bucci, Domenico; Busceti, Carla L; Calierno, Maria T; Di Pietro, Paola; Madonna, Michele; Biagioni, Francesca; Ryskalin, Larisa; Limanaqi, Fiona; Nicoletti, Ferdinando; Fornai, Francesco

2017-01-01

Catecholamine nuclei within the brainstem reticular formation (RF) play a pivotal role in a variety of brain functions. However, a systematic characterization of these nuclei in the very same experimental conditions is missing so far. Tyrosine hydroxylase (TH) immune-positive cells of the brainstem correspond to dopamine (DA)-, norepinephrine (NE)-, and epinephrine (E)-containing cells. Here, we report a systematic count of TH-positive neurons in the RF of the mouse brainstem by using stereological morphometry. All these nuclei were analyzed for anatomical localization, rostro-caudal extension, volume, neuron number, neuron density, and mean neuronal area for each nucleus. The present data apart from inherent informative value wish to represent a reference for neuronal mapping in those studies investigating the functional anatomy of the brainstem RF. These include: the sleep-wake cycle, movement control, muscle tone modulation, mood control, novelty orienting stimuli, attention, archaic responses to internal and external stressful stimuli, anxiety, breathing, blood pressure, and innumerable activities modulated by the archaic iso-dendritic hard core of the brainstem RF. Most TH-immune-positive cells fill the lateral part of the RF, which indeed possesses a high catecholamine content. A few nuclei are medial, although conventional nosography considers all these nuclei as part of the lateral column of the RF. Despite the key role of these nuclei in psychiatric and neurological disorders, only a few of them aspired a great attention in biomedical investigation, while most of them remain largely obscure although intense research is currently in progress. A simultaneous description of all these nuclei is not simply key to comprehend the variety of brainstem catecholamine reticular neurons, but probably represents an intrinsically key base for understanding brain physiology and physiopathology.

Systematic Morphometry of Catecholamine Nuclei in the Brainstem

PubMed Central

Bucci, Domenico; Busceti, Carla L.; Calierno, Maria T.; Di Pietro, Paola; Madonna, Michele; Biagioni, Francesca; Ryskalin, Larisa; Limanaqi, Fiona; Nicoletti, Ferdinando; Fornai, Francesco

2017-01-01

Catecholamine nuclei within the brainstem reticular formation (RF) play a pivotal role in a variety of brain functions. However, a systematic characterization of these nuclei in the very same experimental conditions is missing so far. Tyrosine hydroxylase (TH) immune-positive cells of the brainstem correspond to dopamine (DA)-, norepinephrine (NE)-, and epinephrine (E)-containing cells. Here, we report a systematic count of TH-positive neurons in the RF of the mouse brainstem by using stereological morphometry. All these nuclei were analyzed for anatomical localization, rostro-caudal extension, volume, neuron number, neuron density, and mean neuronal area for each nucleus. The present data apart from inherent informative value wish to represent a reference for neuronal mapping in those studies investigating the functional anatomy of the brainstem RF. These include: the sleep-wake cycle, movement control, muscle tone modulation, mood control, novelty orienting stimuli, attention, archaic responses to internal and external stressful stimuli, anxiety, breathing, blood pressure, and innumerable activities modulated by the archaic iso-dendritic hard core of the brainstem RF. Most TH-immune-positive cells fill the lateral part of the RF, which indeed possesses a high catecholamine content. A few nuclei are medial, although conventional nosography considers all these nuclei as part of the lateral column of the RF. Despite the key role of these nuclei in psychiatric and neurological disorders, only a few of them aspired a great attention in biomedical investigation, while most of them remain largely obscure although intense research is currently in progress. A simultaneous description of all these nuclei is not simply key to comprehend the variety of brainstem catecholamine reticular neurons, but probably represents an intrinsically key base for understanding brain physiology and physiopathology. PMID:29163071

Protective effects of brain-derived neurotrophic factor on the noise-damaged cochlear spiral ganglion.

PubMed

Zhai, S-Q; Guo, W; Hu, Y-Y; Yu, N; Chen, Q; Wang, J-Z; Fan, M; Yang, W-Y

2011-05-01

To explore the protective effects of brain-derived neurotrophic factor on the noise-damaged cochlear spiral ganglion. Recombinant adenovirus brain-derived neurotrophic factor vector, recombinant adenovirus LacZ and artificial perilymph were prepared. Guinea pigs with audiometric auditory brainstem response thresholds of more than 75 dB SPL, measured seven days after four hours of noise exposure at 135 dB SPL, were divided into three groups. Adenovirus brain-derived neurotrophic factor vector, adenovirus LacZ and perilymph were infused into the cochleae of the three groups, variously. Eight weeks later, the cochleae were stained immunohistochemically and the spiral ganglion cells counted. The auditory brainstem response threshold recorded before and seven days after noise exposure did not differ significantly between the three groups. However, eight weeks after cochlear perfusion, the group receiving brain-derived neurotrophic factor had a significantly decreased auditory brainstem response threshold and increased spiral ganglion cell count, compared with the adenovirus LacZ and perilymph groups. When administered via cochlear infusion following noise damage, brain-derived neurotrophic factor appears to improve the auditory threshold, and to have a protective effect on the spiral ganglion cells.

On the single sweep processing of auditory brainstem responses: click vs. chirp stimulations and active vs. passive electrodes.

PubMed

Corona-Strauss, Farah I; Delb, Wolfgang; Bloching, Marc; Strauss, Daniel J

2008-01-01

We have recently shown that click evoked auditory brainstem responses (ABRs) single sweeps can efficiently be processed by a hybrid novelty detection system. This approach allowed for the objective detection of hearing thresholds in a fraction of time of conventional schemes, making it appropriate for the efficient implementation of newborn hearing screening procedures. It is the objective of this study to evaluate whether this approach might further be improved by different stimulation paradigms and electrode settings. In particular, we evaluate chirp stimulations which compensate the basilar-membrane dispersion and active electrodes which are less sensitive to movements. This is the first study which is directed to a single sweep processing of chirp evoked ABRs. By concentrating on transparent features and a minimum number of adjustable parameters, we present an objective comparison of click vs.chirp stimulations and active vs. passive electrodes in the ultrafast ABR detection. We show that chirp evoked brainstem responses and active electrodes might improve the single sweeps analysis of ABRs.Consequently, we conclude that a single sweep processing of ABRs for the objective determination of hearing thresholds can further be improved by the use of optimized chirp stimulations and active electrodes.

Respiratory responses to intermittent hypoxia in unsedated piglets: relation to substance P binding in brainstem.

PubMed

Laferrière, André; Moss, Immanuela Ravé

2004-10-12

Respiratory responses to single intermittent hypoxia (5 min 21% O(2), 5 min 8% O(2) X6) in 5-6, 10-11, 21-22 and 26-27 day-old piglets, and to recurrent six daily intermittent hypoxia in 10-11 and 26-27 day-old piglets were assessed. Substance P binding in the piglets' brainstem immediately after the last hypoxic episode was measured. All piglets hyperventilated during hypoxia. Weight adjusted inspired ventilation, tidal volume and instantaneous flow decreased with age. The oldest piglets uniquely displayed attenuated ventilation and tidal volume during the sixth versus first hypoxic episode with single intermittent hypoxia, and reduced inspired ventilation and tidal volume during the first hypoxic episode on the sixth daily hypoxia compared to single hypoxia. By contrast, substance P binding was greatly reduced in the solitary, hypoglossal, paraambigual and lateral reticular brainstem nuclei of both younger and older piglets following either single or recurrent intermittent hypoxia. Thus, the reduction in membrane-bound neurokinin receptors by intermittent hypoxia, presumably consequent to endogenously released substance P, does not exclusively determine whether the ventilatory response to that hypoxia will be attenuated or not.

Brainstem encoding of speech and musical stimuli in congenital amusia: evidence from Cantonese speakers

PubMed Central

Liu, Fang; Maggu, Akshay R.; Lau, Joseph C. Y.; Wong, Patrick C. M.

2015-01-01

Congenital amusia is a neurodevelopmental disorder of musical processing that also impacts subtle aspects of speech processing. It remains debated at what stage(s) of auditory processing deficits in amusia arise. In this study, we investigated whether amusia originates from impaired subcortical encoding of speech (in quiet and noise) and musical sounds in the brainstem. Fourteen Cantonese-speaking amusics and 14 matched controls passively listened to six Cantonese lexical tones in quiet, two Cantonese tones in noise (signal-to-noise ratios at 0 and 20 dB), and two cello tones in quiet while their frequency-following responses (FFRs) to these tones were recorded. All participants also completed a behavioral lexical tone identification task. The results indicated normal brainstem encoding of pitch in speech (in quiet and noise) and musical stimuli in amusics relative to controls, as measured by FFR pitch strength, pitch error, and stimulus-to-response correlation. There was also no group difference in neural conduction time or FFR amplitudes. Both groups demonstrated better FFRs to speech (in quiet and noise) than to musical stimuli. However, a significant group difference was observed for tone identification, with amusics showing significantly lower accuracy than controls. Analysis of the tone confusion matrices suggested that amusics were more likely than controls to confuse between tones that shared similar acoustic features. Interestingly, this deficit in lexical tone identification was not coupled with brainstem abnormality for either speech or musical stimuli. Together, our results suggest that the amusic brainstem is not functioning abnormally, although higher-order linguistic pitch processing is impaired in amusia. This finding has significant implications for theories of central auditory processing, requiring further investigations into how different stages of auditory processing interact in the human brain. PMID:25646077

Developmental study of the distribution of hypoxia-induced factor-1 alpha and microtubule-associated protein 2 in children's brainstem: comparison between controls and cases with signs of perinatal hypoxia.

PubMed

Coveñas, R; González-Fuentes, J; Rivas-Infante, E; Lagartos-Donate, M J; Cebada-Sánchez, S; Arroyo-Jiménez, M M; Insausti, R; Marcos, P

2014-06-20

Perinatal asphyxia and hypoxia are common causes of morbidity in neonates. Prenatal birth associated with hypoxemia often results in several disorders because of the lack of oxygen in the brain. Survival rates from perinatal hypoxia have improved, but appropriate treatments for recovery are still limited, with great impact on patients, their families, society in general and health systems. The aim of this work is to contribute to a better understanding of the cellular mechanisms underlying the brainstem responses to hypoxia. For this purpose, distributions of two proteins, hypoxia-inducible factor-1 alpha (HIF-1α) and microtubule-associated protein 2 (MAP-2) were analyzed in brainstems of 11 children, four of them showing neuropathological evidence of brain hypoxia. They were included in control or hypoxic groups, and then in several subgroups according to their age. Immunohistochemical labeling for these proteins revealed only cell bodies containing HIF-1α, and both cell bodies and fibers positive for MAP-2 in the children's brainstems. The distribution of HIF-1α was more restricted than that of MAP-2, and it can be suggested that the expression of HIF-1α increased with age. The distribution pattern of MAP-2 in the medulla oblongata could be more due to age-related changes than to a response to hypoxic damage, whereas in the pons several regions, such as the nucleus ambiguus or the solitary nucleus, showed different immunolabeling patterns in controls and hypoxic cases. The distribution patterns of these two proteins suggest that some brainstem regions, such as the reticular formation or the central gray, could be less affected by conditions of hypoxia. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Brainstem encoding of speech and musical stimuli in congenital amusia: evidence from Cantonese speakers.

PubMed

Liu, Fang; Maggu, Akshay R; Lau, Joseph C Y; Wong, Patrick C M

2014-01-01

Congenital amusia is a neurodevelopmental disorder of musical processing that also impacts subtle aspects of speech processing. It remains debated at what stage(s) of auditory processing deficits in amusia arise. In this study, we investigated whether amusia originates from impaired subcortical encoding of speech (in quiet and noise) and musical sounds in the brainstem. Fourteen Cantonese-speaking amusics and 14 matched controls passively listened to six Cantonese lexical tones in quiet, two Cantonese tones in noise (signal-to-noise ratios at 0 and 20 dB), and two cello tones in quiet while their frequency-following responses (FFRs) to these tones were recorded. All participants also completed a behavioral lexical tone identification task. The results indicated normal brainstem encoding of pitch in speech (in quiet and noise) and musical stimuli in amusics relative to controls, as measured by FFR pitch strength, pitch error, and stimulus-to-response correlation. There was also no group difference in neural conduction time or FFR amplitudes. Both groups demonstrated better FFRs to speech (in quiet and noise) than to musical stimuli. However, a significant group difference was observed for tone identification, with amusics showing significantly lower accuracy than controls. Analysis of the tone confusion matrices suggested that amusics were more likely than controls to confuse between tones that shared similar acoustic features. Interestingly, this deficit in lexical tone identification was not coupled with brainstem abnormality for either speech or musical stimuli. Together, our results suggest that the amusic brainstem is not functioning abnormally, although higher-order linguistic pitch processing is impaired in amusia. This finding has significant implications for theories of central auditory processing, requiring further investigations into how different stages of auditory processing interact in the human brain.

Evaluation of the thoraco-laryngeal reflex ('slap test') as an aid to the diagnosis of cervical spinal cord and brainstem disease in horses.

PubMed

Newton-Clarke, M J; Divers, T J; Delahunta, A; Mohammed, H O

1994-09-01

A study was conducted over a 12 month period to assess the specificity and sensitivity of the 'slap test', using endoscopic evaluation, in the detection of cervical spinal cord and caudal brainstem lesions in horses. Fifteen ataxic horses were subjected to the 'slap test' and subsequently examined post mortem. Twelve out of the 15 had histopathological lesions consistent with their clinical signs. Thirteen horses with no history of neurological dysfunction and no histopathological evidence of cervical spinal cord or brainstem disease were used as controls. The laryngeal adductory responses exhibited by all horses were filmed and later scored independently by 3 assessors. The proportion of animals diagnosed with cervical spinal cord and/or brainstem disease, defined by histopathological criteria, was found to be statistically similar to the proportion with abnormal 'slap test' responses, using the McNemar chi-Square test. Despite statistical significance between proportions, sensitivity of the 'slap test' was low, 50% for the left side on both days and 58% for the right side. Specificity was higher, 69% (Day 1) and 75% (Day 2) for the left side and 75% (Day 1) and 69% (Day 2) for the right side. In contrast to this, conventional neurological examination was found to be 100% sensitive and 81% specific in the detection of lesions of histopathological significance in the cervical spinal cord/caudal brainstem. Agreement between scores for the 'slap test' from the same assessor on different days was good, with values for kappa of 0.59 to 0.85. In contrast, agreement between assessors on the 'slap test' score was poor, with kappa 0.35.(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of mild traumatic brain injury on auditory brain stem dysfunction in mouse model.

PubMed

Amanipour, Reza M; Frisina, Robert D; Cresoe, Samantha A; Parsons, Teresa J; Xiaoxia Zhu; Borlongan, Cesario V; Walton, Joseph P

2016-08-01

The auditory brainstem response (ABR) is an electrophysiological test that examines the functionality of the auditory nerve and brainstem. Traumatic brain injury (TBI) can be detected if prolonged peak latency is observed in ABR measurements, since latency measures the neural conduction time in the brainstem, and an increase in latency can be a sign of pathological lesion at the auditory brainstem level. The ABR is elicited by brief sounds that can be used to measure hearing sensitivity as well as temporal processing. Reduction in peak amplitudes and increases in latency are indicative of dysfunction in the auditory nerve and/or central auditory pathways. In this study we used sixteen young adult mice that were divided into two groups: sham and mild traumatic brain injury (mTBI), with ABR measurements obtained prior to, and at 2, 6, and 14 weeks after injury. Abnormal ABRs were observed for the nine TBI cases as early as two weeks after injury and the deficits lasted for fourteen weeks after injury. Results indicated a significant reduction in the Peak 1 (P1) and Peak 4 (P4) amplitudes to the first noise burst, as well as an increase in latency response for P1 and P4 following mTBI. These results are the first to demonstrate auditory sound processing deficits in a rodent model of mild TBI.

Abnormal findings in brainstem auditory evoked response at 36-37weeks of postconceptional age in babies with neonatal chronic lung disease.

PubMed

Jiang, Ze D; Wang, Cui

2016-12-01

To examine brainstem auditory function at 36-37weeks of postconceptional age in preterm infants who are diagnosed to have neonatal chronic lung disease (CLD). Preterm infants, born at 31 and less weeks of gestation, were studied at 36-37weeks of postconceptional age when they were diagnosed to have neonatal CLD. Brainstem auditory evoked response (BAER) was recorded and analyzed at different click rates. Compared with healthy controls at the same postconceptional age, the CLD infants showed a slightly increase in BAER wave V latency. However, the I-V, and III-V interpeak intervals in the CLD infants were significantly increased. The III-V/I-III interval ratio was also significantly increased. The amplitudes of BAER waves III and V in the CLD infants tended to be reduced. These BAER findings were similar at all 21, 51 and 91/s clicks, although the abnormalities tended to be more significant at higher than at low click rates. At 36-37weeks of postconceptional age, BAER was abnormal in preterm infants who were diagnosed to have neonatal CLD. This suggests that at time when the diagnosis of CLD is made there is functional impairment, reflecting poor myelination, in the brainstem auditory pathway in preterm infants with neonatal CLD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Auditory brainstem response to complex sounds predicts self-reported speech-in-noise performance.

PubMed

Anderson, Samira; Parbery-Clark, Alexandra; White-Schwoch, Travis; Kraus, Nina

2013-02-01

To compare the ability of the auditory brainstem response to complex sounds (cABR) to predict subjective ratings of speech understanding in noise on the Speech, Spatial, and Qualities of Hearing Scale (SSQ; Gatehouse & Noble, 2004) relative to the predictive ability of the Quick Speech-in-Noise test (QuickSIN; Killion, Niquette, Gudmundsen, Revit, & Banerjee, 2004) and pure-tone hearing thresholds. Participants included 111 middle- to older-age adults (range = 45-78) with audiometric configurations ranging from normal hearing levels to moderate sensorineural hearing loss. In addition to using audiometric testing, the authors also used such evaluation measures as the QuickSIN, the SSQ, and the cABR. Multiple linear regression analysis indicated that the inclusion of brainstem variables in a model with QuickSIN, hearing thresholds, and age accounted for 30% of the variance in the Speech subtest of the SSQ, compared with significantly less variance (19%) when brainstem variables were not included. The authors' results demonstrate the cABR's efficacy for predicting self-reported speech-in-noise perception difficulties. The fact that the cABR predicts more variance in self-reported speech-in-noise (SIN) perception than either the QuickSIN or hearing thresholds indicates that the cABR provides additional insight into an individual's ability to hear in background noise. In addition, the findings underscore the link between the cABR and hearing in noise.

Round window closure affects cochlear responses to suprathreshold stimuli.

PubMed

Cai, Qunfeng; Whitcomb, Carolyn; Eggleston, Jessica; Sun, Wei; Salvi, Richard; Hu, Bo Hua

2013-12-01

The round window acts as a vent for releasing inner ear pressure and facilitating basilar membrane vibration. Loss of this venting function affects cochlear function, which leads to hearing impairment. In an effort to identify functional changes that might be used in clinical diagnosis of round window atresia, the current investigation was designed to examine how the cochlea responds to suprathreshold stimuli following round window closure. Prospective, controlled, animal study. A rat model of round window occlusion (RWO) was established. With this model, the thresholds of auditory brainstem responses (ABR) and the input/output (IO) functions of distortion product otoacoustic emissions (DPOAEs) and acoustic startle responses were examined. Round window closure caused a mild shift in the thresholds of the auditory brainstem response (13.5 ± 9.1 dB). It also reduced the amplitudes of the distortion product otoacoustic emissions and the slope of the input/output functions. This peripheral change was accompanied by a significant reduction in the amplitude, but not the threshold, of the acoustic startle reflex, a motor response to suprathreshold sounds. In addition to causing mild increase in the threshold of the auditory brainstem response, round window occlusion reduced the slopes of both distortion product otoacoustic emissions and startle reflex input/output functions. These changes differ from those observed for typical conductive or sensory hearing loss, and could be present in patients with round window atresia. However, future clinical observations in patients are needed to confirm these findings. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Brainstem auditory evoked responses in man. 1: Effect of stimulus rise-fall time and duration

NASA Technical Reports Server (NTRS)

Hecox, K.; Squires, N.; Galambos, R.

1975-01-01

Short latency (under 10 msec) responses elicited by bursts of white noise were recorded from the scalps of human subjects. Response alterations produced by changes in the noise burst duration (on-time), inter-burst interval (off-time), and onset and offset shapes were analyzed. The latency of the most prominent response component, wave V, was markedly delayed with increases in stimulus rise time but was unaffected by changes in fall time. Increases in stimulus duration, and therefore in loudness, resulted in a systematic increase in latency. This was probably due to response recovery processes, since the effect was eliminated with increases in stimulus off-time. The amplitude of wave V was insensitive to changes in signal rise and fall times, while increasing signal on-time produced smaller amplitude responses only for sufficiently short off-times. It was concluded that wave V of the human auditory brainstem evoked response is solely an onset response.

Central nervous system prostaglandin endoperoxide synthase-1 and −2 responses to oestradiol and cerebral hypoperfusion in late-gestation fetal sheep

PubMed Central

Wood, Charles E; Giroux, Damian

2003-01-01

Previous work in this laboratory has demonstrated that cerebral hypoperfusion increases the expression of prostaglandin endoperoxide synthase-2 (PGHS-2) in ovine fetal brain regions. Endogenously produced prostaglandins, in turn, partially mediate the fetal hypothalamus- pituitary-adrenal (HPA) axis response to arterial hypotension. In separate experiments, we have found that oestradiol stimulates fetal HPA axis activity. The present experiments were designed to test the hypothesis that oestradiol increases the expression of PGHS isoforms, and that oestradiol augments the PGHS response to cerebral hypoperfusion. Sixteen fetal sheep of known gestational ages (124–128 days' gestation at the time of study) were subjected to chronic catheterization and implantation of extravascular occluder around the brachiocephalic artery. Eight fetuses were subjected to subcutaneous implantation of a pellet containing 17β-oestradiol (release rate 5 mg (21 days)−1). Brachiocephalic occlusion (BCO) stimulated adrenocorticotropin (ACTH), cortisol and arginine vasopressin (AVP) secretion, responses that were augmented by oestradiol. One hour after the beginning of a 10 min period of BCO, PGHS-1 mRNA was increased in fetal brainstem and hypothalamus, and PGHS-2 mRNA was increased in fetal brainstem. Oestradiol, by itself, increased the abundance of PGHS-2 mRNA in brainstem and cerebellum, and augmented the PGHS-2 mRNA response to BCO in brainstem. In contrast, oestradiol had no significant effect on the abundance of PGHS-1 mRNA in any brain region. PGHS-1 and PGHS-2 protein levels did not reflect the changes in the respective mRNAs. The abundance of both proteins was increased in cerebral cortex in response to BCO, and the abundance of PGHS-2 protein was increased by both oestradiol and BCO in the hippocampus. The results of this study confirm and extend the results of our previous studies, demonstrating an effect of cerebral hypoperfusion on the expression of both isoforms of PGHS. We conclude that oestradiol increases the expression of PGHS-2 in specific fetal brain regions, and that there is an interaction between oestradiol and BCO in the control of PGHS-2 expression in the fetal brainstem. We expect that at later time-points, the changes in mRNA would be followed by similar changes in enzyme abundance at the protein level. We speculate that at least a part of the effect of oestradiol on fetal HPA axis function is mediated by an interaction between oestradiol and prostaglandin biosynthesis in the fetal brain. PMID:12702743

Clinical evaluation of the vector algorithm for neonatal hearing screening using automated auditory brainstem response.

PubMed

Keohane, Bernie M; Mason, Steve M; Baguley, David M

2004-02-01

A novel auditory brainstem response (ABR) detection and scoring algorithm, entitled the Vector algorithm is described. An independent clinical evaluation of the algorithm using 464 tests (120 non-stimulated and 344 stimulated tests) on 60 infants, with a mean age of approximately 6.5 weeks, estimated test sensitivity greater than 0.99 and test specificity at 0.87 for one test. Specificity was estimated to be greater than 0.95 for a two stage screen. Test times were of the order of 1.5 minutes per ear for detection of an ABR and 4.5 minutes per ear in the absence of a clear response. The Vector algorithm is commercially available for both automated screening and threshold estimation in hearing screening devices.

Inter- and intrapatient variability of facial nerve response areas in the floor of the fourth ventricle.

PubMed

Bertalanffy, Helmut; Tissira, Nadir; Krayenbühl, Niklaus; Bozinov, Oliver; Sarnthein, Johannes

2011-03-01

Surgical exposure of intrinsic brainstem lesions through the floor of the 4th ventricle requires precise identification of facial nerve (CN VII) fibers to avoid damage. To assess the shape, size, and variability of the area where the facial nerve can be stimulated electrophysiologically on the surface of the rhomboid fossa. Over a period of 18 months, 20 patients were operated on for various brainstem and/or cerebellar lesions. Facial nerve fibers were stimulated to yield compound muscle action potentials (CMAP) in the target muscles. Using the sites of CMAP yield, a detailed functional map of the rhomboid fossa was constructed for each patient. Lesions resected included 14 gliomas, 5 cavernomas, and 1 epidermoid cyst. Of 40 response areas mapped, 19 reached the median sulcus. The distance from the obex to the caudal border of the response area ranged from 8 to 27 mm (median, 17 mm). The rostrocaudal length of the response area ranged from 2 to 15 mm (median, 5 mm). Facial nerve response areas showed large variability in size and position, even in patients with significant distance between the facial colliculus and underlying pathological lesion. Lesions located close to the facial colliculus markedly distorted the response area. This is the first documentation of variability in the CN VII response area in the rhomboid fossa. Knowledge of this remarkable variability may facilitate the assessment of safe entry zones to the brainstem and may contribute to improved outcome following neurosurgical interventions within this sensitive area of the brain.

Phase stability analysis of chirp evoked auditory brainstem responses by Gabor frame operators.

PubMed

Corona-Strauss, Farah I; Delb, Wolfgang; Schick, Bernhard; Strauss, Daniel J

2009-12-01

We have recently shown that click evoked auditory brainstem responses (ABRs) can be efficiently processed using a novelty detection paradigm. Here, ABRs as a large-scale reflection of a stimulus locked neuronal group synchronization at the brainstem level are detected as novel instance-novel as compared to the spontaneous activity which does not exhibit a regular stimulus locked synchronization. In this paper we propose for the first time Gabor frame operators as an efficient feature extraction technique for ABR single sweep sequences that is in line with this paradigm. In particular, we use this decomposition technique to derive the Gabor frame phase stability (GFPS) of sweep sequences of click and chirp evoked ABRs. We show that the GFPS of chirp evoked ABRs provides a stable discrimination of the spontaneous activity from stimulations above the hearing threshold with a small number of sweeps, even at low stimulation intensities. It is concluded that the GFPS analysis represents a robust feature extraction method for ABR single sweep sequences. Further studies are necessary to evaluate the value of the presented approach for clinical applications.

The Physiological Basis and Clinical Use of the Binaural Interaction Component of the Auditory Brainstem Response

PubMed Central

Klump, Georg M.; Tollin, Daniel J.

2016-01-01

The auditory brainstem response (ABR) is a sound-evoked non-invasively measured electrical potential representing the sum of neuronal activity in the auditory brainstem and midbrain. ABR peak amplitudes and latencies are widely used in human and animal auditory research and for clinical screening. The binaural interaction component (BIC) of the ABR stands for the difference between the sum of the monaural ABRs and the ABR obtained with binaural stimulation. The BIC comprises a series of distinct waves, the largest of which (DN1) has been used for evaluating binaural hearing in both normal hearing and hearing-impaired listeners. Based on data from animal and human studies, we discuss the possible anatomical and physiological bases of the BIC (DN1 in particular). The effects of electrode placement and stimulus characteristics on the binaurally evoked ABR are evaluated. We review how inter-aural time and intensity differences affect the BIC and, analyzing these dependencies, draw conclusion about the mechanism underlying the generation of the BIC. Finally, the utility of the BIC for clinical diagnoses are summarized. PMID:27232077

Electroretinogram (ERG) to photic stimuli should be carefully distinct from photic brainstem reflex in patients with deep coma.

PubMed

Mitsuhashi, Masahiro; Hitomi, Takefumi; Aoyama, Akihiro; Kaido, Toshimi; Ikeda, Akio; Takahashi, Ryosuke

2017-08-31

Patient 1: A 35-year-old woman became deep coma because of intracranial hemorrhage after pulmonary surgery. Patient 2: A 39-year-old woman became deep coma because of cerebellar hemorrhage after hepatic surgery. Scalp-recorded digital electroencephalography (EEG) showed electrocerebral inactivity in both cases. In addition, both EEG showed repetitive discharges at bilateral frontopolar electrodes in response to photic stimuli. The amplitude and latency of the discharges was 17 μV and 24 msec in case 1, and 9 μV and 27 msec in case 2 respectively. The activity at left frontopolar electrode disappeared after coverage of the ipsilateral eye. Based on these findings, we could exclude the possibility of brainstem response and judged it as electroretinogram (ERG). Photic stimulation is a useful activation method in EEG recording, and we can also evaluate brainstem function by checking photic blink reflex if it is evoked. However, we should be cautious about the distinction of ERG from photic blink reflex when brain death is clinically suspected.

Adult Plasticity in the Subcortical Auditory Pathway of the Maternal Mouse

PubMed Central

Miranda, Jason A.; Shepard, Kathryn N.; McClintock, Shannon K.; Liu, Robert C.

2014-01-01

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. PMID:24992362

Adult plasticity in the subcortical auditory pathway of the maternal mouse.

PubMed

Miranda, Jason A; Shepard, Kathryn N; McClintock, Shannon K; Liu, Robert C

2014-01-01

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.

Speech auditory brainstem response (speech ABR) characteristics depending on recording conditions, and hearing status: an experimental parametric study.

PubMed

Akhoun, Idrick; Moulin, Annie; Jeanvoine, Arnaud; Ménard, Mikael; Buret, François; Vollaire, Christian; Scorretti, Riccardo; Veuillet, Evelyne; Berger-Vachon, Christian; Collet, Lionel; Thai-Van, Hung

2008-11-15

Speech elicited auditory brainstem responses (Speech ABR) have been shown to be an objective measurement of speech processing in the brainstem. Given the simultaneous stimulation and recording, and the similarities between the recording and the speech stimulus envelope, there is a great risk of artefactual recordings. This study sought to systematically investigate the source of artefactual contamination in Speech ABR response. In a first part, we measured the sound level thresholds over which artefactual responses were obtained, for different types of transducers and experimental setup parameters. A watermelon model was used to model the human head susceptibility to electromagnetic artefact. It was found that impedances between the electrodes had a great effect on electromagnetic susceptibility and that the most prominent artefact is due to the transducer's electromagnetic leakage. The only artefact-free condition was obtained with insert-earphones shielded in a Faraday cage linked to common ground. In a second part of the study, using the previously defined artefact-free condition, we recorded speech ABR in unilateral deaf subjects and bilateral normal hearing subjects. In an additional control condition, Speech ABR was recorded with the insert-earphones used to deliver the stimulation, unplugged from the ears, so that the subjects did not perceive the stimulus. No responses were obtained from the deaf ear of unilaterally hearing impaired subjects, nor in the insert-out-of-the-ear condition in all the subjects, showing that Speech ABR reflects the functioning of the auditory pathways.

Clinical, Radiologic, and Legal Significance of "Extensor Response" in Posttraumatic Coma.

PubMed

Firsching, Raimund; Woischneck, Dieter; Langejürgen, Alexander; Parreidt, Andreas; Bondar, Imre; Skalej, Martin; Röhl, Friedrich; Voellger, Benjamin

2015-11-01

The timely detection of neurologic deterioration can be critical for the survival of a neurosurgical patient following head injury. Because little reliable evidence is available on the prognostic value of the clinical sign "extensor response" in comatose posttraumatic patients, we investigated the correlation of this clinical sign with outcome and with early radiologic findings from magnetic resonance imaging (MRI). This retrospective analysis of prospectively obtained data included 157 patients who had remained in a coma for a minimum of 24 hours after traumatic brain injury. All patients received a 1.5-T MRI within 10 days (median: 2 days) of the injury. The correlations between clinical findings 12 and 24 hours after the injury-in particular, extensor response and pupillary function, MRI findings, and outcome after 1 year-were investigated. Statistical analysis included contingency tables, Fisher exact test, odds ratios (ORs) with confidence intervals (CIs), and weighted κ values. There were 48 patients with extensor response within the first 24 hours after the injury. Patients with extensor response (World Federation of Neurosurgical Societies coma grade III) statistically were significantly more likely to harbor MRI lesions in the brainstem when compared with patients in a coma who had no further deficiencies (coma grade I; p = 0.0004 by Fisher exact test, OR 10.8 with 95% CI, 2.7-42.5) and patients with unilateral loss of pupil function (coma grade II; p = 0.0187, OR 2.8 with 95% CI, 1.2-6.5). The correlation of brainstem lesions as found by MRI and outcome according to the Glasgow Outcome Scale after 1 year was also highly significant (p ≤ 0.016). The correlation of extensor response and loss of pupil function with an unfavorable outcome and with brainstem lesions revealed by MRI is highly significant. Their sudden onset may be associated with the sudden onset of brainstem dysfunction and should therefore be regarded as one of the most fundamental warning signs in the clinical monitoring of comatose patients. Georg Thieme Verlag KG Stuttgart · New York.

Lateralization and Binaural Interaction of Middle-Latency and Late-Brainstem Components of the Auditory Evoked Response.

PubMed

Dykstra, Andrew R; Burchard, Daniel; Starzynski, Christian; Riedel, Helmut; Rupp, Andre; Gutschalk, Alexander

2016-08-01

We used magnetoencephalography to examine lateralization and binaural interaction of the middle-latency and late-brainstem components of the auditory evoked response (the MLR and SN10, respectively). Click stimuli were presented either monaurally, or binaurally with left- or right-leading interaural time differences (ITDs). While early MLR components, including the N19 and P30, were larger for monaural stimuli presented contralaterally (by approximately 30 and 36 % in the left and right hemispheres, respectively), later components, including the N40 and P50, were larger ipsilaterally. In contrast, MLRs elicited by binaural clicks with left- or right-leading ITDs did not differ. Depending on filter settings, weak binaural interaction could be observed as early as the P13 but was clearly much larger for later components, beginning at the P30, indicating some degree of binaural linearity up to early stages of cortical processing. The SN10, an obscure late-brainstem component, was observed consistently in individuals and showed linear binaural additivity. The results indicate that while the MLR is lateralized in response to monaural stimuli-and not ITDs-this lateralization reverses from primarily contralateral to primarily ipsilateral as early as 40 ms post stimulus and is never as large as that seen with fMRI.

Optimization behavior of brainstem respiratory neurons. A cerebral neural network model.

PubMed

Poon, C S

1991-01-01

A recent model of respiratory control suggested that the steady-state respiratory responses to CO2 and exercise may be governed by an optimal control law in the brainstem respiratory neurons. It was not certain, however, whether such complex optimization behavior could be accomplished by a realistic biological neural network. To test this hypothesis, we developed a hybrid computer-neural model in which the dynamics of the lung, brain and other tissue compartments were simulated on a digital computer. Mimicking the "controller" was a human subject who pedalled on a bicycle with varying speed (analog of ventilatory output) with a view to minimize an analog signal of the total cost of breathing (chemical and mechanical) which was computed interactively and displayed on an oscilloscope. In this manner, the visuomotor cortex served as a proxy (homolog) of the brainstem respiratory neurons in the model. Results in 4 subjects showed a linear steady-state ventilatory CO2 response to arterial PCO2 during simulated CO2 inhalation and a nearly isocapnic steady-state response during simulated exercise. Thus, neural optimization is a plausible mechanism for respiratory control during exercise and can be achieved by a neural network with cognitive computational ability without the need for an exercise stimulus.

On the Relevance of Natural Stimuli for the Study of Brainstem Correlates: The Example of Consonance Perception

PubMed Central

Cousineau, Marion; Bidelman, Gavin M.; Peretz, Isabelle; Lehmann, Alexandre

2015-01-01

Some combinations of musical tones sound pleasing to Western listeners, and are termed consonant, while others sound discordant, and are termed dissonant. The perceptual phenomenon of consonance has been traced to the acoustic property of harmonicity. It has been repeatedly shown that neural correlates of consonance can be found as early as the auditory brainstem as reflected in the harmonicity of the scalp-recorded frequency-following response (FFR). “Neural Pitch Salience” (NPS) measured from FFRs—essentially a time-domain equivalent of the classic pattern recognition models of pitch—has been found to correlate with behavioral judgments of consonance for synthetic stimuli. Following the idea that the auditory system has evolved to process behaviorally relevant natural sounds, and in order to test the generalizability of this finding made with synthetic tones, we recorded FFRs for consonant and dissonant intervals composed of synthetic and natural stimuli. We found that NPS correlated with behavioral judgments of consonance and dissonance for synthetic but not for naturalistic sounds. These results suggest that while some form of harmonicity can be computed from the auditory brainstem response, the general percept of consonance and dissonance is not captured by this measure. It might either be represented in the brainstem in a different code (such as place code) or arise at higher levels of the auditory pathway. Our findings further illustrate the importance of using natural sounds, as a complementary tool to fully-controlled synthetic sounds, when probing auditory perception. PMID:26720000

Stress-induced activation of the brainstem Bcl-xL gene expression in rats treated with fluoxetine: correlations with serotonin metabolism and depressive-like behavior.

PubMed

Shishkina, Galina T; Kalinina, Tatyana S; Berezova, Inna V; Dygalo, Nikolay N

2012-01-01

Mechanisms underlying stress-induced depression and antidepressant drug action were shown to involve alterations in serotonergic (5-HT) neurotransmission and expression of genes coding for proteins associated with neurotrophic signaling pathways and cell-survival in the hippocampus and cortex. Expression of these genes in the brainstem containing 5-HT neurons may also be related to vulnerability or resilience to stress-related psychopathology. Here we investigated 5-HT markers and expression of genes for Brain-Derived Neurotrophic Factor (BDNF) and apoptotic proteins in the brainstem in relation to swim stress-induced behavioral despair. We found that anti-apoptotic Bcl-xL gene is sensitive to stress during the course of fluoxetine administration. Responsiveness of this gene to stress appeared concomitantly with an antidepressant-like effect of fluoxetine in the forced swim test. Bcl-xL transcript levels showed negative correlations with duration of immobility in the test and 5-HT turnover in the brainstem. In contrast, BDNF and pro-apoptotic protein Bax mRNA levels were unchanged by either fluoxetine or stress, suggesting specificity of Bcl-xL gene responses to these treatments. We also found that the levels of mRNAs for tryptophan hydroxylase-2 (TPH2) and 5-HT transporter (5-HTT) were significantly down-regulated following prolonged treatment with fluoxetine, but were not affected by stress. Unlike TPH2 and 5-HTT, 5-HT1A receptor mRNA levels were not altered by fluoxetine but significantly increased in response to swim stress. These data show that long-term fluoxetine treatment leads to changes in 5-HT and Bcl-xL responses to stress associated with antidepressant-like effects of the drug. This article is part of a Special Issue entitled 'Anxiety and Depression'. Copyright © 2011 Elsevier Ltd. All rights reserved.

Computational modeling of the human auditory periphery: Auditory-nerve responses, evoked potentials and hearing loss.

PubMed

Verhulst, Sarah; Altoè, Alessandro; Vasilkov, Viacheslav

2018-03-01

Models of the human auditory periphery range from very basic functional descriptions of auditory filtering to detailed computational models of cochlear mechanics, inner-hair cell (IHC), auditory-nerve (AN) and brainstem signal processing. It is challenging to include detailed physiological descriptions of cellular components into human auditory models because single-cell data stems from invasive animal recordings while human reference data only exists in the form of population responses (e.g., otoacoustic emissions, auditory evoked potentials). To embed physiological models within a comprehensive human auditory periphery framework, it is important to capitalize on the success of basic functional models of hearing and render their descriptions more biophysical where possible. At the same time, comprehensive models should capture a variety of key auditory features, rather than fitting their parameters to a single reference dataset. In this study, we review and improve existing models of the IHC-AN complex by updating their equations and expressing their fitting parameters into biophysical quantities. The quality of the model framework for human auditory processing is evaluated using recorded auditory brainstem response (ABR) and envelope-following response (EFR) reference data from normal and hearing-impaired listeners. We present a model with 12 fitting parameters from the cochlea to the brainstem that can be rendered hearing impaired to simulate how cochlear gain loss and synaptopathy affect human population responses. The model description forms a compromise between capturing well-described single-unit IHC and AN properties and human population response features. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Exposure to a high-fat high-sugar diet causes strong up-regulation of proopiomelanocortin and differentially affects dopamine D1 and D2 receptor gene expression in the brainstem of rats.

PubMed

Alsiö, Johan; Rask-Andersen, Mathias; Chavan, Rohit A; Olszewski, Pawel K; Levine, Allen S; Fredriksson, Robert; Schiöth, Helgi B

2014-01-24

A strong link between obesity and dopamine (DA) has been established by studies associating body weight status to variants of genes related to DA signalling. Human and animal studies investigating this relationship have so far focused mainly on the role of DA within the mesolimbic pathway. The aim of this study was to investigate potential DA receptor dysregulation in the brainstem, where these receptors play a potential role in meal termination, during high-fat high-sugar diet (HFHS) exposure. Expression of other key genes, including proopiomelanocortin (POMC), was also analyzed. We randomized rats into three groups; ad libitum access to HFHS (n=24), restricted HFHS access (n=10), or controls (chow-fed, n=10). After 5 weeks, brainstem gene expression was investigated by qRT-PCR. We observed an increase in POMC expression in ad libitum HFHS-fed rats compared to chow-fed controls (p<0.05). Further, expression of DA D2 receptor mRNA was down-regulated in the brainstem of the HFHS ad libitum-fed rats (p<0.05), whereas expression of the DA D1 receptor was upregulated (p<0.05) in these animals compared to chow-fed rats. In control experiments, we observed no effect relative to chow-fed controls on DA-receptor or POMC gene expression in the hypothalamus of HFHS diet-exposed rats, or in the brainstem of acutely food deprived rats. The present findings suggest brainstem POMC to be responsive to palatable foods, and that DA dysregulation after access to energy-dense diets occurs not only in striatal regions, but also in the brainstem, which could be relevant for overeating and for the development and maintenance of obesity. Copyright © 2013. Published by Elsevier Ireland Ltd.

Behavioral State Modulates the Activity of Brainstem Sensorimotor Neurons

PubMed Central

McArthur, Kimberly L.

2011-01-01

Sensorimotor processing must be modulated according to the animal's behavioral state. A previous study demonstrated that motion responses were strongly state dependent in birds. Vestibular eye and head responses were significantly larger and more compensatory during simulated flight, and a flight-specific vestibular tail response was also characterized. In the current study, we investigated the neural substrates for these state-dependent vestibular behaviors by recording extracellularly from neurons in the vestibular nuclear complex and comparing their spontaneous activity and sensory responses during default and simulated flight states. We show that motion-sensitive neurons in the lateral vestibular nucleus are state dependent. Some neurons increased their spontaneous firing rates during flight, though their increased excitability was not reflected in higher sensory gains. However, other neurons exhibited state-dependent gating of sensory inputs, responding to rotational stimuli only during flight. These results demonstrate that vestibular processing in the brainstem is state dependent and lay the foundation for future studies to investigate the synaptic mechanisms responsible for these modifications. PMID:22090497

Electrophysiologic Study of a Method of Euthanasia Using Intrathecal Lidocaine Hydrochloride Administered during Intravenous Anesthesia in Horses.

PubMed

Aleman, M; Davis, E; Williams, D C; Madigan, J E; Smith, F; Guedes, A

2015-01-01

An intravenous (IV) overdose of pentobarbital sodium is the most commonly used method of euthanasia in veterinary medicine. However, this compound is not available in many countries or rural areas resulting in usage of alternative methods such as intrathecal lidocaine administration after IV anesthesia. Its safety and efficacy as a method of euthanasia have not been investigated in the horse. To investigate changes in mean arterial blood pressure and electrical activity of the cerebral cortex, brainstem, and heart during intrathecal administration of lidocaine. Our hypothesis was that intrathecal lidocaine affects the cerebral cortex and brainstem before affecting cardiovascular function. Eleven horses requiring euthanasia for medical reasons. Prospective observational study. Horses were anesthetized with xylazine, midazolam, and ketamine; and instrumented for recording of electroencephalogram (EEG), electrooculogram (EOG), brainstem auditory evoked response (BAER), and electrocardiogram (ECG). Physical and neurological (brainstem reflexes) variables were monitored. Mean arterial blood pressure was recorded throughout the study. Loss of cerebro-cortical electrical activity occurred up to 226 seconds after the end of the infusion of lidocaine solution. Cessation of brainstem function as evidenced by a lack of brainstem reflexes and disappearance of BAER occurred subsequently. Undetectable heart sounds, nonpalpable arterial pulse, and extremely low mean arterial blood pressure supported cardiac death; a recordable ECG was the last variable to disappear after the infusion (300-1,279 seconds). Intrathecal administration of lidocaine is an effective alternative method of euthanasia in anesthetized horses, during which brain death occurs before cardiac death. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

Visual recognition memory and auditory brainstem response in infant rhesus monkeys exposed perinatally to environmental tobacco smoke.

PubMed

Golub, Mari S; Slotkin, Theodore A; Tarantal, Alice F; Pinkerton, Kent E

2007-06-02

The impact of perinatal exposure to environmental tobacco smoke (ETS) on cognitive development is controversial. We exposed rhesus monkeys to ETS or filtered air (5 animals per group) beginning in utero on day 50 of pregnancy and continuing throughout postnatal testing. In infancy, we evaluated both groups for visual recognition memory and auditory function (auditory brainstem response). The ETS group showed significantly less novelty preference in the visual recognition task whereas no effects on auditory function were detected. These preliminary results support the view that perinatal ETS exposure has adverse effects on cognitive function and indicate further that rhesus monkeys may provide a valuable nonhuman primate model for investigating this link.

A brief review of the clinical anatomy of the vestibular-ocular connections-how much do we know?

PubMed

Bronstein, A M; Patel, M; Arshad, Q

2015-02-01

The basic connectivity from the vestibular labyrinth to the eye muscles (vestibular ocular reflex, VOR) has been elucidated in the past decade, and we summarise this in graphic format. We also review the concept of 'velocity storage', a brainstem integrator that prolongs vestibular responses. Finally, we present new discoveries of how complex visual stimuli, such as binocular rivalry, influence VOR processing. In contrast to the basic brainstem circuits, cortical vestibular circuits are far from being understood, but parietal-vestibular nuclei projections are likely to be involved.

Gestational flu exposure induces changes in neurochemicals, affiliative hormones and brainstem inflammation, in addition to autism-like behaviors in mice.

PubMed

Miller, V M; Zhu, Y; Bucher, C; McGinnis, W; Ryan, L K; Siegel, A; Zalcman, S

2013-10-01

The prevalence of neurodevelopmental disorders such as autism is increasing, however the etiology of these disorders is unclear and thought to involve a combination of genetic, environmental and immune factors. A recent epidemiological study found that gestational viral exposure during the first trimester increases risk of autism in offspring by twofold. In mice gestational viral exposures alter behavior of offspring, but the biological mechanisms which underpin these behavioral changes are unclear. We hypothesized that gestational viral exposure induces changes in affiliative hormones, brainstem autonomic nuclei and neurotransmitters which are associated with behavioral alterations in offspring. To address this hypothesis, we exposed pregnant mice to influenza A virus (H3N2) on gestational day 9 and determined behavioral, hormonal and brainstem changes in male and female offspring. We found that gestational flu exposure induced dose-dependent alterations in social and aggressive behaviors (p≤0.05) in male and female offspring and increases in locomotor behaviors particularly in male offspring (p≤0.05). We found that flu exposure was also associated with reductions in oxytocin and serotonin (p≤0.05) levels in male and female offspring and sex-specific changes in dopamine metabolism. In addition we found changes in catecholaminergic and microglia density in brainstem tissues of male flu exposed offspring only (p≤0.05). This study demonstrates that gestational viral exposure induces behavioral changes in mice, which are associated with alterations in affiliative hormones. In addition we found sex-specific changes in locomotor behavior, which may be associated with sex-specific alterations in dopamine metabolism and brainstem inflammation. Further investigations into maternal immune responses are necessary to unravel the molecular mechanisms which underpin abnormal hormonal, immune and behavioral responses in offspring after gestational viral exposure. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of Brain Stem and Dorsal Vagus Complex Dosimetry on Nausea and Vomiting in Head and Neck Intensity-Modulated Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ciura, Katherine; McBurney, Michelle; Nguyen, Baongoc

Intensity-modulated radiation therapy (IMRT) is becoming the treatment of choice for many head and neck cancer patients. IMRT reduces some toxicities by reducing radiation dose to uninvolved normal tissue near tumor targets; however, other tissues not irradiated using previous 3D techniques may receive clinically significant doses, causing undesirable side effects including nausea and vomiting (NV). Irradiation of the brainstem, and more specifically, the area postrema and dorsal vagal complex (DVC), has been linked to NV. We previously reported preliminary hypothesis-generating dose effects associated with NV in IMRT patients. The goal of this study is to relate brainstem dose to NVmore » symptoms. We retrospectively studied 100 consecutive patients that were treated for oropharyngeal cancer with IMRT. We contoured the brainstem, area postrema, and DVC with the assistance of an expert diagnostic neuroradiologist. We correlated dosimetry for the 3 areas contoured with weekly NV rates during IMRT. NV rates were significantly higher for patients who received concurrent chemotherapy. Post hoc analysis demonstrated that chemoradiation cases exhibited a trend towards the same dose-response relationship with both brainstem mean dose (p = 0.0025) and area postrema mean dose (p = 0.004); however, both failed to meet statistical significance at the p {<=} 0.002 level. Duration of toxicity was also greater for chemoradiation patients, who averaged 3.3 weeks with reported Common Terminology Criteria for Adverse Events (CTC-AE), compared with an average of 2 weeks for definitive RT patients (p = 0.002). For definitive RT cases, no dose-response trend could be ascertained. The mean brainstem dose emerged as a key parameter of interest; however, no one dose parameter (mean/median/EUD) best correlated with NV. This study does not address extraneous factors that would affect NV incidence, including the use of antiemetics, nor chemotherapy dose schedule specifics before and during RT. A prospective study will be required to depict exactly how IMRT dose affects NV.« less

Posterior reversible encephalopathy as the first manifestation of Bickerstaff's brainstem encephalitis.

PubMed

Chen, Pei-Ru; Chen, Shih-Pin

2016-11-08

Posterior reversible encephalopathy syndrome (PRES) has been associated with Guillain-Barre syndrome in rare cases. Here we report a patient in whom PRES was the presenting manifestation of Bickerstaff's brainstem encephalitis. A 75-year-old woman presented with acute onset of hypertension, headache, blurred vision, and left eyelid drooping. Magnetic resonance imaging of the brain showed characteristic PRES lesions involving the parietal and occipital lobes bilaterally. On the 6th day after symptom onset, the patient developed complete ptosis and external ophthalmoplegia of both eyes, progressive ataxia, and bilateral lower limb weakness. Cerebrospinal fluid analyses revealed albuminocytological dissociation (protein: 66.6 mg/dL, WBC: 0/μl), and nerve conduction studies showed demyelinating sensorimotor polyneuropathy. The patient developed somnolence and a left extensor plantar response on the 8th day. A diagnosis of Bickerstaff's brainstem encephalitis was made. Treatment with plasmapheresis led to a rapid improvement of clinical symptoms. To date, only five similar cases have been reported, but this is the only case in which PRES developed prior to treatment. PRES can be a comorbid condition with Bickerstaff's brainstem encephalitis, either preceding or following treatment; caution should be used in patients with either syndrome who exhibit atypical presentations.

The Brainstem and Serotonin in the Sudden Infant Death Syndrome

PubMed Central

Kinney, Hannah C.; Richerson, George B.; Dymecki, Susan M.; Darnall, Robert A.; Nattie, Eugene E.

2012-01-01

The sudden infant death syndrome (SIDS) is the sudden death of an infant under one year of age that is typically associated with sleep and that remains unexplained after a complete autopsy and death scene investigation. A leading hypothesis about its pathogenesis is that many cases result from defects in brainstem-mediated protective responses to homeostatic stressors occurring during sleep in a critical developmental period. Here we review the evidence for the brainstem hypothesis in SIDS with a focus upon abnormalities related to the neurotransmitter serotonin in the medulla oblongata, as these are the most robust pathologic findings to date. In this context, we synthesize the human autopsy data with genetic, whole-animal, and cellular data concerning the function and development of the medullary serotonergic system. These emerging data suggest an important underlying mechanism in SIDS that may help lead to identification of infants at risk and specific interventions to prevent death. PMID:19400695

Speech-evoked auditory brainstem responses in children with hearing loss.

PubMed

Koravand, Amineh; Al Osman, Rida; Rivest, Véronique; Poulin, Catherine

2017-08-01

The main objective of the present study was to investigate subcortical auditory processing in children with sensorineural hearing loss. Auditory Brainstem Responses (ABRs) were recorded using click and speech/da/stimuli. Twenty-five children, aged 6-14 years old, participated in the study: 13 with normal hearing acuity and 12 with sensorineural hearing loss. No significant differences were observed for the click-evoked ABRs between normal hearing and hearing-impaired groups. For the speech-evoked ABRs, no significant differences were found for the latencies of the following responses between the two groups: onset (V and A), transition (C), one of the steady-state wave (F), and offset (O). However, the latency of the steady-state waves (D and E) was significantly longer for the hearing-impaired compared to the normal hearing group. Furthermore, the amplitude of the offset wave O and of the envelope frequency response (EFR) of the speech-evoked ABRs was significantly larger for the hearing-impaired compared to the normal hearing group. Results obtained from the speech-evoked ABRs suggest that children with a mild to moderately-severe sensorineural hearing loss have a specific pattern of subcortical auditory processing. Our results show differences for the speech-evoked ABRs in normal hearing children compared to hearing-impaired children. These results add to the body of the literature on how children with hearing loss process speech at the brainstem level. Copyright © 2017 Elsevier B.V. All rights reserved.

Loud Music Exposure and Cochlear Synaptopathy in Young Adults: Isolated Auditory Brainstem Response Effects but No Perceptual Consequences.

PubMed

Grose, John H; Buss, Emily; Hall, Joseph W

2017-01-01

The purpose of this study was to test the hypothesis that listeners with frequent exposure to loud music exhibit deficits in suprathreshold auditory performance consistent with cochlear synaptopathy. Young adults with normal audiograms were recruited who either did ( n = 31) or did not ( n = 30) have a history of frequent attendance at loud music venues where the typical sound levels could be expected to result in temporary threshold shifts. A test battery was administered that comprised three sets of procedures: (a) electrophysiological tests including distortion product otoacoustic emissions, auditory brainstem responses, envelope following responses, and the acoustic change complex evoked by an interaural phase inversion; (b) psychoacoustic tests including temporal modulation detection, spectral modulation detection, and sensitivity to interaural phase; and (c) speech tests including filtered phoneme recognition and speech-in-noise recognition. The results demonstrated that a history of loud music exposure can lead to a profile of peripheral auditory function that is consistent with an interpretation of cochlear synaptopathy in humans, namely, modestly abnormal auditory brainstem response Wave I/Wave V ratios in the presence of normal distortion product otoacoustic emissions and normal audiometric thresholds. However, there were no other electrophysiological, psychophysical, or speech perception effects. The absence of any behavioral effects in suprathreshold sound processing indicated that, even if cochlear synaptopathy is a valid pathophysiological condition in humans, its perceptual sequelae are either too diffuse or too inconsequential to permit a simple differential diagnosis of hidden hearing loss.

Hierarchical neurocomputations underlying concurrent sound segregation: connecting periphery to percept.

PubMed

Bidelman, Gavin M; Alain, Claude

2015-02-01

Natural soundscapes often contain multiple sound sources at any given time. Numerous studies have reported that in human observers, the perception and identification of concurrent sounds is paralleled by specific changes in cortical event-related potentials (ERPs). Although these studies provide a window into the cerebral mechanisms governing sound segregation, little is known about the subcortical neural architecture and hierarchy of neurocomputations that lead to this robust perceptual process. Using computational modeling, scalp-recorded brainstem/cortical ERPs, and human psychophysics, we demonstrate that a primary cue for sound segregation, i.e., harmonicity, is encoded at the auditory nerve level within tens of milliseconds after the onset of sound and is maintained, largely untransformed, in phase-locked activity of the rostral brainstem. As then indexed by auditory cortical responses, (in)harmonicity is coded in the signature and magnitude of the cortical object-related negativity (ORN) response (150-200 ms). The salience of the resulting percept is then captured in a discrete, categorical-like coding scheme by a late negativity response (N5; ~500 ms latency), just prior to the elicitation of a behavioral judgment. Subcortical activity correlated with cortical evoked responses such that weaker phase-locked brainstem responses (lower neural harmonicity) generated larger ORN amplitude, reflecting the cortical registration of multiple sound objects. Studying multiple brain indices simultaneously helps illuminate the mechanisms and time-course of neural processing underlying concurrent sound segregation and may lead to further development and refinement of physiologically driven models of auditory scene analysis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Reduced auditory efferent activity in childhood selective mutism.

PubMed

Bar-Haim, Yair; Henkin, Yael; Ari-Even-Roth, Daphne; Tetin-Schneider, Simona; Hildesheimer, Minka; Muchnik, Chava

2004-06-01

Selective mutism is a psychiatric disorder of childhood characterized by consistent inability to speak in specific situations despite the ability to speak normally in others. The objective of this study was to test whether reduced auditory efferent activity, which may have direct bearings on speaking behavior, is compromised in selectively mute children. Participants were 16 children with selective mutism and 16 normally developing control children matched for age and gender. All children were tested for pure-tone audiometry, speech reception thresholds, speech discrimination, middle-ear acoustic reflex thresholds and decay function, transient evoked otoacoustic emission, suppression of transient evoked otoacoustic emission, and auditory brainstem response. Compared with control children, selectively mute children displayed specific deficiencies in auditory efferent activity. These aberrations in efferent activity appear along with normal pure-tone and speech audiometry and normal brainstem transmission as indicated by auditory brainstem response latencies. The diminished auditory efferent activity detected in some children with SM may result in desensitization of their auditory pathways by self-vocalization and in reduced control of masking and distortion of incoming speech sounds. These children may gradually learn to restrict vocalization to the minimal amount possible in contexts that require complex auditory processing.

Brainstem origins for cortical 'what' and 'where' pathways in the auditory system.

PubMed

Kraus, Nina; Nicol, Trent

2005-04-01

We have developed a data-driven conceptual framework that links two areas of science: the source-filter model of acoustics and cortical sensory processing streams. The source-filter model describes the mechanics behind speech production: the identity of the speaker is carried largely in the vocal cord source and the message is shaped by the ever-changing filters of the vocal tract. Sensory processing streams, popularly called 'what' and 'where' pathways, are well established in the visual system as a neural scheme for separately carrying different facets of visual objects, namely their identity and their position/motion, to the cortex. A similar functional organization has been postulated in the auditory system. Both speaker identity and the spoken message, which are simultaneously conveyed in the acoustic structure of speech, can be disentangled into discrete brainstem response components. We argue that these two response classes are early manifestations of auditory 'what' and 'where' streams in the cortex. This brainstem link forges a new understanding of the relationship between the acoustics of speech and cortical processing streams, unites two hitherto separate areas in science, and provides a model for future investigations of auditory function.

Brainstem auditory responses to resolved and unresolved harmonics of a synthetic vowel in quiet and noise.

PubMed

Laroche, Marilyn; Dajani, Hilmi R; Prévost, François; Marcoux, André M

2013-01-01

This study investigated speech auditory brainstem responses (speech ABR) with variants of a synthetic vowel in quiet and in background noise. Its objectives were to study the noise robustness of the brainstem response at the fundamental frequency F0 and at the first formant F1, evaluate how the resolved/unresolved harmonics regions in speech contribute to the response at F0, and investigate the origin of the response at F0 to resolved and unresolved harmonics in speech. In total, 18 normal-hearing subjects (11 women, aged 18-33 years) participated in this study. Speech ABRs were recorded using variants of a 300 msec formant-synthesized /a/ vowel in quiet and in white noise. The first experiment employed three variants containing the first three formants F1 to F3, F1 only, and F2 and F3 only with relative formant levels following those reported in the literature. The second experiment employed three variants containing F1 only, F2 only, and F3 only, with the formants equalized to the same level and the signal-to-noise ratio (SNR) maintained at -5 dB. Overall response latency was estimated, and the amplitude and local SNR of the envelope following response at F0 and of the frequency following response at F1 were compared for the different stimulus variants in quiet and in noise. The response at F0 was more robust to noise than that at F1. There were no statistically significant differences in the response at F0 caused by the three stimulus variants in both experiments in quiet. However, the response at F0 with the variant dominated by resolved harmonics was more robust to noise than the response at F0 with the stimulus variants dominated by unresolved harmonics. The latencies of the responses in all cases were very similar in quiet, but the responses at F0 due to resolved and unresolved harmonics combined nonlinearly when both were present in the stimulus. Speech ABR has been suggested as a marker of central auditory processing. The results of this study support earlier work on the differential susceptibility to noise of the F0 and F1 components of the evoked response. In the case of F0, the results support the view that in speech, the pitch of resolved harmonics and that of unresolved harmonics are processed in different but interacting pathways that converge in the upper brainstem. Pitch plays an important role in speech perception, and speech ABR can offer a window into the neural extraction of the pitch of speech and how it may change with hearing impairment.

Histopathologic response of the immature rat to diffuse traumatic brain injury.

PubMed

Adelson, P D; Jenkins, L W; Hamilton, R L; Robichaud, P; Tran, M P; Kochanek, P M

2001-10-01

The purpose of this study was to characterize the histopathologic response of rats at postnatal day (PND) 17 following an impact-acceleration diffuse traumatic brain injury (TBI) using a 150-g/2-meter injury as previously described. This injury produces acute neurologic and physiologic derangements as well as enduring motor and Morris water maze (MWM) functional deficits. Histopathologic studies of perfusion-fixed brains were performed by gross examination and light microscopy using hematoxylin and eosin, Bielschowsky silver stain, and glial fibrillary acidic protein (GFAP) immunohistochemistry at 1, 3, 7, 28, and 90 day after injury. Gross pathologic examination revealed diffuse subarachnoid hemorrhage (SAH) at 1-3 days but minimal supratentorial intraparenchymal hemorrhage. Petechial hemorrhages were noted in ventral brainstem segments and in the cerebellum. After 1-3-day survivals, light microscopy revealed diffuse SAH and intraventricular hemorrhage (IVH), mild edema, significant axonal injury, reactive astrogliosis, and localized midline cerebellar hemorrhage. Axonal injury most commonly occurred in the long ascending and descending fiber tracts of the brainstem and occasionally in the forebrain, and was maximal at 3 days, but present until 7 days after injury. Reactive astrocytes were similarly found both in location and timing, but were also significantly identified in the hippocampus, white matter tracts, and corpus callosum. Typically, TBI produced significant diffuse SAH accompanied by cerebral and brainstem astrogliosis and axonal injury without obvious neuronal loss. Since this injury produces some pathologic changes with sustained functional deficits similar to TBI in infants and children, it should be useful for the further study of the pathophysiology and therapy of diffuse TBI and brainstem injury in the immature brain.

The auditory cross-section (AXS) test battery: A new way to study afferent/efferent relations linking body periphery (ear, voice, heart) with brainstem and cortex

NASA Astrophysics Data System (ADS)

Lauter, Judith

2002-05-01

Several noninvasive methods are available for studying the neural bases of human sensory-motor function, but their cost is prohibitive for many researchers and clinicians. The auditory cross section (AXS) test battery utilizes relatively inexpensive methods, yet yields data that are at least equivalent, if not superior in some applications, to those generated by more expensive technologies. The acronym emphasizes access to axes-the battery makes it possible to assess dynamic physiological relations along all three body-brain axes: rostro-caudal (afferent/efferent), dorso-ventral, and right-left, on an individually-specific basis, extending from cortex to the periphery. For auditory studies, a three-level physiological ear-to-cortex profile is generated, utilizing (1) quantitative electroencephalography (qEEG); (2) the repeated evoked potentials version of the auditory brainstem response (REPs/ABR); and (3) otoacoustic emissions (OAEs). Battery procedures will be explained, and sample data presented illustrating correlated multilevel changes in ear, voice, heart, brainstem, and cortex in response to circadian rhythms, and challenges with substances such as antihistamines and Ritalin. Potential applications for the battery include studies of central auditory processing, reading problems, hyperactivity, neural bases of voice and speech motor control, neurocardiology, individually-specific responses to medications, and the physiological bases of tinnitus, hyperacusis, and related treatments.

Test-retest reliability of speech-evoked auditory brainstem response in healthy children at a low sensation level.

PubMed

Zakaria, Mohd Normani; Jalaei, Bahram

2017-11-01

Auditory brainstem responses evoked by complex stimuli such as speech syllables have been studied in normal subjects and subjects with compromised auditory functions. The stability of speech-evoked auditory brainstem response (speech-ABR) when tested over time has been reported but the literature is limited. The present study was carried out to determine the test-retest reliability of speech-ABR in healthy children at a low sensation level. Seventeen healthy children (6 boys, 11 girls) aged from 5 to 9 years (mean = 6.8 ± 3.3 years) were tested in two sessions separated by a 3-month period. The stimulus used was a 40-ms syllable /da/ presented at 30 dB sensation level. As revealed by pair t-test and intra-class correlation (ICC) analyses, peak latencies, peak amplitudes and composite onset measures of speech-ABR were found to be highly replicable. Compared to other parameters, higher ICC values were noted for peak latencies of speech-ABR. The present study was the first to report the test-retest reliability of speech-ABR recorded at low stimulation levels in healthy children. Due to its good stability, it can be used as an objective indicator for assessing the effectiveness of auditory rehabilitation in hearing-impaired children in future studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization and Reduction of Cardiac- and Respiratory-Induced Noise as a Function of the Sampling Rate (TR) in fMRI

PubMed Central

Cordes, Dietmar; Nandy, Rajesh R.; Schafer, Scott; Wager, Tor D.

2014-01-01

It has recently been shown that both high-frequency and low-frequency cardiac and respiratory noise sources exist throughout the entire brain and can cause significant signal changes in fMRI data. It is also known that the brainstem, basal forebrain and spinal cord area are problematic for fMRI because of the magnitude of cardiac-induced pulsations at these locations. In this study, the physiological noise contributions in the lower brain areas (covering the brainstem and adjacent regions) are investigated and a novel method is presented for computing both low-frequency and high-frequency physiological regressors accurately for each subject. In particular, using a novel optimization algorithm that penalizes curvature (i.e. the second derivative) of the physiological hemodynamic response functions, the cardiac -and respiratory-related response functions are computed. The physiological noise variance is determined for each voxel and the frequency-aliasing property of the high-frequency cardiac waveform as a function of the repetition time (TR) is investigated. It is shown that for the brainstem and other brain areas associated with large pulsations of the cardiac rate, the temporal SNR associated with the low-frequency range of the BOLD response has maxima at subject-specific TRs. At these values, the high-frequency aliased cardiac rate can be eliminated by digital filtering without affecting the BOLD-related signal. PMID:24355483

LANGUAGE EXPERIENCE SHAPES PROCESSING OF PITCH RELEVANT INFORMATION IN THE HUMAN BRAINSTEM AND AUDITORY CORTEX: ELECTROPHYSIOLOGICAL EVIDENCE.

PubMed

Krishnan, Ananthanarayan; Gandour, Jackson T

2014-12-01

Pitch is a robust perceptual attribute that plays an important role in speech, language, and music. As such, it provides an analytic window to evaluate how neural activity relevant to pitch undergo transformation from early sensory to later cognitive stages of processing in a well coordinated hierarchical network that is subject to experience-dependent plasticity. We review recent evidence of language experience-dependent effects in pitch processing based on comparisons of native vs. nonnative speakers of a tonal language from electrophysiological recordings in the auditory brainstem and auditory cortex. We present evidence that shows enhanced representation of linguistically-relevant pitch dimensions or features at both the brainstem and cortical levels with a stimulus-dependent preferential activation of the right hemisphere in native speakers of a tone language. We argue that neural representation of pitch-relevant information in the brainstem and early sensory level processing in the auditory cortex is shaped by the perceptual salience of domain-specific features. While both stages of processing are shaped by language experience, neural representations are transformed and fundamentally different at each biological level of abstraction. The representation of pitch relevant information in the brainstem is more fine-grained spectrotemporally as it reflects sustained neural phase-locking to pitch relevant periodicities contained in the stimulus. In contrast, the cortical pitch relevant neural activity reflects primarily a series of transient temporal neural events synchronized to certain temporal attributes of the pitch contour. We argue that experience-dependent enhancement of pitch representation for Chinese listeners most likely reflects an interaction between higher-level cognitive processes and early sensory-level processing to improve representations of behaviorally-relevant features that contribute optimally to perception. It is our view that long-term experience shapes this adaptive process wherein the top-down connections provide selective gating of inputs to both cortical and subcortical structures to enhance neural responses to specific behaviorally-relevant attributes of the stimulus. A theoretical framework for a neural network is proposed involving coordination between local, feedforward, and feedback components that can account for experience-dependent enhancement of pitch representations at multiple levels of the auditory pathway. The ability to record brainstem and cortical pitch relevant responses concurrently may provide a new window to evaluate the online interplay between feedback, feedforward, and local intrinsic components in the hierarchical processing of pitch relevant information.

LANGUAGE EXPERIENCE SHAPES PROCESSING OF PITCH RELEVANT INFORMATION IN THE HUMAN BRAINSTEM AND AUDITORY CORTEX: ELECTROPHYSIOLOGICAL EVIDENCE

PubMed Central

Krishnan, Ananthanarayan; Gandour, Jackson T.

2015-01-01

Pitch is a robust perceptual attribute that plays an important role in speech, language, and music. As such, it provides an analytic window to evaluate how neural activity relevant to pitch undergo transformation from early sensory to later cognitive stages of processing in a well coordinated hierarchical network that is subject to experience-dependent plasticity. We review recent evidence of language experience-dependent effects in pitch processing based on comparisons of native vs. nonnative speakers of a tonal language from electrophysiological recordings in the auditory brainstem and auditory cortex. We present evidence that shows enhanced representation of linguistically-relevant pitch dimensions or features at both the brainstem and cortical levels with a stimulus-dependent preferential activation of the right hemisphere in native speakers of a tone language. We argue that neural representation of pitch-relevant information in the brainstem and early sensory level processing in the auditory cortex is shaped by the perceptual salience of domain-specific features. While both stages of processing are shaped by language experience, neural representations are transformed and fundamentally different at each biological level of abstraction. The representation of pitch relevant information in the brainstem is more fine-grained spectrotemporally as it reflects sustained neural phase-locking to pitch relevant periodicities contained in the stimulus. In contrast, the cortical pitch relevant neural activity reflects primarily a series of transient temporal neural events synchronized to certain temporal attributes of the pitch contour. We argue that experience-dependent enhancement of pitch representation for Chinese listeners most likely reflects an interaction between higher-level cognitive processes and early sensory-level processing to improve representations of behaviorally-relevant features that contribute optimally to perception. It is our view that long-term experience shapes this adaptive process wherein the top-down connections provide selective gating of inputs to both cortical and subcortical structures to enhance neural responses to specific behaviorally-relevant attributes of the stimulus. A theoretical framework for a neural network is proposed involving coordination between local, feedforward, and feedback components that can account for experience-dependent enhancement of pitch representations at multiple levels of the auditory pathway. The ability to record brainstem and cortical pitch relevant responses concurrently may provide a new window to evaluate the online interplay between feedback, feedforward, and local intrinsic components in the hierarchical processing of pitch relevant information. PMID:25838636

Bilingualism increases neural response consistency and attentional control: Evidence for sensory and cognitive coupling

PubMed Central

Krizman, Jennifer; Skoe, Erika; Marian, Viorica; Kraus, Nina

2014-01-01

Auditory processing is presumed to be influenced by cognitive processes – including attentional control – in a top-down manner. In bilinguals, activation of both languages during daily communication hones inhibitory skills, which subsequently bolster attentional control. We hypothesize that the heightened attentional demands of bilingual communication strengthens connections between cognitive (i.e., attentional control) and auditory processing, leading to greater across-trial consistency in the auditory evoked response (i.e., neural consistency) in bilinguals. To assess this, we collected passively-elicited auditory evoked responses to the syllable [da] and separately obtained measures of attentional control and language ability in adolescent Spanish-English bilinguals and English monolinguals. Bilinguals demonstrated enhanced attentional control and more consistent brainstem and cortical responses. In bilinguals, but not monolinguals, brainstem consistency tracked with language proficiency and attentional control. We interpret these enhancements in neural consistency as the outcome of strengthened attentional control that emerged from experience communicating in two languages. PMID:24413593

Development of auditory sensitivity in budgerigars (Melopsittacus undulatus)

NASA Astrophysics Data System (ADS)

Brittan-Powell, Elizabeth F.; Dooling, Robert J.

2004-06-01

Auditory feedback influences the development of vocalizations in songbirds and parrots; however, little is known about the development of hearing in these birds. The auditory brainstem response was used to track the development of auditory sensitivity in budgerigars from hatch to 6 weeks of age. Responses were first obtained from 1-week-old at high stimulation levels at frequencies at or below 2 kHz, showing that budgerigars do not hear well at hatch. Over the next week, thresholds improved markedly, and responses were obtained for almost all test frequencies throughout the range of hearing by 14 days. By 3 weeks posthatch, birds' best sensitivity shifted from 2 to 2.86 kHz, and the shape of the auditory brainstem response (ABR) audiogram became similar to that of adult budgerigars. About a week before leaving the nest, ABR audiograms of young budgerigars are very similar to those of adult birds. These data complement what is known about vocal development in budgerigars and show that hearing is fully developed by the time that vocal learning begins.

A novel DARS2 mutation in a Japanese patient with leukoencephalopathy with brainstem and spinal cord involvement but no lactate elevation

PubMed Central

Shimojima, Keiko; Higashiguchi, Takafumi; Kishimoto, Kanako; Miyatake, Satoko; Miyake, Noriko; Takanashi, Jun-ichi; Matsumoto, Naomichi; Yamamoto, Toshiyuki

2017-01-01

The mitochondrial aspartyl-tRNA synthetase 2 gene (DARS2) is responsible for leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL). A Japanese patient with LBSL showed compound heterozygous DARS2 mutations c.358_359delinsTC (p.Gly120Ser) and c.228-15C>G (splicing error). This provides further evidence that most patients with LBSL show compound heterozygous mutations in DARS2 in association with a common splicing mutation in the splicing acceptor site of intron 2. PMID:29138691

BAER - brainstem auditory evoked response

MedlinePlus

... Updated by: Sumana Jothi, MD, specialist in laryngology, Assistant Clinical Professor, UCSF Otolaryngology, NCHCS VA, SFVA, San Francisco, CA. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, ...

Auditory brainstem response in neonates: influence of gender and weight/gestational age ratio

PubMed Central

Angrisani, Rosanna M. Giaffredo; Bautzer, Ana Paula D.; Matas, Carla Gentile; de Azevedo, Marisa Frasson

2013-01-01

OBJECTIVE: To investigate the influence of gender and weight/gestational age ratio on the Auditory Brainstem Response (ABR) in preterm (PT) and term (T) newborns. METHODS: 176 newborns were evaluated by ABR; 88 were preterm infants - 44 females (22 small and 22 appropriate for gestational age) and 44 males (22 small and 22 appropriate for gestational age). The preterm infants were compared to 88 term infants - 44 females (22 small and 22 appropriate for gestational age) and 44 males (22 small and 22 appropriate for gestational age). All newborns had bilateral presence of transient otoacoustic emissions and type A tympanometry. RESULTS: No interaural differences were found. ABR response did not differentiate newborns regarding weight/gestational age in males and females. Term newborn females showed statistically shorter absolute latencies (except on wave I) than males. This finding did not occur in preterm infants, who had longer latencies than term newborns, regardless of gender. CONCLUSIONS: Gender and gestational age influence term infants' ABR, with lower responses in females. The weight/gestational age ratio did not influence ABR response in either groups. PMID:24473955

Musicians and tone-language speakers share enhanced brainstem encoding but not perceptual benefits for musical pitch

PubMed Central

Bidelman, Gavin M.; Gandour, Jackson T.; Krishnan, Ananthanarayan

2011-01-01

Behavioral and neurophysiological transfer effects from music experience to language processing are well-established but it is currently unclear whether or not linguistic expertise (e.g., speaking a tone language) benefits music-related processing and its perception. Here, we compare brainstem responses of English-speaking musicians/non-musicians and native speakers of Mandarin Chinese elicited by tuned and detuned musical chords, to determine if enhancements in subcortical processing translate to improvements in the perceptual discrimination of musical pitch. Relative to non-musicians, both musicians and Chinese had stronger brainstem representation of the defining pitches of musical sequences. In contrast, two behavioral pitch discrimination tasks revealed that neither Chinese nor non-musicians were able to discriminate subtle changes in musical pitch with the same accuracy as musicians. Pooled across all listeners, brainstem magnitudes predicted behavioral pitch discrimination performance but considering each group individually, only musicians showed connections between neural and behavioral measures. No brain-behavior correlations were found for tone language speakers or non-musicians. These findings point to a dissociation between subcortical neurophysiological processing and behavioral measures of pitch perception in Chinese listeners. We infer that sensory-level enhancement of musical pitch information yields cognitive-level perceptual benefits only when that information is behaviorally relevant to the listener. PMID:21835531

Phrenic nerve deficits and neurological immunopathology associated with acute West Nile virus infection in mice and hamsters.

PubMed

Zukor, Katherine; Wang, Hong; Hurst, Brett L; Siddharthan, Venkatraman; Van Wettere, Arnaud; Pilowsky, Paul M; Morrey, John D

2017-04-01

Neurological respiratory deficits are serious outcomes of West Nile virus (WNV) disease. WNV patients requiring intubation have a poor prognosis. We previously reported that WNV-infected rodents also appear to have respiratory deficits when assessed by whole-body plethysmography and diaphragmatic electromyography. The purpose of this study was to determine if the nature of the respiratory deficits in WNV-infected rodents is neurological and if deficits are due to a disorder of brainstem respiratory centers, cervical spinal cord (CSC) phrenic motor neuron (PMN) circuitry, or both. We recorded phrenic nerve (PN) activity and found that in WNV-infected mice, PN amplitude is reduced, corroborating a neurological basis for respiratory deficits. These results were associated with a reduction in CSC motor neuron number. We found no dramatic deficits, however, in brainstem-mediated breathing rhythm generation or responses to hypercapnia. PN frequency and pattern parameters were normal, and all PN parameters changed appropriately upon a CO 2 challenge. Histological analysis revealed generalized microglia activation, astrocyte reactivity, T cell and neutrophil infiltration, and mild histopathologic lesions in both the brainstem and CSC, but none of these were tightly correlated with PN function. Similar results in PN activity, brainstem function, motor neuron number, and histopathology were seen in WNV-infected hamsters, except that histopathologic lesions were more severe. Taken together, the results suggest that respiratory deficits in acute WNV infection are primarily due to a lower motor neuron disorder affecting PMNs and the PN rather than a brainstem disorder. Future efforts should focus on markers of neuronal dysfunction, axonal degeneration, and myelination.

Tonotopic alterations in inhibitory input to the medial nucleus of the trapezoid body in a mouse model of Fragile X syndrome.

PubMed

McCullagh, Elizabeth A; Salcedo, Ernesto; Huntsman, Molly M; Klug, Achim

2017-11-01

Hyperexcitability and the imbalance of excitation/inhibition are one of the leading causes of abnormal sensory processing in Fragile X syndrome (FXS). The precise timing and distribution of excitation and inhibition is crucial for auditory processing at the level of the auditory brainstem, which is responsible for sound localization ability. Sound localization is one of the sensory abilities disrupted by loss of the Fragile X Mental Retardation 1 (Fmr1) gene. Using triple immunofluorescence staining we tested whether there were alterations in the number and size of presynaptic structures for the three primary neurotransmitters (glutamate, glycine, and GABA) in the auditory brainstem of Fmr1 knockout mice. We found decreases in either glycinergic or GABAergic inhibition to the medial nucleus of the trapezoid body (MNTB) specific to the tonotopic location within the nucleus. MNTB is one of the primary inhibitory nuclei in the auditory brainstem and participates in the sound localization process with fast and well-timed inhibition. Thus, a decrease in inhibitory afferents to MNTB neurons should lead to greater inhibitory output to the projections from this nucleus. In contrast, we did not see any other significant alterations in balance of excitation/inhibition in any of the other auditory brainstem nuclei measured, suggesting that the alterations observed in the MNTB are both nucleus and frequency specific. We furthermore show that glycinergic inhibition may be an important contributor to imbalances in excitation and inhibition in FXS and that the auditory brainstem is a useful circuit for testing these imbalances. © 2017 Wiley Periodicals, Inc.

Hidden Hearing Loss and Computational Models of the Auditory Pathway: Predicting Speech Intelligibility Decline

DTIC Science & Technology

2016-11-28

of low spontaneous rate auditory nerve fibers (ANFs) and reduction of auditory brainstem response wave-I amplitudes. The goal of this research is...auditory nerve (AN) responses to speech stimuli under a variety of difficult listening conditions. The resulting cochlear neurogram, a spectrogram

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koyfman, Shlomo A.; Tendulkar, Rahul D.; Chao, Samuel T.

Purpose: To assess the imaging and clinical outcomes of patients with single brainstem metastases treated with stereotactic radiosurgery (SRS). Materials and Methods: We retrospectively reviewed the data from patients with single brainstem metastases treated with SRS. Locoregional control and survival were calculated using the Kaplan-Meier method. Prognostic factors were assessed using a Cox proportional hazards model. Results: Between 1997 and 2007, 43 patients with single brainstem metastases were treated with SRS. The median age at treatment was 59 years, the median Karnofsky performance status was 80, and the median follow-up was 5.3 months. The median dose was 15 Gy (range,more » 9.6-24), and the median conformality and heterogeneity index was 1.7 and 1.9, respectively. The median survival was 5.8 months from the procedure date. Of the 33 patient with post-treatment imaging available, a complete radiographic response was achieved in 2 (4.7%), a partial response in 8 (18.6%), and stable disease in 23 (53.5%). The 1-year actuarial rate of local control, distant brain control, and overall survival was 85%, 38.3%, and 31.5%, respectively. Of the 43 patients, 8 (19%) died within 2 months of undergoing SRS, and 15 (36%) died within 3 months. On multivariate analysis, greater performance status (hazard ratio [HR], 0.95, p = .004), score index for radiosurgery (HR, 0.7; p = .004), graded prognostic assessment score (HR, 0.48; p = .003), and smaller tumor volume (HR, 1.23, p = .002) were associated with improved survival. No Grade 3 or 4 toxicities were observed. Conclusion: The results of our study have shown that SRS is a safe and effective local therapy for patients with brainstem metastases.« less

Effect of pinching-evoked pain on jaw-stretch reflexes and exteroceptive suppression periods in healthy subjects.

PubMed

Biasiotta, A; Peddireddy, A; Wang, K; Romaniello, A; Frati, A; Svensson, P; Arendt-Nielsen, L

2007-10-01

To investigate the influence of conditioning cutaneous nociceptive inputs by a new "pinch" model on the jaw-stretch reflex and the exteroceptive suppression periods (ES1 and ES2) in jaw muscles. The jaw-stretch reflex was evoked with the use of a custom-made muscle stretcher and electrical stimuli were used to evoke an early and late exteroceptive suppression period (ES1 and ES2) in the jaw-closing muscles. Electromyographic (EMG) activity was recorded bilaterally from the masseter and temporalis muscles. These brainstem reflexes were recorded in 19 healthy men (28.8+/-1.1 years) during three different conditions: one painful clip applied to the earlobe; one painful clip applied to the nostril, and four painful clips applied simultaneously to the earlobe, nostril, eyebrow, and lower lip. Pain intensity induced by the application of the clips was scored continuously by the subjects on a 100mm visual analogue scale (VAS). The highest VAS pain scores were evoked by placement of four clips (79+/-0.5mm). There was no significant modulation of the jaw-stretch reflex (ANOVAs: P=0.929), the ES1 (P=0.298) or ES2 (P=0.082) in any of the three painful conditions. Intense and tonic cutaneous pain could be elicited by this new "pinch" pain model; however, there was no significant modulation on either excitatory or inhibitory brainstem reflex responses. The novel observation that high-intensity pinch stimuli applied to the craniofacial region fail to modulate two different brainstem reflexes is in contrast to other experimental pain studies documented facilitation of the jaw-stretch reflexes or inhibition of exteroceptive suppression periods. The clinical implication of the present findings is that only some craniofacial pain conditions could be expected to show perturbation of the brainstem reflex responses.

Sensitization of trigeminal brainstem pathways in a model for tear deficient dry eye

PubMed Central

Rahman, Mostafeezur; Okamoto, Keiichiro; Thompson, Randall; Katagiri, Ayano; Bereiter, David A.

2015-01-01

Abstract Chronic dry eye disease (DE) is associated with an unstable tear film and symptoms of ocular discomfort. The characteristics of symptoms suggest a key role for central neural processing; however, little is known about central neuroplasticity and DE. We used a model for tear deficient DE and assessed effects on eye blink behavior, orbicularis oculi muscle activity (OOemg), and trigeminal brainstem neural activity in male rats. Ocular-responsive neurons were recorded at the interpolaris/caudalis transition (Vi/Vc) and Vc/upper cervical cord (Vc/C1) regions under isoflurane, whereas OOemg activity was recorded under urethane. Spontaneous tear volume was reduced by ∼50% at 14 days after exorbital gland removal. Hypertonic saline–evoked eye blink behavior in awake rats was enhanced throughout the 14 days after surgery. Saline-evoked neural activity at the Vi/Vc transition and in superficial and deep laminae at the Vc/C1 region was greatly enhanced in DE rats. Neurons from DE rats classified as wide dynamic range displayed enlarged convergent periorbital receptive fields consistent with central sensitization. Saline-evoked OOemg activity was markedly enhanced in DE rats compared with controls. Synaptic blockade at the Vi/Vc transition or the Vc/C1 region greatly reduced hypertonic saline–evoked OOemg activity in DE and sham rats. These results indicated that persistent tear deficiency caused sensitization of ocular-responsive neurons at multiple regions of the caudal trigeminal brainstem and enhanced OOemg activity. Central sensitization of ocular-related brainstem circuits is a significant factor in DE and likely contributes to the apparent weak correlation between peripheral signs of tear dysfunction and symptoms of irritation. PMID:25734990

The effect of device use after sequential bilateral cochlear implantation in children: An electrophysiological approach.

PubMed

Sparreboom, Marloes; Beynon, Andy J; Snik, Ad F M; Mylanus, Emmanuel A M

2016-07-01

In many studies evaluating the effect of sequential bilateral cochlear implantation in congenitally deaf children, device use is not taken into account. In this study, however, device use was analyzed in relation to auditory brainstem maturation and speech recognition, which were measured in children with early-onset deafness, 5-6 years after bilateral cochlear implantation. We hypothesized that auditory brainstem maturation is mostly functionally driven by auditory stimulation and is therefore influenced by device use and not mainly by inter-implant delay. Twenty-one children participated and had inter-implant delays between 1.2 and 7.2 years. The electrically-evoked auditory brainstem response was measured for both implants separately. The difference in interaural wave V latency and speech recognition between both implants were used in the analyses. Device use was measured with a Likert scale. Results showed that the less the second device is used, the larger the difference in interaural wave V latencies is, which consequently leads to larger differences in interaural speech recognition. In children with early-onset deafness, after various periods of unilateral deprivation, full-time device use can lead to similar auditory brainstem responses and speech recognition between both ears. Therefore, device use should be considered as a relevant factor contributing to outcomes after sequential bilateral cochlear implantation. These results are indicative for a longer window between implantations in children with early-onset deafness to obtain symmetrical auditory pathway maturation than is mentioned in the literature. Results, however, must be interpreted as preliminary findings as actual device use with data logging was not yet available at the time of the study. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Subcortical encoding of speech cues in children with attention deficit hyperactivity disorder.

PubMed

Jafari, Zahra; Malayeri, Saeed; Rostami, Reza

2015-02-01

There is little information about processing of nonspeech and speech stimuli at the subcortical level in individuals with attention deficit hyperactivity disorder (ADHD). The auditory brainstem response (ABR) provides information about the function of the auditory brainstem pathways. We aim to investigate the subcortical function in neural encoding of click and speech stimuli in children with ADHD. The subjects include 50 children with ADHD and 34 typically developing (TD) children between the ages of 8 and 12 years. Click ABR (cABR) and speech ABR (sABR) with 40 ms synthetic /da/ syllable stimulus were recorded. Latencies of cABR in waves of III and V and duration of V-Vn (P⩽0.027), and latencies of sABR in waves A, D, E, F and O and duration of V-A (P⩽0.034) were significantly longer in children with ADHD than in TD children. There were no apparent differences in components the sustained frequency following response (FFR). We conclude that children with ADHD have deficits in temporal neural encoding of both nonspeech and speech stimuli. There is a common dysfunction in the processing of click and speech stimuli at the brainstem level in children with suspected ADHD. Copyright © 2015. Published by Elsevier Ireland Ltd.

Noradrenergic Regulation of Central Amygdala in Aversive Pavlovian-to-Instrumental Transfer

PubMed Central

Soroeta, Jose M.

2017-01-01

Abstract The neural mechanisms through which a Pavlovian conditioned stimulus (CS) elicits innate defense responses are well understood. But a Pavlovian CS can also invigorate ongoing instrumental responding, as shown by studies of aversive Pavlovian-to-instrumental transfer (PIT). While the neural circuitry of appetitive PIT has been studied extensively, little is known about the brain mechanisms of aversive PIT. We recently showed the central amygdala (CeA) is essential for aversive PIT. In the current studies, using pharmacology and designer receptors in rodents, we demonstrate that noradrenergic (NE) activity negatively regulates PIT via brainstem locus coeruleus (LC) activity and LC projections to CeA. Our results provide evidence for a novel pathway through which response modulation occurs between brainstem neuromodulatory systems and CeA to invigorate adaptive behavior in the face of threat. PMID:29071299

Fos-defined activity in rat brainstem following centripetal acceleration.

PubMed

Kaufman, G D; Anderson, J H; Beitz, A J

1992-11-01

To identify rat brainstem nuclei involved in the initial, short-term response to a change in gravito-inertial force, adult Long-Evans rats were rotated in the horizontal plane for 90 min in complete darkness after they were eccentrically positioned off the axis of rotation (off-axis) causing a centripetal acceleration of 2 g. Neural activation was defined by the brainstem distribution of the c-fos primary response gene protein, Fos, using immunohistochemistry. The Fos labeling in off-axis animals was compared with that of control animals who were rotated on the axis of rotation (on-axis) with no centripetal acceleration, or who were restrained but not rotated. In the off-axis animals there was a significant labeling of neurons: in the inferior, medial, and y-group subnuclei of the vestibular complex; in subnuclei of the inferior olive, especially the dorsomedial cell column; in midbrain nuclei, including the interstitial nucleus of Cajal, nucleus of Darkschewitsch, Edinger-Westphal nucleus, and dorsolateral periaqueductal gray; in autonomic centers including the solitary nucleus, area postrema, and locus coeruleus; and in reticular nuclei including the lateral reticular nucleus and the lateral parabrachial nucleus. Also, there was greater Fos expression in the dorsomedial cell column, the principal inferior olive subnuclei, inferior vestibular nucleus, the dorsolateral central gray, and the locus coeruleus in animals who had their heads restrained compared to animals whose heads were not restrained. As one control, the vestibular neuroepithelium was destroyed by injecting sodium arsanilate into the middle ear, bilaterally. This resulted in a complete lack of Fos labeling in the vestibular nuclei and the inferior olive, and a significant reduction in labeling in other nuclei in the off-axis condition, indicating that these nuclei have a significant labyrinth-sensitive component to their Fos labeling. The data indicate that several novel brainstem regions, including the dorsomedial cell column of the inferior olive and the periaqueductal gray, as well as more traditional brainstem nuclei including vestibular and oculomotor related nuclei, respond to otolith activation during a sustained centripetal acceleration.

Antibodies to dendritic neuronal surface antigens in opsoclonus myoclonus ataxia syndrome

PubMed Central

Panzer, Jessica A.; Anand, Ronan; Dalmau, Josep; Lynch, David R.

2015-01-01

Opsoclonus myoclonus ataxia syndrome (OMAS) is an autoimmune disorder characterized by rapid, random, conjugate eye movements (opsoclonus), myoclonus, and ataxia. Given these symptoms, autoantibodies targeting the cerebellum or brainstem could mediate the disease or be markers of autoimmunity. In a subset of patients with OMAS, we identified such autoantibodies, which bind to non-synaptic puncta on the surface of live cultured cerebellar and brainstem neuronal dendrites. These findings implicate autoimmunity to a neuronal surface antigen in the pathophysiology of OMAS. Identification of the targeted antigen(s) could elucidate the mechanisms underlying OMAS and provide a biomarker for diagnosis and response to therapy. PMID:26298330

Successful Retreatment of a Child with a Refractory Brainstem Ganglioglioma with Vemurafenib.

PubMed

Aguilera, Dolly; Janss, Anna; Mazewski, Claire; Castellino, Robert Craig; Schniederjan, Matthew; Hayes, Laura; Brahma, Barunashish; Fogelgren, Lauren; MacDonald, Tobey J

2016-03-01

A child with brainstem ganglioglioma underwent subtotal resection and focal radiation. Magnetic resonance imaging confirmed tumor progression 6 months later. Another partial resection revealed viable BRAF V600E-positive residual tumor. Vemurafenib (660 mg/m(2) /dose) was administered twice daily, resulting in >70% tumor reduction with sustained clinical improvement for 1 year. Vemurafenib was then terminated, but significant tumor progression occurred 3 months later. Vemurafenib was restarted, resulting in partial response. Toxicities included Grade I pruritus and Grade II rash. Vemurafenib was effectively crushed and administered in solution via nasogastric tube. We demonstrate benefit from restarting vemurafenib therapy. © 2015 Wiley Periodicals, Inc.

Brainstem ischemic lesions on MRI in children with tuberculous meningitis: with diffusion weighted confirmation.

PubMed

van der Merwe, Dirk Johannes; Andronikou, Savvas; Van Toorn, Ronald; Pienaar, Manana

2009-08-01

The Western Cape in South Africa has one of the highest incidences of tuberculous meningitis (TBM) in the world. Despite therapy, the outcome in children with advanced TBM remains dismal. Magnetic resonance imaging (MRI) has been shown to be superior to computed tomography (CT) in demonstrating ischemia in TBM, especially of the brainstem. The objective of this study was to characterize brainstem lesions and association with clinical findings in children with TBM by using MRI. CT and multiplanar MRI scans were performed in 30 children with proven TBM. From this group, a subgroup with radiological ischemic changes of the brainstem were identified. Radiological findings in these patients were then correlated with severity of disease, motor deficit, and outcome after 6 months. Radiological brainstem abnormalities were identified in 14 out of 30 children. Thirty-eight brainstem lesions were confirmed to be ischemic. The severity of disease at presentation, degree of motor deficit, and developmental outcome after 6 months of the children with ischemic brainstem lesions was poorer compared to those children without brainstem involvement. However, both sensitivity and specificity of the MRI brainstem lesion detection for clinical outcome proved low. A significant percentage of children with TBM have ischemic brainstem lesions. These are poorly visualized on conventional CT. MRI scanning is more sensitive in detecting these lesions and localizing them. There appears to be some association between MRI-detected brainstem lesions and clinical outcome. The exact meaning of these lesions and their implication for the patient's management require further clarification.

Subacute Sclerosing Panencephalitis of the Brainstem as a Clinical Entity.

PubMed

Upadhyayula, Pavan S; Yang, Jason; Yue, John K; Ciacci, Joseph D

2017-11-07

Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurological disorder of early adolescence caused by persistent infection of the measles virus, which remains prevalent worldwide despite an effective vaccine. SSPE is a devastating disease with a characteristic clinical course in subcortical white matter; however, atypical presentations of brainstem involvement may be seen in rare cases. This review summarizes reports to date on brainstem involvement in SSPE, including the clinical course of disease, neuroimaging presentations, and guidelines for treatment. A comprehensive literature search was performed for English-language publications with keywords "subacute sclerosing panencephalitis" and "brainstem" using the National Library of Medicine PubMed database (March 1981-September 2017). Eleven articles focusing on SSPE of the brainstem were included. Predominant brainstem involvement remains uncharacteristic of SSPE, which may lead to misdiagnosis and poor outcome. A number of case reports have demonstrated brainstem involvement associated with other intracranial lesions commonly presenting in later SSPE stages (III and IV). However, brainstem lesions can appear in all stages, independent of higher cortical structures. The varied clinical presentations complicate diagnosis from a neuroimaging perspective. SSPE of the brainstem is a rare but important clinical entity. It may present like canonical SSPE or with unique clinical features such as absence seizures and pronounced ataxia. While SSPE generally progresses to the brainstem, it can also begin with a primary focus of infection in the brainstem. Awareness of varied SSPE presentations can aid in early diagnosis as well as guide management and treatment.

Relating the variability of tone-burst otoacoustic emission and auditory brainstem response latencies to the underlying cochlear mechanics

NASA Astrophysics Data System (ADS)

Verhulst, Sarah; Shera, Christopher A.

2015-12-01

Forward and reverse cochlear latency and its relation to the frequency tuning of the auditory filters can be assessed using tone bursts (TBs). Otoacoustic emissions (TBOAEs) estimate the cochlear roundtrip time, while auditory brainstem responses (ABRs) to the same stimuli aim at measuring the auditory filter buildup time. Latency ratios are generally close to two and controversy exists about the relationship of this ratio to cochlear mechanics. We explored why the two methods provide different estimates of filter buildup time, and ratios with large inter-subject variability, using a time-domain model for OAEs and ABRs. We compared latencies for twenty models, in which all parameters but the cochlear irregularities responsible for reflection-source OAEs were identical, and found that TBOAE latencies were much more variable than ABR latencies. Multiple reflection-sources generated within the evoking stimulus bandwidth were found to shape the TBOAE envelope and complicate the interpretation of TBOAE latency and TBOAE/ABR ratios in terms of auditory filter tuning.

A kernel-based novelty detection scheme for the ultra-fast detection of chirp evoked Auditory Brainstem Responses.

PubMed

Corona-Strauss, Farah I; Delb, Wolfgang; Schick, Bernhard; Strauss, Daniel J

2010-01-01

Auditory Brainstem Responses (ABRs) are used as objective method for diagnostics and quantification of hearing loss. Many methods for automatic recognition of ABRs have been developed, but none of them include the individual measurement setup in the analysis. The purpose of this work was to design a fast recognition scheme for chirp-evoked ABRs that is adjusted to the individual measurement condition using spontaneous electroencephalographic activity (SA). For the classification, the kernel-based novelty detection scheme used features based on the inter-sweep instantaneous phase synchronization as well as energy and entropy relations in the time-frequency domain. This method provided SA discrimination from stimulations above the hearing threshold with a minimum number of sweeps, i.e., 200 individual responses. It is concluded that the proposed paradigm, processing procedures and stimulation techniques improve the detection of ABRs in terms of the degree of objectivity, i.e., automation of procedure, and measurement time.

Difference of auditory brainstem responses by stimulating to round and oval window in animal experiments.

PubMed

Lee, Jyung Hyun; Park, Hyo Soon; Wei, Qun; Kim, Myoung Nam; Cho, Jin-Ho

2017-01-02

ABSTACT To ensure the safety and efficacy of implantable hearing aids, animal experiments are an essential developmental procedure, in particular, auditory brainstem responses (ABRs) can be used to verify the objective effectiveness of implantable hearing aids. This study measured and compared the ABRs generated when applying the same vibration stimuli to an oval window and round window. The ABRs were measured using a TDT system 3 (TDT, USA), while the vibration stimuli were applied to a round window and oval window in 4 guinea pigs using a piezo-electric transducer with a proper contact tip. A paired t-test was used to determine any differences between the ABR amplitudes when applying the stimulation to an oval window and round window. The paired t-test revealed a significant difference between the ABR amplitudes generated by the round and oval window stimulation (t = 10.079, α < .0001). Therefore, the results confirmed that the biological response to round window stimulation was not the same as that to oval window stimulation.

The H3.3 K27M mutation results in a poorer prognosis in brainstem gliomas than thalamic gliomas in adults.

PubMed

Feng, Jie; Hao, Shuyu; Pan, Changcun; Wang, Yu; Wu, Zhen; Zhang, Junting; Yan, Hai; Zhang, Liwei; Wan, Hong

2015-11-01

Brainstem and thalamic gliomas are rare, and they are poorly understood in adults. Genetic aberrations that occur in these tumors are still unknown. In this study, we investigated whether thalamic gliomas have different genetic aberrations and clinical outcomes compared with brainstem gliomas in adults. Forty-three glioma samples were selected, including 28 brainstem and 15 thalamic gliomas. The frequency of the K27M mutation in adult midline gliomas was 58.1%. High-grade gliomas in the thalamus were statistically significantly more numerous than brainstem gliomas. Patients with K27M mutant brainstem gliomas had a significantly shorter overall survival than patients with wild-type tumors (P = .020) by Cox regression after adjustment for other independent risk factors. However, there was no statistical tendency toward a poorer overall survival in thalamic gliomas containing the K27M mutation compared with wild-type tumors. The presence of the K27M mutation significantly corresponded with mutations in TP53 in thalamic gliomas. Interestingly, the K27M mutation was mutually exclusive with mutations in IDH1, which was detected only in brainstem gliomas. The microarray data identified 86 differentially expressed genes between brainstem and thalamic gliomas with the K27M mutation. The cyclin-dependent kinase 6 (CDK6) gene, which plays an important role in cancer pathways, was found to be differentially expressed between brainstem and thalamic gliomas with K27M mutations. Although the K27M mutation was frequently observed in adult brainstem and thalamic gliomas, this mutation tended to be associated with a poorer prognosis in brainstem gliomas but not in thalamic gliomas. Brainstem gliomas may present different genetic aberrations from thalamic gliomas. These differences may provide guidance for therapeutic decisions for the treatment of adult brainstem and thalamic gliomas, which may have different molecular targets. Copyright © 2015. Published by Elsevier Inc.

A direct approach for the design of chirp stimuli used for the recording of auditory brainstem responses

PubMed Central

Elberling, Claus; Don, Manuel

2010-01-01

A recent study evaluates auditory brainstem responses (ABRs) evoked by chirps of different durations (sweeping rates) [Elberling et al. (2010). J. Acoust. Soc. Am. 128, 215–223]. The study demonstrates that shorter chirps are most efficient at higher levels of stimulation whereas longer chirps are most efficient at lower levels. Mechanisms other than the traveling wave delay, in particular, upward spread of excitation and changes in cochlear-neural delay with level, are suggested to be responsible for these findings. As a consequence, delay models based on estimates of the traveling wave delay are insufficient for the design of chirp stimuli, and another delay model based on a direct approach is therefore proposed. The direct approach uses ABR-latencies from normal-hearing subjects in response to octave-band chirps over a wide range of levels. The octave-band chirps are constructed by decomposing a broad-band chirp, and constitute a subset of the chirp. The delay compensations of the proposed model are similar to those found in the previous experimental study, which thus verifies the results of the proposed model. PMID:21110591

Congenital brainstem disconnection associated with a syrinx of the brainstem.

PubMed

Barth, P G; de Vries, L S; Nikkels, P G J; Troost, D

2008-02-01

We report a case of congenital brainstem disconnection including the second detailed autopsy. A full-term newborn presented with irreversible apnoea and died on the fifth day. MRI revealed disconnection of the brainstem. The autopsy included a series of transverse sections of the mesencephalon, medulla oblongata and bridging tissue fragments. A fragile tube walled by mature brainstem tissue could be reconstructed. It enveloped a cylinder of fluid within the ventral pons extending to the mesencephalon and the lower brainstem. The aqueduct was patent and outside the lesion. The basilar artery was represented by a tiny median vessel. The ventral and lateral parts of the posterior brainstem were surrounded by heterotopic glial tissue. The olivary nucleus was absent and the cerebellar dentate nucleus was dysplastic. Considering the maturity of the remaining parts of the pons, the onset of structural decline is likely to be close to the time of birth. Probable causes are progressively insufficient perfusion through an hypoplastic basilar artery, and obstructed venous drainage through an abnormal glial barrier surrounding the posterior brainstem. The morphological findings can be characterized as a syrinx, known from disorders in which brainstem or spinal cord are damaged by a combination of mechanical and circulatory factors.

Brainstem auditory evoked potentials with the use of acoustic clicks and complex verbal sounds in young adults with learning disabilities.

PubMed

Kouni, Sophia N; Giannopoulos, Sotirios; Ziavra, Nausika; Koutsojannis, Constantinos

2013-01-01

Acoustic signals are transmitted through the external and middle ear mechanically to the cochlea where they are transduced into electrical impulse for further transmission via the auditory nerve. The auditory nerve encodes the acoustic sounds that are conveyed to the auditory brainstem. Multiple brainstem nuclei, the cochlea, the midbrain, the thalamus, and the cortex constitute the central auditory system. In clinical practice, auditory brainstem responses (ABRs) to simple stimuli such as click or tones are widely used. Recently, complex stimuli or complex auditory brain responses (cABRs), such as monosyllabic speech stimuli and music, are being used as a tool to study the brainstem processing of speech sounds. We have used the classic 'click' as well as, for the first time, the artificial successive complex stimuli 'ba', which constitutes the Greek word 'baba' corresponding to the English 'daddy'. Twenty young adults institutionally diagnosed as dyslexic (10 subjects) or light dyslexic (10 subjects) comprised the diseased group. Twenty sex-, age-, education-, hearing sensitivity-, and IQ-matched normal subjects comprised the control group. Measurements included the absolute latencies of waves I through V, the interpeak latencies elicited by the classical acoustic click, the negative peak latencies of A and C waves, as well as the interpeak latencies of A-C elicited by the verbal stimulus 'baba' created on a digital speech synthesizer. The absolute peak latencies of waves I, III, and V in response to monoaural rarefaction clicks as well as the interpeak latencies I-III, III-V, and I-V in the dyslexic subjects, although increased in comparison with normal subjects, did not reach the level of a significant difference (p<0.05). However, the absolute peak latencies of the negative wave C and the interpeak latencies of A-C elicited by verbal stimuli were found to be increased in the dyslexic group in comparison with the control group (p=0.0004 and p=0.045, respectively). In the subgroup consisting of 10 patients suffering from 'other learning disabilities' and who were characterized as with 'light' dyslexia according to dyslexia tests, no significant delays were found in peak latencies A and C and interpeak latencies A-C in comparison with the control group. Acoustic representation of a speech sound and, in particular, the disyllabic word 'baba' was found to be abnormal, as low as the auditory brainstem. Because ABRs mature in early life, this can help to identify subjects with acoustically based learning problems and apply early intervention, rehabilitation, and treatment. Further studies and more experience with more patients and pathological conditions such as plasticity of the auditory system, cochlear implants, hearing aids, presbycusis, or acoustic neuropathy are necessary until this type of testing is ready for clinical application. © 2013 Elsevier Inc. All rights reserved.

Insights into the central pathways involved in the emetic and behavioural responses to exendin-4 in the ferret.

PubMed

Lu, Zengbing; Yeung, Chi-Kong; Lin, Ge; Yew, David T W; Andrews, P L R; Rudd, John A

2017-01-01

GLP-1 receptor agonists are utilised for the treatment of Type-2 diabetes but can be associated with undesirable effects of nausea and vomiting. To investigate the role of GLP-1 receptors in mechanisms of emesis, behaviours indicative of nausea (BIN) and food intake in the ferret. Exendin-4 (10 and 30nmol, i.c.v.) induced emesis, inhibited food intake, and increased the frequency of BIN. Increases in c-Fos in the brainstem, midbrain and forebrain occurred in animals exhibiting emesis; no activation of the brainstem occurred in animals not vomiting. Exendin-4 (10nmol, i.c.v.) when preceded by i.c.v. saline (15μl), was not emetic but induced BIN and inhibited food intake; exendin (9-39) (100nmol) reduced BIN only. c-Fos showed that consistent with the absence of emesis in saline/exendin-4 treated animals there was no increase in c-Fos in the brainstem, but it increased in midbrain and forebrain nuclei. Excepting the amygdala, exendin (9-39) was without efffect on the increases in c-Fos. Analysis of c-Fos data showed a positive linear relationship between midbrain and forebrain areas irrespective of the occurrence of emesis induced by exendin-4. In contrast, brainstem and midbrain c-Fos levels were positively correlated, but only in animals with emesis. The brainstem is critical for exendin-4-induced emesis but suppression of food intake and BIN involves more rostral brain sites. Exendin-4-induced BIN and c-Fos activation of the amygdala are sensitive to exendin (9-39), whereas the suppression of food intake is not implicating separate control mechanisms for emesis and BIN. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed Central

Holiga, Štefan; Mueller, Karsten; Möller, Harald E.; Urgošík, Dušan; Růžička, Evžen; Schroeter, Matthias L.; Jech, Robert

2015-01-01

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. PMID:26509113

Imaging of glial cell morphology, SOD1 distribution and elemental composition in the brainstem and hippocampus of the ALS hSOD1G93A rat.

PubMed

Stamenković, Stefan; Dučić, Tanja; Stamenković, Vera; Kranz, Alexander; Andjus, Pavle R

2017-08-15

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting motor and cognitive domains of the CNS. Mutations in the Cu,Zn-superoxide dismutase (SOD1) cause 20% of familial ALS and provoke formation of intracellular aggregates and copper and zinc unbinding, leading to glial activation and neurodegeneration. Therefore, we investigated glial cell morphology, intracellular SOD1 distribution, and elemental composition in the brainstem and hippocampus of the hSOD1 G93A transgenic rat model of ALS. Immunostaining for astrocytes, microglia and SOD1 revealed glial proliferation and progressive tissue accumulation of SOD1 in both brain regions of ALS rats starting already at the presymptomatic stage. Glial cell morphology analysis in the brainstem of ALS rats revealed astrocyte activation occurring before disease symptoms onset, followed by activation of microglia. Hippocampal ALS astrocytes exhibited an identical reactive profile, while microglial morphology was unchanged. Additionally, ALS brainstem astrocytes demonstrated progressive SOD1 accumulation in the cell body and processes, while microglial SOD1 levels were reduced and its distribution limited to distal cell processes. In the hippocampus both glial cell types exhibited SOD1 accumulation in the cell body. X-ray fluorescence imaging revealed decreased P and increased Ca, Cl, K, Ni, Cu and Zn in the brainstem, and higher levels of Cl, Ni and Cu, but lower levels of Zn in the hippocampus of symptomatic ALS rats. These results bring new insights into the glial response during disease development and progression in motor as well as in non-motor CNS structures, and indicate disturbed tissue elemental homeostasis as a prominent hallmark of disease pathology. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

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.

PubMed

Holiga, Štefan; Mueller, Karsten; Möller, Harald E; Urgošík, Dušan; Růžička, Evžen; Schroeter, Matthias L; Jech, Robert

2015-01-01

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.

Hemodynamic Signal Changes Accompanying Execution and Imagery of Swallowing in Patients with Dysphagia: A Multiple Single-Case Near-Infrared Spectroscopy Study

PubMed Central

Kober, Silvia Erika; Bauernfeind, Günther; Woller, Carina; Sampl, Magdalena; Grieshofer, Peter; Neuper, Christa; Wood, Guilherme

2015-01-01

In the present multiple case study, we examined hemodynamic changes in the brain in response to motor execution (ME) and motor imagery (MI) of swallowing in dysphagia patients compared to healthy matched controls using near-infrared spectroscopy (NIRS). Two stroke patients with cerebral lesions in the right hemisphere, two stroke patients with lesions in the brainstem, and two neurologically healthy control subjects actively swallowed saliva (ME) and mentally imagined to swallow saliva (MI) in a randomized order while changes in concentration of oxygenated hemoglobin (oxy-Hb) and deoxygenated hemoglobin (deoxy-Hb) were assessed. In line with recent findings in healthy young adults, MI and ME of swallowing led to the strongest NIRS signal change in the inferior frontal gyrus in stroke patients as well as in healthy elderly. We found differences in the topographical distribution and time course of the hemodynamic response in dependence on lesion location. Dysphagia patients with lesions in the brainstem showed bilateral hemodynamic signal changes in the inferior frontal gyrus during active swallowing comparable to healthy controls. In contrast, dysphagia patients with cerebral lesions in the right hemisphere showed more unilateral activation patterns during swallowing. Furthermore, patients with cerebral lesions showed a prolonged time course of the hemodynamic response during MI and ME of swallowing compared to healthy controls and patients with brainstem lesions. Brain activation patterns associated with ME and MI of swallowing were largely comparable, especially for changes in deoxy-Hb. Hence, the present results provide new evidence regarding timing and topographical distribution of the hemodynamic response during ME and MI of swallowing in dysphagia patients and may have practical impact on future dysphagia treatment. PMID:26217298

Deciphering the Neural Control of Sympathetic Nerve Activity: Status Report and Directions for Future Research.

PubMed

Barman, Susan M; Yates, Bill J

2017-01-01

Sympathetic nerve activity (SNA) contributes appreciably to the control of physiological function, such that pathological alterations in SNA can lead to a variety of diseases. The goal of this review is to discuss the characteristics of SNA, briefly review the methodology that has been used to assess SNA and its control, and to describe the essential role of neurophysiological studies in conscious animals to provide additional insights into the regulation of SNA. Studies in both humans and animals have shown that SNA is rhythmic or organized into bursts whose frequency varies depending on experimental conditions and the species. These rhythms are generated by brainstem neurons, and conveyed to sympathetic preganglionic neurons through several pathways, including those emanating from the rostral ventrolateral medulla. Although rhythmic SNA is present in decerebrate animals (indicating that neurons in the brainstem and spinal cord are adequate to generate this activity), there is considerable evidence that a variety of supratentorial structures including the insular and prefrontal cortices, amygdala, and hypothalamic subnuclei provide inputs to the brainstem regions that regulate SNA. It is also known that the characteristics of SNA are altered during stress and particular behaviors such as the defense response and exercise. While it is a certainty that supratentorial structures contribute to changes in SNA during these behaviors, the neural underpinnings of the responses are yet to be established. Understanding how SNA is modified during affective responses and particular behaviors will require neurophysiological studies in awake, behaving animals, including those that entail recording activity from neurons that generate SNA. Recent studies have shown that responses of neurons in the central nervous system to most sensory inputs are context-specific. Future neurophysiological studies in conscious animals should also ascertain whether this general rule also applies to sensory signals that modify SNA.

Benign paroxysmal vertigo of childhood: diagnostic value of vestibular test and high stimulus rate auditory brainstem response test.

PubMed

Zhang, Daogong; Fan, Zhaomin; Han, Yuechen; Wang, Mingming; Xu, Lei; Luo, Jianfen; Ai, Yu; Wang, Haibo

2012-01-01

To investigate the diagnostic value of vestibular test and high stimulus rate auditory brainstem response (ABR) test and the possible mechanism responsible for benign paroxysmal vertigo of childhood (BPVC). Data of 56 patients with BPVC in vertigo clinic of our hospital from May 2007 to September 2008 were retrospectively analyzed in this study. Patients with BPVC were tested with pure tone audiometry, high stimulus rate auditory brainstem response test (ABR), transcranial Doppler sonography (TCD), bithermal caloric test, and VEMP. The results of the hearing and vestibular function test were compared and analyzed. There were 56 patients with BPVC, including 32 men, 24 women, aged 3-12 years old, with an average of 6.5 years. Among 56 cases of BPVC patients, the results of pure tone audiometry were all normal. High stimulus rate ABR was abnormal in 66.1% (37/56) of cases. TCD showed 57.1% abnormality in 56 cases, including faster flow rate in 28 cases and slower flow rate in 4 cases. High stimulus rate ABR and TCD were both abnormal in 48.2% (27/56) of cases. Bithermal caloric test was abnormal in 14.3% (8/56) of cases. VEMP showed 32.1% abnormality, including amplitude abnormality in 16 cases and latency abnormality in 2 cases. The abnormal rate of VEMP was much higher than that of caloric test. Vascular mechanisms might be involved in the pathogenesis of BPVC and there is strong evidence for close relationship between BPVC and migraine. High stimulus rate ABR is helpful in the diagnosis of BPVC. The inferior vestibular pathway is much more impaired than the superior vestibular pathway in BPVC. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Cardiorespiratory concerns shape brain responses during automatic panic-related scene processing in patients with panic disorder

PubMed Central

Feldker, Katharina; Heitmann, Carina Yvonne; Neumeister, Paula; Brinkmann, Leonie; Bruchmann, Maximillan; Zwitserlood, Pienie; Straube, Thomas

2018-01-01

Background Increased automatic processing of threat-related stimuli has been proposed as a key element in panic disorder. Little is known about the neural basis of automatic processing, in particular to task-irrelevant, panic-related, ecologically valid stimuli, or about the association between brain activation and symptomatology in patients with panic disorder. Methods The present event-related functional MRI (fMRI) study compared brain responses to task-irrelevant, panic-related and neutral visual stimuli in medication-free patients with panic disorder and healthy controls. Panic-related and neutral scenes were presented while participants performed a spatially non-overlapping bar orientation task. Correlation analyses investigated the association between brain responses and panic-related aspects of symptomatology, measured using the Anxiety Sensitivity Index (ASI). Results We included 26 patients with panic disorder and 26 heatlhy controls in our analysis. Compared with controls, patients with panic disorder showed elevated activation in the amygdala, brainstem, thalamus, insula, anterior cingulate cortex and midcingulate cortex in response to panic-related versus neutral task-irrelevant stimuli. Furthermore, fear of cardiovascular symptoms (a subcomponent of the ASI) was associated with insula activation, whereas fear of respiratory symptoms was associated with brainstem hyperactivation in patients with panic disorder. Limitations The additional implementation of measures of autonomic activation, such as pupil diameter, heart rate, or electrodermal activity, would have been informative during the fMRI scan as well as during the rating procedure. Conclusion Results reveal a neural network involved in the processing of panic-related distractor stimuli in patients with panic disorder and suggest an automatic weighting of panic-related information depending on the magnitude of cardiovascular and respiratory symptoms. Insula and brainstem activations show function-related associations with specific components of panic symptomatology. PMID:29252163

Cardiorespiratory concerns shape brain responses during automatic panic-related scene processing in patients with panic disorder.

PubMed

Feldker, Katharina; Heitmann, Carina Yvonne; Neumeister, Paula; Brinkmann, Leonie; Bruchmann, Maximillan; Zwitserlood, Pienie; Straube, Thomas

2018-01-01

Increased automatic processing of threat-related stimuli has been proposed as a key element in panic disorder. Little is known about the neural basis of automatic processing, in particular to task-irrelevant, panic-related, ecologically valid stimuli, or about the association between brain activation and symptomatology in patients with panic disorder. The present event-related functional MRI (fMRI) study compared brain responses to task-irrelevant, panic-related and neutral visual stimuli in medication-free patients with panic disorder and healthy controls. Panic-related and neutral scenes were presented while participants performed a spatially nonoverlapping bar orientation task. Correlation analyses investigated the association between brain responses and panic-related aspects of symptomatology, measured using the Anxiety Sensitivity Index (ASI). We included 26 patients with panic disorder and 26 heatlhy controls in our analysis. Compared with controls, patients with panic disorder showed elevated activation in the amygdala, brainstem, thalamus, insula, anterior cingulate cortex and midcingulate cortex in response to panic-related versus neutral task-irrelevant stimuli. Furthermore, fear of cardiovascular symptoms (a subcomponent of the ASI) was associated with insula activation, whereas fear of respiratory symptoms was associated with brainstem hyperactivation in patients with panic disorder. The additional implementation of measures of autonomic activation, such as pupil diameter, heart rate, or electrodermal activity, would have been informative during the fMRI scan as well as during the rating procedure. Results reveal a neural network involved in the processing of panic-related distractor stimuli in patients with panic disorder and suggest an automatic weighting of panic-related information depending on the magnitude of cardiovascular and respiratory symptoms. Insula and brainstem activations show function-related associations with specific components of panic symptomatology.

Cardiorespiratory concerns shape brain responses during automatic panic-related scene processing in patients with panic disorder.

PubMed

Feldker, Katharina; Heitmann, Carina Yvonne; Neumeister, Paula; Brinkmann, Leonie; Bruchmann, Maximillan; Zwitserlood, Pienie; Straube, Thomas

2017-09-26

Increased automatic processing of threat-related stimuli has been proposed as a key element in panic disorder. Little is known about the neural basis of automatic processing, in particular to task-irrelevant, panic-related, ecologically valid stimuli, or about the association between brain activation and symptomatology in patients with panic disorder. The present event-related fMRI study compared brain responses to task-irrelevant, panic-related and neutral visual stimuli in medication-free patients with panic disorder and healthy controls. Panic-related and neutral scenes were presented while participants performed a spatially nonoverlapping bar orientation task. Correlation analyses investigated the association between brain responses and panic-related aspects of symptomatology, measured using the Anxiety Sensitivity Index (ASI). We included 26 patients with panic disorder and 26 heatlhy controls in our analysis. Compared with controls, patients with panic disorder showed elevated activation in the amygdala, brainstem, thalamus, insula, anterior cingulate cortex and midcingulate cortex in response to panic-related versus neutral task-irrelevant stimuli. Furthermore, fear of cardiovascular symptoms (a subcomponent of the ASI) was associated with insula activation, whereas fear of respiratory symptoms was associated with brainstem hyperactivation in patients with panic disorder. The additional implementation of measures of autonomic activation, such as pupil diameter, heart rate, or electrodermal activity, would have been informative during the fMRI scan as well as during the rating procedure. Results reveal a neural network involved in the processing of panic-related distractor stimuli in patients with panic disorder and suggest an automatic weighting of panic-related information depending on the magnitude of cardiovascular and respiratory symptoms. Insula and brainstem activations show function-related associations with specific components of panic symptomatology.

Physiological Characterization of Vestibular Efferent Brainstem Neurons Using a Transgenic Mouse Model

PubMed Central

Leijon, Sara; Magnusson, Anna K.

2014-01-01

The functional role of efferent innervation of the vestibular end-organs in the inner ear remains elusive. This study provides the first physiological characterization of the cholinergic vestibular efferent (VE) neurons in the brainstem by utilizing a transgenic mouse model, expressing eGFP under a choline-acetyltransferase (ChAT)-locus spanning promoter in combination with targeted patch clamp recordings. The intrinsic electrical properties of the eGFP-positive VE neurons were compared to the properties of the lateral olivocochlear (LOC) brainstem neurons, which gives rise to efferent innervation of the cochlea. Both VE and the LOC neurons were marked by their negative resting membrane potential <−75 mV and their passive responses in the hyperpolarizing range. In contrast, the response properties of VE and LOC neurons differed significantly in the depolarizing range. When injected with positive currents, VE neurons fired action potentials faithfully to the onset of depolarization followed by sparse firing with long inter-spike intervals. This response gave rise to a low response gain. The LOC neurons, conversely, responded with a characteristic delayed tonic firing upon depolarizing stimuli, giving rise to higher response gain than the VE neurons. Depolarization triggered large TEA insensitive outward currents with fast inactivation kinetics, indicating A-type potassium currents, in both the inner ear-projecting neuronal types. Immunohistochemistry confirmed expression of Kv4.3 and 4.2 ion channel subunits in both the VE and LOC neurons. The difference in spiking responses to depolarization is related to a two-fold impact of these transient outward currents on somatic integration in the LOC neurons compared to in VE neurons. It is speculated that the physiological properties of the VE neurons might be compatible with a wide-spread control over motion and gravity sensation in the inner ear, providing likewise feed-back amplification of abrupt and strong phasic signals from the semi-circular canals and of tonic signals from the gravito-sensitive macular organs. PMID:24867596

Auditory brainstem response as a diagnostic tool for patients suffering from schizophrenia, attention deficit hyperactivity disorder, and bipolar disorder: protocol.

PubMed

Wahlström, Viktor; Åhlander, Fredrik; Wynn, Rolf

2015-02-12

Psychiatric disorders, such as schizophrenia, attention deficit hyperactivity disorder (ADHD), and bipolar disorder, may sometimes be difficult to diagnose. There is a great need for a valid and reliable diagnostic tool to aid clinicians in arriving at the diagnoses in a timely and accurate manner. Prior studies have suggested that patients suffering from schizophrenia and ADHD may process certain sound stimuli in the brainstem in an unusual manner. When these patient groups have been examined with the electrophysiological method of brainstem audiometry, some studies have found illness-specific aberrations. Such aberrations may also exist for patients suffering from bipolar disorder. In this study, we will examine whether the method of brainstem audiometry can be used as a diagnostic tool for patients suffering from schizophrenia, ADHD, and bipolar disorder. The method includes three steps: (1) auditory stimulation with specific sound stimuli, (2) simultaneous measurement of brainstem activity, and (3) automated interpretation of the resulting brain stem audiograms with data-based signal analysis. We will compare three groups of 12 individuals with confirmed diagnoses of schizophrenia, ADHD, or bipolar disorder with 12 healthy subjects under blinded conditions for a total of 48 participants. The extent to which the method can be used to reach the correct diagnosis will be investigated. The project is now in a recruiting phase. When all patients and controls have been recruited and the measurements have been performed, the data will be analyzed according to a previously arranged algorithm. We expect the recruiting phase and measurements to be completed in early 2015, the analyses to be performed in mid-2015, and the results of the study to be published in early 2016. If the results support previous findings, this will lend strength to the idea that brainstem audiometry can offer objective diagnostic support for patients suffering from schizophrenia, ADHD, and bipolar disorder. A positive result from the study could imply that brainstem audiometry could become an important supportive tool for clinicians in their efforts to diagnose patients with these disorders in a timely and accurate manner. ClinicalTrials.gov NCT01629355; https://clinicaltrials.gov/ct2/show/NCT01629355 (Archived by WebCite at http://www.webcitation.org/6VBfTwx5H).

In-air hearing of a diving duck: A comparison of psychoacoustic and auditory brainstem response thresholds

USGS Publications Warehouse

Crowell, Sara E.; Wells-Berlin, Alicia M.; Therrien, Ronald E.; Yannuzzi, Sally E.; Carr, Catherine E.

2016-01-01

Auditory sensitivity was measured in a species of diving duck that is not often kept in captivity, the lesser scaup. Behavioral (psychoacoustics) and electrophysiological [the auditory brainstem response (ABR)] methods were used to measure in-air auditory sensitivity, and the resulting audiograms were compared. Both approaches yielded audiograms with similar U-shapes and regions of greatest sensitivity (2000−3000 Hz). However, ABR thresholds were higher than psychoacoustic thresholds at all frequencies. This difference was least at the highest frequency tested using both methods (5700 Hz) and greatest at 1000 Hz, where the ABR threshold was 26.8 dB higher than the behavioral measure of threshold. This difference is commonly reported in studies involving many different species. These results highlight the usefulness of each method, depending on the testing conditions and availability of the animals.

An Analysis of The Parameters Used In Speech ABR Assessment Protocols.

PubMed

Sanfins, Milaine D; Hatzopoulos, Stavros; Donadon, Caroline; Diniz, Thais A; Borges, Leticia R; Skarzynski, Piotr H; Colella-Santos, Maria Francisca

2018-04-01

The aim of this study was to assess the parameters of choice, such as duration, intensity, rate, polarity, number of sweeps, window length, stimulated ear, fundamental frequency, first formant, and second formant, from previously published speech ABR studies. To identify candidate articles, five databases were assessed using the following keyword descriptors: speech ABR, ABR-speech, speech auditory brainstem response, auditory evoked potential to speech, speech-evoked brainstem response, and complex sounds. The search identified 1288 articles published between 2005 and 2015. After filtering the total number of papers according to the inclusion and exclusion criteria, 21 studies were selected. Analyzing the protocol details used in 21 studies suggested that there is no consensus to date on a speech-ABR protocol and that the parameters of analysis used are quite variable between studies. This inhibits the wider generalization and extrapolation of data across languages and studies.

In-air hearing of a diving duck: A comparison of psychoacoustic and auditory brainstem response thresholds.

PubMed

Crowell, Sara E; Wells-Berlin, Alicia M; Therrien, Ronald E; Yannuzzi, Sally E; Carr, Catherine E

2016-05-01

Auditory sensitivity was measured in a species of diving duck that is not often kept in captivity, the lesser scaup. Behavioral (psychoacoustics) and electrophysiological [the auditory brainstem response (ABR)] methods were used to measure in-air auditory sensitivity, and the resulting audiograms were compared. Both approaches yielded audiograms with similar U-shapes and regions of greatest sensitivity (2000-3000 Hz). However, ABR thresholds were higher than psychoacoustic thresholds at all frequencies. This difference was least at the highest frequency tested using both methods (5700 Hz) and greatest at 1000 Hz, where the ABR threshold was 26.8 dB higher than the behavioral measure of threshold. This difference is commonly reported in studies involving many different species. These results highlight the usefulness of each method, depending on the testing conditions and availability of the animals.

Mechanism of alpha-lipoic acid in attenuating kanamycin-induced ototoxicity☆

PubMed Central

Wang, Aimei; Hou, Ning; Bao, Dongyan; Liu, Shuangyue; Xu, Tao

2012-01-01

In view of the theory that alpha-lipoic acid effectively prevents cochlear cells from injury caused by various factors such as cisplatin and noise, this study examined whether alpha-lipoic acid can prevent kanamycin-induced ototoxicity. To this end, healthy BALB/c mice were injected subcutaneously with alpha-lipoic acid and kanamycin for 14 days. Auditory brainstem response test showed that increased auditory brainstem response threshold shifts caused by kanamycin were significantly inhibited. Immunohistochemical staining and western blot analysis showed that the expression of phosphorylated p38 mitogen-activated protein kinase and phosphorylated c-Jun N-terminal kinase in mouse cochlea was significantly decreased. The experimental findings suggest that phosphorylated p38 and phosphorylated c-Jun N-terminal kinase mediated kanamycin-induced ototoxic injury in BALB/c mice. Alpha-lipoic acid effectively attenuated kanamycin ototoxicity by inhibiting the kanamycin-induced high expression of phosphorylated p38 and phosphorylated c-Jun N-terminal kinase. PMID:25317129

Magnetic resonance imaging differential diagnosis of brainstem lesions in children

PubMed Central

Quattrocchi, Carlo Cosimo; Errante, Yuri; Rossi Espagnet, Maria Camilla; Galassi, Stefania; Della Sala, Sabino Walter; Bernardi, Bruno; Fariello, Giuseppe; Longo, Daniela

2016-01-01

Differential diagnosis of brainstem lesions, either isolated or in association with cerebellar and supra-tentorial lesions, can be challenging. Knowledge of the structural organization is crucial for the differential diagnosis and establishment of prognosis of pathologies with involvement of the brainstem. Familiarity with the location of the lesions in the brainstem is essential, especially in the pediatric population. Magnetic resonance imaging (MRI) is the most sensitive and specific imaging technique for diagnosing disorders of the posterior fossa and, particularly, the brainstem. High magnetic static field MRI allows detailed visualization of the morphology, signal intensity and metabolic content of the brainstem nuclei, together with visualization of the normal development and myelination. In this pictorial essay we review the brainstem pathology in pediatric patients and consider the MR imaging patterns that may help the radiologist to differentiate among vascular, toxico-metabolic, infective-inflammatory, degenerative and neoplastic processes. Helpful MR tips can guide the differential diagnosis: These include the location and morphology of lesions, the brainstem vascularization territories, gray and white matter distribution and tissue selective vulnerability. PMID:26834941

[Results from ten years newborn hearing screening in a secondary hospital].

PubMed

Sequi Canet, José Miguel; Sala Langa, Maria José; Collar Del Castillo, José Ignacio

2016-10-01

A critical analysis is performed on the results of a newborn hearing screening program in a regional hospital. Screening results from 14,247 newborns in our maternity ward from 2002 to 2013. Two step recordings of bilateral otoacoustic emissions (initial and repeat, if failed, at about one month of life). Assessment by clinical brainstem responses. The first step was performed on 14,015 newborns (98.3% of the total) reaching the screening objective. The first step pass figures were 93.7%, which implies a good pass rate with a few patients to repeat. The second step is also good because it has a pass rate of 88.9% of newborns examined (only 0.63% of initial group needed brainstem responses assessment), but 10.6% were lost to follow up, and that is a major problem. In newborns, scheduled for brainstem responses, the loss to follow-up is worse, with a figure of 29.5%, despite the high accuracy of this test given that 69.4% of those assessed showed hearing loss. This figure represents a 0.31% of the initial group, and is a similar to that published for congenital hearing loss. Including patients that were lost to follow up this figure could be greater. Newborn hearing screening is useful but needs stronger control to avoid the follow up loss. In order to achieve this, it is crucial to have a good database and a screening coordinator. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Short GSM mobile phone exposure does not alter human auditory brainstem response.

PubMed

Stefanics, Gábor; Kellényi, Lóránd; Molnár, Ferenc; Kubinyi, Györgyi; Thuróczy, György; Hernádi, István

2007-11-12

There are about 1.6 billion GSM cellular phones in use throughout the world today. Numerous papers have reported various biological effects in humans exposed to electromagnetic fields emitted by mobile phones. The aim of the present study was to advance our understanding of potential adverse effects of the GSM mobile phones on the human hearing system. Auditory Brainstem Response (ABR) was recorded with three non-polarizing Ag-AgCl scalp electrodes in thirty young and healthy volunteers (age 18-26 years) with normal hearing. ABR data were collected before, and immediately after a 10 minute exposure to 900 MHz pulsed electromagnetic field (EMF) emitted by a commercial Nokia 6310 mobile phone. Fifteen subjects were exposed to genuine EMF and fifteen to sham EMF in a double blind and counterbalanced order. Possible effects of irradiation was analyzed by comparing the latency of ABR waves I, III and V before and after genuine/sham EMF exposure. Paired sample t-test was conducted for statistical analysis. Results revealed no significant differences in the latency of ABR waves I, III and V before and after 10 minutes of genuine/sham EMF exposure. The present results suggest that, in our experimental conditions, a single 10 minute exposure of 900 MHz EMF emitted by a commercial mobile phone does not produce measurable immediate effects in the latency of auditory brainstem waves I, III and V.

Auditory Brainstem Circuits That Mediate the Middle Ear Muscle Reflex

PubMed Central

Mukerji, Sudeep; Windsor, Alanna Marie; Lee, Daniel J.

2010-01-01

The middle ear muscle (MEM) reflex is one of two major descending systems to the auditory periphery. There are two middle ear muscles (MEMs): the stapedius and the tensor tympani. In man, the stapedius contracts in response to intense low frequency acoustic stimuli, exerting forces perpendicular to the stapes superstructure, increasing middle ear impedance and attenuating the intensity of sound energy reaching the inner ear (cochlea). The tensor tympani is believed to contract in response to self-generated noise (chewing, swallowing) and nonauditory stimuli. The MEM reflex pathways begin with sound presented to the ear. Transduction of sound occurs in the cochlea, resulting in an action potential that is transmitted along the auditory nerve to the cochlear nucleus in the brainstem (the first relay station for all ascending sound information originating in the ear). Unknown interneurons in the ventral cochlear nucleus project either directly or indirectly to MEM motoneurons located elsewhere in the brainstem. Motoneurons provide efferent innervation to the MEMs. Although the ascending and descending limbs of these reflex pathways have been well characterized, the identity of the reflex interneurons is not known, as are the source of modulatory inputs to these pathways. The aim of this article is to (a) provide an overview of MEM reflex anatomy and physiology, (b) present new data on MEM reflex anatomy and physiology from our laboratory and others, and (c) describe the clinical implications of our research. PMID:20870664

Subacute Sclerosing Panencephalitis of the Brainstem as a Clinical Entity

PubMed Central

Yang, Jason; Ciacci, Joseph D.

2017-01-01

Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurological disorder of early adolescence caused by persistent infection of the measles virus, which remains prevalent worldwide despite an effective vaccine. SSPE is a devastating disease with a characteristic clinical course in subcortical white matter; however, atypical presentations of brainstem involvement may be seen in rare cases. This review summarizes reports to date on brainstem involvement in SSPE, including the clinical course of disease, neuroimaging presentations, and guidelines for treatment. A comprehensive literature search was performed for English-language publications with keywords “subacute sclerosing panencephalitis” and “brainstem” using the National Library of Medicine PubMed database (March 1981–September 2017). Eleven articles focusing on SSPE of the brainstem were included. Predominant brainstem involvement remains uncharacteristic of SSPE, which may lead to misdiagnosis and poor outcome. A number of case reports have demonstrated brainstem involvement associated with other intracranial lesions commonly presenting in later SSPE stages (III and IV). However, brainstem lesions can appear in all stages, independent of higher cortical structures. The varied clinical presentations complicate diagnosis from a neuroimaging perspective. SSPE of the brainstem is a rare but important clinical entity. It may present like canonical SSPE or with unique clinical features such as absence seizures and pronounced ataxia. While SSPE generally progresses to the brainstem, it can also begin with a primary focus of infection in the brainstem. Awareness of varied SSPE presentations can aid in early diagnosis as well as guide management and treatment. PMID:29112137

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giantsoudi, D; Adams, J; MacDonald, S

Purpose: In proton radiation therapy of posterior fossa tumors, to spare other sensitive structures, the preferred beam geometry results in placing the treatment field distal edge within or just beyond the brainstem, including in at least partially in the treatment volume. Concerns for brainstem toxicity are increased and a controversy exists as to weather the beam’s distal edge should be placed within the brainstem or beyond it, to avoid elevated linear energy transfer (LET) and relative biological effectiveness (RBE) within the brainstem. The dosimetric efficacy of these techniques was examined, accounting for LET- and dose-dependent variable RBE distributions. Methods: Threemore » treatment planning techniques were applied in six ependymoma cases: (a) three-field dose-sparing, with beams’ distal edge within the brainstem; (b) three-field LET-sparing, using same beam directions as (a) but extended field ranges beyond the brainstem; (c) two-posterior-oblique LET-sparing, with extended ranges as (b). Monte Carlo calculated dose, LET and RBE-weighted dose distributions were compared. Results: Lower LET values in the brainstem were accompanied by higher median dose: 53.7 Gy[RBE] and 54.3 Gy[RBE] for techniques (b) and (c) versus 52.1 Gy[RBE] for (a). Accounting for variable RBE, a 15% increase of the brainstem volume receiving at least 60 Gy[RBE] was observed for technique (c) versus (a). Maximum variable-RBE-weighted brainstem dose was comparable for all techniques. Conclusion: Extending the treatment beam range beyond the brainstem, significantly increased its volume receiving high dose radiation, even when accounting for the decreased LET values. The dosimetric benefits of techniques limiting the brainstem dose may outweigh the impact of LET reduction achieved through this technique, especially since clinical consequences of increased LET at the end of range have not been proven yet.« less

Dissociation of spontaneous seizures and brainstem seizure thresholds in mice exposed to eight flurothyl-induced generalized seizures.

PubMed

Kadiyala, Sridhar B; Ferland, Russell J

2017-03-01

C57BL/6J mice exposed to eight flurothyl-induced generalized clonic seizures exhibit a change in seizure phenotype following a 28-day incubation period and subsequent flurothyl rechallenge. Mice now develop a complex seizure semiology originating in the forebrain and propagating into the brainstem seizure network (a forebrain→brainstem seizure). In contrast, this phenotype change does not occur in seizure-sensitive DBA/2J mice. The underlying mechanism(s) was the focus of these studies. DBA2/J mice were exposed to eight flurothyl-induced seizures (1/day) followed by 24-hour video-electroencephalographic recordings for 28-days. Forebrain and brainstem seizure thresholds were determined in C57BL/6J and DBA/2J mice following one or eight flurothyl-induced seizures, or after eight flurothyl-induced seizures, a 28-day incubation period, and final flurothyl rechallenge. Similar to C57BL/6J mice, DBA2/J mice expressed spontaneous seizures. However, unlike C57BL/6J mice, DBA2/J mice continued to have spontaneous seizures without remission. Because DBA2/J mice do not express forebrain→brainstem seizures following flurothyl rechallenge after a 28-day incubation period, this indicated that spontaneous seizures were not sufficient for the evolution of forebrain→brainstem seizures. Therefore, we determined whether brainstem seizure thresholds were changing during this repeated-flurothyl model and whether this could account for the expression of forebrain→brainstem seizures. Brainstem seizure thresholds were not different between C57BL/6J and DBA/2J mice on day one or on the last induction seizure trial (day eight). However, brainstem seizure thresholds did differ significantly on flurothyl rechallenge (day 28) with DBA/2J mice showing no lowering of their brainstem seizure thresholds. These results demonstrated that DBA/2J mice exposed to the repeated-flurothyl model develop spontaneous seizures without evidence of seizure remission and provide a new model of epileptogenesis. Moreover, these findings indicated that the transition of forebrain ictal discharge into the brainstem seizure network occurs due to changes in brainstem seizure thresholds that are independent of spontaneous seizure expression.

Electrically-evoked frequency-following response (EFFR) in the auditory brainstem of guinea pigs.

PubMed

He, Wenxin; Ding, Xiuyong; Zhang, Ruxiang; Chen, Jing; Zhang, Daoxing; Wu, Xihong

2014-01-01

It is still a difficult clinical issue to decide whether a patient is a suitable candidate for a cochlear implant and to plan postoperative rehabilitation, especially for some special cases, such as auditory neuropathy. A partial solution to these problems is to preoperatively evaluate the functional integrity of the auditory neural pathways. For evaluating the strength of phase-locking of auditory neurons, which was not reflected in previous methods using electrically evoked auditory brainstem response (EABR), a new method for recording phase-locking related auditory responses to electrical stimulation, called the electrically evoked frequency-following response (EFFR), was developed and evaluated using guinea pigs. The main objective was to assess feasibility of the method by testing whether the recorded signals reflected auditory neural responses or artifacts. The results showed the following: 1) the recorded signals were evoked by neuron responses rather than by artifact; 2) responses evoked by periodic signals were significantly higher than those evoked by the white noise; 3) the latency of the responses fell in the expected range; 4) the responses decreased significantly after death of the guinea pigs; and 5) the responses decreased significantly when the animal was replaced by an electrical resistance. All of these results suggest the method was valid. Recording obtained using complex tones with a missing fundamental component and using pure tones with various frequencies were consistent with those obtained using acoustic stimulation in previous studies.

Sensory-Cognitive Interaction in the Neural Encoding of Speech in Noise: A Review

PubMed Central

Anderson, Samira; Kraus, Nina

2011-01-01

Background Speech-in-noise (SIN) perception is one of the most complex tasks faced by listeners on a daily basis. Although listening in noise presents challenges for all listeners, background noise inordinately affects speech perception in older adults and in children with learning disabilities. Hearing thresholds are an important factor in SIN perception, but they are not the only factor. For successful comprehension, the listener must perceive and attend to relevant speech features, such as the pitch, timing, and timbre of the target speaker’s voice. Here, we review recent studies linking SIN and brainstem processing of speech sounds. Purpose To review recent work that has examined the ability of the auditory brainstem response to complex sounds (cABR), which reflects the nervous system’s transcription of pitch, timing, and timbre, to be used as an objective neural index for hearing-in-noise abilities. Study Sample We examined speech-evoked brainstem responses in a variety of populations, including children who are typically developing, children with language-based learning impairment, young adults, older adults, and auditory experts (i.e., musicians). Data Collection and Analysis In a number of studies, we recorded brainstem responses in quiet and babble noise conditions to the speech syllable /da/ in all age groups, as well as in a variable condition in children in which /da/ was presented in the context of seven other speech sounds. We also measured speech-in-noise perception using the Hearing-in-Noise Test (HINT) and the Quick Speech-in-Noise Test (QuickSIN). Results Children and adults with poor SIN perception have deficits in the subcortical spectrotemporal representation of speech, including low-frequency spectral magnitudes and the timing of transient response peaks. Furthermore, auditory expertise, as engendered by musical training, provides both behavioral and neural advantages for processing speech in noise. Conclusions These results have implications for future assessment and management strategies for young and old populations whose primary complaint is difficulty hearing in background noise. The cABR provides a clinically applicable metric for objective assessment of individuals with SIN deficits, for determination of the biologic nature of disorders affecting SIN perception, for evaluation of appropriate hearing aid algorithms, and for monitoring the efficacy of auditory remediation and training. PMID:21241645

Focal brainstem gliomas

PubMed Central

Sabbagh, Abdulrahman J.; Alaqeel, Ahmed M.

2015-01-01

Improved neuronavigation guidance as well as intraoperative imaging and neurophysiologic monitoring technologies have enhanced the ability of neurosurgeons to resect focal brainstem gliomas. In contrast, diffuse brainstem gliomas are considered to be inoperable lesions. This article is a continuation of an article that discussed brainstem glioma diagnostics, imaging, and classification. Here, we address open surgical treatment of and approaches to focal, dorsally exophytic, and cervicomedullary brainstem gliomas. Intraoperative neuronavigation, intraoperative neurophysiologic monitoring, as well as intraoperative imaging are discussed as adjunctive measures to help render these procedures safer, more acute, and closer to achieving surgical goals. PMID:25864061

Pinpointing brainstem mechanisms responsible for autonomic dysfunction in Rett syndrome: therapeutic perspectives for 5-HT1A agonists

PubMed Central

Abdala, Ana P.; Bissonnette, John M.; Newman-Tancredi, Adrian

2014-01-01

Rett syndrome is a neurological disorder caused by loss of function of methyl-CpG-binding protein 2 (MeCP2). Reduced function of this ubiquitous transcriptional regulator has a devastating effect on the central nervous system. One of the most severe and life-threatening presentations of this syndrome is brainstem dysfunction, which results in autonomic disturbances such as breathing deficits, typified by episodes of breathing cessation intercalated with episodes of hyperventilation or irregular breathing. Defects in numerous neurotransmitter systems have been observed in Rett syndrome both in animal models and patients. Here we dedicate special attention to serotonin due to its role in promoting regular breathing, increasing vagal tone, regulating mood, alleviating Parkinsonian-like symptoms and potential for therapeutic translation. A promising new symptomatic strategy currently focuses on regulation of serotonergic function using highly selective serotonin type 1A (5-HT1A) “biased agonists.” We address this newly emerging therapy for respiratory brainstem dysfunction and challenges for translation with a holistic perspective of Rett syndrome, considering potential mood and motor effects. PMID:24910619

Extensive basal ganglia edema caused by a traumatic carotid-cavernous fistula: a rare presentation related to a basal vein of Rosenthal anatomical variation.

PubMed

Ract, Isabelle; Drier, Aurélie; Leclercq, Delphine; Sourour, Nader; Gabrieli, Joseph; Yger, Marion; Nouet, Aurélien; Dormont, Didier; Chiras, Jacques; Clarençon, Frédéric

2014-07-01

The authors report a very rare presentation of traumatic carotid-cavernous fistula (CCF) with extensive edema of the basal ganglia and brainstem because of an anatomical variation of the basal vein of Rosenthal (BVR). A 45-year-old woman was admitted to the authors' institution for left hemiparesis, dysarthria, and a comatose state caused by right orbital trauma from a thin metal rod. Brain MRI showed a right CCF and vasogenic edema of the right side of the brainstem, right temporal lobe, and basal ganglia. Digital subtraction angiography confirmed a high-flow direct CCF and revealed a hypoplastic second segment of the BVR responsible for the hypertension in inferior striate veins and venous congestion. Endovascular treatment was performed on an emergency basis. One month after treatment, the patient's symptoms and MRI signal abnormalities almost totally disappeared. Basal ganglia and brainstem venous congestion may occur in traumatic CCF in cases of a hypoplastic or agenetic second segment of the BVR and may provoke emergency treatment.

Processing Complex Sounds Passing through the Rostral Brainstem: The New Early Filter Model

PubMed Central

Marsh, John E.; Campbell, Tom A.

2016-01-01

The rostral brainstem receives both “bottom-up” input from the ascending auditory system and “top-down” descending corticofugal connections. Speech information passing through the inferior colliculus of elderly listeners reflects the periodicity envelope of a speech syllable. This information arguably also reflects a composite of temporal-fine-structure (TFS) information from the higher frequency vowel harmonics of that repeated syllable. The amplitude of those higher frequency harmonics, bearing even higher frequency TFS information, correlates positively with the word recognition ability of elderly listeners under reverberatory conditions. Also relevant is that working memory capacity (WMC), which is subject to age-related decline, constrains the processing of sounds at the level of the brainstem. Turning to the effects of a visually presented sensory or memory load on auditory processes, there is a load-dependent reduction of that processing, as manifest in the auditory brainstem responses (ABR) evoked by to-be-ignored clicks. Wave V decreases in amplitude with increases in the visually presented memory load. A visually presented sensory load also produces a load-dependent reduction of a slightly different sort: The sensory load of visually presented information limits the disruptive effects of background sound upon working memory performance. A new early filter model is thus advanced whereby systems within the frontal lobe (affected by sensory or memory load) cholinergically influence top-down corticofugal connections. Those corticofugal connections constrain the processing of complex sounds such as speech at the level of the brainstem. Selective attention thereby limits the distracting effects of background sound entering the higher auditory system via the inferior colliculus. Processing TFS in the brainstem relates to perception of speech under adverse conditions. Attentional selectivity is crucial when the signal heard is degraded or masked: e.g., speech in noise, speech in reverberatory environments. The assumptions of a new early filter model are consistent with these findings: A subcortical early filter, with a predictive selectivity based on acoustical (linguistic) context and foreknowledge, is under cholinergic top-down control. A prefrontal capacity limitation constrains this top-down control as is guided by the cholinergic processing of contextual information in working memory. PMID:27242396

Alteration of glycine receptor immunoreactivity in the auditory brainstem of mice following three months of exposure to radiofrequency radiation at SAR 4.0 W/kg.

PubMed

Maskey, Dhiraj; Kim, Hyung Gun; Suh, Myung-Whan; Roh, Gu Seob; Kim, Myeung Ju

2014-08-01

The increasing use of mobile communication has triggered an interest in its possible effects on the regulation of neurotransmitter signals. Due to the close proximity of mobile phones to hearing-related brain regions during usage, its use may lead to a decrease in the ability to segregate sounds, leading to serious auditory dysfunction caused by the prolonged exposure to radiofrequency (RF) radiation. The interplay among auditory processing, excitation and inhibitory molecule interactions plays a major role in auditory function. In particular, inhibitory molecules, such a glycine, are predominantly localized in the auditory brainstem. However, the effects of exposure to RF radiation on auditory function have not been reported to date. Thus, the aim of the present study was to investigate the effects of exposure to RF radiation on glycine receptor (GlyR) immunoreactivity (IR) in the auditory brainstem region at 835 MHz with a specific absorption rate of 4.0 W/kg for three months using free-floating immunohistochemistry. Compared with the sham control (SC) group, a significant loss of staining intensity of neuropils and cells in the different subdivisions of the auditory brainstem regions was observed in the mice exposed to RF radiation (E4 group). A decrease in the number of GlyR immunoreactive cells was also noted in the cochlear nuclear complex [anteroventral cochlear nucleus (AVCN), 31.09%; dorsal cochlear nucleus (DCN), 14.08%; posteroventral cochlear nucleus (PVCN), 32.79%] and the superior olivary complex (SOC) [lateral superior olivary nucleus (LSO), 36.85%; superior paraolivary nucleus (SPN), 24.33%, medial superior olivary nucleus (MSO), 23.23%; medial nucleus of the trapezoid body (MNTB), 10.15%] of the mice in the E4 group. Auditory brainstem response (ABR) analysis also revealed a significant threshold elevation of in the exposed (E4) group, which may be associated with auditory dysfunction. The present study suggests that the auditory brainstem region is susceptible to chronic exposure to RF radiation, which may affect the function of the central auditory system.

Processing Complex Sounds Passing through the Rostral Brainstem: The New Early Filter Model.

PubMed

Marsh, John E; Campbell, Tom A

2016-01-01

The rostral brainstem receives both "bottom-up" input from the ascending auditory system and "top-down" descending corticofugal connections. Speech information passing through the inferior colliculus of elderly listeners reflects the periodicity envelope of a speech syllable. This information arguably also reflects a composite of temporal-fine-structure (TFS) information from the higher frequency vowel harmonics of that repeated syllable. The amplitude of those higher frequency harmonics, bearing even higher frequency TFS information, correlates positively with the word recognition ability of elderly listeners under reverberatory conditions. Also relevant is that working memory capacity (WMC), which is subject to age-related decline, constrains the processing of sounds at the level of the brainstem. Turning to the effects of a visually presented sensory or memory load on auditory processes, there is a load-dependent reduction of that processing, as manifest in the auditory brainstem responses (ABR) evoked by to-be-ignored clicks. Wave V decreases in amplitude with increases in the visually presented memory load. A visually presented sensory load also produces a load-dependent reduction of a slightly different sort: The sensory load of visually presented information limits the disruptive effects of background sound upon working memory performance. A new early filter model is thus advanced whereby systems within the frontal lobe (affected by sensory or memory load) cholinergically influence top-down corticofugal connections. Those corticofugal connections constrain the processing of complex sounds such as speech at the level of the brainstem. Selective attention thereby limits the distracting effects of background sound entering the higher auditory system via the inferior colliculus. Processing TFS in the brainstem relates to perception of speech under adverse conditions. Attentional selectivity is crucial when the signal heard is degraded or masked: e.g., speech in noise, speech in reverberatory environments. The assumptions of a new early filter model are consistent with these findings: A subcortical early filter, with a predictive selectivity based on acoustical (linguistic) context and foreknowledge, is under cholinergic top-down control. A prefrontal capacity limitation constrains this top-down control as is guided by the cholinergic processing of contextual information in working memory.

A two-year longitudinal pilot MRI study of the brainstem in autism.

PubMed

Jou, Roger J; Frazier, Thomas W; Keshavan, Matcheri S; Minshew, Nancy J; Hardan, Antonio Y

2013-08-15

Research has demonstrated the potential role of the brainstem in the pathobiology of autism. Previous studies have suggested reductions in brainstem volume and a relationship between this structure and sensory abnormalities. However, little is known regarding the developmental aspects of the brainstem across childhood and adolescence. The goal of this pilot study was to examine brainstem development via MRI volumetry using a longitudinal research design. Participants included 23 boys with autism and 23 matched controls (age range=8-17 years), all without intellectual disability. Participants underwent structural MRI scans once at baseline and again at two-year follow-up. Brainstem volumetric measurements were performed using the BRAINS2 software package. There were no significant group differences in age, gender, handedness, and total brain volume; however, full-scale IQ was higher in controls. Autism and control groups showed different patterns of growth in brainstem volume. While whole brainstem volume remained stable in controls over the two-year period, the autism group showed increases with age reaching volumes comparable to controls by age 15 years. This increase of whole brainstem volume was primarily driven by bilateral increases in gray matter volume. Findings from this preliminary study are suggestive of developmental brainstem abnormalities in autism primarily involving gray matter structures. These findings are consistent with autism being conceptualized as a neurodevelopmental disorder with alterations in brain-growth trajectories. More longitudinal MRI studies are needed integrating longitudinal cognitive/behavioral data to confirm and elucidate the clinical significance of these atypical growth patterns. Copyright © 2013 Elsevier B.V. All rights reserved.

Brainstem timing: implications for cortical processing and literacy.

PubMed

Banai, Karen; Nicol, Trent; Zecker, Steven G; Kraus, Nina

2005-10-26

The search for a unique biological marker of language-based learning disabilities has so far yielded inconclusive findings. Previous studies have shown a plethora of auditory processing deficits in learning disabilities at both the perceptual and physiological levels. In this study, we investigated the association among brainstem timing, cortical processing of stimulus differences, and literacy skills. To that end, brainstem timing and cortical sensitivity to acoustic change [mismatch negativity (MMN)] were measured in a group of children with learning disabilities and normal-learning children. The learning-disabled (LD) group was further divided into two subgroups with normal and abnormal brainstem timing. MMNs, literacy, and cognitive abilities were compared among the three groups. LD individuals with abnormal brainstem timing were more likely to show reduced processing of acoustic change at the cortical level compared with both normal-learning individuals and LD individuals with normal brainstem timing. This group was also characterized by a more severe form of learning disability manifested by poorer reading, listening comprehension, and general cognitive ability. We conclude that abnormal brainstem timing in learning disabilities is related to higher incidence of reduced cortical sensitivity to acoustic change and to deficient literacy skills. These findings suggest that abnormal brainstem timing may serve as a reliable marker of a subgroup of individuals with learning disabilities. They also suggest that faulty mechanisms of neural timing at the brainstem may be the biological basis of malfunction in this group.

Binaural interaction in the auditory brainstem response: a normative study.

PubMed

Van Yper, Lindsey N; Vermeire, Katrien; De Vel, Eddy F J; Battmer, Rolf-Dieter; Dhooge, Ingeborg J M

2015-04-01

Binaural interaction can be investigated using auditory evoked potentials. A binaural interaction component can be derived from the auditory brainstem response (ABR-BIC) and is considered evidence for binaural interaction at the level of the brainstem. Although click ABR-BIC has been investigated thoroughly, data on 500 Hz tone-burst (TB) ABR-BICs are scarce. In this study, characteristics of click and 500 Hz TB ABR-BICs are described. Furthermore, reliability of both click and 500 Hz TB ABR-BIC are investigated. Eighteen normal hearing young adults (eight women, ten men) were included. ABRs were recorded in response to clicks and 500 Hz TBs. ABR-BICs were derived by subtracting the binaural response from the sum of the monaural responses measured in opposite ears. Good inter-rater reliability is obtained for both click and 500 Hz TB ABR-BICs. The most reliable peak in click ABR-BIC occurs at a mean latency of 6.06 ms (SD 0.354 ms). Reliable 500 Hz TB ABR-BIC are obtained with a mean latency of 9.47 ms (SD 0.678 ms). Amplitudes are larger for 500 Hz TB ABR-BIC than for clicks. The most reliable peak in click ABR-BIC occurs at the downslope of wave V. Five hundred Hertz TB ABR-BIC is characterized by a broad positivity occurring at the level of wave V. The ABR-BIC is a useful technique to investigate binaural interaction in certain populations. Examples are bilateral hearing aid users, bilateral cochlear implant users and bimodal listeners. The latter refers to the combination of unilateral cochlear implantation and contralateral residual hearing. The majority of these patients have residual hearing in the low frequencies. The current study suggests that 500 Hz TB ABR-BIC may be a suitable technique to assess binaural interaction in this specific population of cochlear implant users. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Long-term survival of an infant with diffuse brainstem lesion diagnosed by prenatal MRI: a case report and review of the literature.

PubMed

Suo-Palosaari, M; Rantala, H; Lehtinen, S; Kumpulainen, T; Salokorpi, N

2016-06-01

We describe a unique case of expansive diffuse brainstem lesion diagnosed prenatally by magnetic resonance imaging (MRI) with long-term survival. Findings of fetal and postpartum MRI were highly consistent with the characteristics of diffuse brainstem glioma. Diagnosis was based on the features of MRI, and histopathology was not confirmed by biopsy. Although the prognosis of diffuse brainstem tumor is usually poor, this child was asymptomatic at birth and the neurological condition is still normal at 4 years of age without any treatment. During routine imaging follow-up, diameters of the expansion have remained stable, while the size of the lesion compared to the posterior fossa size has diminished. In addition to brainstem tumor, a skin lesion of the back was observed and MRI of the thoracic spine showed a large asymptomatic extradural cystic lesion suggesting an arachnoid cyst. The pontine tumor of this infant, in agreement with a few previously reported cases, suggests a subgroup of beneficial outcome of expansive diffuse brainstem lesions, particularly in the neonatal period. In this article, we discuss the prognosis and characteristics of pediatric brainstem tumors and differential diagnosis of neonatal brainstem lesions.

Neural Mechanisms of Emotion.

ERIC Educational Resources Information Center

Derryberry, Douglas; Tucker, Don M.

1992-01-01

Views neural mechanisms of emotion from an evolutionary perspective, seeing them distributed across the brainstem, limbic, paralimbic, and neocortical regions. Discusses descending and ascending connections among these levels in relation to three types of emotional processes: peripheral effects on patterned bodily responses, central effects on…

Audiological characteristics of infants with abnormal transient evoked otoacoustic emission and normal auditory brainstem response.

PubMed

Huang, Lihui; Han, Demin; Guo, Ying; Liu, Sha; Cui, Xiaoyan; Mo, Lingyan; Qi, Beier; Cai, Zhenghua; Liu, Hui; En, Hui; Guo, Liansheng

2008-10-01

Audiological characteristics were investigated in 81 ears of 53 infants with abnormal transient evoked otoacoustic emission (TEOAE) and normal auditory brainstem response (ABR). The relationship between ABR and other hearing testing methods, including 40Hz auditory event-related potential (40Hz-AERP), auditory steady state response (ASSR), distortion product otoacoustic emission (DPOAE), tympanometry, and acoustic reflex, was analyzed. Of the 81 ears, 18 ears (22.2%) were normal, while 63 ears (77.8%) were abnormal according to the tests. Testing of the 40 Hz AERP (36 ears) and ASSR (45 ears) revealed that 14 ears (38.9%) and 27 ears (60.0%) were abnormal, respectively. Testing of DPOAE in 68 ears revealed that 50 ears (73.5%) were abnormal. Testing of tympanometry in 50 ears and acoustic reflex in 47 ears revealed that 9 ears (18%) and 27 ears (57.4%) were abnormal, respectively. The present data suggests that the hearing of infants cannot be sufficiently evaluated with ABR only and that it must be evaluated with integrative audiological testing methods.

Lung respiratory rhythm and pattern generation in the bullfrog: role of neurokinin-1 and mu-opioid receptors.

PubMed

Davies, B L; Brundage, C M; Harris, M B; Taylor, B E

2009-07-01

Location of the lung respiratory rhythm generator (RRG) in the bullfrog brainstem was investigated by examining neurokinin-1 and mu-opioid receptor (NK1R, muOR) colocalization by immunohistochemistry and characterizing the role of these receptors in lung rhythm and episodic pattern generation. NK1R and muOR occurred in brainstems from all developmental stages. In juvenile bullfrogs a distinct area of colocalization was coincident with high-intensity fluorescent labeling of muOR; high-intensity labeling of muOR was not distinctly and consistently localized in tadpole brainstems. NK1R labeling intensity did not change with development. Similarity in colocalization is consistent with similarity in responses to substance P (SP, NK1R agonist) and DAMGO (muOR agonist) when bath applied to bullfrog brainstems of different developmental stages. In early stage tadpoles and juvenile bullfrogs, SP increased and DAMGO decreased lung burst frequency. In juvenile bullfrogs, SP increased lung burst frequency, episode frequency, but decreased number of lung bursts per episode and lung burst duration. In contrast, DAMGO decreased lung burst frequency and burst cycle frequency, episode frequency, and number of lung bursts per episode but increased all other lung burst parameters. Based on these results, we hypothesize that NK1R and muOR colocalization together with a metamorphosis-related increase in muOR intensity marks the location of the lung RRG but not necessarily the lung episodic pattern generator.

Correlation of Acute and Late Brainstem Toxicities With Dose-Volume Data for Pediatric Patients With Posterior Fossa Malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nanda, Ronica H., E-mail: rhazari@emory.edu; Ganju, Rohit G.; Schreibmann, Edward

Purpose: Radiation-induced brainstem toxicity after treatment of pediatric posterior fossa malignancies is incompletely understood, especially in the era of intensity modulated radiation therapy (IMRT). The rates of, and predictive factors for, brainstem toxicity after photon RT for posterior fossa tumors were examined. Methods and Materials: After institutional review board approval, 60 pediatric patients treated at our institution for nonmetastatic infratentorial ependymoma and medulloblastoma with IMRT were included in the present analysis. Dosimetric variables, including the mean and maximum dose to the brainstem, the dose to 10% to 90% of the brainstem (in 10% increments), and the volume of the brainstemmore » receiving 40, 45, 50, and 55 Gy were recorded for each patient. Acute (onset within 3 months) and late (>3 months of RT completion) RT-induced brainstem toxicities with clinical and radiographic correlates were scored using Common Terminology Criteria for Adverse Events, version 4.0. Results: Patients aged 1.4 to 21.8 years underwent IMRT or volumetric arc therapy postoperatively to the posterior fossa or tumor bed. At a median clinical follow-up period of 2.8 years, 14 patients had developed symptomatic brainstem toxicity (crude incidence 23.3%). No correlation was found between the dosimetric variables examined and brainstem toxicity. Vascular injury or ischemia showed a strong trend toward predicting brainstem toxicity (P=.054). Patients with grade 3 to 5 brainstem toxicity had undergone treatment to significant volumes of the posterior fossa. Conclusion: The results of the present series demonstrate a low, but not negligible, risk of brainstem radiation necrosis for pediatric patients with posterior fossa malignancies treated with IMRT. No specific dose-volume correlations were identified; however, modern treatment volumes might help limit the incidence of severe toxicity. Additional work investigating inherent biologic sensitivity might also provide further insight into this clinical problem.« less

[An evaluation of clinical characteristics and prognosis of brain-stem infarction in diabetics].

PubMed

Lu, Zheng-qi; Li, Hai-yan; Hu, Xue-qiang; Zhang, Bing-jun

2011-01-01

To analyze the relationship between diabetics and the onset, clinical outcomes and prognosis of brainstem infarction, and to evaluate the impact of diabetes on brainstem infarction. Compare 172 cases of acute brainstem infarction in patients with or without diabetes. Analyze the associated risk factors of patients with brain-stem infarction in diabetics by multi-variate logistic regression analysis. Compare the National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin scale (mRS) Score, pathogenetic condition and the outcome of the two groups in different times. The systolic blood pressure (SBP), TG, LDL-C, apolipoprotein B (Apo B), glutamyl transpeptidase (γ-GT), fibrinogen (Fb), fasting blood glucose (FPG) and glycosylated hemoglobin(HbA1c)in diabetic group were higher than those in non-diabetic group, which was statistically significant (P < 0.05). From multi-variate logistic regression analysis, γ-GT, Apo B and FPG were the risk predictors of diabetes with brainstem infarction(OR = 1.017, 4.667 and 3.173, respectively), while HDL-C was protective (OR = 0.288). HbA1c was a risk predictor of severity for acute brainstem infarction (OR = 1.299), while Apo A was beneficial (OR = 0.212). Compared with brain-stem infarction in non-diabetic group, NIHSS score and intensive care therapy of diabetic groups on the admission had no statistically significance, while the NIHSS score on discharge and the outcome at 6 months' of follow-up were statistically significant. Diabetes is closely associated with brainstem infarction. Brainstem infarction with diabetes cause more rapid progression, poorer prognosis, higher rates of mortality as well as disability and higher recurrence rate of cerebral infarction.

Pinniped Hearing in Complex Acoustic Environments

DTIC Science & Technology

2013-09-30

published] Mulsow, J. & Reichmuth, C. (2013). The binaural click-evoked auditory brainstem response of the California sea lion (Zalophus...California sea lion can keep the beat : Motor entrainment to rhythmic auditory stimuli in a non vocal mimic. Journal of Comparative Psychology, online first. [published

Brainstem Auditory Evoked Potential in HIV-Positive Adults.

PubMed

Matas, Carla Gentile; Samelli, Alessandra Giannella; Angrisani, Rosanna Giaffredo; Magliaro, Fernanda Cristina Leite; Segurado, Aluísio C

2015-10-20

To characterize the findings of brainstem auditory evoked potential in HIV-positive individuals exposed and not exposed to antiretroviral treatment. This research was a cross-sectional, observational, and descriptive study. Forty-five HIV-positive individuals (18 not exposed and 27 exposed to the antiretroviral treatment - research groups I and II, respectively - and 30 control group individuals) were assessed through brainstem auditory evoked potential. There were no significant between-group differences regarding wave latencies. A higher percentage of altered brainstem auditory evoked potential was observed in the HIV-positive groups when compared to the control group. The most common alteration was in the low brainstem. HIV-positive individuals have a higher percentage of altered brainstem auditory evoked potential that suggests central auditory pathway impairment when compared to HIV-negative individuals. There was no significant difference between individuals exposed and not exposed to antiretroviral treatment.

Distribution of CGRP in the minipig brainstem.

PubMed

Lisardo Sánchez, Manuel; Vecino, Elena; Coveñas, Rafael

2014-05-01

For the first time, an in-depth study has been made of the distribution of fibers and cell bodies containing calcitonin gene-related peptide (CGRP) in the minipig brainstem using an indirect immunoperoxidase technique. The animals studied were not treated with colchicine. Cell bodies containing CGRP were found in 20 nuclei/regions of the brainstem. These perikarya were located in somatomotor, brachiomotor and raphae nuclei, nucleus ambiguus, substantia nigra, nucleus reticularis tegmenti pontis, nucleus prepositus hypoglossi, nuclei olivaris inferior and superior, nuclei pontis, formatio reticularis, nucleus dorsalis tegmenti of Gudden, and in the nucleus reticularis lateralis. Fourteen of the 20 brainstem nuclei showed a high density of immunoreactive cell bodies. In comparison with other species, the minipig, together with the rat, show the most widespread distribution of cell bodies containing CGRP in the mammalian brainstem. Immunoreactive fibers were also observed in the brainstem. However, in the minipig brainstem the density of these fibers is low, as in many brainstem nuclei only single immunoreactive fibers were observed. A high density of immunoreactive fibers was only observed in the pars caudalis of the nucleus tractus spinalis nervi trigemini and in the nucleus ventralis tegmenti of Gudden. According to the observed anatomical distribution of the immunoreactive structures containing CGRP, the peptide could be involved in motor, somatosensory, gustative, and autonomic mechanisms. Copyright © 2014 Wiley Periodicals, Inc.

Transcranial sonography of brainstem structures in panic disorder.

PubMed

Šilhán, Petr; Jelínková, Monika; Walter, Uwe; Pavlov Praško, Ján; Herzig, Roman; Langová, Kateřina; Školoudík, David

2015-10-30

Panic disorder has been associated with altered serotonin metabolism in the brainstem raphe. The aim of study was to evaluate the BR echogenicity on transcranial sonography (TCS) in panic disorder. A total of 96 healthy volunteers were enrolled in the "derivation" cohort, and 26 healthy volunteers and 26 panic disorder patients were enrolled in the "validation" cohort. TCS echogenicity of brainstem raphe and substantia nigra was assessed on anonymized images visually and by means of digitized image analysis. Significantly reduced brainstem raphe echogenicity was detected more frequently in panic disorder patients than in controls using both visual (68% vs. 31%) and digitized image analysis (52% vs. 12%). The optimal cut-off value of digitized brainstem raphe echogenicity indicated the diagnosis of panic disorder with a sensitivity of 64% and a specificity of 73%, and corresponded to the 30th percentile in the derivation cohort. Reduced brainstem raphe echogenicity was associated with shorter treatment duration, and, by trend, lower severity of anxiety. No relationship was found between echogenicity of brainstem raphe or substantia nigra and age, gender, severity of panic disorder, or severity of depression. Patients with panic disorder exhibit changes of brainstem raphe on TCS suggesting an alteration of the central serotonergic system. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Neonate Auditory Brainstem Responses to CE-Chirp and CE-Chirp Octave Band Stimuli II: Versus Adult Auditory Brainstem Responses.

PubMed

Cobb, Kensi M; Stuart, Andrew

The purpose of the study was to examine the differences in auditory brainstem response (ABR) latency and amplitude indices to the CE-Chirp stimuli in neonates versus young adults as a function of stimulus level, rate, polarity, frequency and gender. Participants were 168 healthy neonates and 20 normal-hearing young adults. ABRs were obtained to air- and bone-conducted CE-Chirps and air-conducted CE-Chirp octave band stimuli. The effects of stimulus level, rate, and polarity were examined with air-conducted CE-Chirps. The effect of stimulus level was also examined with bone-conducted CE-Chirps and CE-Chirp octave band stimuli. The effect of gender was examined across all stimulus manipulations. In general, ABR wave V amplitudes were significantly larger (p < 0.0001) and latencies were significantly shorter (p < 0.0001) for adults versus neonates for all air-conducted CE-Chirp stimuli with all stimulus manipulations. For bone-conducted CE-Chirps, infants had significantly shorter wave V latencies than adults at 15 dB nHL and 45 dB nHL (p = 0.02). Adult wave V amplitude was significantly larger for bone-conducted CE-Chirps only at 30 dB nHL (p = 0.02). The effect of gender was not statistically significant across all measures (p > 0.05). Significant differences in ABR latencies and amplitudes exist between newborns and young adults using CE-Chirp stimuli. These differences are consistent with differences to traditional click and tone burst stimuli and reflect maturational differences as a function of age. These findings continue to emphasize the importance of interpreting ABR results using age-based normative data.

Non-homeostatic body weight regulation through a brainstem-restricted receptor for GDF15

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsu, Jer-Yuan; Crawley, Suzanne; Chen, Michael

Under homeostatic conditions, animals use well-defined hypothalamic neural circuits to help maintain stable body weight, by integrating metabolic and hormonal signals from the periphery to balance food consumption and energy expenditure1,2. In stressed or disease conditions, however, animals use alternative neuronal pathways to adapt to the metabolic challenges of altered energy demand3. Recent studies have identified brain areas outside the hypothalamus that are activated under these ‘non-homeostatic’ conditions4,5,6, but the molecular nature of the peripheral signals and brain-localized receptors that activate these circuits remains elusive. Here we identify glial cell-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) as a brainstem-restricted receptormore » for growth and differentiation factor 15 (GDF15). GDF15 regulates food intake, energy expenditure and body weight in response to metabolic and toxin-induced stresses; we show that Gfral knockout mice are hyperphagic under stressed conditions and are resistant to chemotherapy-induced anorexia and body weight loss. GDF15 activates GFRAL-expressing neurons localized exclusively in the area postrema and nucleus tractus solitarius of the mouse brainstem. It then triggers the activation of neurons localized within the parabrachial nucleus and central amygdala, which constitute part of the ‘emergency circuit’ that shapes feeding responses to stressful conditions7. GDF15 levels increase in response to tissue stress and injury, and elevated levels are associated with body weight loss in numerous chronic human diseases8,9. By isolating GFRAL as the receptor for GDF15-induced anorexia and weight loss, we identify a mechanistic basis for the non-homeostatic regulation of neural circuitry by a peripheral signal associated with tissue damage and stress. These findings provide opportunities to develop therapeutic agents for the treatment of disorders with altered energy demand.« less

Perinatal Fluoxetine Exposure Impairs the CO2 Chemoreflex. Implications for Sudden Infant Death Syndrome.

PubMed

Bravo, Karina; Eugenín, Jaime L; Llona, Isabel

2016-09-01

High serotonin levels during pregnancy affect central nervous system development. Whether a commonly used antidepressant such as fluoxetine (a selective serotonin reuptake inhibitor) taken during pregnancy may adversely affect respiratory control in offspring has not been determined. The objective was to determine the effect of prenatal-perinatal fluoxetine exposure on the respiratory neural network in offspring, particularly on central chemoreception. Osmotic minipumps implanted into CF-1 mice on Days 5-7 of pregnancy delivered 7 milligrams per kilogram per day of fluoxetine, achieving plasma levels within the range found in patients. Ventilation was assessed in offspring at postnatal Days 0-40 using head-out body plethysmography. Neuronal activation was evaluated in the raphe nuclei and in the nucleus tractus solitarius by c-Fos immunohistochemistry during normoxic eucapnia and hypercapnia (10% CO2). Respiratory responses to acidosis were evaluated in brainstem slices. Prenatal-perinatal fluoxetine did not affect litter size, birth weight, or the postnatal growth curve. Ventilation under eucapnic normoxic conditions was similar to that of control offspring. Fluoxetine exposure reduced ventilatory responses to hypercapnia at P8-P40 (P < 0.001) but not at P0-P5. At P8, it reduced hypercapnia-induced neuronal activation in raphe nuclei (P < 0.05) and nucleus tractus solitarius (P < 0.01) and the acidosis-induced increase in the respiratory frequency in brainstem slices (P < 0.05). Fluoxetine applied acutely on control slices did not modify their respiratory response to acidosis. We concluded that prenatal-perinatal fluoxetine treatment impairs central respiratory chemoreception during postnatal life. These results are relevant in understanding the pathogenesis of respiratory failures, such as sudden infant death syndrome, associated with brainstem serotonin abnormalities and the failure of respiratory chemoreflexes.

Auditory evoked functions in ground crew working in high noise environment of Mumbai airport.

PubMed

Thakur, L; Anand, J P; Banerjee, P K

2004-10-01

The continuous exposure to the relatively high level of noise in the surroundings of an airport is likely to affect the central pathway of the auditory system as well as the cognitive functions of the people working in that environment. The Brainstem Auditory Evoked Responses (BAER), Mid Latency Response (MLR) and P300 response of the ground crew employees working in Mumbai airport were studied to evaluate the effects of continuous exposure to high level of noise of the surroundings of the airport on these responses. BAER, P300 and MLR were recorded by using a Nicolet Compact-4 (USA) instrument. Audiometry was also monitored with the help of GSI-16 Audiometer. There was a significant increase in the peak III latency of the BAER in the subjects exposed to noise compared to controls with no change in their P300 values. The exposed group showed hearing loss at different frequencies. The exposure to the high level of noise caused a considerable decline in the auditory conduction upto the level of the brainstem with no significant change in conduction in the midbrain, subcortical areas, auditory cortex and associated areas. There was also no significant change in cognitive function as measured by P300 response.

Rapid adenosine release in the nucleus tractus solitarii during defence response in rats: real-time measurement in vivo

PubMed Central

Dale, Nicholas; Gourine, Alexander V; Llaudet, Enrique; Bulmer, David; Thomas, Teresa; Spyer, K Michael

2002-01-01

We have measured the release of adenosine and inosine from the dorsal surface of the brainstem and from within the nucleus tractus solitarii (NTS) during the defence response evoked by hypothalamic stimulation in the anaesthetised rat. At the surface of the brainstem, only release of inosine was detected on hypothalamic defence area stimulation. This inosine signal was greatly reduced by addition of the ecto-5′-nucleotidase inhibitor α,β-methylene ADP (200 μM), suggesting that the inosine arose from adenosine that was produced in the extracellular space by the prior release of ATP. By placing a microelectrode biosensor into the NTS under stereotaxic control we have recorded release of adenosine within this nucleus. By contrast to the brainstem surface, a fast increase in adenosine, accompanied only by a much smaller change in inosine levels, was seen following stimulation of the hypothalamic defence area. The release of adenosine following hypothalamic stimulation was mainly confined to a narrow region of the NTS some 500 μm in length around the level of the obex. Interestingly the release of adenosine was depletable: when the defence reaction was evoked at short time intervals, much less adenosine was released on the second stimulus. Our novel techniques have given unprecedented real-time measurement and localisation of adenosine release in vivo and demonstrate that adenosine is released at the right time and in sufficient quantities to contribute to the cardiovascular components of the defence reaction. PMID:12356888

Plasticity of vagal brainstem circuits in the control of gastric function

PubMed Central

Browning, Kirsteen N.; Travagli, R. Alberto

2010-01-01

Background Sensory information from the viscera, including the gastrointestinal (GI) tract, is transmitted through the afferent vagus via a glutamatergic synapse to neurons of the nucleus tractus solitarius (NTS), which integrate this sensory information to regulate autonomic functions and homeostasis. The integrated response is conveyed to, amongst other nuclei, the preganglionic neurons of the dorsal motor nucleus of the vagus (DMV) using mainly GABA, glutamate and catecholamines as neurotransmitters. Despite being modulated by almost all the neurotransmitters tested so far, the glutamatergic synapse between NTS and DMV does not appear to be tonically active in the control of gastric motility and tone. Conversely, tonic inhibitory GABAergic neurotransmission from the NTS to the DMV appears critical in setting gastric tone and motility, yet, under basal conditions, this synapse appears resistant to modulation. Purpose Here, we review the available evidence suggesting that vagal efferent output to the GI tract is regulated, perhaps even controlled, in an “on-demand” and efficient manner in response to ever-changing homeostatic conditions. The focus of this review is on the plasticity induced by variations in the levels of second messengers in the brainstem neurons that form vago-vagal reflex circuits. Emphasis is placed upon the modulation of GABAergic transmission to DMV neurons and the modulation of afferent input from the GI tract by neurohormones/neurotransmitters and macronutrients. Derangement of this “on-demand” organization of brainstem vagal circuits may be one of the factors underlying the pathophysiological changes observed in functional dyspepsia or hyperglycemic gastroparesis. PMID:20804520

Value of intracochlear electrically evoked auditory brainstem response after cochlear implantation in patients with narrow internal auditory canal.

PubMed

Song, Mee Hyun; Bae, Mi Ran; Kim, Hee Nam; Lee, Won-Sang; Yang, Won Sun; Choi, Jae Young

2010-08-01

Cochlear implantation in patients with narrow internal auditory canal (IAC) can result in variable outcomes; however, preoperative evaluations have limitations in accurately predicting outcomes. In this study, we analyzed the outcomes of cochlear implantation in patients with narrow IAC and correlated the intracochlear electrically evoked auditory brainstem response (EABR) findings to postoperative performance to determine the prognostic significance of intracochlear EABR. Retrospective case series at a tertiary hospital. Thirteen profoundly deaf patients with narrow IAC who received cochlear implantation from 2002 to 2008 were included in this study. Postoperative performance was evaluated after at least 12 months of follow-up, and postoperative intracochlear EABR was measured to determine its correlation with outcome. The clinical significance of electrically evoked compound action potential (ECAP) was also analyzed. Patients with narrow IAC showed postoperative auditory performances ranging from CAP 0 to 4 after cochlear implantation. Intracochlear EABR measured postoperatively demonstrated prognostic value in the prediction of long-term outcomes, whereas ECAP measurements failed to show a significant correlation with outcome. Consistent with the advantages of intracochlear EABR over extracochlear EABR, this study demonstrates that intracochlear EABR has prognostic significance in predicting long-term outcomes in patients with narrow IAC. Intracochlear EABR measured either intraoperatively or in the early postoperative period may play an important role in deciding whether to continue with auditory rehabilitation using a cochlear implant or to switch to an auditory brainstem implant so as not to miss the optimal timing for language development.

Bone-Conduction ABR Tests.

ERIC Educational Resources Information Center

Cone-Wesson, Barbara

1995-01-01

This article discusses the accuracy of bone-conduction auditory brainstem response (BC-ABR) tests to determine the presence and severity of conductive hearing impairment. It provides warnings about technical pitfalls and recommends incorporating BC-ABR protocols for routine clinical use. It concludes that the method allows estimating cochlear…

Identification and Treatment of Very Young Children with Hearing Loss.

ERIC Educational Resources Information Center

Madell, Jane R.

1988-01-01

Hearing loss in infants and young children can be identified through behavioral observation audiometry, visual reinforcement audiometry, or auditory brainstem response testing. Habilitation may involve amplification with hearing aids, other assistive listening devices, or cochlear implants. Expectations for children with different degrees of…

Motor evoked potential monitoring of the vagus nerve with transcranial electrical stimulation during skull base surgeries.

PubMed

Ito, Eiji; Ichikawa, Masahiro; Itakura, Takeshi; Ando, Hitoshi; Matsumoto, Yuka; Oda, Keiko; Sato, Taku; Watanabe, Tadashi; Sakuma, Jun; Saito, Kiyoshi

2013-01-01

Dysphasia is one of the most serious complications of skull base surgeries and results from damage to the brainstem and/or cranial nerves involved in swallowing. Here, the authors propose a method to monitor the function of the vagus nerve using endotracheal tube surface electrodes and transcranial electrical stimulation during skull base surgeries. Fifteen patients with skull base or brainstem tumors were enrolled. The authors used surface electrodes of an endotracheal tube to record compound electromyographic responses from the vocalis muscle. Motor neurons were stimulated using corkscrew electrodes placed subdermally on the scalp at C3 and C4. During surgery, the operator received a warning when the amplitude of the vagal motor evoked potential (MEP) decreased to less than 50% of the control level. After surgery, swallowing function was assessed clinically using grading criteria. In 5 patients, vagal MEP amplitude permanently deteriorated to less than 50% of the control level on the right side when meningiomas were dissected from the pons or basilar artery, or when a schwannoma was dissected from the vagal rootlets. These 5 patients had postoperative dysphagia. At 4 weeks after surgery, 2 patients still had dysphagia. In 2 patients, vagal MEPs of one side transiently disappeared when the tumors were dissected from the brainstem or the vagal rootlets. After surgery, both patients had dysphagia, which recovered in 4 weeks. In 7 patients, MEP amplitude was consistent, maintaining more than 50% of the control level throughout the operative procedures. After surgery all 7 patients were neurologically intact with normal swallowing function. Vagal MEP monitoring with transcranial electrical stimulation and endotracheal tube electrode recording was a safe and effective method to provide continuous real-time information on the integrity of both the supranuclear and infranuclear vagal pathway. This method is useful to prevent intraoperative injury of the brainstem corticobulbar tract or the vagal rootlets and to avoid the postoperative dysphagia that is often associated with brainstem or skull base surgeries.

Auditory brainstem responses in the Eastern Screech Owl: An estimate of auditory thresholds

USGS Publications Warehouse

Brittan-Powell, E.F.; Lohr, B.; Hahn, D.C.; Dooling, R.J.

2005-01-01

The auditory brainstem response (ABR), a measure of neural synchrony, was used to estimate auditory sensitivity in the eastern screech owl (Megascops asio). The typical screech owl ABR waveform showed two to three prominent peaks occurring within 5 ms of stimulus onset. As sound pressure levels increased, the ABR peak amplitude increased and latency decreased. With an increasing stimulus presentation rate, ABR peak amplitude decreased and latency increased. Generally, changes in the ABR waveform to stimulus intensity and repetition rate are consistent with the pattern found in several avian families. The ABR audiogram shows that screech owls hear best between 1.5 and 6.4 kHz with the most acute sensitivity between 4?5.7 kHz. The shape of the average screech owl ABR audiogram is similar to the shape of the behaviorally measured audiogram of the barn owl, except at the highest frequencies. Our data also show differences in overall auditory sensitivity between the color morphs of screech owls.

Gender Disparities in Speech-evoked Auditory Brainstem Response in Healthy Adults.

PubMed

Jalaei, Bahram; Zakaria, Mohd Normani; Mohd Azmi, Mohd Hafiz Afifi; Nik Othman, Nik Adilah; Sidek, Dinsuhaimi

2017-04-01

Gender disparities in speech-evoked auditory brainstem response (speech-ABR) outcomes have been reported, but the literature is limited. The present study was performed to further verify this issue and determine the influence of head size on speech-ABR results between genders. Twenty-nine healthy Malaysian subjects (14 males and 15 females) aged 19 to 30 years participated in this study. After measuring the head circumference, speech-ABR was recorded by using synthesized syllable /da/ from the right ear of each participant. Speech-ABR peaks amplitudes, peaks latencies, and composite onset measures were computed and analyzed. Significant gender disparities were noted in the transient component but not in the sustained component of speech-ABR. Statistically higher V/A amplitudes and less steeper V/A slopes were found in females. These gender differences were partially affected after controlling for the head size. Head size is not the main contributing factor for gender disparities in speech-ABR outcomes. Gender-specific normative data can be useful when recording speech-ABR for clinical purposes.

Principal cells of the brainstem's interaural sound level detector are temporal differentiators rather than integrators.

PubMed

Franken, Tom P; Joris, Philip X; Smith, Philip H

2018-06-14

The brainstem's lateral superior olive (LSO) is thought to be crucial for localizing high-frequency sounds by coding interaural sound level differences (ILD). Its neurons weigh contralateral inhibition against ipsilateral excitation, making their firing rate a function of the azimuthal position of a sound source. Since the very first in vivo recordings, LSO principal neurons have been reported to give sustained and temporally integrating 'chopper' responses to sustained sounds. Neurons with transient responses were observed but largely ignored and even considered a sign of pathology. Using the Mongolian gerbil as a model system, we have obtained the first in vivo patch clamp recordings from labeled LSO neurons and find that principal LSO neurons, the most numerous projection neurons of this nucleus, only respond at sound onset and show fast membrane features suggesting an importance for timing. These results provide a new framework to interpret previously puzzling features of this circuit. © 2018, Franken et al.

A probabilistic atlas of human brainstem pathways based on connectome imaging data.

PubMed

Tang, Yuchun; Sun, Wei; Toga, Arthur W; Ringman, John M; Shi, Yonggang

2018-04-01

The brainstem is a critical structure that regulates vital autonomic functions, houses the cranial nerves and their nuclei, relays motor and sensory information between the brain and spinal cord, and modulates cognition, mood, and emotions. As a primary relay center, the fiber pathways of the brainstem include efferent and afferent connections among the cerebral cortex, spinal cord, and cerebellum. While diffusion MRI has been successfully applied to map various brain pathways, its application for the in vivo imaging of the brainstem pathways has been limited due to inadequate resolution and large susceptibility-induced distortion artifacts. With the release of high-resolution data from the Human Connectome Project (HCP), there is increasing interest in mapping human brainstem pathways. Previous works relying on HCP data to study brainstem pathways, however, did not consider the prevalence (>80%) of large distortions in the brainstem even after the application of correction procedures from the HCP-Pipeline. They were also limited in the lack of adequate consideration of subject variability in either fiber pathways or region of interests (ROIs) used for bundle reconstruction. To overcome these limitations, we develop in this work a probabilistic atlas of 23 major brainstem bundles using high-quality HCP data passing rigorous quality control. For the large-scale data from the 500-Subject release of HCP, we conducted extensive quality controls to exclude subjects with severe distortions in the brainstem area. After that, we developed a systematic protocol to manually delineate 1300 ROIs on 20 HCP subjects (10 males; 10 females) for the reconstruction of fiber bundles using tractography techniques. Finally, we leveraged our novel connectome modeling techniques including high order fiber orientation distribution (FOD) reconstruction from multi-shell diffusion imaging and topography-preserving tract filtering algorithms to successfully reconstruct the 23 fiber bundles for each subject, which were then used to calculate the probabilistic atlases in the MNI152 space for public release. In our experimental results, we demonstrate that our method yielded anatomically faithful reconstruction of the brainstem pathways and achieved improved performance in comparison with an existing atlas of cerebellar peduncles based on HCP data. These atlases have been publicly released on NITRIC (https://www.nitrc.org/projects/brainstem_atlas/) and can be readily used by brain imaging researchers interested in studying brainstem pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Brainstem involvement in subacute sclerosing panencephalitis.

PubMed

Sharma, Pawan; Singh, Dileep; Singh, Maneesh Kumar; Garg, Ravindra Kumar; Kohli, Neera

2011-01-01

The parieto-occipital region of the brain is most frequently and severely affected in subacute sclerosing panencephalitis (SSPE). The basal ganglia, cerebellum and corpus callosum are less commonly involved. Brainstem involvement is rarely described in SSPE, and usually there is involvement of other regions of the brain. We describe a patient with subacute sclerosing panencephalitis with brain magnetic resonance imaging showing extensive brainstem involvement without significant involvement of other cortical structures. Though rarely described in SSPE, one should be aware of such brainstem and cerebellum involvement, and SSPE should be kept in mind when brainstem signal changes are seen in brain MRI with or without involvement of other regions of brain to avoid erroneous reporting.

Brainstem cavernous malformations: anatomical, clinical, and surgical considerations.

PubMed

Giliberto, Giuliano; Lanzino, Desiree J; Diehn, Felix E; Factor, David; Flemming, Kelly D; Lanzino, Giuseppe

2010-09-01

Symptomatic brainstem cavernous malformations carry a high risk of permanent neurological deficit related to recurrent hemorrhage, which justifies aggressive management. Detailed knowledge of the microscopic and surface anatomy is important for understanding the clinical presentation, predicting possible surgical complications, and formulating an adequate surgical plan. In this article the authors review and illustrate the surgical and microscopic anatomy of the brainstem, provide anatomoclinical correlations, and illustrate a few clinical cases of cavernous malformations in the most common brainstem areas.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gong, G; Liu, C; Liu, C

Purpose: To analyze the error in contouring the brainstem for patients with head and neck cancer who underwent radiotherapy based on computed tomography (CT) and magnetic resonance (MR) images. Methods: 20 brain tumor and 17 nasopharyngeal cancer patients were randomly selected. Each patient underwent MR and CT scanning. For each patient, one observer contoured the brainstem on CT and MR images for 10 times, and 10 observers from five centers delineated the brainstem on CT and MR images only one time. The inter- and intra-observers volume and outline variations were compared. Results: The volumes of brainstem contoured by inter- andmore » intra-observers on CT and MR images were similar (p>0.05). The reproducibility of contouring brainstem on MR images was better than that on CT images (p<0.05) for both inter- and intra-observer variability. The inter- and intra-observer for contouring on CT images reached mean values of 0.81±0.05 (p>0.05) and of 0.85±0.05 (p>0.05), respectively, while on MR images these respective values were 0.90±0.05 (p>0.05) and 0.92±0.04 (p>0.05). Conclusion: Contouring the brainstem on MR images was more accurate and reproducible than that on CT images. Precise information might be more helpful for protecting the brainstem radiation injury the patients whose lesion were closed to brainstem.« less

[Distribution of human enterovirus 71 in brainstem of infants with brain stem encephalitis and infection mechanism].

PubMed

Hao, Bo; Gao, Di; Tang, Da-Wei; Wang, Xiao-Guang; Liu, Shui-Ping; Kong, Xiao-Ping; Liu, Chao; Huang, Jing-Lu; Bi, Qi-Ming; Quan, Li; Luo, Bin

2012-04-01

To explore the mechanism that how human enterovirus 71 (EV71) invades the brainstem and how intercellular adhesion molecules-1 (ICAM-1) participates by analyzing the expression and distribution of human EV71, and ICAM-1 in brainstem of infants with brain stem encephalitis. Twenty-two brainstem of infants with brain stem encephalitis were collected as the experimental group and 10 brainstems of fatal congenital heart disease were selected as the control group. The sections with perivascular cuffings were selected to observe EV71-VP1 expression by immunohistochemistry method and ICAM-1 expression was detected for the sections with EV71-VP1 positive expression. The staining image analysis and statistics analysis were performed. The experiment and control groups were compared. (1) EV71-VP1 positive cells in the experimental group were mainly astrocytes in brainstem with nigger-brown particles, and the control group was negative. (2) ICAM-1 positive cells showed nigger-brown. The expression in inflammatory cells (around blood vessels of brain stem and in glial nodules) and gliocytes increased. The results showed statistical difference comparing with control group (P < 0.05). The brainstem encephalitis can be used to diagnose fatal EV71 infection in infants. EV71 can invade the brainstem via hematogenous route. ICAM-1 may play an important role in the pathogenic process.

Neural Correlates of the Binaural Masking Level Difference in Human Frequency-Following Responses.

PubMed

Clinard, Christopher G; Hodgson, Sarah L; Scherer, Mary Ellen

2017-04-01

The binaural masking level difference (BMLD) is an auditory phenomenon where binaural tone-in-noise detection is improved when the phase of either signal or noise is inverted in one of the ears (S π N o or S o N π , respectively), relative to detection when signal and noise are in identical phase at each ear (S o N o ). Processing related to BMLDs and interaural time differences has been confirmed in the auditory brainstem of non-human mammals; in the human auditory brainstem, phase-locked neural responses elicited by BMLD stimuli have not been systematically examined across signal-to-noise ratio. Behavioral and physiological testing was performed in three binaural stimulus conditions: S o N o , S π N o , and S o N π . BMLDs at 500 Hz were obtained from 14 young, normal-hearing adults (ages 21-26). Physiological BMLDs used the frequency-following response (FFR), a scalp-recorded auditory evoked potential dependent on sustained phase-locked neural activity; FFR tone-in-noise detection thresholds were used to calculate physiological BMLDs. FFR BMLDs were significantly smaller (poorer) than behavioral BMLDs, and FFR BMLDs did not reflect a physiological release from masking, on average. Raw FFR amplitude showed substantial reductions in the S π N o condition relative to S o N o and S o N π conditions, consistent with negative effects of phase summation from left and right ear FFRs. FFR amplitude differences between stimulus conditions (e.g., S o N o amplitude-S π N o amplitude) were significantly predictive of behavioral S π N o BMLDs; individuals with larger amplitude differences had larger (better) behavioral B MLDs and individuals with smaller amplitude differences had smaller (poorer) behavioral B MLDs. These data indicate a role for sustained phase-locked neural activity in BMLDs of humans and are the first to show predictive relationships between behavioral BMLDs and human brainstem responses.

Audiological and electrophysiological alterations in HIV-infected individuals subjected or not to antiretroviral therapy.

PubMed

Matas, Carla Gentile; Samelli, Alessandra Giannella; Magliaro, Fernanda Cristina Leite; Segurado, Aluisio

2017-08-02

The Human Immunodeficiency Virus (HIV) and infections related to it can affect multiple sites in the hearing system. The use of High-Activity Anti-Retroviral Therapy (HAART) can cause side effects such as ototoxicity. Thus, no consistent patterns of hearing impairment in adults with Human Immunodeficiency Virus / Acquired Immune Deficiency Syndrome have been established, and the problems that affect the hearing system of this population warrant further research. This study aimed to compare the audiological and electrophysiological data of Human Immunodeficiency Virus-positive patients with and without Acquired Immune Deficiency Syndrome, who were receiving High-Activity Anti-Retroviral Therapy, to healthy individuals. It was a cross-sectional study conducted with 71 subjects (30-48 years old), divided into groups: Research Group I: 16 Human Immunodeficiency Virus-positive individuals without Acquired Immunodeficiency Syndrome (not receiving antiretroviral treatment); Research Group II: 25 Human Immunodeficiency Virus-positive individuals with Acquired Immunodeficiency Syndrome (receiving antiretroviral treatment); Control Group: 30 healthy subjects. All individuals were tested by pure-tone air conduction thresholds at 0.25-8kHz, extended high frequencies at 9-20kHz, electrophysiological tests (Auditory Brainstem Response - ABR, Middle Latency Responses - MLR, Cognitive Potential - P300). Research Group I and Research Group II had higher hearing thresholds in both conventional and high frequency audiometry when compared to the control group, prolonged latency of waves I, III, V and interpeak I-V in Auditory Brainstem Response and prolonged latency of P300 Cognitive Potential. Regarding Middle Latency Responses, there was a decrease in the amplitude of the Pa wave of Research Group II compared to the Research Group I. Both groups with Human Immunodeficiency Virus had higher hearing thresholds when compared to healthy individuals (group exposed to antiretroviral treatment showed the worst hearing threshold) and seemed to have lower neuroelectric transmission speed along the auditory pathway in the brainstem, subcortical and cortical regions. Copyright © 2017. Published by Elsevier Editora Ltda.

Deviance detection based on regularity encoding along the auditory hierarchy: electrophysiological evidence in humans.

PubMed

Escera, Carles; Leung, Sumie; Grimm, Sabine

2014-07-01

Detection of changes in the acoustic environment is critical for survival, as it prevents missing potentially relevant events outside the focus of attention. In humans, deviance detection based on acoustic regularity encoding has been associated with a brain response derived from the human EEG, the mismatch negativity (MMN) auditory evoked potential, peaking at about 100-200 ms from deviance onset. By its long latency and cerebral generators, the cortical nature of both the processes of regularity encoding and deviance detection has been assumed. Yet, intracellular, extracellular, single-unit and local-field potential recordings in rats and cats have shown much earlier (circa 20-30 ms) and hierarchically lower (primary auditory cortex, medial geniculate body, inferior colliculus) deviance-related responses. Here, we review the recent evidence obtained with the complex auditory brainstem response (cABR), the middle latency response (MLR) and magnetoencephalography (MEG) demonstrating that human auditory deviance detection based on regularity encoding-rather than on refractoriness-occurs at latencies and in neural networks comparable to those revealed in animals. Specifically, encoding of simple acoustic-feature regularities and detection of corresponding deviance, such as an infrequent change in frequency or location, occur in the latency range of the MLR, in separate auditory cortical regions from those generating the MMN, and even at the level of human auditory brainstem. In contrast, violations of more complex regularities, such as those defined by the alternation of two different tones or by feature conjunctions (i.e., frequency and location) fail to elicit MLR correlates but elicit sizable MMNs. Altogether, these findings support the emerging view that deviance detection is a basic principle of the functional organization of the auditory system, and that regularity encoding and deviance detection is organized in ascending levels of complexity along the auditory pathway expanding from the brainstem up to higher-order areas of the cerebral cortex.

A new view of “dream enactment” in REM sleep behavior disorder

PubMed Central

Blumberg, Mark S.; Plumeau, Alan M.

2015-01-01

SUMMARY REM sleep behavior disorder (RBD) is a disorder in which patients exhibit increased muscle tone and exaggerated myoclonic twitching during REM sleep. In addition, violent movements of the limbs, and complex behaviors that can sometimes appear to involve the enactment of dreams, are associated with RBD. These behaviors are widely thought to result from a dysfunction involving atonia-producing neural circuitry in the brainstem, thereby unmasking cortically generated dreams. Here we scrutinize the assumptions that led to this interpretation of RBD. In particular, we challenge the assumption that motor cortex produces twitches during REM sleep, thus calling into question the related assumption that motor cortex is primarily responsible for all of the pathological movements of RBD. Moreover, motor cortex is not even necessary to produce complex behavior; for example, stimulation of some brainstem structures can produce defensive and aggressive behaviors in rats and monkeys that are striking similar to those reported in human patients with RBD. Accordingly, we suggest an interpretation of RBD that focuses increased attention on the brainstem as a source of the pathological movements and that considers sensory feedback from moving limbs as an important influence on the content of dream mentation. PMID:26802823

Brainstem auditory-evoked potentials as an objective tool for evaluating hearing dysfunction in traumatic brain injury.

PubMed

Lew, Henry L; Lee, Eun Ha; Miyoshi, Yasushi; Chang, Douglas G; Date, Elaine S; Jerger, James F

2004-03-01

Because of the violent nature of traumatic brain injury, traumatic brain injury patients are susceptible to various types of trauma involving the auditory system. We report a case of a 55-yr-old man who presented with communication problems after traumatic brain injury. Initial results from behavioral audiometry and Weber/Rinne tests were not reliable because of poor cooperation. He was transferred to our service for inpatient rehabilitation, where review of the initial head computed tomographic scan showed only left temporal bone fracture. Brainstem auditory-evoked potential was then performed to evaluate his hearing function. The results showed bilateral absence of auditory-evoked responses, which strongly suggested bilateral deafness. This finding led to a follow-up computed tomographic scan, with focus on bilateral temporal bones. A subtle transverse fracture of the right temporal bone was then detected, in addition to the left temporal bone fracture previously identified. Like children with hearing impairment, traumatic brain injury patients may not be able to verbalize their auditory deficits in a timely manner. If hearing loss is suspected in a patient who is unable to participate in traditional behavioral audiometric testing, brainstem auditory-evoked potential may be an option for evaluating hearing dysfunction.

Effect of edaravone on acute brainstem-cerebellar infarction with vertigo and sudden hearing loss.

PubMed

Inoue, Yuta; Yabe, Takao; Okada, Kazunari; Nakamura, Yuka

2014-06-01

We report 2 cases with acute brainstem and brainstem-cerebellar infarction showed improvement of their signs and symptoms after administration of edaravone. Case 1, a 74-year-old woman who experienced sudden vertigo, also had dysarthria and left hemiplegia. Magnetic resonance imaging (MRI) showed an abnormal region in the right ventrolateral medulla oblongata. The patient's vertigo and hemiplegia improved completely after treatment. Case 2, a 50-year-old man who experienced sudden vertigo and sensorineural hearing loss (SNHL), developed dysarthria after admission. MRI revealed acute infarction in the right cerebellar hemisphere. Magnetic resonance angiography revealed dissection of the basilar artery and occlusion of the right anterior inferior cerebellar artery. The patient's vertigo and hearing remarkably improved. We have described 2 patients whose early symptoms were vertigo and sudden SNHL, but who were later shown to have ischemic lesions of the central nervous system. Edaravone is neuroprotective drug with free radical-scavenging actions. Free radicals in the ear are responsible for ischemic damage. Edaravone, a free radical scavenger, may be useful in the treatment of vertigo and SNHL. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The effect of preterm birth on brainstem, middle latency and cortical auditory evoked responses (BMC AERs).

PubMed

Pasman, J W; Rotteveel, J J; de Graaf, R; Stegeman, D F; Visco, Y M

1992-12-01

Recent studies on the maturation of auditory brainstem evoked responses (ABRs) present conflicting results, whereas only sparse reports exist with respect to the maturation of middle latency auditory evoked responses (MLRs) and auditory cortical evoked responses (ACRs). The present study reports the effect of preterm birth on the maturation of auditory evoked responses in low risk preterm infants (27-34 weeks conceptional age). The ABRs indicate a consistent trend towards longer latencies for all individual ABR components and towards longer interpeak latencies in preterm infants. The MLR shows longer latencies for early component P0 in preterm infants. The ACRs show a remarkable difference between preterm and term infants. At 40 weeks CA the latencies of ACR components Na and P2 are significantly longer in term infants, whereas at 52 weeks CA the latencies of the same ACR components are shorter in term infants. The results support the hypothesis that retarded myelination of the central auditory pathway is partially responsible for differences found between preterm infants and term infants with respect to late ABR components and early MLR component P0. Furthermore, mild conductive hearing loss in preterm infants may also play its role. A more complex mechanism is implicated to account for the findings noted with respect to MLR component Na and ACR components Na and P2.

The Brainstem Tau Cytoskeletal Pathology of Alzheimer's Disease: A Brief Historical Overview and Description of its Anatomical Distribution Pattern, Evolutional Features, Pathogenetic and Clinical Relevance.

PubMed

Rüb, Udo; Stratmann, Katharina; Heinsen, Helmut; Turco, Domenico Del; Seidel, Kay; Dunnen, Wilfred den; Korf, Horst-Werner

2016-01-01

The human brainstem is involved in the regulation of the sleep/waking cycle and normal sleep architectonics and is crucial for the performance of a variety of somatomotor, vital autonomic, oculomotor, vestibular, auditory, ingestive and somatosensory functions. It harbors the origins of the ascending dopaminergic, cholinergic, noradrenergic, serotonergic systems, as well the home base of the descending serotonergic system. In contrast to the cerebral cortex the affection of the brainstem in Alzheimer's disease (AD) by the neurofibrillary or tau cytoskeletal pathology was recognized only approximately fourty years ago in initial brainstem studies. Detailed pathoanatomical investigations of silver stained or tau immunostained brainstem tissue sections revealed nerve cell loss and prominent ADrelated cytoskeletal changes in the raphe nuclei, locus coeruleus, and in the compact parts of the substantia nigra and pedunculopontine nucleus. An additional conspicuous AD-related cytoskeletal pathology was also detected in the auditory brainstem system of AD patients (i.e. inferior colliculus, superior olive, dorsal cochlear nucleus), in the oculomotor brainstem network (i.e. rostral interstitial nucleus of the medial longitudinal fascicle, Edinger-Westphal nucleus, reticulotegmental nucleus of pons), autonomic system (i.e. central and periaqueductal grays, parabrachial nuclei, gigantocellular reticular nucleus, dorsal motor vagal and solitary nuclei, intermediate reticular zone). The alterations in these brainstem nuclei offered for the first time adequate explanations for a variety of less understood disease symptoms of AD patients: Parkinsonian extrapyramidal motor signs, depression, hallucinations, dysfunctions of the sleep/wake cycle, changes in sleeping patterns, attentional deficits, exaggerated pupil dilatation, autonomic dysfunctions, impairments of horizontal and vertical saccades, dysfunctional smooth pursuits. The very early occurrence of the AD-related cytoskeletal pathology in some of these brainstem nuclei points to a major and strategic role of the brainstem in the induction and brain spread of the AD-related cytoskeletal pathology.

Pharmacological and Morphological Evidence of AMPK-Mediated Energy Sensing in the Lower Brain Stem Ependymocytes to Control Reproduction in Female Rodents.

PubMed

Minabe, Shiori; Deura, Chikaya; Ikegami, Kana; Goto, Teppei; Sanbo, Makoto; Hirabayashi, Masumi; Inoue, Naoko; Uenoyama, Yoshihisa; Maeda, Kei-Ichiro; Tsukamura, Hiroko

2015-06-01

Ependymocytes are one of the energy-sensing cells that regulate animal reproduction through their responsiveness to changes in extracellular glucose levels and the expression of pancreatic-type glucokinase and glucose transporter 2, which play a critical role in sensing blood glucose levels in pancreatic β-cells. Molecular mechanisms underlying glucose sensing in the ependymocytes remain poorly understood. The AMP-activated protein kinase (AMPK), a serine/threonine kinase highly conserved in all eukaryotic cells, has been suggested to be an intracellular fuel gauge that detects cellular energy status. The present study aims to clarify the role AMPK of the lower brainstem ependymocytes has in sensing glucose levels to regulate reproductive functions. First, we will show that administration of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, an AMPK activator, into the 4th ventricle suppressed pulsatile LH release in female rats. Second, we will demonstrate the presence of AMPK catalytic subunit immunoreactivities in the rat lower brainstem ependymocytes. Third, transgenic mice were generated to visualize the ependymocytes with Venus, a green fluorescent protein, expressed under the control of the mouse vimentin promoter for further in vitro study. The Venus-labeled ependymocytes taken from the lower brainstem of transgenic mice revealed that AMPK activation by 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, an AMPK activator, increased in vitro intracellular calcium concentrations. Taken together, malnutrition-induced AMPK activation of ependymocytes of the lower brainstem might be involved in suppression of GnRH/LH release and then gonadal activities.

Pharmacological and Morphological Evidence of AMPK-Mediated Energy Sensing in the Lower Brain Stem Ependymocytes to Control Reproduction in Female Rodents

PubMed Central

Minabe, Shiori; Deura, Chikaya; Ikegami, Kana; Goto, Teppei; Sanbo, Makoto; Hirabayashi, Masumi; Inoue, Naoko; Uenoyama, Yoshihisa; Maeda, Kei-ichiro

2015-01-01

Ependymocytes are one of the energy-sensing cells that regulate animal reproduction through their responsiveness to changes in extracellular glucose levels and the expression of pancreatic-type glucokinase and glucose transporter 2, which play a critical role in sensing blood glucose levels in pancreatic β-cells. Molecular mechanisms underlying glucose sensing in the ependymocytes remain poorly understood. The AMP-activated protein kinase (AMPK), a serine/threonine kinase highly conserved in all eukaryotic cells, has been suggested to be an intracellular fuel gauge that detects cellular energy status. The present study aims to clarify the role AMPK of the lower brainstem ependymocytes has in sensing glucose levels to regulate reproductive functions. First, we will show that administration of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, an AMPK activator, into the 4th ventricle suppressed pulsatile LH release in female rats. Second, we will demonstrate the presence of AMPK catalytic subunit immunoreactivities in the rat lower brainstem ependymocytes. Third, transgenic mice were generated to visualize the ependymocytes with Venus, a green fluorescent protein, expressed under the control of the mouse vimentin promoter for further in vitro study. The Venus-labeled ependymocytes taken from the lower brainstem of transgenic mice revealed that AMPK activation by 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, an AMPK activator, increased in vitro intracellular calcium concentrations. Taken together, malnutrition-induced AMPK activation of ependymocytes of the lower brainstem might be involved in suppression of GnRH/LH release and then gonadal activities. PMID:25822714

Management of a severe forceful breather with Rett syndrome using carbogen.

PubMed

Smeets, Eric E J; Julu, Peter O O; van Waardenburg, Dick; Engerström, Ingegerd Witt; Hansen, Stig; Apartopoulos, Flora; Curfs, Leopold M G; Schrander-Stumpel, Connie T R M

2006-11-01

We have used a novel neurophysiological technique in the NeuroScope system in combination with conventional electroencephalography (EEG) to monitor both brainstem and cortical activity simultaneously in real-time in a girl with Rett syndrome. The presenting clinical features in our patient were severe sleep disturbances, irregular breathing in the awake state dominated by Valsalva's type of breathing followed by tachypnoea and very frequent attacks of seizures and vacant spells. Our novel neurophysiological data showed that the patient was a Forceful Breather according to the breathing categories in Rett syndrome. She had frequent abnormal spontaneous brainstem activation (ASBA) preceded by severe attacks of hypocapnoea, which was caused by a combination of Valsalva's type of breathing and tachypnoea and all these together were responsible for the seizures and non-epileptic vacant spells. The ASBA was not detectable in conventional EEG and there were no epileptiform changes in the EEG during the seizures and vacant spells caused by the hypocapnic attacks, therefore these were pseudo-seizures. The record of brainstem activity confirmed that these were autonomic events, a kind of "brainstem epilepsy". We successfully treated the sleep disturbance with Pipamperone, a 5-hydroxytryptophan antagonist of receptor type 2 and we prevented the severe hypocapnoea during Valsalva's type of breathing and during tachypnoea using carbogen (a mixture of 5% carbon dioxide and 95% oxygen), which we gave by inhalation. Our treatment drastically reduced the autonomic events, promoted whole night sleep and significantly improved the quality of life in our patient. She can now participate in normal family activity which was previously impossible before treatment.

Cortico-fugal output from visual cortex promotes plasticity of innate motor behaviour.

PubMed

Liu, Bao-Hua; Huberman, Andrew D; Scanziani, Massimo

2016-10-20

The mammalian visual cortex massively innervates the brainstem, a phylogenetically older structure, via cortico-fugal axonal projections. Many cortico-fugal projections target brainstem nuclei that mediate innate motor behaviours, but the function of these projections remains poorly understood. A prime example of such behaviours is the optokinetic reflex (OKR), an innate eye movement mediated by the brainstem accessory optic system, that stabilizes images on the retina as the animal moves through the environment and is thus crucial for vision. The OKR is plastic, allowing the amplitude of this reflex to be adaptively adjusted relative to other oculomotor reflexes and thereby ensuring image stability throughout life. Although the plasticity of the OKR is thought to involve subcortical structures such as the cerebellum and vestibular nuclei, cortical lesions have suggested that the visual cortex might also be involved. Here we show that projections from the mouse visual cortex to the accessory optic system promote the adaptive plasticity of the OKR. OKR potentiation, a compensatory plastic increase in the amplitude of the OKR in response to vestibular impairment, is diminished by silencing visual cortex. Furthermore, targeted ablation of a sparse population of cortico-fugal neurons that specifically project to the accessory optic system severely impairs OKR potentiation. Finally, OKR potentiation results from an enhanced drive exerted by the visual cortex onto the accessory optic system. Thus, cortico-fugal projections to the brainstem enable the visual cortex, an area that has been principally studied for its sensory processing function, to plastically adapt the execution of innate motor behaviours.

Plasticity in the adult human auditory brainstem following short-term linguistic training

PubMed Central

Song, Judy H.; Skoe, Erika; Wong, Patrick C. M.; Kraus, Nina

2009-01-01

Peripheral and central structures along the auditory pathway contribute to speech processing and learning. However, because speech requires the use of functionally and acoustically complex sounds which necessitates high sensory and cognitive demands, long-term exposure and experience using these sounds is often attributed to the neocortex with little emphasis placed on subcortical structures. The present study examines changes in the auditory brainstem, specifically the frequency following response (FFR), as native English-speaking adults learn to incorporate foreign speech sounds (lexical pitch patterns) in word identification. The FFR presumably originates from the auditory midbrain, and can be elicited pre-attentively. We measured FFRs to the trained pitch patterns before and after training. Measures of pitch-tracking were then derived from the FFR signals. We found increased accuracy in pitch-tracking after training, including a decrease in the number of pitch-tracking errors and a refinement in the energy devoted to encoding pitch. Most interestingly, this change in pitch-tracking accuracy only occurred in the most acoustically complex pitch contour (dipping contour), which is also the least familiar to our English-speaking subjects. These results not only demonstrate the contribution of the brainstem in language learning and its plasticity in adulthood, but they also demonstrate the specificity of this contribution (i.e., changes in encoding only occurs in specific, least familiar stimuli, not all stimuli). Our findings complement existing data showing cortical changes after second language learning, and are consistent with models suggesting that brainstem changes resulting from perceptual learning are most apparent when acuity in encoding is most needed. PMID:18370594

Spinal and pontine relay pathways mediating respiratory rhythm entrainment by limb proprioceptive inputs in the neonatal rat.

PubMed

Giraudin, Aurore; Le Bon-Jégo, Morgane; Cabirol, Marie-Jeanne; Simmers, John; Morin, Didier

2012-08-22

The coordination of locomotion and respiration is widespread among mammals, although the underlying neural mechanisms are still only partially understood. It was previously found in neonatal rat that cyclic electrical stimulation of spinal cervical and lumbar dorsal roots (DRs) can fully entrain (1:1 coupling) spontaneous respiratory activity expressed by the isolated brainstem/spinal cord. Here, we used a variety of preparations to determine the type of spinal sensory inputs responsible for this respiratory rhythm entrainment, and to establish the extent to which limb movement-activated feedback influences the medullary respiratory networks via direct or relayed ascending pathways. During in vivo overground locomotion, respiratory rhythm slowed and became coupled 1:1 with locomotion. In hindlimb-attached semi-isolated preparations, passive flexion-extension movements applied to a single hindlimb led to entrainment of fictive respiratory rhythmicity recorded in phrenic motoneurons, indicating that the recruitment of limb proprioceptive afferents could participate in the locomotor-respiratory coupling. Furthermore, in correspondence with the regionalization of spinal locomotor rhythm-generating circuitry, the stimulation of DRs at different segmental levels in isolated preparations revealed that cervical and lumbosacral proprioceptive inputs are more effective in this entraining influence than thoracic afferent pathways. Finally, blocking spinal synaptic transmission and using a combination of electrophysiology, calcium imaging and specific brainstem lesioning indicated that the ascending entraining signals from the cervical or lumbar limb afferents are transmitted across first-order synapses, probably monosynaptic, in the spinal cord. They are then conveyed to the brainstem respiratory centers via a brainstem pontine relay located in the parabrachial/Kölliker-Fuse nuclear complex.

The relationship of age, gender, and IQ with the brainstem and thalamus in healthy children and adolescents: a magnetic resonance imaging volumetric study

PubMed Central

Xie, Yuhuan; Chen, Yian Ann; De Bellis, Michael D.

2011-01-01

In healthy children, there is a paucity of information on the growth of the brainstem and thalamus measured by anatomical magnetic resonance imaging. The relationships of age, gender, and age by gender with brainstem and thalamus volumes were analyzed from magnetic resonance brain images of 122 healthy children and adolescents (62 males, 60 females; ages four to seventeen). Results showed that age is a significant predictor of brainstem and thalamus volumes. The volume of the brainstem increases with age, while thalamus volume declines with age. The volumes of right thalami are significantly larger than that of left in both genders with greater rightward asymmetry and greater thalamus/grey matter ratio in females. Males have larger brainstems, but these differences are not significant when covarying for cerebral volumes. Larger thalami were associated with higher verbal IQ. This normative pediatric data is of value to researchers who study these regions in neurodevelopmental disorders. PMID:21954432

The relationship of age, gender, and IQ with the brainstem and thalamus in healthy children and adolescents: a magnetic resonance imaging volumetric study.

PubMed

Xie, Yuhuan; Chen, Yian Ann; De Bellis, Michael D

2012-03-01

In healthy children, there is a paucity of information on the growth of the brainstem and thalamus measured anatomically magnetic resonance imaging. The relations of age, gender, and age by gender with brainstem and thalamus volumes were analyzed from magnetic resonance brain images of 122 healthy children and adolescents (62 males, 60 females; ages 4 to 17). Results showed that age is a significant predictor of brainstem and thalamus volumes. The volume of the brainstem increases with age, while thalamus volume declines with age. The volume of the right thalamus is significantly larger than that of the left in both genders, with greater rightward asymmetry and greater thalamus to grey matter ratio in females. Males have larger brainstems, but these differences are not significant when covarying for cerebral volume. Larger thalami were associated with higher Verbal IQ. These normative pediatric data are of value to researchers who study these regions in neurodevelopmental disorders.

Dorsally exophytic glioblastoma arising from the medulla oblongata in an adult presenting as 4th ventricular mass.

PubMed

Das, Kuntal Kanti; Bettaswamy, Guru Prasad; Mehrotra, Anant; Jaiswal, Sushila; Jaiswal, Awadhesh Kumar; Behari, Sanjay

2017-01-01

Brainstem gliomas are relatively rare in adults (<2% of all gliomas). Exophytic gliomas are focal brainstem lesions, which project into the 4 th ventricle or cerebellopontine angles. These exophytic lesions are usually of low-grade histology (pilocytic astrocytoma or ganglioglioma) and have a relatively better outcome compared with brainstem gliomas as a whole. Glioblastoma is the commonest primary glial cell neoplasm and mostly occurs in the supratentorial compartment. It is rather uncommon in the brainstem and seldom has been described as having an exophytic growth pattern. Here we describe an exophytic brainstem glioblastoma arising from the medulla oblongata in a 55-year-old lady who presented with a 4 th ventricular mass, and present a brief review of the literature. Till now, six cases of glioblastoma arising from the medulla oblongata have been reported. So, ours is the seventh such report. To the best of our knowledge, it also happens to be the sixth reported case of dorsally exophytic brainstem glioblastoma till date.

Early spinal cord and brainstem involvement in infantile Leigh syndrome possibly caused by a novel variant.

PubMed

Tenney, Jeffrey R; Prada, Carlos E; Hopkin, Robert J; Hallinan, Barbara E

2013-12-01

Leigh syndrome, due to a dysfunction of mitochondrial energy metabolism, is a genetically heterogeneous and progressive neurologic disorder that usually occurs in infancy and childhood. Its clinical presentation and neuroimaging findings can be variable, especially early in the course of the disease. This report presents a patient with infantile Leigh syndrome who had atypical radiologic findings on serial neuroimaging studies with early and severe involvement of the cervical spinal cord and brainstem and injury to the thalami and basal ganglia occurring only late in the clinical course. Postmortem microscopic examination supported this timing of injury within the central nervous system. In addition, mitochondrial deoxyribonucleic acid sequencing showed a novel homoplasmic variant that could be responsible for this unique lethal form of Leigh syndrome.

Feasibility of creating a high-resolution 3D diffusion tensor imaging based atlas of the human brainstem: A case study at 11.7T

PubMed Central

Aggarwal, Manisha; Zhang, Jiangyang; Pletnikova, Olga; Crain, Barbara; Troncoso, Juan; Mori, Susumu

2013-01-01

A three-dimensional stereotaxic atlas of the human brainstem based on high resolution ex vivo diffusion tensor imaging (DTI) is introduced. The atlas consists of high resolution (125–255 μm isotropic) three-dimensional DT images of the formalin-fixed brainstem acquired at 11.7T. The DTI data revealed microscopic neuroanatomical details, allowing three-dimensional visualization and reconstruction of fiber pathways including the decussation of the pyramidal tract fibers, and interdigitating fascicles of the corticospinal and transverse pontine fibers. Additionally, strong grey-white matter contrasts in the apparent diffusion coefficient (ADC) maps enabled precise delineation of grey matter nuclei in the brainstem, including the cranial nerve and the inferior olivary nuclei. Comparison with myelin-stained histology shows that at the level of resolution achieved in this study, the structural details resolved with DTI contrasts in the brainstem were comparable to anatomical delineation obtained with histological sectioning. Major neural structures delineated from DTI contrasts in the brainstem are segmented and three-dimensionally reconstructed. Further, the ex vivo DTI data are nonlinearly mapped to a widely-used in vivo human brain atlas, to construct a high-resolution atlas of the brainstem in the Montreal Neurological Institute (MNI) stereotaxic coordinate space. The results demonstrate the feasibility of developing a 3D DTI based atlas for detailed characterization of brainstem neuroanatomy with high resolution and contrasts, which will be a useful resource for research and clinical applications. PMID:23384518

The Structural Connectome of the Human Central Homeostatic Network.

PubMed

Edlow, Brian L; McNab, Jennifer A; Witzel, Thomas; Kinney, Hannah C

2016-04-01

Homeostatic adaptations to stress are regulated by interactions between the brainstem and regions of the forebrain, including limbic sites related to respiratory, autonomic, affective, and cognitive processing. Neuroanatomic connections between these homeostatic regions, however, have not been thoroughly identified in the human brain. In this study, we perform diffusion spectrum imaging tractography using the MGH-USC Connectome MRI scanner to visualize structural connections in the human brain linking autonomic and cardiorespiratory nuclei in the midbrain, pons, and medulla oblongata with forebrain sites critical to homeostatic control. Probabilistic tractography analyses in six healthy adults revealed connections between six brainstem nuclei and seven forebrain regions, several over long distances between the caudal medulla and cerebral cortex. The strongest evidence for brainstem-homeostatic forebrain connectivity in this study was between the brainstem midline raphe and the medial temporal lobe. The subiculum and amygdala were the sampled forebrain nodes with the most extensive brainstem connections. Within the human brainstem-homeostatic forebrain connectome, we observed that a lateral forebrain bundle, whose connectivity is distinct from that of rodents and nonhuman primates, is the primary conduit for connections between the brainstem and medial temporal lobe. This study supports the concept that interconnected brainstem and forebrain nodes form an integrated central homeostatic network (CHN) in the human brain. Our findings provide an initial foundation for elucidating the neuroanatomic basis of homeostasis in the normal human brain, as well as for mapping CHN disconnections in patients with disorders of homeostasis, including sudden and unexpected death, and epilepsy.

Screening Procedures Used to Identify Children with Hearing Loss.

ERIC Educational Resources Information Center

Barringer, Donald G.; And Others

1993-01-01

Analysis of data on 1,404 young children with hearing losses indicated that 80% of the children were identified via informal hearing-screening procedures, such as parental suspicion and referral. Auditory brainstem response technology provided the lowest mean identification age. The study concludes that formal screening programs are not locating…

POSSIBLE ROLE OF THE BRAINSTEM IN THE MEDIATION OF PREPULSE INHIBITION IN THE RAT (JOURNAL VERSION)

EPA Science Inventory

Bilateral stimulation of electrodes aimed at the cuneiform nucleus produced significant inhibition of the startle response produced by presentation of an 8 KHz, 110 dB tone. Stimulation of electrodes aimed at the deep mesencephalic nucleus also reduced the magnitude of the startl...

Auditory brainstem response to complex sounds: a tutorial

PubMed Central

Skoe, Erika; Kraus, Nina

2010-01-01

This tutorial provides a comprehensive overview of the methodological approach to collecting and analyzing auditory brainstem responses to complex sounds (cABRs). cABRs provide a window into how behaviorally relevant sounds such as speech and music are processed in the brain. Because temporal and spectral characteristics of sounds are preserved in this subcortical response, cABRs can be used to assess specific impairments and enhancements in auditory processing. Notably, subcortical function is neither passive nor hardwired but dynamically interacts with higher-level cognitive processes to refine how sounds are transcribed into neural code. This experience-dependent plasticity, which can occur on a number of time scales (e.g., life-long experience with speech or music, short-term auditory training, online auditory processing), helps shape sensory perception. Thus, by being an objective and non-invasive means for examining cognitive function and experience-dependent processes in sensory activity, cABRs have considerable utility in the study of populations where auditory function is of interest (e.g., auditory experts such as musicians, persons with hearing loss, auditory processing and language disorders). This tutorial is intended for clinicians and researchers seeking to integrate cABRs into their clinical and/or research programs. PMID:20084007

Responses evoked from man by acoustic stimulation

NASA Technical Reports Server (NTRS)

Galambos, R.; Hecox, K.; Picton, T.

1974-01-01

Clicks and other acoustic stimuli evoke time-locked responses from the brain of man. The properties of the waves recordable within the interval from 1 to 10 msec after the stimuli strike the eardrum are discussed along with factors influencing the waves in the 100 to 500 msec epoch. So-called brainstem responses from a normal young adult are considered. No waves were observed for clicks to weak to be heard. With increasing stimulus strength the waves become larger in amplitude and their latency shortens.

Brainstem Auditory Evoked Potential Study in Children with Autistic Disorder.

ERIC Educational Resources Information Center

Wong, Virginia; Wong, Sik Nin

1991-01-01

Brainstem auditory evoked potentials were compared in 109 children with infantile autism, 38 with autistic condition, 19 with mental retardation, and 20 normal children. Children with infantile autism or autistic condition had significantly longer brainstem transmission time than normal children suggesting neurological damage as the basis of…

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mayo, Charles, E-mail: charles.mayo@umassmemorial.or; Yorke, Ellen; Merchant, Thomas E.

Publications relating brainstem radiation toxicity to quantitative dose and dose-volume measures derived from three-dimensional treatment planning were reviewed. Despite the clinical importance of brainstem toxicity, most studies reporting brainstem effects after irradiation have fewer than 100 patients. There is limited evidence relating toxicity to small volumes receiving doses above 60-64 Gy using conventional fractionation and no definitive criteria regarding more subtle dose-volume effects or effects after hypofractionated treatment. On the basis of the available data, the entire brainstem may be treated to 54 Gy using conventional fractionation using photons with limited risk of severe or permanent neurological effects. Smaller volumesmore » of the brainstem (1-10 mL) may be irradiated to maximum doses of 59 Gy for dose fractions <=2 Gy; however, the risk appears to increase markedly at doses >64 Gy.« less

Auditory Brainstem and Middle Latency Responses Measured Pre- and Posttreatment for Hyperacusic Hearing-Impaired Persons Successfully Treated to Improve Sound Tolerance and to Expand the Dynamic Range for Loudness: Case Evidence.

PubMed

Formby, Craig; Korczak, Peggy; Sherlock, LaGuinn P; Hawley, Monica L; Gold, Susan

2017-02-01

In this report of three cases, we consider electrophysiologic measures from three hyperacusic hearing-impaired individuals who, prior to treatment to expand their dynamic ranges for loudness, were problematic hearing aid candidates because of their diminished sound tolerance and reduced dynamic ranges. Two of these individuals were treated with structured counseling combined with low-level broadband sound therapy from bilateral sound generators and the third case received structured counseling in combination with a short-acting placebo sound therapy. Each individual was highly responsive to his or her assigned treatment as revealed by expansion of the dynamic range by at least 20 dB at one or more frequencies posttreatment. Of specific interest in this report are their latency and amplitude measures taken from tone burst-evoked auditory brainstem response (ABR) and cortically derived middle latency response (MLR) recordings, measured as a function of increasing loudness at 500 and 2,000 Hz pre- and posttreatment. The resulting ABR and MLR latency and amplitude measures for each case are considered here in terms of pre- and posttreatment predictions. The respective pre- and posttreatment predictions anticipated larger pretreatment response amplitudes and shorter pretreatment response latencies relative to typical normal control values and smaller normative-like posttreatment response amplitudes and longer posttreatment response latencies relative to the corresponding pretreatment values for each individual. From these results and predictions, we conjecture about the neural origins of the hyperacusis conditions (i.e., brainstem versus cortical) and the neuronal sites responsive to treatment. The only consistent finding in support of the pre- and posttreatment predictions and, thus, the strongest index of hyperacusis and positive treatment-related effects was measured for MLR latency responses for wave Pa at 2,000 Hz. Other response indices, including ABR wave V latency and wave V-V' amplitude and MLR wave Na-Pa amplitude for 500 and 2,000 Hz, appear either ambiguous across and/or within these individuals. Notwithstanding significant challenges for interpreting these findings, including associated confounding effects of their sensorineural hearing losses and differences in the presentation levels of the toneburst stimuli used to collect these measures for each individual, our limited analyses of three cases suggest measures of MLR wave Pa latency at 2,000 Hz (reflecting cortical contributions) may be a promising objective indicator of hyperacusis and dynamic range expansion treatment effects.

Linear summation in the barn owl's brainstem underlies responses to interaural time differences.

PubMed

Kuokkanen, Paula T; Ashida, Go; Carr, Catherine E; Wagner, Hermann; Kempter, Richard

2013-07-01

The neurophonic potential is a synchronized frequency-following extracellular field potential that can be recorded in the nucleus laminaris (NL) in the brainstem of the barn owl. Putative generators of the neurophonic are the afferent axons from the nucleus magnocellularis, synapses onto NL neurons, and spikes of NL neurons. The outputs of NL, i.e., action potentials of NL neurons, are only weakly represented in the neurophonic. Instead, the inputs to NL, i.e., afferent axons and their synaptic potentials, are the predominant origin of the neurophonic (Kuokkanen PT, Wagner H, Ashida G, Carr CE, Kempter R. J Neurophysiol 104: 2274-2290, 2010). Thus in NL the monaural inputs from the two brain sides converge and create a binaural neurophonic. If these monaural inputs contribute independently to the extracellular field, the response to binaural stimulation can be predicted from the sum of the responses to ipsi- and contralateral stimulation. We found that a linear summation model explains the dependence of the responses on interaural time difference as measured experimentally with binaural stimulation. The fit between model predictions and data was excellent, even without taking into account the nonlinear responses of NL coincidence detector neurons, although their firing rate and synchrony strongly depend on the interaural time difference. These results are consistent with the view that the afferent axons and their synaptic potentials in NL are the primary origin of the neurophonic.

Neural Timing is Linked to Speech Perception in Noise

PubMed Central

Samira, Anderson; Erika, Skoe; Bharath, Chandrasekaran; Nina, Kraus

2010-01-01

Understanding speech in background noise is challenging for every listener, including those with normal peripheral hearing. This difficulty is due in part to the disruptive effects of noise on neural synchrony, resulting in degraded representation of speech at cortical and subcortical levels as reflected by electrophysiological responses. These problems are especially pronounced in clinical populations such as children with learning impairments. Given the established effects of noise on evoked responses, we hypothesized that listening-in-noise problems are associated with degraded processing of timing information at the brainstem level. Participants (66 children, ages 8 to 14 years, 22 females) were divided into groups based on their performance on clinical measures of speech-in-noise perception (SIN) and reading. We compared brainstem responses to speech syllables between top and bottom SIN and reading groups in the presence and absence of competing multi-talker babble. In the quiet condition, neural response timing was equivalent between groups. In noise, however, the bottom groups exhibited greater neural delays relative to the top groups. Group-specific timing delays occurred exclusively in response to the noise-vulnerable formant transition, not to the more perceptually-robust, steady-state portion of the stimulus. These results demonstrate that neural timing is disrupted by background noise and that greater disruptions are associated with the inability to perceive speech in challenging listening conditions. PMID:20371812

Overactive bladder and pontine reticular formation.

PubMed

Zorba, Orhan Ünal; Kırbaş, Serkan; Uzun, Hakkı; Cetinkaya, Mehmet; Önem, Kadir; Rifaioğlu, Mehmet Murat

2013-01-01

The etiology of overactive bladder (OAB) remains unclear. Observed neurogenic factors in the literature are limited to suprapontine or spinal pathologies. The blink reflex is a useful tool in the evaluation of brainstem functions. Blink reflex latency times were evaluated in order to reveal pathology in the brainstem. A total of 60 women, 30 patients with idiopathic OAB and 30 healthy controls, were enrolled in the study. Blink reflex latency times were analyzed by electrical stimulation of the supraorbital nerve. Two responses in the orbicularis oculi muscle, early ipsilateral response (R1) and late bilateral response (R2) latency times, were recorded. Mean ages of the patients and controls were 51.9 ± 5.3 and 49.2 ± 6.2 years, respectively. R2 latency times were significantly higher in patients than in controls. However, R1 latency times were similar between the two groups. The results of the study suggest a significant relation between late blink latency times and OAB. An oligosynaptic path via the trigeminal nuclei is responsible for R1; however, R2 response is relayed through the reticular formation. Stimulation of pontine reticular formation inhibits micturition contraction. In some patients, idiopathic OAB may result from reticular formation-originated pathology. Additional studies on other reticular formation-mediated reflexes are needed to reveal possible dysfunction of reticular formation. Copyright © 2013 S. Karger AG, Basel.

Endoscopic Endonasal Transclival Approach to the Ventral Brainstem: Anatomic Study of the Safe Entry Zones Combining Fiber Dissection Technique with 7 Tesla Magnetic Resonance Guided Neuronavigation.

PubMed

Weiss, Alessandro; Perrini, Paolo; De Notaris, Matteo; Soria, Guadalupe; Carlos, Alarcon; Castagna, Maura; Lutzemberger, Lodovico; Santonocito, Orazio Santo; Catapano, Giuseppe; Kassam, Amin; Galino, Alberto Prats

2018-05-10

Treatment of intrinsic lesions of the ventral brainstem is a surgical challenge that requires complex skull base antero- and posterolateral approaches. More recently, endoscopic endonasal transclival approach (EETA) has been reported in the treatment of selected ventral brainstem lesions. In this study we explored the endoscopic ventral brainstem anatomy with the aim to describe the degree of exposure of the ventral safe entry zones. In addition, we used a newly developed method combining traditional white matter dissection with high-resolution 7T magnetic resonance imaging (MRI) of the same specimen coregistered using a neuronavigation system. Eight fresh-frozen latex-injected cadaver heads underwent EETA. Additional 8 formalin-fixed brainstems were dissected using Klingler technique guided by ultra-high resolution MRI. The EETA allows a wide exposure of different safe entry zones located on the ventral brainstem: the exposure of perioculomotor zone requires pituitary transposition and can be hindered by superior cerebellar artery. The peritrigeminal zone was barely visible and its exposure required an extradural anterior petrosectomy. The anterolateral sulcus of the medulla was visible in most of specimens, although its close relationship with the corticospinal tract makes it suboptimal as an entry point for intrinsic lesions. In all cases, the use of 7T-MRI allowed the identification of tiny fiber bundles, improving the quality of the dissection. Exposure of the ventral brainstem with EETA requires mastering surgical maneuvers, including pituitary transposition and extradural petrosectomy. The correlation of fiber dissection with 7T-MRI neuronavigation significantly improves the understanding of the brainstem anatomy.

Development of the Brainstem and Cerebellum in Autistic Patients.

ERIC Educational Resources Information Center

Hashimoto, Toshiaki; And Others

1995-01-01

This study of 102 individuals with autism found that the brainstem and cerebellum increased in size with age but were significantly smaller in autistic patients than in controls. Analysis of the speed of development suggests that brainstem and vermian abnormalities in autism were due to an early insult and hypoplasia rather than to progressive…

Brain-stem laceration and blunt rupture of thoracic aorta: is the intrapleural bleeding postmortem in origin?: an autopsy study.

PubMed

Zivković, Vladimir; Nikolić, Slobodan; Babić, Dragan; Juković, Fehim

2011-12-01

Some of the fatally injured car occupants could have had both blunt rupture of thoracic aorta with great amount of intrapleural blood, and pontomedullar laceration of brain-stem as well, with both injuries being fatal. The aim of this study was to answer if all intrapleural bleeding in these cases was antemortem, or the bleeding could also be partially postmortem. We observed the group of 66 cases of blunt aortic rupture: 21 case with brain-stem laceration, and 45 cases without it. The average amount of intrapleural bleeding in cases without brain-stem laceration (1993 ± 831 mL) was significantly higher than in those with this injury (1100 ± 708 mL) (t = 4.252, df = 64, P = 0.000). According to our results, in cases of the thoracic aorta rupture with concomitant brain-stem laceration, the amount of intrapleural bleeding less than 1500 mL, should be considered mostly as postmortem in origin, and in such cases, only the brain-stem injury should be considered as cause of death.

Loss of pons-to-hypothalamic white matter tracks in brainstem obesity.

PubMed

Purnell, J Q; Lahna, D L; Samuels, M H; Rooney, W D; Hoffman, W F

2014-12-01

Hyperphagia and obesity have been reported following damage to the hypothalamus in humans. Other brain sites are also postulated to be involved in the control of food intake and body weight regulation, such as the amygdala and brainstem. The brainstem, however, is thought to primarily integrate short-term meal-related signals but not affect long-term alterations in body weight, which is controlled by higher centers. The objective of this study was to identify structural pathways damaged in a patient with a brainstem cavernoma who experienced sudden onset of hyperphagia and >50 kg weight gain in <1 year following surgical drainage via a midline suboccipital craniotomy. Diffusion tensor imaging revealed loss of nerve fiber connections between her brainstem, hypothalamus and higher brain centers with preservation of motor tracks. Imaging and endocrine testing confirmed normal hypothalamic structure and function. Gastric bypass surgery restored normal appetite and body weight to baseline. This is the first report of 'brainstem obesity' and adds to the brain regions that can determine the long-term body weight set point in humans.

Air pollution is associated with brainstem auditory nuclei pathology and delayed brainstem auditory evoked potentials

PubMed Central

Calderón-Garcidueñas, Lilian; D’Angiulli, Amedeo; Kulesza, Randy J; Torres-Jardón, Ricardo; Osnaya, Norma; Romero, Lina; Keefe, Sheyla; Herritt, Lou; Brooks, Diane M; Avila-Ramirez, Jose; Delgado-Chávez, Ricardo; Medina-Cortina, Humberto; González-González, Luis Oscar

2011-01-01

We assessed brainstem inflammation in children exposed to air pollutants by comparing brainstem auditory evoked potentials (BAEPs) and blood inflammatory markers in children age 96.3± 8.5 months from highly polluted (n=34) versus a low polluted city (n=17). The brainstems of nine children with accidental deaths were also examined. Children from the highly polluted environment had significant delays in wave III (t(50)=17.038; p<0.0001) and wave V (t(50)=19.730; p<0.0001) but no delay in wave I (p=0.548). They also had significantly longer latencies than controls for interwave intervals I–III, III–V, and I–V (all t(50)> 7.501; p<0.0001), consisting with delayed central conduction time of brainstem neural transmission. Highly exposed children showed significant evidence of inflammatory markers and their auditory and vestibular nuclei accumulated α synuclein and/or β amyloid 1–42. Medial superior olive neurons, critically involved in BAEPs, displayed significant pathology. Children’s exposure to urban air pollution increases their risk for auditory and vestibular impairment. PMID:21458557

Huntington’s disease (HD): Degeneration of select nuclei and widespread occurrence of neuronal nuclear and axonal inclusions in the brainstem

PubMed Central

Rüb, U; Hentschel, M; Stratmann, K; Brunt, ER; Heinsen, H; Seidel, K; Bouzrou, M; Auburger, G; Paulson, HL; Vonsattel, JP; Lange, HW; Korf, HW; den Dunnen, WF

2014-01-01

Huntington’s disease (HD) is a progressive polyglutamine disease that leads to a severe striatal and layer-specific neuronal loss in the cerebral neo-and allocortex. Since some of the clinical symptoms (e.g. oculomotor dysfunctions) suggested a degeneration of select brainstem nuclei we performed a systematic investigation of the brainstem of eight clinically diagnosed and genetically confirmed HD patients. This postmortem investigation revealed a consistent neuronal loss in the substantia nigra, pontine nuclei, reticulotegmental nucleus of the pons, superior and inferior olives, in the area of the excitatory burst neurons for horizontal saccades, raphe interpositus nucleus, and vestibular nuclei. Immunoreactive intranuclear neuronal inclusions were present in all degenerated and apparently spared brainstem nuclei, and immunoreactive axonal inclusions were observed in all brainstem fiber tracts of the HD patients. Degeneration of brainstem nuclei can account for a number of less well understood clinical HD symptoms (i.e. cerebellar, oculomotor and vestibular symptoms), while the formation of axonal aggregates may represent a crucial event in the cascades of pathological events leading to neurodegeneration in HD. PMID:24779419

Magnetization transfer and adiabatic R 1ρ MRI in the brainstem of Parkinson's disease.

PubMed

Tuite, Paul J; Mangia, Silvia; Tyan, Andrew E; Lee, Michael K; Garwood, Michael; Michaeli, Shalom

2012-06-01

In addition to classic midbrain pathology, Parkinson's disease (PD) is accompanied by changes in pontine and medullary brainstem structures. These additional abnormalities may underlie non-motor features as well as play a role in motor disability. Using novel magnetic resonance imaging (MRI) methods based on rotating frame adiabatic R(1ρ) (i.e., measurements of longitudinal relaxation during adiabatic full passage pulses) and modified magnetization transfer (MT) MRI mapping, we sought to identify brainstem alterations in nine individuals with mild-moderate PD (off medication) and ten age-matched controls at 4 T. We discovered significant differences in MRI parameters between midbrain and medullary brainstem structures in control subjects as compared to PD patients. These findings support the presence of underlying functional/structural brainstem changes in mild-moderate PD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Incidence and dosimetric parameters for brainstem necrosis following intensity modulated radiation therapy in nasopharyngeal carcinoma.

PubMed

Li, Yang-Chan; Chen, Fo-Ping; Zhou, Guan-Qun; Zhu, Jin-Han; Hu, Jiang; Kang, De-Hua; Wu, Chen-Fei; Lin, Li; Wang, Xiao-Ju; Ma, Jun; Sun, Ying

2017-10-01

To clarify the incidence of brainstem toxicity and perform a dose-volume analysis for the brainstem after long-term follow-up of a large cohort of nasopharyngeal carcinoma (NPC) patients who underwent intensity-modulated radiation therapy (IMRT). All patients with NPC treated with IMRT at Sun Yat-sen University Cancer Center between April 2009 and March 2012 were retrospectively reviewed. A total of 1544 patients with follow-up >12months and detailed treatment plan data were included. Radiotherapy was administered using the simultaneous integrated boost technique in 2.0-2.48Gy per fractions/28-33 fractions. Brainstem necrosis was defined as lesions with high signal intensity on T2-weighted images and low signal intensity on T1-weighted images, with or without enhancement after administration of contrast in follow-up MRI. After median follow-up of 79.7months (range, 12.2-85.6months), 2/1544 (0.13%) patients developed brainstem necrosis after intervals of 12.3 and 18.5months. Actuarial incidence of brainstem necrosis was 0.07%, 0.13%, 0.13% and 0.13% after 1, 2, 3 and 5years, respectively. Overall, 384 (24.9%), 153 (9.9%), 67 (4.3%), 39 (2.5%), 78 (5.1%), and 114 (7.4%) patients had excessive doses of D max ≥64Gy, D1cc>59Gy, D2cc>59Gy, aV50>5.9cc, aV55>2.7cc and aV60>0.9cc respectively, of whom only two developed brainstem necrosis. Brainstem necrosis is rare in NPC. The definitive criteria based on conventional radiotherapy cannot accurately predict the occurrence of brainstem necrosis after IMRT, thus more flexible definitive criteria with strict restrictions need to be defined. Copyright © 2017 Elsevier Ltd. All rights reserved.

The maturation state of the auditory nerve and brainstem in rats exposed to lead acetate and supplemented with ferrous sulfate.

PubMed

Zucki, Fernanda; Morata, Thais C; Duarte, Josilene L; Ferreira, Maria Cecília F; Salgado, Manoel H; Alvarenga, Kátia F

The literature has reported the association between lead and auditory effects, based on clinical and experimental studies. However, there is no consensus regarding the effects of lead in the auditory system, or its correlation with the concentration of the metal in the blood. To investigate the maturation state of the auditory system, specifically the auditory nerve and brainstem, in rats exposed to lead acetate and supplemented with ferrous sulfate. 30 weanling male rats (Rattus norvegicus, Wistar) were distributed into six groups of five animals each and exposed to one of two concentrations of lead acetate (100 or 400mg/L) and supplemented with ferrous sulfate (20mg/kg). The maturation state of the auditory nerve and brainstem was analyzed using Brainstem Auditory Evoked Potential before and after lead exposure. The concentration of lead in blood and brainstem was analyzed using Inductively Coupled Plasma-Mass Spectrometry. We verified that the concentration of Pb in blood and in brainstem presented a high correlation (r=0.951; p<0.0001). Both concentrations of lead acetate affected the maturation state of the auditory system, being the maturation slower in the regions corresponding to portion of the auditory nerve (wave I) and cochlear nuclei (wave II). The ferrous sulfate supplementation reduced significantly the concentration of lead in blood and brainstem for the group exposed to the lowest concentration of lead (100mg/L), but not for the group exposed to the higher concentration (400mg/L). This study indicate that the lead acetate can have deleterious effects on the maturation of the auditory nerve and brainstem (cochlear nucleus region), as detected by the Brainstem Auditory Evoked Potentials, and the ferrous sulphate can partially amend this effect. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. All rights reserved.

Organization, development, and effects of infraorbital nerve transection on galanin binding sites in the trigeminal brainstem complex.

PubMed

Bodie, D; Bennett-Clarke, C A; Davis, K; Postelwaite, J P; Chiaia, N L; Rhoades, R W

1997-01-01

Previous experiments from this laboratory have indicated that transection of the infraorbital nerve (ION, the trigeminal [V] branch that supplies the mystacial vibrissae follicles) at birth and in adulthood has markedly different effects on galanin immunoreactivity in the V brainstem complex. Adult nerve transection increases galanin immunoreactivity in the superficial layers of V subnucleus caudalis (SpC) only, while neonatal nerve transection results in increased galanin expression in vibrissae-related primary afferents throughout the V brainstem complex. The present study describes the distribution of binding sites for this peptide in the mature and developing V ganglion and brainstem complex and determines the effects of neonatal and adult ION damage and the associated changes in galanin levels upon their distribution and density. Galanin binding sites are densely distributed in all V brainstem subnuclei and are particularly dense in V subnucleus interpolaris and the superficial layers of SpC. They are present at birth (P-0) and their distribution is similar to that in adult animals. Transection of the ION in adulthood and examination of brainstem 7 days later indicated marked reductions in the density of galanin binding sites in the V brainstem complex. With the exception of the superficial laminae of SpC, the same reduction in density remained apparent in rats that survived > 45 days after nerve cuts. Transection of the ION on P-0 resulted in no change in the density of galanin binding sites in the brainstem after either 7 or > 60 days survival. These results indicate that densely distributed galanin binding sites are present in the V brainstem complex of both neonatal and adult rats, that they are located in regions not innervated by galanin-positive axons, and that their density is not significantly influenced by large lesion-induced changes in the primary afferent content of their natural ligand.

Chronic exposure to hypergravity affects thyrotropin-releasing hormone levels in rat brainstem and cerebellum

NASA Technical Reports Server (NTRS)

Daunton, N. G.; Tang, F.; Corcoran, M. L.; Fox, R. A.; Man, S. Y.

1998-01-01

In studies to determine the neurochemical mechanisms underlying adaptation to altered gravity we have investigated changes in neuropeptide levels in brainstem, cerebellum, hypothalamus, striatum, hippocampus, and cerebral cortex by radioimmunoassay. Fourteen days of hypergravity (hyperG) exposure resulted in significant increases in thyrotropin-releasing hormone (TRH) content of brainstem and cerebellum, but no changes in levels of other neuropeptides (beta-endorphin, cholecystokinin, met-enkephalin, somatostatin, and substance P) examined in these areas were found, nor were TRH levels significantly changed in any other brain regions investigated. The increase in TRH in brainstem and cerebellum was not seen in animals exposed only to the rotational component of centrifugation, suggesting that this increase was elicited by the alteration in the gravitational environment. The only other neuropeptide affected by chronic hyperG exposure was met-enkephalin, which was significantly decreased in the cerebral cortex. However, this alteration in met-enkephalin was found in both hyperG and rotation control animals and thus may be due to the rotational rather than the hyperG component of centrifugation. Thus it does not appear as if there is a generalized neuropeptide response to chronic hyperG following 2 weeks of exposure. Rather, there is an increase only of TRH and that occurs only in areas of the brain known to be heavily involved with vestibular inputs and motor control (both voluntary and autonomic). These results suggest that TRH may play a role in adaptation to altered gravity as it does in adaptation to altered vestibular input following labyrinthectomy, and in cerebellar and vestibular control of locomotion, as seen in studies of ataxia.

Effects of swim stress and fluoxetine on 5-HT1A receptor gene expression and monoamine metabolism in the rat brain regions.

PubMed

Shishkina, G T; Kalinina, T S; Dygalo, N N

2012-07-01

Changes in gene expression of the brain serotonin (5-HT) 1A receptors may be important for the development and ameliorating depression, however identification of specific stimuli that activate or reduce the receptor transcriptional activity is far from complete. In the present study, the forced swim test (FST) exposure, the first stress session of which is already sufficient to induce behavioral despair in rats, significantly increased 5-HT1A receptor mRNA levels in the brainstem, frontal cortex, and hippocampus at 24 h. In the brainstem and frontal cortex, the elevation in the receptor gene expression after the second forced swim session was not affected following chronic administration of fluoxetine, while in the cortex, both control and FST values were significantly reduced in fluoxetine-treated rats. In contrast to untreated rats, no increase in hippocampal 5-HT1A receptor mRNA was observed in response to FST in rats chronically treated with fluoxetine. Metabolism of 5-HT (5-HIAA/5-HT) in the brainstem was significantly decreased by fluoxetine and further reduced by swim stress, showing a certain degree of independence of these changes on 5-HT1A receptor gene expression that was increased in this brain region only after the FST, but not after fluoxetine. FST exposure also decreased the brainstem dopamine metabolism, which was unexpectedly positively correlated with 5-HT1A receptor mRNA levels in the frontal cortex. Together, these data suggest that the effects of the forced swim stress as well as fluoxetine involve brain region-dependent alterations in 5-HT1A receptor gene transcription, some of which may be interrelated with concomitant changes in catecholamine metabolism.

Nociceptive Afferents to the Premotor Neurons That Send Axons Simultaneously to the Facial and Hypoglossal Motoneurons by Means of Axon Collaterals

PubMed Central

Dong, Yulin; Li, Jinlian; Zhang, Fuxing; Li, Yunqing

2011-01-01

It is well known that the brainstem premotor neurons of the facial nucleus and hypoglossal nucleus coordinate orofacial nociceptive reflex (ONR) responses. However, whether the brainstem PNs receive the nociceptive projection directly from the caudal spinal trigeminal nucleus is still kept unclear. Our present study focuses on the distribution of premotor neurons in the ONR pathways of rats and the collateral projection of the premotor neurons which are involved in the brainstem local pathways of the orofacial nociceptive reflexes of rat. Retrograde tracer Fluoro-gold (FG) or FG/tetramethylrhodamine-dextran amine (TMR-DA) were injected into the VII or/and XII, and anterograde tracer biotinylated dextran amine (BDA) was injected into the caudal spinal trigeminal nucleus (Vc). The tracing studies indicated that FG-labeled neurons receiving BDA-labeled fibers from the Vc were mainly distributed bilaterally in the parvicellular reticular formation (PCRt), dorsal and ventral medullary reticular formation (MdD, MdV), supratrigeminal nucleus (Vsup) and parabrachial nucleus (PBN) with an ipsilateral dominance. Some FG/TMR-DA double-labeled premotor neurons, which were observed bilaterally in the PCRt, MdD, dorsal part of the MdV, peri-motor nucleus regions, contacted with BDA-labeled axonal terminals and expressed c-fos protein-like immunoreactivity which induced by subcutaneous injection of formalin into the lip. After retrograde tracer wheat germ agglutinated horseradish peroxidase (WGA-HRP) was injected into VII or XII and BDA into Vc, electron microscopic study revealed that some BDA-labeled axonal terminals made mainly asymmetric synapses on the dendritic and somatic profiles of WGA-HRP-labeled premotor neurons. These data indicate that some premotor neurons could integrate the orofacial nociceptive input from the Vc and transfer these signals simultaneously to different brainstem motonuclei by axonal collaterals. PMID:21980505

Cortico-fugal output from visual cortex promotes plasticity of innate motor behaviour

PubMed Central

Liu, Bao-hua; Huberman, Andrew D.; Scanziani, Massimo

2017-01-01

The mammalian visual cortex massively innervates the brainstem, a phylogenetically older structure, via cortico-fugal axonal projections1. Many cortico-fugal projections target brainstem nuclei that mediate innate motor behaviours, but the function of these projections remains poorly understood1–4. A prime example of such behaviours is the optokinetic reflex (OKR), an innate eye movement mediated by the brainstem accessory optic system3,5,6, that stabilizes images on the retina as the animal moves through the environment and is thus crucial for vision5. The OKR is plastic, allowing the amplitude of this reflex to be adaptively adjusted relative to other oculomotor reflexes and thereby ensuring image stability throughout life7–11. Although the plasticity of the OKR is thought to involve subcortical structures such as the cerebellum and vestibular nuclei10–13, cortical lesions have suggested that the visual cortex might also be involved9,14,15. Here we show that projections from the mouse visual cortex to the accessory optic system promote the adaptive plasticity of the OKR. OKR potentiation, a compensatory plastic increase in the amplitude of the OKR in response to vestibular impairment11,16–18, is diminished by silencing visual cortex. Furthermore, targeted ablation of a sparse population of cortico-fugal neurons that specifically project to the accessory optic system severely impairs OKR potentiation. Finally, OKR potentiation results from an enhanced drive exerted by the visual cortex onto the accessory optic system. Thus, cortico-fugal projections to the brainstem enable the visual cortex, an area that has been principally studied for its sensory processing function19, to plastically adapt the execution of innate motor behaviours. PMID:27732573

The role of eABR with intracochlear test electrode in decision making between cochlear and brainstem implants: preliminary results.

PubMed

Cinar, Betul Cicek; Yarali, Mehmet; Atay, Gamze; Bajin, Munir Demir; Sennaroglu, Gonca; Sennaroglu, Levent

2017-09-01

The objective of the study was to discuss the findings of intraoperative electrically evoked auditory brainstem response (eABR) test results with a recently designed intracochlear test electrode (ITE) in terms of their relation to decisions of cochlear or auditory brainstem implantation. This clinical study was conducted in Hacettepe University, Department of Otolaryngology, Head and Neck Surgery and Department of Audiology. Subjects were selected from inner ear malformation (IEM) database. Eleven subjects with profound sensorineural hearing loss were included in the current study with age range from 1 year 3 months to 4 years 3 months for children with prelingual hearing loss. There was only one 42-year-old post-lingual subject. eABR was recorded with an ITE and intraoperatively with an original cochlear implant (CI) electrode in 11 cases with different IEMs. Findings of eABR with ITE and their relation to the decision for CI or auditory brainstem implant (ABI) are discussed. Positive eABR test results were found to be dependent on close to normal cochlear structures and auditory nerve. The probability of positive result decreases with increasing degree of malformation severity. The prediction value of eABR via ITE on decision for hearing restoration was found to be questionable in this study. The results of eABR with ITE have predictive value on what we will get with the actual CI electrode. ITE appears to stimulate the cochlea like an actual CI. If the eABR is positive, the results are reliable. However, if eABR is negative, the results should be evaluated with preoperative audiological testing and MRI findings.

Neural Control of Fundamental Frequency Rise and Fall in Mandarin Tones

ERIC Educational Resources Information Center

Howell, Peter; Jiang, Jing; Peng, Danling; Lu, Chunming

2012-01-01

The neural mechanisms used in tone rises and falls in Mandarin were investigated. Nine participants were scanned while they named one-character pictures that required rising or falling tone responses in Mandarin: the left insula and right putamen showed stronger activation between rising and falling tones; the left brainstem showed weaker…

Evaluation of Hearing in Children with Autism by Using TEOAE and ABR

ERIC Educational Resources Information Center

Tas, Abdullah; Yagiz, Recep; Tas, Memduha; Esme, Meral; Uzun, Cem; Karasalihoglu, Ahmet Rifat

2007-01-01

Assessment of auditory abilities is important in the diagnosis and treatment of children with autism. The aim was to evaluate hearing objectively by using transient evoked otoacoustic emission (TEOAE) and auditory brainstem response (ABR). Tests were performed on 30 children with autism and 15 typically developing children, following otomicroscopy…

Neurobehavioral and Neurophysiological Assessment of Healthy and "At-Risk" Full-Term Infants.

ERIC Educational Resources Information Center

Eldredge, Lynnette; Salamy, Alan

1988-01-01

Study evaluates the functioning of the central nervous system (CNS) of 15 neonates born at-risk for neurological sequelae and 15 healthy controls. CNS information was generated through the use of two measures: (1) the Neurological and Adaptive Capacity Score (NACS) and the auditory brainstem response (ABR). (Author/RWB)

Microglia PACAP and glutamate: Friends or foes in seizure-induced autonomic dysfunction and SUDEP?

PubMed

Bhandare, Amol M; Kapoor, Komal; Farnham, Melissa M J; Pilowsky, Paul M

2016-06-01

Seizure-induced cardiorespiratory autonomic dysfunction is a major cause of sudden unexpected death in epilepsy (SUDEP), and the underlying mechanism is unclear. Seizures lead to increased synthesis, and release of glutamate, pituitary adenylate cyclase activating polypeptide (PACAP), and other neurotransmitters, and cause extensive activation of microglia at multiple regions in the brain including central autonomic cardiorespiratory brainstem nuclei. Glutamate contributes to neurodegeneration, and inflammation in epilepsy. PACAP has neuroprotective, and anti-inflammatory properties, whereas microglia are key players in inflammatory responses in CNS. Seizure-induced increase in PACAP is neuroprotective. PACAP produces neuroprotective effects acting on microglial PAC1 and VPAC1 receptors. Microglia also express glutamate transporters, and their expression can be increased by PACAP in response to harmful or stressful situations such as seizures. Here we discuss the mechanism of autonomic cardiorespiratory dysfunction in seizure, and the role of PACAP, glutamate and microglia in regulating cardiorespiratory brainstem neurons in their physiological state that could provide future therapeutic options for SUDEP. Copyright © 2016 Elsevier B.V. All rights reserved.

Brain magnetic resonance imaging findings and auditory brainstem response in a child with spastic paraplegia 2 due to a PLP1 splice site mutation.

PubMed

Kubota, Kazuo; Saito, Yoshiaki; Ohba, Chihiro; Saitsu, Hirotomo; Fukuyama, Tetsuhiro; Ishiyama, Akihiko; Saito, Takashi; Komaki, Hirofumi; Nakagawa, Eiji; Sugai, Kenji; Sasaki, Masayuki; Matsumoto, Naomichi

2015-01-01

A boy with spastic paraplegia type 2 (SPG2) due to a novel splice site mutation of PLP1 presented with progressive spasticity of lower limbs, which was first observed during late infancy, when he gained the ability to walk with support. His speech was slow and he had dysarthria. The patient showed mildly delayed intellectual development. Subtotal dysmyelination in the central nervous system was revealed, which was especially prominent in structures known to be myelinated during earlier period, whereas structures that are myelinated later were better myelinated. These findings on the brain magnetic resonance imaging were unusual for subjects with PLP1 mutations. Peaks I and II of the auditory brainstem response (ABR) were normally provoked, but peaks III-V were not clearly demarcated, similarly to the findings in Pelizaeus-Merzbacher disease. These findings of brain MRI and ABR may be characteristic for a subtype of SPG2 patients. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Efficacy of Distortion Product Oto-Acoustic Emission (OAE)/Auditory Brainstem Evoked Response (ABR) Protocols in Universal Neonatal Hearing Screening and Detecting Hearing Loss in Children <2 Years of Age.

PubMed

Mishra, Girish; Sharma, Yojana; Mehta, Kanishk; Patel, Gunjan

2013-04-01

Deafness is commonest curable childhood handicap. Most remedies and programmes don't address this issue at childhood level leading to detrimental impact on development of newborns. Aims and objectives are (A) screen all newborns for deafness and detect prevalence of deafness in children less than 2 years of age. and (B) assess efficacy of multi-staged OAE/ABR protocol for hearing screening. Non-randomized, prospective study from August 2008 to August 2011. All infants underwent a series of oto-acoustic emission (OAE) and final confirmatory auditory brainstem evoked response (ABR) audiometry. Finally, out of 1,101 children, 1,069 children passed the test while 12 children had impaired hearing after final testing, confirmed by ABR. Positive predictive value of OAE after multiple test increased to 100 %. OAE-ABR test series is effective in screening neonates and multiple tests reduce economic burden. High risk screening will miss nearly 50 % deaf children, thus universal screening is indispensable in picking early deafness.

The thermogenic effect of leptin is dependent on a distinct population of prolactin-releasing peptide neurons in the dorsomedial hypothalamus.

PubMed

Dodd, Garron T; Worth, Amy A; Nunn, Nicolas; Korpal, Aaron K; Bechtold, David A; Allison, Margaret B; Myers, Martin G; Statnick, Michael A; Luckman, Simon M

2014-10-07

Leptin is a critical regulator of metabolism, which acts on brain receptors (Lepr) to reduce energy intake and increase energy expenditure. Some of the cellular pathways mediating leptin's anorectic actions are identified, but those mediating the thermogenic effects have proven more difficult to decipher. We define a population of neurons in the dorsomedial hypothalamic nucleus (DMH) containing the RFamide PrRP, which is activated by leptin. Disruption of Lepr selectively in these cells blocks thermogenic responses to leptin and causes obesity. A separate population of leptin-insensitive PrRP neurons in the brainstem is required, instead, for the satiating actions of the gut-derived hormone cholecystokinin (CCK). Global deletion of PrRP (in a loxSTOPlox-PrRP mouse) results in obesity and attenuated responses to leptin and CCK. Cre-recombinase-mediated reactivation of PrRP in brainstem rescues the anorectic actions of CCK, but reactivation in the hypothalamus is required to re-establish the thermogenic effect of leptin. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Bilirubin-Induced Neurological Dysfunction: A Clinico-Radiological-Neurophysiological Correlation in 30 Consecutive Children.

PubMed

van Toorn, Ronald; Brink, Philip; Smith, Johan; Ackermann, Christelle; Solomons, Regan

2016-12-01

The clinical expression of bilirubin-induced neurological dysfunction varies according to severity and location of the disease. Definitions have been proposed to describe different bilirubin-induced neurological dysfunction subtypes. Our objective was to describe the severity and clinico-radiological-neurophysiological correlation in 30 consecutive children with bilirubin-induced neurological dysfunction seen over a period of 5 years. Thirty children exposed to acute neonatal bilirubin encephalopathy were included in the study. The mean peak total serum bilirubin level was 625 μmol/L (range 480-900 μmol/L). Acoustic brainstem responses were abnormal in 73% (n = 22). Pallidal hyperintensity was observed on magnetic resonance imaging in 20 children. Peak total serum bilirubin levels correlated with motor severity (P = .03). Children with severe motor impairment were likely to manifest severe auditory neuropathy (P < .01). We found that in a resource-constrained setting, classical kernicterus was the most common bilirubin-induced neurological dysfunction subtype, and the majority of children had abnormal acoustic brainstem responses and magnetic resonance imaging. © The Author(s) 2016.

Auditory processing deficits in individuals with primary open-angle glaucoma.

PubMed

Rance, Gary; O'Hare, Fleur; O'Leary, Stephen; Starr, Arnold; Ly, Anna; Cheng, Belinda; Tomlin, Dani; Graydon, Kelley; Chisari, Donella; Trounce, Ian; Crowston, Jonathan

2012-01-01

The high energy demand of the auditory and visual pathways render these sensory systems prone to diseases that impair mitochondrial function. Primary open-angle glaucoma, a neurodegenerative disease of the optic nerve, has recently been associated with a spectrum of mitochondrial abnormalities. This study sought to investigate auditory processing in individuals with open-angle glaucoma. DESIGN/STUDY SAMPLE: Twenty-seven subjects with open-angle glaucoma underwent electrophysiologic (auditory brainstem response), auditory temporal processing (amplitude modulation detection), and speech perception (monosyllabic words in quiet and background noise) assessment in each ear. A cohort of age, gender and hearing level matched control subjects was also tested. While the majority of glaucoma subjects in this study demonstrated normal auditory function, there were a significant number (6/27 subjects, 22%) who showed abnormal auditory brainstem responses and impaired auditory perception in one or both ears. The finding that a significant proportion of subjects with open-angle glaucoma presented with auditory dysfunction provides evidence of systemic neuronal susceptibility. Affected individuals may suffer significant communication difficulties in everyday listening situations.

Mitochondria-Targeted Antioxidant Mitoquinone Reduces Cisplatin-Induced Ototoxicity in Guinea Pigs.

PubMed

Tate, Alan D; Antonelli, Patrick J; Hannabass, Kyle R; Dirain, Carolyn O

2017-03-01

Objective To determine if mitoquinone (MitoQ) attenuates cisplatin-induced hearing loss in guinea pigs. Study Design Prospective and controlled animal study. Setting Academic, tertiary medical center. Subjects and Methods Guinea pigs were injected subcutaneously with either 5 mg/kg MitoQ (n = 9) or normal saline (control, n = 9) for 7 days and 1 hour before receiving a single dose of 10 mg/kg cisplatin. Auditory brainstem response thresholds were measured before MitoQ or saline administration and 3 to 4 days after cisplatin administration. Results Auditory brainstem response threshold shifts after cisplatin treatment were smaller by 28 to 47 dB in guinea pigs injected with MitoQ compared with those in the control group at all tested frequencies (4, 8, 16, and 24 kHz, P = .0002 to .04). Scanning electron microscopy of cochlear hair cells showed less outer hair cell loss and damage in the MitoQ group. Conclusion MitoQ reduced cisplatin-induced hearing loss in guinea pigs. MitoQ appears worthy of further investigation as a means of preventing cisplatin ototoxicity in humans.

Dose-volume histogram analysis of brainstem necrosis in head and neck tumors treated using carbon-ion radiotherapy.

PubMed

Shirai, Katsuyuki; Fukata, Kyohei; Adachi, Akiko; Saitoh, Jun-Ichi; Musha, Atsushi; Abe, Takanori; Kanai, Tatsuaki; Kobayashi, Daijiro; Shigeta, Yuka; Yokoo, Satoshi; Chikamatsu, Kazuaki; Ohno, Tatsuya; Nakano, Takashi

2017-10-01

We aimed to evaluate the relationship between brainstem necrosis and dose-volume histograms in patients with head and neck tumors after carbon-ion radiotherapy. We evaluated 85 patients with head and neck tumors who underwent carbon-ion radiotherapy and were followed-up for ≥12months. Brainstem necrosis was evaluated using the Common Terminology Criteria for Adverse Events (version 4.0). The median follow-up was 24months, and four patients developed grade 1 brainstem necrosis, with 2-year and 3-year cumulative rates of 2.8% and 6.5%, respectively. Receiver operating characteristic curve analysis revealed the following significant cut-off values: a maximum brainstem dose of 48Gy (relative biological effectiveness [RBE]), D1cm 3 of 27Gy (RBE), V40Gy (RBE) of 0.1cm 3 , V30Gy (RBE) of 0.7cm 3 , and V20Gy (RBE) of 1.4cm 3 . Multivariate analysis revealed that V30Gy (RBE) was most significantly associated with brainstem necrosis. The 2-year cumulative rates were 33% and 0% for V30Gy (RBE) of ≥0.7cm 3 and <0.7cm 3 , respectively (p<0.001). The present study indicated that the dose constraints might help minimize brainstem necrosis after carbon-ion radiotherapy. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Why middle-aged listeners have trouble hearing in everyday settings.

PubMed

Ruggles, Dorea; Bharadwaj, Hari; Shinn-Cunningham, Barbara G

2012-08-07

Anecdotally, middle-aged listeners report difficulty conversing in social settings, even when they have normal audiometric thresholds [1-3]. Moreover, young adult listeners with "normal" hearing vary in their ability to selectively attend to speech amid similar streams of speech. Ignoring age, these individual differences correlate with physiological differences in temporal coding precision present in the auditory brainstem, suggesting that the fidelity of encoding of suprathreshold sound helps explain individual differences [4]. Here, we revisit the conundrum of whether early aging influences an individual's ability to communicate in everyday settings. Although absolute selective attention ability is not predicted by age, reverberant energy interferes more with selective attention as age increases. Breaking the brainstem response down into components corresponding to coding of stimulus fine structure and envelope, we find that age alters which brainstem component predicts performance. Specifically, middle-aged listeners appear to rely heavily on temporal fine structure, which is more disrupted by reverberant energy than temporal envelope structure is. In contrast, the fidelity of envelope cues predicts performance in younger adults. These results hint that temporal envelope cues influence spatial hearing in reverberant settings more than is commonly appreciated and help explain why middle-aged listeners have particular difficulty communicating in daily life. Copyright © 2012 Elsevier Ltd. All rights reserved.

Gamma Knife Radiosurgery Treatment for Metastatic Melanoma of the Trigeminal Nerve and Brainstem: A Case Report and a Review of the Literature

PubMed Central

Peterson, Halloran E.; Larson, Erik W.; Fairbanks, Robert K.; Lamoreaux, Wayne T.; Mackay, Alexander R.; Call, Jason A.; Demakas, John J.; Cooke, Barton S.; Lee, Christopher M.

2013-01-01

Objective and Importance. Brainstem metastases (BSMs) are uncommon but serious complications of some cancers. They cause significant neurological deficit, and options for treatment are limited. Stereotactic radiosurgery (SRS) has been shown to be a safe and effective treatment for BSMs that prolongs survival and can preserve or in some cases improve neurological function. This case illustrates the use of repeated SRS, specifically Gamma Knife radiosurgery (GKRS) for management of a unique brainstem metastasis. Clinical Presentation. This patient presented 5 years after the removal of a lentigo maligna melanoma from her left cheek with left sided facial numbness and paresthesias with no reported facial weakness. Initial MRI revealed a mass on the left trigeminal nerve that appeared to be a trigeminal schwannoma. Intervention. After only limited response to the first GKRS treatment, a biopsy of the tumor revealed it to be metastatic melanoma, not schwannoma. Over the next two years, the patient would receive 3 more GKRS treatments. These procedures were effective in controlling growth in the treated areas, and the patient has maintained a good quality of life. Conclusion. GKRS has proven in this case to be effective in limiting the growth of this metastatic melanoma without acute adverse effects. PMID:24194991

Operative management of brainstem cavernous malformations.

PubMed

Asaad, Wael F; Walcott, Brian P; Nahed, Brian V; Ogilvy, Christopher S

2010-09-01

Brainstem cavernous malformations (CMs) are complex lesions associated with hemorrhage and neurological deficit. In this review, the authors describe the anatomical nuances relating to the operative techniques for these challenging lesions. The resection of brainstem CMs in properly selected patients has been demonstrated to reduce the risk of rehemorrhage and can be achieved relatively safely in experienced hands.

The Role of the Auditory Brainstem in Processing Linguistically-Relevant Pitch Patterns

ERIC Educational Resources Information Center

Krishnan, Ananthanarayan; Gandour, Jackson T.

2009-01-01

Historically, the brainstem has been neglected as a part of the brain involved in language processing. We review recent evidence of language-dependent effects in pitch processing based on comparisons of native vs. nonnative speakers of a tonal language from electrophysiological recordings in the auditory brainstem. We argue that there is enhancing…

Quantitative Magnetic Resonance Diffusion-Weighted Imaging Evaluation of the Supratentorial Brain Regions in Patients Diagnosed with Brainstem Variant of Posterior Reversible Encephalopathy Syndrome: A Preliminary Study.

PubMed

Chen, Tai-Yuan; Wu, Te-Chang; Ko, Ching-Chung; Feng, I-Jung; Tsui, Yu-Kun; Lin, Chien-Jen; Chen, Jeon-Hor; Lin, Ching-Po

2017-07-01

Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic entity with several causes, characterized by rapid onset of symptoms and typical neuroimaging features, which usually resolve if promptly recognized and treated. Brainstem variant of PRES presents with vasogenic edema in brainstem regions on magnetic resonance (MR) images and there is sparing of the supratentorial regions. Because PRES is usually caused by a hypertensive crisis, which would likely have a systemic effect and global manifestations on the brain tissue, we thus proposed that some microscopic abnormalities of the supratentorial regions could be detected with diffusion-weighted imaging (DWI) using apparent diffusion coefficient (ADC) analysis in brainstem variant of PRES and hypothesized that "normal-looking" supratentorial regions will increase water diffusion. We retrospectively identified patients with PRES who underwent brain magnetic resonance imaging studies. We identified 11 brainstem variants of PRES patients, who formed the study cohort, and 11 typical PRES patients and 20 normal control subjects as the comparison cohorts for this study. Nineteen regions of interest were drawn and systematically placed. The mean ADC values were measured and compared among these 3 groups. ADC values of the typical PRES group were consistently elevated compared with those in normal control subjects. ADC values of the brainstem variant group were consistently elevated compared with those in normal control subjects. ADC values of the typical PRES group and brainstem variant group did not differ significantly, except for the pons area. Quantitative MR DWI may aid in the evaluation of supratentorial microscopic abnormalities in brainstem variant of PRES patients. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Imaging White Matter in Human Brainstem

PubMed Central

Ford, Anastasia A.; Colon-Perez, Luis; Triplett, William T.; Gullett, Joseph M.; Mareci, Thomas H.; FitzGerald, David B.

2013-01-01

The human brainstem is critical for the control of many life-sustaining functions, such as consciousness, respiration, sleep, and transfer of sensory and motor information between the brain and the spinal cord. Most of our knowledge about structure and organization of white and gray matter within the brainstem is derived from ex vivo dissection and histology studies. However, these methods cannot be applied to study structural architecture in live human participants. Tractography from diffusion-weighted magnetic resonance imaging (MRI) may provide valuable insights about white matter organization within the brainstem in vivo. However, this method presents technical challenges in vivo due to susceptibility artifacts, functionally dense anatomy, as well as pulsatile and respiratory motion. To investigate the limits of MR tractography, we present results from high angular resolution diffusion imaging of an intact excised human brainstem performed at 11.1 T using isotropic resolution of 0.333, 1, and 2 mm, with the latter reflecting resolution currently used clinically. At the highest resolution, the dense fiber architecture of the brainstem is evident, but the definition of structures degrades as resolution decreases. In particular, the inferred corticopontine/corticospinal tracts (CPT/CST), superior (SCP) and middle cerebellar peduncle (MCP), and medial lemniscus (ML) pathways are clearly discernable and follow known anatomical trajectories at the highest spatial resolution. At lower resolutions, the CST/CPT, SCP, and MCP pathways are artificially enlarged due to inclusion of collinear and crossing fibers not inherent to these three pathways. The inferred ML pathways appear smaller at lower resolutions, indicating insufficient spatial information to successfully resolve smaller fiber pathways. Our results suggest that white matter tractography maps derived from the excised brainstem can be used to guide the study of the brainstem architecture using diffusion MRI in vivo. PMID:23898254

Imaging white matter in human brainstem.

PubMed

Ford, Anastasia A; Colon-Perez, Luis; Triplett, William T; Gullett, Joseph M; Mareci, Thomas H; Fitzgerald, David B

2013-01-01

The human brainstem is critical for the control of many life-sustaining functions, such as consciousness, respiration, sleep, and transfer of sensory and motor information between the brain and the spinal cord. Most of our knowledge about structure and organization of white and gray matter within the brainstem is derived from ex vivo dissection and histology studies. However, these methods cannot be applied to study structural architecture in live human participants. Tractography from diffusion-weighted magnetic resonance imaging (MRI) may provide valuable insights about white matter organization within the brainstem in vivo. However, this method presents technical challenges in vivo due to susceptibility artifacts, functionally dense anatomy, as well as pulsatile and respiratory motion. To investigate the limits of MR tractography, we present results from high angular resolution diffusion imaging of an intact excised human brainstem performed at 11.1 T using isotropic resolution of 0.333, 1, and 2 mm, with the latter reflecting resolution currently used clinically. At the highest resolution, the dense fiber architecture of the brainstem is evident, but the definition of structures degrades as resolution decreases. In particular, the inferred corticopontine/corticospinal tracts (CPT/CST), superior (SCP) and middle cerebellar peduncle (MCP), and medial lemniscus (ML) pathways are clearly discernable and follow known anatomical trajectories at the highest spatial resolution. At lower resolutions, the CST/CPT, SCP, and MCP pathways are artificially enlarged due to inclusion of collinear and crossing fibers not inherent to these three pathways. The inferred ML pathways appear smaller at lower resolutions, indicating insufficient spatial information to successfully resolve smaller fiber pathways. Our results suggest that white matter tractography maps derived from the excised brainstem can be used to guide the study of the brainstem architecture using diffusion MRI in vivo.

Automated brainstem co-registration (ABC) for MRI.

PubMed

Napadow, Vitaly; Dhond, Rupali; Kennedy, David; Hui, Kathleen K S; Makris, Nikos

2006-09-01

Group data analysis in brainstem neuroimaging is predicated on accurate co-registration of anatomy. As the brainstem is comprised of many functionally heterogeneous nuclei densely situated adjacent to one another, relatively small errors in co-registration can manifest in increased variance or decreased sensitivity (or significance) in detecting activations. We have devised a 2-stage automated, reference mask guided registration technique (Automated Brainstem Co-registration, or ABC) for improved brainstem co-registration. Our approach utilized a brainstem mask dataset to weight an automated co-registration cost function. Our method was validated through measurement of RMS error at 12 manually defined landmarks. These landmarks were also used as guides for a secondary manual co-registration option, intended for outlier individuals that may not adequately co-register with our automated method. Our methodology was tested on 10 healthy human subjects and compared to traditional co-registration techniques (Talairach transform and automated affine transform to the MNI-152 template). We found that ABC had a significantly lower mean RMS error (1.22 +/- 0.39 mm) than Talairach transform (2.88 +/- 1.22 mm, mu +/- sigma) and the global affine (3.26 +/- 0.81 mm) method. Improved accuracy was also found for our manual-landmark-guided option (1.51 +/- 0.43 mm). Visualizing individual brainstem borders demonstrated more consistent and uniform overlap for ABC compared to traditional global co-registration techniques. Improved robustness (lower susceptibility to outliers) was demonstrated with ABC through lower inter-subject RMS error variance compared with traditional co-registration methods. The use of easily available and validated tools (AFNI and FSL) for this method should ease adoption by other investigators interested in brainstem data group analysis.

Brainstem projections of neurons located in various subdivisions of the dorsolateral hypothalamic area-an anterograde tract-tracing study.

PubMed

Papp, Rege S; Palkovits, Miklós

2014-01-01

The projections from the dorsolateral hypothalamic area (DLH) to the lower brainstem have been investigated by using biotinylated dextran amine (BDA), an anterograde tracer in rats. The DLH can be divided into 3 areas (dorsomedial hypothalamus, perifornical area, lateral hypothalamic area), and further subdivided into 8 subdivisions. After unilateral stereotaxic injections of BDA into individual DLH subdivisions, the correct sites of injections were controlled histologically, and the distribution patterns of BDA-positive fibers were mapped on serial sections between the hypothalamus and spinal cord in 22 rats. BDA-labeled fibers were observable over 100 different brainstem areas, nuclei, or subdivisions. Injections into the 8 DLH subdivisions established distinct topographical patterns. In general, the density of labeled fibers was low in the lower brainstem. High density of fibers was seen only 4 of the 116 areas: in the lateral and ventrolateral parts of the periaqueductal gray, the Barrington's, and the pedunculopontine tegmental nuclei. All of the biogenic amine cell groups in the lower brainstem (9 noradrenaline, 3 adrenaline, and 9 serotonin cell groups) received labeled fibers, some of them from all, or at least 7 DLH subdivisions, mainly from perifornical and ventral lateral hypothalamic neurons. Some of the tegmental nuclei and nuclei of the reticular formation were widely innervated, although the density of the BDA-labeled fibers was generally low. No definitive descending BDA-positive pathway, but long-run solitaire BDA-labeled fibers were seen in the lower brainstem. These descending fibers joined some of the large tracts or fasciculi in the brainstem. The distribution pattern of BDA-positive fibers of DLH origin throughout the lower brainstem was comparable to patterns of previously published orexin- or melanin-concentrating hormone-immunoreactive fibers with somewhat differences.

Brainstem projections of neurons located in various subdivisions of the dorsolateral hypothalamic area—an anterograde tract-tracing study

PubMed Central

Papp, Rege S.; Palkovits, Miklós

2014-01-01

The projections from the dorsolateral hypothalamic area (DLH) to the lower brainstem have been investigated by using biotinylated dextran amine (BDA), an anterograde tracer in rats. The DLH can be divided into 3 areas (dorsomedial hypothalamus, perifornical area, lateral hypothalamic area), and further subdivided into 8 subdivisions. After unilateral stereotaxic injections of BDA into individual DLH subdivisions, the correct sites of injections were controlled histologically, and the distribution patterns of BDA-positive fibers were mapped on serial sections between the hypothalamus and spinal cord in 22 rats. BDA-labeled fibers were observable over 100 different brainstem areas, nuclei, or subdivisions. Injections into the 8 DLH subdivisions established distinct topographical patterns. In general, the density of labeled fibers was low in the lower brainstem. High density of fibers was seen only 4 of the 116 areas: in the lateral and ventrolateral parts of the periaqueductal gray, the Barrington's, and the pedunculopontine tegmental nuclei. All of the biogenic amine cell groups in the lower brainstem (9 noradrenaline, 3 adrenaline, and 9 serotonin cell groups) received labeled fibers, some of them from all, or at least 7 DLH subdivisions, mainly from perifornical and ventral lateral hypothalamic neurons. Some of the tegmental nuclei and nuclei of the reticular formation were widely innervated, although the density of the BDA-labeled fibers was generally low. No definitive descending BDA-positive pathway, but long-run solitaire BDA-labeled fibers were seen in the lower brainstem. These descending fibers joined some of the large tracts or fasciculi in the brainstem. The distribution pattern of BDA-positive fibers of DLH origin throughout the lower brainstem was comparable to patterns of previously published orexin- or melanin-concentrating hormone-immunoreactive fibers with somewhat differences. PMID:24904303

Altered Levels of Zinc and N-methyl-D-aspartic Acid Receptor Underlying Multiple Organ Dysfunctions After Severe Trauma

PubMed Central

Wang, Guanghuan; Yu, Xiaojun; Wang, Dian; Xu, Xiaohu; Chen, Guang; Jiang, Xuewu

2015-01-01

Background Severe trauma can cause secondary multiple organ dysfunction syndrome (MODS) and death. Oxidative stress and/or excitatory neurotoxicity are considered as the final common pathway in nerve cell injuries. Zinc is the cofactor of the redox enzyme, and the effect of the excitatory neurotoxicity is related to N-methyl-D-aspartic acid receptor (NMDAR). Material/Methods We investigated the levels of zinc and brainstem NMDAR in a rabbit model of severe trauma. Zinc and serum biochemical profiles were determined. Immunohistochemistry was used to detect brainstem N-methyl-D-aspartic acid receptor 1 (NR1), N-methyl-D-aspartic acid receptor 2A (NR2A), and N-methyl-D-aspartic acid receptor 2B (NR2B) expression. Results Brain and brainstem Zn levels increased at 12 h, but serum Zn decreased dramatically after the trauma. NR1 in the brainstem dorsal regions increased at 6 h after injury and then decreased. NR2A in the dorsal regions decreased to a plateau at 12 h after trauma. The levels of NR2B were lowest in the death group in the brainstem. Serum zinc was positively correlated with NR2A and 2B and negatively correlated with zinc in the brain. Correlations were also found between the brainstem NR2A and that of the dorsal brainstem, as well as between brainstem NR2A and changes in NR2B. There was a negative correlation between zinc and NR2A. Conclusions Severe trauma led to an acute reduction of zinc enhancing oxidative stress and the changes of NMDAR causing the neurotoxicity of the nerve cells. This may be a mechanism for the occurrence of MODS or death after trauma. PMID:26335029

The direct pathway from the brainstem reticular formation to the cerebral cortex in the ascending reticular activating system: A diffusion tensor imaging study.

PubMed

Jang, Sung Ho; Kwon, Hyeok Gyu

2015-10-08

Precise evaluation of the ascending reticular activating system (ARAS) is important for diagnosis, prediction of prognosis, and management of patients with disorders of impaired consciousness. In the current study, we attempted to reconstruct the direct neural pathway between the brainstem reticular formation (RF) and the cerebral cortex in normal subjects, using diffusion tensor imaging (DTI). Forty-one healthy subjects were recruited for this study. DTIs were performed using a sensitivity-encoding head coil at 1.5Tesla with FMRIB Software Library. For connectivity of the brainstem RF, we used two regions of interest (ROIs) for the brainstem RF (seed ROI) and the thalamus and hypothalamus (exclusion ROI). Connectivity was defined as the incidence of connection between the brainstem RF and target brain regions at the threshold of 5 and 50 streamlines. Regarding the thresholds of 5 and 50, the brainstem RF showed high connectivity to the lateral prefrontal cortex (lPFC, 67.1% and 20.7%) and ventromedial prefrontal cortex (vmPFC, 50.0% and 18.3%), respectively. In contrast, the brainstem RF showed low connectivity to the primary motor cortex (31.7% and 3.7%), premotor cortex (24.4% and 3.7%), primary somatosensory cortex (23.2% and 2.4%), orbitofrontal cortex (17.1% and 7.3%), and posterior parietal cortex (12.2% and 0%), respectively. The brainstem RF was mainly connected to the prefrontal cortex, particularly lPFC and vmPFC. We believe that the methodology and results of this study would be useful to clinicians involved in the care of patients with impaired consciousness and researchers in studies of the ARAS. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Anti-Hu paraneoplastic brainstem encephalitis caused by a pancreatic neuroendocrine tumor presenting with central hypoventilation.

PubMed

Najjar, Marc; Taylor, Andrew; Agrawal, Surbhi; Fojo, Tito; Merkler, Alexander E; Rosenblum, Marc K; Lennihan, Laura; Kluger, Michael D

2017-06-01

Paraneoplastic neurological syndromes are rare autoimmune manifestations of malignancies associated with specific antibodies. Anti-Hu associated brainstem encephalitis, a well-described syndrome, usually presents subacutely with preferential involvement of the medulla. Anti-Hu antibodies target intraneuronal antigens and are therefore highly correlated with neurological syndromes when present concomitantly with a neoplasm. Reported is a case of anti-Hu brainstem encephalitis associated with a pancreatic neuroendocrine tumor (PNET) presenting with central hypoventilation. This is the first described case of brainstem encephalitis associated with a well-differentiated PNET as well as the first case of Anti-Hu antibodies associated with a PNET. There are no standardized protocols for the treatment of paraneoplastic brainstem encephalitis however, as in the present case, surgical resection and oncological treatment of the tumor is the first line treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mapping of somatostatin-28 (1-12) in the alpaca (Lama pacos) brainstem.

PubMed

De Souza, Eliana; Sánchez, Manuel Lisardo; Aguilar, Luís Ángel; Díaz-Cabiale, Zaida; Narváez, José Ángel; Coveñas, Rafael

2015-05-01

Using an indirect immunoperoxidase technique, we studied the distribution of cell bodies and fibers containing somatostatin-28 (1-12) in the alpaca brainstem. Immunoreactive fibers were widely distributed throughout the whole brainstem: 34 brainstem nuclei/regions showed a high or a moderate density of these fibers. Perikarya containing the peptide were widely distributed throughout the mesencephalon, pons and medulla oblongata. Cell bodies containing somatostatin-28 (1-12) were observed in the lateral and medial divisions of the marginal nucleus of the brachium conjunctivum, reticular formation (mesencephalon, pons and medulla oblongata), inferior colliculus, periaqueductal gray, superior colliculus, pericentral division of the dorsal tegmental nucleus, interpeduncular nucleus, nucleus of the trapezoid body, vestibular nucleus, motor dorsal nucleus of the vagus, nucleus of the solitary tract, nucleus praepositus hypoglossi, and in the substantia nigra. This widespread distribution indicates that somatostatin-28 (1-12) is involved in multiple physiological actions in the alpaca brainstem. © 2015 Wiley Periodicals, Inc.

Cerebellar and Brainstem Malformations.

PubMed

Poretti, Andrea; Boltshauser, Eugen; Huisman, Thierry A G M

2016-08-01

The frequency and importance of the evaluation of the posterior fossa have increased significantly over the past 20 years owing to advances in neuroimaging. Conventional and advanced neuroimaging techniques allow detailed evaluation of the complex anatomic structures within the posterior fossa. A wide spectrum of cerebellar and brainstem malformations has been shown. Familiarity with the spectrum of cerebellar and brainstem malformations and their well-defined diagnostic criteria is crucial for optimal therapy, an accurate prognosis, and correct genetic counseling. This article discusses cerebellar and brainstem malformations, with emphasis on neuroimaging findings (including diagnostic criteria), neurologic presentation, systemic involvement, prognosis, and recurrence. Copyright © 2016 Elsevier Inc. All rights reserved.

Calcified pilocytic astrocytoma of the medulla mimicking a brainstem "stone".

PubMed

Berhouma, M; Jemel, H; Kchir, N

2008-10-01

Brainstem gliomas are a heterogeneous group of tumours commonly found in children, comprising about 10% of central nervous system tumours in paediatric patients, but less than 2% in adults. Pilocytic astrocytomas usually involve the midbrain and the medulla, and their surgical resection, when feasible, is generally curative. Thin calcifications can be normally found within low grade gliomas, but densely calcified pilocytic astrocytomas of the brainstem have been only rarely reported. We present the case of a young man presenting with a large brainstem calcification involving the medulla, which was subtotally resected using a posterior suboccipital approach. The definitive pathological diagnosis was calcified pilocytic astrocytoma.

[Forensic application of brainstem auditory evoked potential in patients with brain concussion].

PubMed

Zheng, Xing-Bin; Li, Sheng-Yan; Huang, Si-Xing; Ma, Ke-Xin

2008-12-01

To investigate changes of brainstem auditory evoked potential (BAEP) in patients with brain concussion. Nineteen patients with brain concussion were studied with BAEP examination. The data was compared to the healthy persons reported in literatures. The abnormal rate of BAEP for patients with brain concussion was 89.5%. There was a statistically significant difference between the abnormal rate of patients and that of healthy persons (P<0.05). The abnormal rate of BAEP in the brainstem pathway for patients with brain concussion was 73.7%, indicating dysfunction of the brainstem in those patients. BAEP might be helpful in forensic diagnosis of brain concussion.

Evidence for a distributed respiratory rhythm generating network in the goldfish (Carsssius auratus).

PubMed

Duchcherer, Maryana; Kottick, Andrew; Wilson, R J A

2010-01-01

Central pattern generators located in the brainstem regulate ventilatory behaviors in vertebrates. The development of the isolated brainstem preparation has allowed these neural networks to be characterized in a number of aquatic species. The aim of this study was to explore the architecture of the respiratory rhythm-generating site in the goldfish (Carassius auratus) and to determine the utility of a newly developed isolated brainstem preparation, the Sheep Dip. Here we provide evidence for a distributed organization of respiratory rhythm generating neurons along the rostrocaudal axis of the goldfish brainstem and outline the advantages of the Sheep Dip as a tool used to survey neural networks.

Abnormal trajectories in cerebellum and brainstem volumes in carriers of the fragile X premutation.

PubMed

Wang, Jun Yi; Hessl, David; Hagerman, Randi J; Simon, Tony J; Tassone, Flora; Ferrer, Emilio; Rivera, Susan M

2017-07-01

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder typically affecting male premutation carriers with 55-200 CGG trinucleotide repeat expansions in the FMR1 gene after age 50. The aim of this study was to examine whether cerebellar and brainstem changes emerge during development or aging in late life. We retrospectively analyzed magnetic resonance imaging scans from 322 males (age 8-81 years). Volume changes in the cerebellum and brainstem were contrasted with those in the ventricles and whole brain. Compared to the controls, premutation carriers without FXTAS showed significantly accelerated volume decrease in the cerebellum and whole brain, flatter inverted U-shaped trajectory of the brainstem, and larger ventricles. Compared to both older controls and premutation carriers without FXTAS, carriers with FXTAS exhibited significant volume decrease in the cerebellum and whole brain and accelerated volume decrease in the brainstem. We therefore conclude that cerebellar and brainstem volumes were likely affected during both development and progression of neurodegeneration in premutation carriers, suggesting that interventions may need to start early in adulthood to be most effective. Copyright © 2017 Elsevier Inc. All rights reserved.

Air pollution is associated with brainstem auditory nuclei pathology and delayed brainstem auditory evoked potentials.

PubMed

Calderón-Garcidueñas, Lilian; D'Angiulli, Amedeo; Kulesza, Randy J; Torres-Jardón, Ricardo; Osnaya, Norma; Romero, Lina; Keefe, Sheyla; Herritt, Lou; Brooks, Diane M; Avila-Ramirez, Jose; Delgado-Chávez, Ricardo; Medina-Cortina, Humberto; González-González, Luis Oscar

2011-06-01

We assessed brainstem inflammation in children exposed to air pollutants by comparing brainstem auditory evoked potentials (BAEPs) and blood inflammatory markers in children age 96.3±8.5 months from highly polluted (n=34) versus a low polluted city (n=17). The brainstems of nine children with accidental deaths were also examined. Children from the highly polluted environment had significant delays in wave III (t(50)=17.038; p<0.0001) and wave V (t(50)=19.730; p<0.0001) but no delay in wave I (p=0.548). They also had significantly longer latencies than controls for interwave intervals I-III, III-V, and I-V (all t(50)>7.501; p<0.0001), consisting with delayed central conduction time of brainstem neural transmission. Highly exposed children showed significant evidence of inflammatory markers and their auditory and vestibular nuclei accumulated α synuclein and/or β amyloid(1-42). Medial superior olive neurons, critically involved in BAEPs, displayed significant pathology. Children's exposure to urban air pollution increases their risk for auditory and vestibular impairment. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

Task-Related Suppression of the Brainstem Frequency following Response

DTIC Science & Technology

2013-02-18

from switching between attention-demanding task stimuli. However, it is also possible that the opposite may be true – the addition of a task, instead...of a resting, passive state may suppress the FFR. Here we examined the influence of a subsequent task, and the relevance of the task modality, on...as a baseline consisting of the same background stimuli in the absence of a task. FFR pitch strength and amplitude of the primary frequency response

Anticholinesterase Effects on Number and Function of Brain Muscarinic Receptors and Central Cholinergic Activity: Drug Intervention.

DTIC Science & Technology

1986-04-11

Leudee NWI 5th England 18. brain;striatum;hippocampus;cortex;brainstem;rat;hydrophilic drugs;hydrophobic drugs; oxotremorine ;physostigmine;choline...challenged with oxotremorine , marked cross-tolerance to the ACh-increasing action f the muscarinic receptor agonist was induced in both striatum and...responses except for slight tremor.A Fig. 2 shows the dose-response curves of the muscarinic agonists oxotremorine and the butynyl base, McN-A-343, a

Functional modeling of the human auditory brainstem response to broadband stimulationa)

PubMed Central

Verhulst, Sarah; Bharadwaj, Hari M.; Mehraei, Golbarg; Shera, Christopher A.; Shinn-Cunningham, Barbara G.

2015-01-01

Population responses such as the auditory brainstem response (ABR) are commonly used for hearing screening, but the relationship between single-unit physiology and scalp-recorded population responses are not well understood. Computational models that integrate physiologically realistic models of single-unit auditory-nerve (AN), cochlear nucleus (CN) and inferior colliculus (IC) cells with models of broadband peripheral excitation can be used to simulate ABRs and thereby link detailed knowledge of animal physiology to human applications. Existing functional ABR models fail to capture the empirically observed 1.2–2 ms ABR wave-V latency-vs-intensity decrease that is thought to arise from level-dependent changes in cochlear excitation and firing synchrony across different tonotopic sections. This paper proposes an approach where level-dependent cochlear excitation patterns, which reflect human cochlear filter tuning parameters, drive AN fibers to yield realistic level-dependent properties of the ABR wave-V. The number of free model parameters is minimal, producing a model in which various sources of hearing-impairment can easily be simulated on an individualized and frequency-dependent basis. The model fits latency-vs-intensity functions observed in human ABRs and otoacoustic emissions while maintaining rate-level and threshold characteristics of single-unit AN fibers. The simulations help to reveal which tonotopic regions dominate ABR waveform peaks at different stimulus intensities. PMID:26428802

A human brain network derived from coma-causing brainstem lesions.

PubMed

Fischer, David B; Boes, Aaron D; Demertzi, Athena; Evrard, Henry C; Laureys, Steven; Edlow, Brian L; Liu, Hesheng; Saper, Clifford B; Pascual-Leone, Alvaro; Fox, Michael D; Geerling, Joel C

2016-12-06

To characterize a brainstem location specific to coma-causing lesions, and its functional connectivity network. We compared 12 coma-causing brainstem lesions to 24 control brainstem lesions using voxel-based lesion-symptom mapping in a case-control design to identify a site significantly associated with coma. We next used resting-state functional connectivity from a healthy cohort to identify a network of regions functionally connected to this brainstem site. We further investigated the cortical regions of this network by comparing their spatial topography to that of known networks and by evaluating their functional connectivity in patients with disorders of consciousness. A small region in the rostral dorsolateral pontine tegmentum was significantly associated with coma-causing lesions. In healthy adults, this brainstem site was functionally connected to the ventral anterior insula (AI) and pregenual anterior cingulate cortex (pACC). These cortical areas aligned poorly with previously defined resting-state networks, better matching the distribution of von Economo neurons. Finally, connectivity between the AI and pACC was disrupted in patients with disorders of consciousness, and to a greater degree than other brain networks. Injury to a small region in the pontine tegmentum is significantly associated with coma. This brainstem site is functionally connected to 2 cortical regions, the AI and pACC, which become disconnected in disorders of consciousness. This network of brain regions may have a role in the maintenance of human consciousness. © 2016 American Academy of Neurology.

Right-sided dominance of the bilateral vestibular system in the upper brainstem and thalamus.

PubMed

Dieterich, Marianne; Kirsch, V; Brandt, T

2017-10-01

MRI diffusion tensor imaging tractography was performed on the bilateral vestibular brainstem pathways, which run from the vestibular nuclei via the paramedian and posterolateral thalamic subnuclei to the parieto-insular vestibular cortex. Twenty-one right-handed healthy subjects participated. Quantitative analysis revealed a rope-ladder-like system of vestibular pathways in the brainstem with crossings at pontine and mesencephalic levels. Three structural types of right-left fiber distributions could be delineated: (1) evenly distributed pathways at the lower pontine level from the vestibular nuclei to the pontine crossing, (2) a moderate, pontomesencephalic right-sided lateralization between the pontine and mesencephalic crossings, and (3) a further increase of the right-sided lateralization above the mesencephalic crossing leading to the thalamic vestibular subnuclei. The increasing lateralization along the brainstem was the result of an asymmetric number of pontine and mesencephalic crossing fibers which was higher for left-to-right crossings. The dominance of the right vestibular meso-diencephalic circuitry in right-handers corresponds to the right-hemispheric dominance of the vestibular cortical network. The structural asymmetry apparent in the upper brainstem might be interpreted in relation to the different functions of the vestibular system depending on their anatomical level: a symmetrical sensorimotor reflex control of eye, head, and body mediated by the lower brainstem; a lateralized right-sided upper brainstem-thalamic function as part of the dominant right-sided cortical/subcortical vestibular system that enables a global percept of body motion and orientation in space.

Brainstem metabotropic glutamate receptors reduce food intake and activate dorsal pontine and medullar structures after peripheral bacterial lipopolysaccharide administration.

PubMed

Chaskiel, Léa; Paul, Flora; Gerstberger, Rüdiger; Hübschle, Thomas; Konsman, Jan Pieter

2016-08-01

During infection-induced inflammation food intake is reduced. Vagal and brainstem pathways are important both in feeding regulation and immune-to-brain communication. Glutamate is released by vagal afferent terminals in the nucleus of the solitary tract and by its neurons projecting to the parabrachial nuclei. We therefore studied the role of brainstem glutamate receptors in spontaneous food intake of healthy animals and during sickness-associated hypophagia after peripheral administration of bacterial lipopolysaccharides or interleukin-1beta. Brainstem group I and II metabotropic, but not ionotropic, glutamate receptor antagonism increased food intake both in saline- and lipopolysaccharide-treated rats. In these animals, expression of the cellular activation marker c-Fos in the lateral parabrachial nuclei and lipopolysaccharide-induced activation of the nucleus of the solitary tract rostral to the area postrema were suppressed. Group I metabotropic glutamate receptors did not colocalize with c-Fos or neurons regulating gastric function in these structures. Group I metabotropic glutamate receptors were, however, found on raphé magnus neurons that were part of the brainstem circuit innervating the stomach and on trigeminal and hypoglossal motor neurons. In conclusion, our findings show that brainstem metabotropic glutamate receptors reduce food intake and activate the lateral parabrachial nuclei as well as the rostral nucleus of the solitary tract after peripheral bacterial lipopolysaccharide administration. They also provide insight into potential group I metabotropic glutamate receptor-dependent brainstem circuits mediating these effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

A human brain network derived from coma-causing brainstem lesions

PubMed Central

Boes, Aaron D.; Demertzi, Athena; Evrard, Henry C.; Laureys, Steven; Edlow, Brian L.; Liu, Hesheng; Saper, Clifford B.; Pascual-Leone, Alvaro; Geerling, Joel C.

2016-01-01

Objective: To characterize a brainstem location specific to coma-causing lesions, and its functional connectivity network. Methods: We compared 12 coma-causing brainstem lesions to 24 control brainstem lesions using voxel-based lesion-symptom mapping in a case-control design to identify a site significantly associated with coma. We next used resting-state functional connectivity from a healthy cohort to identify a network of regions functionally connected to this brainstem site. We further investigated the cortical regions of this network by comparing their spatial topography to that of known networks and by evaluating their functional connectivity in patients with disorders of consciousness. Results: A small region in the rostral dorsolateral pontine tegmentum was significantly associated with coma-causing lesions. In healthy adults, this brainstem site was functionally connected to the ventral anterior insula (AI) and pregenual anterior cingulate cortex (pACC). These cortical areas aligned poorly with previously defined resting-state networks, better matching the distribution of von Economo neurons. Finally, connectivity between the AI and pACC was disrupted in patients with disorders of consciousness, and to a greater degree than other brain networks. Conclusions: Injury to a small region in the pontine tegmentum is significantly associated with coma. This brainstem site is functionally connected to 2 cortical regions, the AI and pACC, which become disconnected in disorders of consciousness. This network of brain regions may have a role in the maintenance of human consciousness. PMID:27815400

Killer whale (Orcinus orca) hearing: auditory brainstem response and behavioral audiograms.

PubMed

Szymanski, M D; Bain, D E; Kiehl, K; Pennington, S; Wong, S; Henry, K R

1999-08-01

Killer whale (Orcinus orca) audiograms were measured using behavioral responses and auditory evoked potentials (AEPs) from two trained adult females. The mean auditory brainstem response (ABR) audiogram to tones between 1 and 100 kHz was 12 dB (re 1 mu Pa) less sensitive than behavioral audiograms from the same individuals (+/- 8 dB). The ABR and behavioral audiogram curves had shapes that were generally consistent and had the best threshold agreement (5 dB) in the most sensitive range 18-42 kHz, and the least (22 dB) at higher frequencies 60-100 kHz. The most sensitive frequency in the mean Orcinus audiogram was 20 kHz (36 dB), a frequency lower than many other odontocetes, but one that matches peak spectral energy reported for wild killer whale echolocation clicks. A previously reported audiogram of a male Orcinus had greatest sensitivity in this range (15 kHz, approximately 35 dB). Both whales reliably responded to 100-kHz tones (95 dB), and one whale to a 120-kHz tone, a variation from an earlier reported high-frequency limit of 32 kHz for a male Orcinus. Despite smaller amplitude ABRs than smaller delphinids, the results demonstrated that ABR audiometry can provide a useful suprathreshold estimate of hearing range in toothed whales.

Auditory Brainstem Responses in Young Males with Fragile X Syndrome

ERIC Educational Resources Information Center

Roberts, Joanne; Hennon, Elizabeth A.; Anderson, Kathleen; Roush, Jackson; Gravel, Judith; Skinner, Martie; Misenheimer, Jan; Reitz, Patricia

2005-01-01

Fragile X syndrome (FXS) is the most common inherited cause of mental retardation resulting in developmental delays in males. Atypical outer ear morphology is characteristic of FXS and may serve as a marker for abnormal auditory function. Despite this abnormality, studies of the hearing of young males with FXS are generally lacking. A few studies…

Central and peripheral components of short latency vestibular responses in the chicken

NASA Technical Reports Server (NTRS)

Nazareth, A. M.; Jones, T. A.

1998-01-01

Far-field recordings of short latency vestibular responses to pulsed cranial translation are composed of a series of positive and negative peaks occurring within 10 ms following stimulus onset. In the bird, these vestibular evoked potentials (VsEPs) can be recorded noninvasively and have been shown in the chicken and quail to depend strictly upon the activation of the vestibular component of the eighth nerve. The utility of the VsEP in the study of vestibular systems is dependent upon a clear understanding of the neural sources of response components. The primary aim of the current research in the chicken was to critically test the hypotheses that 1) responses are generated by both peripheral and central neurons and 2) peaks P1 and N1 originate from first order vestibular neurons, whereas later waves primarily depend on activity in higher order neurons. The principal strategy used here was to surgically isolate the eighth nerve as it enters the brainstem. Interruption of primary afferents of the eighth nerve in the brainstem substantially reduced or eliminated peaks beyond P2, whereas P1 and N1 were generally spared. Surgical sections that spared vestibular pathways had little effect on responses. The degree of change in response components beyond N1 was correlated with the extent of damage to central vestibular relays. These findings support the conclusion that responses are produced by both peripheral and central elements of the vestibular system. Further, response peaks later than N1 appear to be dependent upon central relays, whereas P1 and N1 reflect activity of the peripheral nerve. These findings clarify the roles of peripheral and central neurons in the generation of vestibular evoked potentials and provide the basis for a more useful and detailed interpretation of data from vestibular response testing.

Chemoreception and asphyxia-induced arousal

PubMed Central

Guyenet, Patrice G.; Abbott, Stephen B.G.

2013-01-01

Arousal protects against the adverse and potentially fatal effects of asphyxia during sleep. Asphyxia stimulates the carotid bodies and central chemoreceptors but the sequence of events leading to arousal is uncertain. In this review, the theoretical mechanisms leading to arousal from sleep are briefly summarized and the issue of whether central respiratory chemoreceptors (CRCs) or other types of CO2-responsive CNS neurons contribute to asphyxia-induced arousal is discussed. We focus on the role of the retrotrapezoid nucleus, the raphe and the locus coeruleus and emphasize the anatomical and neurophysiological evidence which suggests that these putative central chemoreceptors could contribute to arousal independently of their effects on breathing. Finally, we describe recent attempts to test the contribution of specific brainstem pathways to asphyxia-induced arousal using optogenetic and other tools and the possible contribution of a group of hypoxia-sensitive brainstem neurons (the C1 cells) to breathing and arousal. PMID:23608705

Leucoencephalopathy following abuse of sniffed heroin.

PubMed

Lefaucheur, Romain; Lebas, Axel; Gérardin, Emmanuel; Grangeon, Lou; Ozkul-Wermester, Ozlem; Aubier-Girard, Carole; Martinaud, Olivier; Maltête, David

2017-01-01

A 29-year-old man was admitted for acute cognitive impairment. Three weeks earlier, he had been admitted for coma due to sniffed heroin abuse responsive to naloxone infusion. At admission, the patient presented with apraxia, severe memory impairment and anosognosia. Brain MRI revealed symmetric hyperintensities of supratentorial white matter, sparing brainstem and cerebellum, on FLAIR and B1000 sequences. Four months later, repeated neuropsychological assessment revealed dramatic improvement of global cognitive functions. Toxic leucoencephalopathy excluding the cerebellum and brainstem is a rare complication of heroin abuse, and seems to concern especially patients that use heroin by sniff or injection. In these patients, cognitive troubles are predominant, prognosis seems better and infratentorial brain structures can be spared. In conclusion, our observation emphasizes that heroin-induced encephalopathy can have a favourable outcome and that imaging and clinical patterns can indicate the mode of drug administration. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemoreception and asphyxia-induced arousal.

PubMed

Guyenet, Patrice G; Abbott, Stephen B G

2013-09-15

Arousal protects against the adverse and potentially fatal effects of asphyxia during sleep. Asphyxia stimulates the carotid bodies and central chemoreceptors but the sequence of events leading to arousal is uncertain. In this review, the theoretical mechanisms leading to arousal from sleep are briefly summarized and the issue of whether central respiratory chemoreceptors (CRCs) or other types of CO2-responsive CNS neurons contribute to asphyxia-induced arousal is discussed. We focus on the role of the retrotrapezoid nucleus, the raphe and the locus coeruleus and emphasize the anatomical and neurophysiological evidence which suggests that these putative central chemoreceptors could contribute to arousal independently of their effects on breathing. Finally, we describe recent attempts to test the contribution of specific brainstem pathways to asphyxia-induced arousal using optogenetic and other tools and the possible contribution of a group of hypoxia-sensitive brainstem neurons (the C1 cells) to breathing and arousal. Copyright © 2013 Elsevier B.V. All rights reserved.

Methamphetamine-related brainstem haemorrhage.

PubMed

Chiu, Zelia K; Bennett, Iwan E; Chan, Patrick; Rosenfeld, Jeffrey V

2016-10-01

We report the case of an otherwise healthy 29-year-old woman who presented with a brainstem haemorrhage following intravenous methamphetamine use. Extensive investigation did not reveal an underlying pathology, and the development of symptoms was temporally related to methamphetamine injection. Although intracerebral haemorrhage secondary to methamphetamine use is well documented, this report describes a haemorrhage within the brainstem which is a rare location. While animal studies have demonstrated the potential of methamphetamines to produce brainstem haemorrhages, there has only been one previous report describing a haemorrhage in this location due to amphetamine use in humans. We conclude with a brief discussion of the clinical features and aetiology of methamphetamine-related stroke. Copyright © 2016 Elsevier Ltd. All rights reserved.

Brainstem death: A comprehensive review in Indian perspective

PubMed Central

Dhanwate, Anant Dattatray

2014-01-01

With the advent of cardiopulmonary resuscitation techniques, the cardiopulmonary definition of death lost its significance in favor of brain death. Brain death is a permanent cessation of all functions of the brain in which though individual organs may function but lack of integrating function of the brain, lack of respiratory drive, consciousness, and cognition confirms to the definition that death is an irreversible cessation of functioning of the organism as a whole. In spite of medical and legal acceptance globally, the concept of brain death and brain-stem death is still unclear to many. Brain death is not promptly declared due to lack of awareness and doubts about the legal procedure of certification. Many brain dead patients are kept on life supporting systems needlessly. In this comprehensive review, an attempt has been made to highlight the history and concept of brain death and brain-stem death; the anatomical and physiological basis of brain-stem death, and criteria to diagnose brain-stem death in India. PMID:25249744

In vivo functional connectome of human brainstem nuclei of the ascending arousal, autonomic, and motor systems by high spatial resolution 7-Tesla fMRI.

PubMed

Bianciardi, Marta; Toschi, Nicola; Eichner, Cornelius; Polimeni, Jonathan R; Setsompop, Kawin; Brown, Emery N; Hämäläinen, Matti S; Rosen, Bruce R; Wald, Lawrence L

2016-06-01

Our aim was to map the in vivo human functional connectivity of several brainstem nuclei with the rest of the brain by using seed-based correlation of ultra-high magnetic field functional magnetic resonance imaging (fMRI) data. We used the recently developed template of 11 brainstem nuclei derived from multi-contrast structural MRI at 7 Tesla as seed regions to determine their connectivity to the rest of the brain. To achieve this, we used the increased contrast-to-noise ratio of 7-Tesla fMRI compared with 3 Tesla and time-efficient simultaneous multi-slice imaging to cover the brain with high spatial resolution (1.1-mm isotropic nominal resolution) while maintaining a short repetition time (2.5 s). The delineated Pearson's correlation-based functional connectivity diagrams (connectomes) of 11 brainstem nuclei of the ascending arousal, motor, and autonomic systems from 12 controls are presented and discussed in the context of existing histology and animal work. Considering that the investigated brainstem nuclei play a crucial role in several vital functions, the delineated preliminary connectomes might prove useful for future in vivo research and clinical studies of human brainstem function and pathology, including disorders of consciousness, sleep disorders, autonomic disorders, Parkinson's disease, and other motor disorders.

Gamma Knife Treatment of Brainstem Metastases

PubMed Central

Peterson, Halloran E.; Larson, Erik W.; Fairbanks, Robert K.; MacKay, Alexander R.; Lamoreaux, Wayne T.; Call, Jason A.; Carlson, Jonathan D.; Ling, Benjamin C.; Demakas, John J.; Cooke, Barton S.; Peressini, Ben; Lee, Christopher M.

2014-01-01

The management of brainstem metastases is challenging. Surgical treatment is usually not an option, and chemotherapy is of limited utility. Stereotactic radiosurgery has emerged as a promising palliative treatment modality in these cases. The goal of this study is to assess our single institution experience treating brainstem metastases with Gamma Knife radiosurgery (GKRS). This retrospective chart review studied 41 patients with brainstem metastases treated with GKRS. The most common primary tumors were lung, breast, renal cell carcinoma, and melanoma. Median age at initial treatment was 59 years. Nineteen (46%) of the patients received whole brain radiation therapy (WBRT) prior to or concurrent with GKRS treatment. Thirty (73%) of the patients had a single brainstem metastasis. The average GKRS dose was 17 Gy. Post-GKRS overall survival at six months was 42%, at 12 months was 22%, and at 24 months was 13%. Local tumor control was achieved in 91% of patients, and there was one patient who had a fatal brain hemorrhage after treatment. Karnofsky performance score (KPS) >80 and the absence of prior WBRT were predictors for improved survival on multivariate analysis (HR 0.60 (p = 0.02), and HR 0.28 (p = 0.02), respectively). GKRS was an effective treatment for brainstem metastases, with excellent local tumor control. PMID:24886816

Individual differences in brainstem and basal ganglia structure predict postural control and balance loss in young and older adults.

PubMed

Boisgontier, Matthieu P; Cheval, Boris; Chalavi, Sima; van Ruitenbeek, Peter; Leunissen, Inge; Levin, Oron; Nieuwboer, Alice; Swinnen, Stephan P

2017-02-01

It remains unclear which specific brain regions are the most critical for human postural control and balance, and whether they mediate the effect of age. Here, associations between postural performance and corticosubcortical brain regions were examined in young and older adults using multiple structural imaging and linear mixed models. Results showed that of the regions involved in posture, the brainstem was the strongest predictor of postural control and balance: lower brainstem volume predicted larger center of pressure deviation and higher odds of balance loss. Analyses of white and gray matter in the brainstem showed that the pedunculopontine nucleus area appeared to be critical for postural control in both young and older adults. In addition, the brainstem mediated the effect of age on postural control, underscoring the brainstem's fundamental role in aging. Conversely, lower basal ganglia volume predicted better postural performance, suggesting an association between greater neural resources in the basal ganglia and greater movement vigor, resulting in exaggerated postural adjustments. Finally, results showed that practice, shorter height and heavier weight (i.e., higher body mass index), higher total physical activity, and larger ankle active (but not passive) range of motion were predictive of more stable posture, irrespective of age. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantitative Comparison of Retrosigmoid Intradural Suprameatal Approach and Retrosigmoid Transtentorial Approach: Implications for Tumors in the Petroclival Region

PubMed Central

Ambekar, Sudheer; Amene, Chiazo; Sonig, Ashish; Guthikonda, Bharat; Nanda, Anil

2013-01-01

Background Retrosigmoid transtentorial (RTT) and retrosigmoid intradural suprameatal (RISA) approaches have been used in the treatment of petroclival tumors. Objective To compare the area of exposure of brainstem and petroclival region obtained through RTT and RISA in cadaveric specimens. Methods Five cadaveric specimens with a total of 10 sides were analyzed. RTT and RISA were performed on five sides each. Brainstem and petroclival surface exposure were measured using both the approaches. These values were compared between the two approaches. Results Brainstem area exposure with RTT was 441 ± 63 mm2 and that with RISA was 311 ± 61 mm2. Student's t-test revealed that the difference was significant (p = 0.01). The area of petroclival exposure medial to the Meckel cave through RTT was 696 ± 57 mm2, and that through RISA was 716 ± 51 mm2 (p = 0.69). The area of brainstem exposure between V and VII-VII complex through RTT and RISA was 387 ± 86 mm2 and 378 ± 76 mm2 (p = 0.87). Conclusion The RTT approach is an excellent approach to ventrolateral brainstem and petroclival region. It provides greater superoventral exposure of the ventrolateral brainstem than RISA and provides similar petroclival exposure. PMID:24436928

The vesicular glutamate transporter VGLUT3 contributes to protection against neonatal hypoxic stress

PubMed Central

Miot, Stéphanie; Voituron, Nicolas; Sterlin, Adélaïde; Vigneault, Erika; Morel, Lydie; Matrot, Boris; Ramanantsoa, Nelina; Amilhon, Bénédicte; Poirel, Odile; Lepicard, Ève; El Mestikawy, Salah; Hilaire, Gérard; Gallego, Jorge

2012-01-01

Neonates respond to hypoxia initially by increasing ventilation, and then by markedly decreasing both ventilation (hypoxic ventilatory decline) and oxygen consumption (hypoxic hypometabolism). This latter process, which vanishes with age, reflects a tight coupling between ventilatory and thermogenic responses to hypoxia. The neurological substrate of hypoxic hypometabolism is unclear, but it is known to be centrally mediated, with a strong involvement of the 5-hydroxytryptamine (5-HT, serotonin) system. To clarify this issue, we investigated the possible role of VGLUT3, the third subtype of vesicular glutamate transporter. VGLUT3 contributes to glutamate signalling by 5-HT neurons, facilitates 5-HT transmission and is expressed in strategic regions for respiratory and thermogenic control. We therefore assumed that VGLUT3 might significantly contribute to the response to hypoxia. To test this possibility, we analysed this response in newborn mice lacking VGLUT3 using anatomical, biochemical, electrophysiological and integrative physiology approaches. We found that the lack of VGLUT3 did not affect the histological organization of brainstem respiratory networks or respiratory activity under basal conditions. However, it impaired respiratory responses to 5-HT and anoxia, showing a marked alteration of central respiratory control. These impairments were associated with altered 5-HT turnover at the brainstem level. Furthermore, under cold conditions, the lack of VGLUT3 disrupted the metabolic rate, body temperature, baseline breathing and the ventilatory response to hypoxia. We conclude that VGLUT3 expression is dispensable under basal conditions but is required for optimal response to hypoxic stress in neonates. PMID:22890712

Possible structural abnormality of the brainstem in unipolar depressive illness: a transcranial ultrasound and diffusion tensor magnetic resonance imaging study.

PubMed

Steele, J D; Bastin, M E; Wardlaw, J M; Ebmeier, K P

2005-11-01

Most empirically derived antidepressants increase monoamine levels. The nuclei of cells synthesising these monoamines are located in the brainstem, and projection tracts such as the medial forebrain bundle reach virtually all other brain areas. Two studies of unipolar depressive illness using transcranial ultrasound have reported reduced echogenicity of the brainstem midline in unipolar depressed patients. This may be consistent with disruption of white matter tracts, including the medial forebrain bundle, and it has been suggested that the effect of such disruption could be reversed by antidepressants. To replicate these findings in a group of unipolar depressed patients and controls. Fifteen unipolar depressed patients and 15 controls were studied using transcranial ultrasound imaging and diffusion tensor magnetic resonance imaging (DT-MRI). No difference in echogenicity of the brainstem midline of unipolar depressed patients was found. A possible trend (Cohen's d = 0.39) in the direction of previous studies was found. Although the echogenicity of the brainstem midline of the control group was found to be similar to previous reports, there was no reduction in the patient group. Additionally, no structural abnormality of the brainstem was identified using DT-MRI. While these data do not replicate the findings of previous studies reporting a significant reduction in the echogenicity of the brainstem midline in unipolar depressed patients, the ultrasound investigation indicated that there may be a trend in this direction. Given the importance of identifying the causes of depressive illness, it is important that other groups attempt similar studies.

DTI fiber tracking to differentiate demyelinating diseases from diffuse brain stem glioma.

PubMed

Giussani, Carlo; Poliakov, Andrew; Ferri, Raymond T; Plawner, Lauren L; Browd, Samuel R; Shaw, Dennis W W; Filardi, Tanya Z; Hoeppner, Corrine; Geyer, J Russell; Olson, James M; Douglas, James G; Villavicencio, Elisabeth H; Ellenbogen, Richard G; Ojemann, Jeffrey G

2010-08-01

Intrinsic diffuse brainstem tumors and demyelinating diseases primarily affecting the brainstem can share common clinical and radiological features, sometimes making the diagnosis difficult especially at the time of first clinical presentation. To explore the potential usefulness of new MRI sequences in particular diffusion tensor imaging fiber tracking in differentiating these two pathological entities, we review a series of brainstem tumors and demyelinating diseases treated at our institution. The clinical history including signs and symptoms and MRI findings of three consecutive demyelinating diseases involving the brainstem that presented with diagnostic uncertainty and three diffuse intrinsic brainstem tumors were reviewed, along with a child with a supratentorial tumor for comparison. Fiber tracking of the pyramidal tracts was performed for each patient using a DTI study at the time of presentation. Additionally Fractional Anisotropy values were calculated for each patient in the pons and the medulla oblongata. Routine MR imaging was unhelpful in differentiating between intrinsic tumor and demyelination. In contrast, retrospective DTI fiber tracking clearly differentiated the pathology showing deflection of the pyramidal tracts posteriorly and laterally in the case of intrinsic brainstem tumors and, in the case of demyelinating disease, poorly represented and truncated fibers. Regionalized FA values were variable and of themselves were not predictive either pathology. DTI fiber tracking of the pyramid tracts in patients with suspected intrinsic brainstem tumor or demyelinating disease presents two clearly different patterns that may help in differentiating between these two pathologies when conventional MRI and clinical data are inconclusive. Copyright 2010 Elsevier Inc. All rights reserved.

The vestibular evoked myogenic potentials (VEMP) score: a promising tool for evaluation of brainstem involvement in multiple sclerosis.

PubMed

Gabelić, T; Krbot Skorić, M; Adamec, I; Barun, B; Zadro, I; Habek, M

2015-02-01

Concerning the great importance of brainstem involvement in multiple sclerosis (MS), the aim of this study was to explore the role of the newly developed vestibular evoked myogenic potentials (VEMP) score as a possible marker of brainstem involvement in MS patients. This was a prospective case-control study which included 100 MS patients divided into two groups (without and with clinical signs of brainstem involvement) and 50 healthy controls. Ocular VEMP (oVEMP) and cervical VEMP (cVEMP) measurements were performed in all participants and analyzed for latencies, conduction block and amplitude asymmetry ratio. Based on this the VEMP score was calculated and compared with Expanded Disability Status Scale (EDSS), disease duration and magnetic resonance imaging data. Multiple sclerosis patients with clinical signs of brainstem involvement (group 2) had a statistically significant higher percentage of VEMP conduction blocks compared with patients without clinical signs of brainstem involvement (group 1) and healthy controls (P = 0.027 and P < 0.0001, respectively). Similarly, the VEMP score was significantly higher in group 2 compared with group 1 (P = 0.018) and correlated with EDSS and disease duration (P = 0.011 and P = 0.032, respectively). Multivariate linear regression analysis showed that the VEMP score has a statistically significant influence on the EDSS score (P < 0.001, R(2) = 0.239). Interpretation of the oVEMP and cVEMP results in the form of the VEMP score enables better evaluation of brainstem involvement than either of these evoked potentials alone and correlates well with disability. © 2014 EAN.

Convection enhanced delivery of carmustine to the murine brainstem: a feasibility study.

PubMed

Sewing, A Charlotte P; Caretti, Viola; Lagerweij, Tonny; Schellen, Pepijn; Jansen, Marc H A; van Vuurden, Dannis G; Idema, Sander; Molthoff, Carla F M; Vandertop, W Peter; Kaspers, Gertjan J L; Noske, David P; Hulleman, Esther

2014-12-30

Systemic delivery of therapeutic agents remains ineffective against diffuse intrinsic pontine glioma (DIPG), possibly due to an intact blood-brain-barrier (BBB) and to dose-limiting toxicity of systemic chemotherapeutic agents. Convection-enhanced delivery (CED) into the brainstem may provide an effective local delivery alternative for DIPG patients. The aim of this study is to develop a method to perform CED into the murine brainstem and to test this method using the chemotherapeutic agent carmustine (BiCNU). To this end, a newly designed murine CED catheter was tested in vitro and in vivo. After determination of safety and distribution, mice bearing VUMC-DIPG-3 and E98FM-DIPG brainstem tumors were treated with carmustine dissolved in DW 5% or carmustine dissolved in 10% ethanol. Our results show that CED into the murine brainstem is feasible and well tolerated by mice with and without brainstem tumors. CED of carmustine dissolved in 5% DW increased median survival of mice with VUMC-DIPG-3 and E98FM-DIPG tumors with 35% and 25% respectively. Dissolving carmustine in 10% ethanol further improved survival to 45% in mice with E98FM-DIPG tumors. Since genetically engineered and primary DIPG models are currently only available in mice, murine CED studies have clear advantages over CED studies in other animals. CED in the murine brainstem can be performed safely, is well tolerated and can be used to study efficacy of chemotherapeutic agents orthotopically. These results set the foundation for more CED studies in murine DIPG models. Copyright © 2014 Elsevier B.V. All rights reserved.

Normative Bilateral Brainstem Evoked Response Data for a Naval Aviation Student Population: Group Statistics

DTIC Science & Technology

1979-08-07

laus levels of the present study all fall within the plus and sinus one -standard deviation boundar; limits of the composite laboratory data plotted by...to be the case in the present study in that the =pz!Aude of the contralateral response prtduced by a given stimulus level follcuzd, in general, that...equivalent Gaussian distribution was applied to Cia study data. Such an analysis, performed by Thornton (36) on the latcncy and amplitude measurements

Preclinical Biosafety Evaluation of Genetically Modified Human Adipose Tissue-Derived Mesenchymal Stem Cells for Clinical Applications to Brainstem Glioma.

PubMed

Choi, Seung Ah; Yun, Jun-Won; Joo, Kyeung Min; Lee, Ji Yeoun; Kwak, Pil Ae; Lee, Young Eun; You, Ji-Ran; Kwon, Euna; Kim, Woo Ho; Wang, Kyu-Chang; Phi, Ji Hoon; Kang, Byeong-Cheol; Kim, Seung-Ki

2016-06-15

Stem-cell based gene therapy is a promising novel therapeutic approach for inoperable invasive tumors, including brainstem glioma. Previously, we demonstrated the therapeutic potential of human adipose tissue-derived mesenchymal stem cells (hAT-MSC) genetically engineered to express a secreted form of tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) against brainstem glioma. However, safety concerns should be comprehensively investigated before clinical applications of hAT-MSC.sTRAIL. At first, we injected stereotactically low (1.2 × 10(5) cells/18 μL), medium (2.4 × 10(5)/18 μL), or high dose (3.6 × 10(5)/18 μL) of hAT-MSC.sTRAIL into the brainstems of immunodeficient mice reflecting the plan of the future clinical trial. Local toxicity, systemic toxicity, secondary tumor formation, and biodistribution of hAT-MSC.sTRAIL were investigated. Next, presence of hAT-MSC.sTRAIL was confirmed in the brain and major organs at 4, 9, and 14 weeks in brainstem glioma-bearing mice. In the 15-week subchronic toxicity test, no serious adverse events in terms of body weight, food consumption, clinical symptom, urinalysis, hematology, clinical chemistry, organ weight, and histopathology were observed. In the 26-week tumorigenicity test, hAT-MSC.sTRAIL made no detectable tumors, whereas positive control U-87 MG cells made huge tumors in the brainstem. No remaining hAT-MSC.sTRAIL was observed in any organs examined, including the brainstem at 15 or 26 weeks. In brainstem glioma-bearing mice, injected hAT-MSC.sTRAIL was observed, but gradually decreased over time in the brain. The mRNA of human specific GAPDH and TRAIL was not detected in all major organs. These results indicate that the hAT-MSC.sTRAIL could be applicable to the future clinical trials in terms of biosafety.

Gap prepulse inhibition and auditory brainstem-evoked potentials as objective measures for tinnitus in guinea pigs

PubMed Central

Dehmel, Susanne; Eisinger, Daniel; Shore, Susan E.

2012-01-01

Tinnitus or ringing of the ears is a subjective phantom sensation necessitating behavioral models that objectively demonstrate the existence and quality of the tinnitus sensation. The gap detection test uses the acoustic startle response elicited by loud noise pulses and its gating or suppression by preceding sub-startling prepulses. Gaps in noise bands serve as prepulses, assuming that ongoing tinnitus masks the gap and results in impaired gap detection. This test has shown its reliability in rats, mice, and gerbils. No data exists for the guinea pig so far, although gap detection is similar across mammals and the acoustic startle response is a well-established tool in guinea pig studies of psychiatric disorders and in pharmacological studies. Here we investigated the startle behavior and prepulse inhibition (PPI) of the guinea pig and showed that guinea pigs have a reliable startle response that can be suppressed by 15 ms gaps embedded in narrow noise bands preceding the startle noise pulse. After recovery of auditory brainstem response (ABR) thresholds from a unilateral noise over-exposure centered at 7 kHz, guinea pigs showed diminished gap-induced reduction of the startle response in frequency bands between 8 and 18 kHz. This suggests the development of tinnitus in frequency regions that showed a temporary threshold shift (TTS) after noise over-exposure. Changes in discharge rate and synchrony, two neuronal correlates of tinnitus, should be reflected in altered ABR waveforms, which would be useful to objectively detect tinnitus and its localization to auditory brainstem structures. Therefore, we analyzed latencies and amplitudes of the first five ABR waves at suprathreshold sound intensities and correlated ABR abnormalities with the results of the behavioral tinnitus testing. Early ABR wave amplitudes up to N3 were increased for animals with tinnitus possibly stemming from hyperactivity and hypersynchrony underlying the tinnitus percept. Animals that did not develop tinnitus after noise exposure showed the opposite effect, a decrease in wave amplitudes for the later waves P4–P5. Changes in latencies were only observed in tinnitus animals, which showed increased latencies. Thus, tinnitus-induced changes in the discharge activity of the auditory nerve and central auditory nuclei are represented in the ABR. PMID:22666193

Perception of speech in noise: neural correlates.

PubMed

Song, Judy H; Skoe, Erika; Banai, Karen; Kraus, Nina

2011-09-01

The presence of irrelevant auditory information (other talkers, environmental noises) presents a major challenge to listening to speech. The fundamental frequency (F(0)) of the target speaker is thought to provide an important cue for the extraction of the speaker's voice from background noise, but little is known about the relationship between speech-in-noise (SIN) perceptual ability and neural encoding of the F(0). Motivated by recent findings that music and language experience enhance brainstem representation of sound, we examined the hypothesis that brainstem encoding of the F(0) is diminished to a greater degree by background noise in people with poorer perceptual abilities in noise. To this end, we measured speech-evoked auditory brainstem responses to /da/ in quiet and two multitalker babble conditions (two-talker and six-talker) in native English-speaking young adults who ranged in their ability to perceive and recall SIN. Listeners who were poorer performers on a standardized SIN measure demonstrated greater susceptibility to the degradative effects of noise on the neural encoding of the F(0). Particularly diminished was their phase-locked activity to the fundamental frequency in the portion of the syllable known to be most vulnerable to perceptual disruption (i.e., the formant transition period). Our findings suggest that the subcortical representation of the F(0) in noise contributes to the perception of speech in noisy conditions.

Reconstructed glacier geometry and inferred Equilibrium Line Altitude changes during the Late Pleistocene deglaciation in the Retezat Mountains, Southern Carpathians

NASA Astrophysics Data System (ADS)

Madarász, Balázs; Ruszkiczay-Rüdiger, Zsófia; Kern, Zoltán; Urdea, Petru

2016-04-01

Quaternary glaciations had a major imprint on the landscape and topography of the Southern Carpathians. Their transitional position between continental and Mediterranean climate zones arouses special interest concerning the timing and pattern of glaciations in this area. Probably the Retezat Mts hosted the most extended glaciation during the Late Pleistocene within this range. The peak elevations of the study area reach 2500 m asl, and the most extended glaciers descended to 1040 m in the northern and to 1130 m on the southern valleys. Major cirque floors are typically situated at 2000-2100 m asl. Glacial landforms have been mapped in order to reconstruct the past ice bodies and the elevation shifts of the paleo equilibrium line altitudes (ELA) during several deglaciation phases of the Last Glacial Maximum (LGM) and Lateglacial in the Retezat Mts. On the basis of published 10Be exposure age data on the northern valleys of the study area, deglaciation of the Retezat Mts occurred at least in five phases between ~21.0 ka and 13.5 ka [1]. Various methods (THAR, AAR, AABR) have been tested using a GIS tool to estimate the ELA of the reconstructed paleoglaciers [2] and paleo ELAs were calculated for each of the deglaciation phases. Preliminary estimates of regional LGM paleoELA employing the simplest THAR method (with a ratio of 0.5) ranged from ~1670 m during the LGM to ~2210 m for the smallest cirque glacier at 13.5 ka, respectively. The AAR and AABR methods provide somewhat higher ELAs for each phase. The obtained paleoELAs were compared to ELA reconstructions available from other Carpathian ranges and also to the Alps and Dinarides. Our data will contribute to a more accurate ELA distribution during the LGM, which may be indicative of the past state of the climate system (moisture gradient, circulation regimes). Thanks to OTKA PD83610, PD104899; NKM-96/2014, NKM-31/2015; OMAA 90öu17; LP2012-27/2012. References: [1] Ruszkiczay-Rüdiger et al. 2016 Quat. Int. (in press) doi:10.1016/j.quaint.2015.10.085 [2] Pellitero et al. 2015 Computers & Geosciences 82: 55-62

Systemic leukotriene B4 receptor antagonism lowers arterial blood pressure and improves autonomic function in the spontaneously hypertensive rat

PubMed Central

Marvar, Paul J.; Hendy, Emma B.; Cruise, Thomas D.; Walas, Dawid; DeCicco, Danielle; Vadigepalli, Rajanikanth; Schwaber, James S.; Waki, Hidefumi; Murphy, David

2016-01-01

Key points Evidence indicates an association between hypertension and chronic systemic inflammation in both human hypertension and experimental animal models.Previous studies in the spontaneously hypertensive rat (SHR) support a role for leukotriene B4 (LTB4), a potent chemoattractant involved in the inflammatory response, but its mode of action is poorly understood.In the SHR, we observed an increase in T cells and macrophages in the brainstem; in addition, gene expression profiling data showed that LTB4 production, degradation and downstream signalling in the brainstem of the SHR are dynamically regulated during hypertension.When LTB4 receptor 1 (BLT1) receptors were blocked with CP‐105,696, arterial pressure was reduced in the SHR compared to the normotensive control and this reduction was associated with a significant decrease in systolic blood pressure (BP) indicators.These data provide new evidence for the role of LTB4 as an important neuro‐immune pathway in the development of hypertension and therefore may serve as a novel therapeutic target for the treatment of neurogenic hypertension. Abstract Accumulating evidence indicates an association between hypertension and chronic systemic inflammation in both human hypertension and experimental animal models. Previous studies in the spontaneously hypertensive rat (SHR) support a role for leukotriene B4 (LTB4), a potent chemoattractant involved in the inflammatory response. However, the mechanism for LTB4‐mediated inflammation in hypertension is poorly understood. Here we report in the SHR, increased brainstem infiltration of T cells and macrophages plus gene expression profiling data showing that LTB4 production, degradation and downstream signalling in the brainstem of the SHR are dynamically regulated during hypertension. Chronic blockade of the LTB4 receptor 1 (BLT1) receptor with CP‐105,696, reduced arterial pressure in the SHR compared to the normotensive control and this reduction was associated with a significant decrease in low and high frequency spectra of systolic blood pressure, and an increase in spontaneous baroreceptor reflex gain (sBRG). These data provide new evidence for the role of LTB4 as an important neuro‐immune pathway in the development of hypertension and therefore may serve as a novel therapeutic target for the treatment of neurogenic hypertension. PMID:27230966

Cochlear Hair Cell Electrochemistry: Mechanisms for Bidirectional Transduction.

DTIC Science & Technology

1988-06-30

cytoplasm in the cell’s laminated cisternal system. More specifically, we postulate that intracochlear potential gradients associated with acoustic...transduction drive intracellular fluids through an electo-osmotic "pump" formed by the plasma membrane and the morphologically unique laminated cisternal ...laminated cisternal system in the hearing loss measured with brainstem evoked response. The highly polycationic nature of the polyamines suggest their

Auditory brainstem responses of CBA/J mice with neonatal conductive hearing losses and treatment with GM1 ganglioside.

PubMed

Money, M K; Pippin, G W; Weaver, K E; Kirsch, J P; Webster, D B

1995-07-01

Exogenous administration of GM1 ganglioside to CBA/J mice with a neonatal conductive hearing loss ameliorates the atrophy of spiral ganglion neurons, ventral cochlear nucleus neurons, and ventral cochlear nucleus volume. The present investigation demonstrates the extent of a conductive loss caused by atresia and tests the hypothesis that GM1 ganglioside treatment will ameliorate the conductive hearing loss. Auditory brainstem responses were recorded from four groups of seven mice each: two groups received daily subcutaneous injections of saline (one group had normal hearing; the other had a conductive hearing loss); the other two groups received daily subcutaneous injections of GM1 ganglioside (one group had normal hearing; the other had a conductive hearing loss). In mice with a conductive loss, decreases in hearing sensitivity were greatest at high frequencies. The decreases were determined by comparing mean ABR thresholds of the conductive loss mice with those of normal hearing mice. The conductive hearing loss induced in the mice in this study was similar to that seen in humans with congenital aural atresias. GM1 ganglioside treatment had no significant effect on ABR wave I thresholds or latencies in either group.

Auditory brainstem response (ABR) profiling tests as diagnostic support for schizophrenia and adult attention-deficit hyperactivity disorder (ADHD).

PubMed

Juselius Baghdassarian, Eva; Nilsson Markhed, Maria; Lindström, Eva; Nilsson, Björn M; Lewander, Tommy

2018-06-01

To evaluate the performances of two auditory brainstem response (ABR) profiling tests as potential biomarkers and diagnostic support for schizophrenia and adult attention-deficit hyperactivity disorder (ADHD), respectively, in an investigator-initiated blinded study design. Male and female patients with schizophrenia (n=26) and adult ADHD (n=24) meeting Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM IV) diagnostic criteria and healthy controls (n=58) comprised the analysis set (n=108) of the total number of study participants (n=119). Coded sets of randomized ABR recordings were analysed by an independent party blinded to clinical diagnoses before a joint code-breaking session. The ABR profiling test for schizophrenia identified schizophrenia patients versus controls with a sensitivity of 84.6% and a specificity of 93.1%. The ADHD test identified patients with adult ADHD versus controls with a sensitivity of 87.5% and a specificity of 91.4%. The ABR profiling tests discriminated schizophrenia and ADHD versus healthy controls with high sensitivity and specificity. The methods deserve to be further explored in larger clinical studies including a broad range of psychiatric disorders to determine their utility as potential diagnostic biomarkers.

Brain stem evoked response audiometry of former drug users.

PubMed

Weich, Tainara Milbradt; Tochetto, Tania Maria; Seligman, Lilian

2012-10-01

Illicit drugs are known for their deleterious effects upon the central nervous system and more specifically for how they adversely affect hearing. This study aims to analyze and compare the hearing complaints and the results of brainstem evoked response audiometry (BERA) of former drug user support group goers. This is a cross-sectional non-experimental descriptive quantitative study. The sample consisted of 17 subjects divided by their preferred drug of use. Ten individuals were placed in the marijuana group (G1) and seven in the crack/cocaine group (G2). The subjects were further divided based on how long they had been using drugs: 1 to 5 years, 6 to 10 years, and over 15 years. They were interviewed, and assessed by pure tone audiometry, acoustic impedance tests, and BERA. No statistically significant differences were found between G1 and G2 or time of drug use in absolute latencies and interpeak intervals. However, only five of the 17 individuals had BERA results with adequate results for their ages. Marijuana and crack/cocaine may cause diffuse disorders in the brainstem and compromise the transmission of auditory stimuli regardless of how long these substances are used for.

Sensorineural hearing loss among cerebellopontine-angle tumor patients examined with pure tone audiometry and brainstem-evoked response audiometry

NASA Astrophysics Data System (ADS)

Rinindra, A. M.; Zizlavsky, S.; Bashiruddin, J.; Aman, R. A.; Wulani, V.; Bardosono, S.

2017-08-01

Tumor in the cerebellopontine angle (CPA) accurs for approximately 5-10% of all intracranial tumors, where unilateral hearing loss and tinnitus are the most frequent symptoms. This study aimed to collect data on sensorineural hearing loss in CPA tumor patients in Dr. Cipto Mangunkusumo Hospital (CMH) using pure tone audiometry and brainstem-evoked response audiometry (BERA). It also aimed to obtaine data on CPA-tumor imaging through magnetic resonance imaging (MRI). This was a descriptive, analytic, and cross-sectional study. The subjects of this study were gathered using a total sampling method from secondary data between July 2012 and November 2016. From 104 patients, 30 matched the inclusion criteria. The CPA-tumor patients in the ENT CMH outpatient clinic were mostly female, middle-aged patients (41-60 years) whose clinical presentation was mostly tinnitus and severe, asymmetric sensorineural hearing loss in 10 subjects. From 30 subjects, 29 showed ipsilaterally impaired BERA results, and 17 subjects showed contralaterally impaired BERA results. There were 24 subjects who with large-sized tumors and 19 subjects who had intracanal tumors that had spread until they were extracanal in 19 subjects.

Abnormal auditory forward masking pattern in the brainstem response of individuals with Asperger syndrome

PubMed Central

Källstrand, Johan; Olsson, Olle; Nehlstedt, Sara Fristedt; Sköld, Mia Ling; Nielzén, Sören

2010-01-01

Abnormal auditory information processing has been reported in individuals with autism spectrum disorders (ASD). In the present study auditory processing was investigated by recording auditory brainstem responses (ABRs) elicited by forward masking in adults diagnosed with Asperger syndrome (AS). Sixteen AS subjects were included in the forward masking experiment and compared to three control groups consisting of healthy individuals (n = 16), schizophrenic patients (n = 16) and attention deficit hyperactivity disorder patients (n = 16), respectively, of matching age and gender. The results showed that the AS subjects exhibited abnormally low activity in the early part of their ABRs that distinctly separated them from the three control groups. Specifically, wave III amplitudes were significantly lower in the AS group than for all the control groups in the forward masking condition (P < 0.005), which was not the case in the baseline condition. Thus, electrophysiological measurements of ABRs to complex sound stimuli (eg, forward masking) may lead to a better understanding of the underlying neurophysiology of AS. Future studies may further point to specific ABR characteristics in AS individuals that separate them from individuals diagnosed with other neurodevelopmental diseases. PMID:20628629

Auditory brainstem response screening for hearing loss in high risk neonates.

PubMed

Watson, D R; McClelland, R J; Adams, D A

1996-07-01

The present paper reports the findings of a 7 year study evaluating the use of the auditory brainstem response (ABR) as the basis of a hearing screening procedure in a group of newborns at increased risk of hearing impairment. A Special Care Baby Unit (SCBU) population of 417 infants with diverse clinical backgrounds and treatment histories was tested for hearing impairment at birth using ABR audiometry. Some 332 passed the original screen at 30 dBnHL test level in both ears. Of the failure group, 18 did not survive and 32 had some degree of hearing impairment confirmed, nine of which were sensorineural in origin. An increased incidence of persistent middle ear disease was also noted in the failure group. A detailed operational analysis demonstrates that provided appropriate pass/fail criteria are adopted, the ABR technique offers excellent sensitivity and specificity for the detection of significant hearing loss in the test population. Furthermore, the study establishes that implementation of an ABR-based screening programme could reduce the average age at detection of permanent hearing loss by 7 months. A cost assessment shows that the introduction of such a targetted screening procedure could be done at a reasonable outlay.

Test-retest reliability of auditory brainstem responses to chirp stimuli in newborns.

PubMed

Cobb, Kensi M; Stuart, Andrew

2014-11-01

The purpose of this study was to examine the test-retest reliability of auditory brainstem responses (ABRs) to air- and bone-conducted chirp stimuli in newborns as a function of intensity. A repeated measures quasi-experimental design was employed. Thirty healthy newborns participated. ABRs were evoked using 60, 45, and 30 dB nHL air-conducted CE-Chirps and 45, 30, and 15 dB nHL bone-conducted CE-Chirps at a rate of 57.7/s. Measures were repeated by a second tester. Statistically significant correlations (p <.0001) and predictive linear relations (p <.0001) were found between testers for wave V latencies and amplitudes to air- and bone-conducted CE-Chirps. There were also no statistically significant differences between testers with wave V latencies and amplitudes to air- and bone-conducted CE-Chirps (p >.05). As expected, significant differences in wave V latencies and amplitudes were seen as a function of stimulus intensity for air- and bone-conducted CE-Chirps (p <.0001). These results suggest that ABRs to air- and bone-conducted CE-Chirps can be reliably repeated in newborns with different testers. The CE-Chirp may be valuable for both screening and diagnostic audiologic assessments of newborns.

Audiological findings in Noonan syndrome.

PubMed

Tokgoz-Yilmaz, Suna; Turkyilmaz, Meral Didem; Cengiz, Filiz Basak; Sjöstrand, Alev Pektas; Kose, Serdal Kenan; Tekin, Mustafa

2016-10-01

The aim of this study was to evaluate audiologic properties of patients with Noonan syndrome and compare these findings with those of unaffected peers. The study included 17 children with Noonan syndrome and 20 typically developing children without Noonan syndrome. Pure tone and speech audiometry, immitancemetric measurement, otoacoustic emissions measurement and auditory brainstem response tests were applied to all (n = 37) children. Hearing thresholds of children with Noonan syndrome were higher (poorer) than those observed unaffected peers, while the hearing sensitivity of the both groups were normal limits (p = 0.013 for right, p = 0.031 for left ear). Transient evoked otoacoustic emissions amplitudes of the children with Noonan syndrome were lower than the children without Noonan syndrome (p = 0.005 for right, p = 0.002 for left ear). Middle ear pressures and auditory brainstem response values were within normal limits and there was no difference between the two groups (p > 0.05). General benefit of the present study is to characterize the audiologic findings of children with Noonan syndrome, which is beneficial in clinics evaluating children with Noonan syndrome. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Minocycline Protection of Neomycin Induced Hearing Loss in Gerbils

PubMed Central

Robinson, Alan M.; Vujanovic, Irena; Richter, Claus-Peter

2015-01-01

This animal study was designed to determine if minocycline ameliorates cochlear damage is caused by intratympanic injection of the ototoxic aminoglycoside antibiotic neomycin. Baseline auditory-evoked brainstem responses were measured in gerbils that received 40 mM intratympanic neomycin either with 0, 1.2, or 1.5 mg/kg intraperitoneal minocycline. Four weeks later auditory-evoked brainstem responses were measured and compared to the baseline measurements. Minocycline treatments of 1.2 mg/kg and 1.5 mg/kg resulted in significantly lower threshold increases compared to 0 mg/kg, indicating protection of hearing loss between 6 kHz and 19 kHz. Cochleae were processed for histology and sectioned to allow quantification of the spiral ganglion neurons and histological evaluation of organ of Corti. Significant reduction of spiral ganglion neuron density was demonstrated in animals that did not receive minocycline, indicating that those receiving minocycline demonstrated enhanced survival of spiral ganglion neurons, enhanced survival of sensory hairs cells and spiral ganglion neurons, and reduced hearing threshold elevation correlates with minocycline treatment demonstrating that neomycin induced hearing loss can be reduced by the simultaneous application of minocycline. PMID:25950003

[The characteristics of auditory brainstem response in preterm very low birth weight babies].

PubMed

Wang, Xiaoya; Luo, Renzhong; Wen, Ruijin; Chen, Qian; Zhou, Jialin; Zou, Yu

2009-08-01

To discuss the characteristics of auditory brainstem response in preterm very low birth weight (VLBW) babies and to investigate the correlations between the ABR and clinical characteristics. Fifty-nine VLBW babies (118 ears) were enrolled in the study and 30 term normal babies as the control group. Tympanometry, acoustic reflex, DPOAE, ABR were obtained in all the babies. The prevalence of hearing loss in VLBW babies was higher than normal term babies and babies with perinatal complications higher than those without perinatal complications. There was no correlations between ABR threshold and gestational age, birth weight, postconceptional age, negative correlations between wave I, III and V latencies I - III, III - V and I - V intervals and postconceptional age. Wave I and V latencies, I - III and III - V intervals differed significantly between the two groups. The perinatal complications were the most important causes of the hearing loss in preterm VLBW babies than the gestational age and birth weight. There was a high prevalence of peripheral hearing loss in the preterm VLBW babies. Combining OAE and automated ABR should be applied for hearing screening. Regular follow-up was very important in all the preterm VLBW neonatal.

Conjunct SEP and MEP monitoring in resection of infratentorial lesions: lessons learned in a cohort of 210 patients.

PubMed

Kodama, Kunihiko; Javadi, Mani; Seifert, Volker; Szelényi, Andrea

2014-12-01

During the surgical removal of infratentorial lesions, intraoperative neuromonitoring is mostly focused on cranial nerve assessment and brainstem auditory potentials. Despite the known risk of perforating vessel injury during microdissection within the vicinity of the brainstem, there are few reports about intraoperative neuromonitoring with somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) assessing the medial lemniscus and corticospinal tract. This study analyses the occurrence of intraoperative changes in MEPs and SEPs with regard to lesion location and postoperative neurological outcome. The authors analyzed 210 cases in which patients (mean age 49 ± 13 years, 109 female) underwent surgeries involving the skull base (n = 104), cerebellum (n = 63), fourth ventricle (n = 28), brainstem (n = 12), and foramen magnum (n = 3). Of 210 surgeries, 171 (81.4%) were uneventful with respect to long-tract monitoring. Nine (23%) of the 39 SEP and/or MEP alterations were transient and were only followed by a slight permanent deficit in 1 case. Permanent deterioration only was seen in 19 (49%) of 39 cases; the deterioration was related to tumor dissection in 4 of these cases, and permanent deficit (moderate-severe) was seen in only 1 of these 4 cases. Eleven patients (28%) had losses of at least 1 modality, and in 9 of these 11 cases, the loss was related to surgical microdissection within the vicinity of the brainstem. Four of these 9 patients suffered a moderate-to-severe long-term deficit. For permanent changes, the positive predictive value for neuromonitoring of the long tracts was 0.467, the negative predictive value was 0.989, the sensitivity was 0.875, and the specificity 0.918. Twenty-eight (72%) of 39 SEP and MEP alterations occurred in 66 cases involving intrinsic brainstem tumors or tumors adjacent to the brainstem. Lesion location and alterations in intraoperative neuromonitoring significantly correlated with patients' outcome (p < 0.001, chi-square test). In summary, long-tract monitoring with SEPs and MEPs in infratentorial surgeries has a high sensitivity and negative predictive value with respect to postoperative neurological status. It is recommended especially in those surgeries in which microdissection within and in the vicinity of the brainstem might lead to injury of the brainstem parenchyma or perforating vessels and a subsequent perfusion deficit within the brainstem.

Our first decade of experience in deep brain stimulation of the brainstem: elucidating the mechanism of action of stimulation of the ventrolateral pontine tegmentum.

PubMed

Mazzone, Paolo; Vilela Filho, Osvaldo; Viselli, Fabio; Insola, Angelo; Sposato, Stefano; Vitale, Flora; Scarnati, Eugenio

2016-07-01

The region of the pedunculopontine tegmental nucleus (PPTg) has been proposed as a novel target for deep brain stimulation (DBS) to treat levodopa resistant symptoms in motor disorders. Recently, the anatomical organization of the brainstem has been revised and four new distinct structures have been represented in the ventrolateral pontine tegmentum area in which the PPTg was previously identified. Given this anatomical reassessment, and considering the increasing of our experience, in this paper we revisit the value of DBS applied to that area. The reappraisal of clinical outcomes in the light of this revisitation may also help to understand the consequences of DBS applied to structures located in the ventrolateral pontine tegmentum, apart from the PPTg. The implantation of 39 leads in 32 patients suffering from Parkinson's disease (PD, 27 patients) and progressive supranuclear palsy (PSP, four patients) allowed us to reach two major conclusions. The first is that the results of the advancement of our technique in brainstem DBS matches the revision of brainstem anatomy. The second is that anatomical and functional aspects of our findings may help to explain how DBS acts when applied in the brainstem and to identify the differences when it is applied either in the brainstem or in the subthalamic nucleus. Finally, in this paper we discuss how the loss of neurons in brainstem nuclei occurring in both PD and PSP, the results of intraoperative recording of somatosensory evoked potentials, and the improvement of postural control during DBS point toward the potential role of ascending sensory pathways and/or other structures in mediating the effects of DBS applied in the ventrolateral pontine tegmentum region.

Mapping of enkephalins and adrenocorticotropic hormone in the squirrel monkey brainstem.

PubMed

Duque-Díaz, Ewing; Díaz-Cabiale, Zaida; Narváez, José Angel; Coveñas, Rafael

2017-03-01

An immunocytochemical technique has been used to study for the first time the distribution of fibers and cell bodies containing leucine-enkephalin (leu-enk), methionine-enkephalin (met-enk) or adrenocorticotropic hormone (ACTH) in the whole brainstem of the squirrel monkey Saimiri sciureus. Cell bodies containing leu-enk or met-enk were found in the superior colliculus and the formatio reticularis tegmenti mesencephali, respectively. No immunoreactive cell bodies containing ACTH were observed. Leu-enk-immunoreactive fibers were observed in 40 brainstem nuclei/tracts/regions, fibers containing met-enk were found in 38 brainstem nuclei/tracts/regions and fibers containing ACTH were found in 26 nuclei/tracts/regions. In the latter case, the density of immunoreactive fibers was always low. A high/moderate density of leu-enk- or met-enk-immunoreactive fibers were found in 18 and 16 brainstem nuclei/tracts/regions, respectively. The distribution of immunoreactive fibers containing leu-enk or met-enk was quite similar, with both leu-enk and met-enk observed in 82.5 % of the squirrel monkey brainstem nuclei/tracts/regions. This relationship is less marked for met-enk and ACTH (60.5 %) and even lower for leu-enk and ACTH (52.5 %). In 42.5 % of the nuclei/tracts/regions of the squirrel monkey brainstem (colliculus superior, substantia grisea centralis, nucleus interpeduncularis, nucleus tractus spinalis nervi trigemini, nucleus tractus solitarii, nucleus parabrachialis, formatio reticularis, substantia nigra), we observed fibers containing all three neuropeptides. The widespread distribution reported here suggests that enkephalins and ACTH can be involved in several physiological functions. The distribution of the immunoreactive fibers reported here is quite similar to that previously reported for enkephalins and ACTH in Macaca species and humans.

Enhanced Excitatory Connectivity and Disturbed Sound Processing in the Auditory Brainstem of Fragile X Mice.

PubMed

Garcia-Pino, Elisabet; Gessele, Nikodemus; Koch, Ursula

2017-08-02

Hypersensitivity to sounds is one of the prevalent symptoms in individuals with Fragile X syndrome (FXS). It manifests behaviorally early during development and is often used as a landmark for treatment efficacy. However, the physiological mechanisms and circuit-level alterations underlying this aberrant behavior remain poorly understood. Using the mouse model of FXS ( Fmr1 KO ), we demonstrate that functional maturation of auditory brainstem synapses is impaired in FXS. Fmr1 KO mice showed a greatly enhanced excitatory synaptic input strength in neurons of the lateral superior olive (LSO), a prominent auditory brainstem nucleus, which integrates ipsilateral excitation and contralateral inhibition to compute interaural level differences. Conversely, the glycinergic, inhibitory input properties remained unaffected. The enhanced excitation was the result of an increased number of cochlear nucleus fibers converging onto one LSO neuron, without changing individual synapse properties. Concomitantly, immunolabeling of excitatory ending markers revealed an increase in the immunolabeled area, supporting abnormally elevated excitatory input numbers. Intrinsic firing properties were only slightly enhanced. In line with the disturbed development of LSO circuitry, auditory processing was also affected in adult Fmr1 KO mice as shown with single-unit recordings of LSO neurons. These processing deficits manifested as an increase in firing rate, a broadening of the frequency response area, and a shift in the interaural level difference function of LSO neurons. Our results suggest that this aberrant synaptic development of auditory brainstem circuits might be a major underlying cause of the auditory processing deficits in FXS. SIGNIFICANCE STATEMENT Fragile X Syndrome (FXS) is the most common inheritable form of intellectual impairment, including autism. A core symptom of FXS is extreme sensitivity to loud sounds. This is one reason why individuals with FXS tend to avoid social interactions, contributing to their isolation. Here, a mouse model of FXS was used to investigate the auditory brainstem where basic sound information is first processed. Loss of the Fragile X mental retardation protein leads to excessive excitatory compared with inhibitory inputs in neurons extracting information about sound levels. Functionally, this elevated excitation results in increased firing rates, and abnormal coding of frequency and binaural sound localization cues. Imbalanced early-stage sound level processing could partially explain the auditory processing deficits in FXS. Copyright © 2017 the authors 0270-6474/17/377403-17$15.00/0.

Exploring brainstem function in multiple sclerosis by combining brainstem reflexes, evoked potentials, clinical and MRI investigations.

PubMed

Magnano, Immacolata; Pes, Giovanni Mario; Pilurzi, Giovanna; Cabboi, Maria Paola; Ginatempo, Francesca; Giaconi, Elena; Tolu, Eusebio; Achene, Antonio; Salis, Antonio; Rothwell, John C; Conti, Maurizio; Deriu, Franca

2014-11-01

To investigate vestibulo-masseteric (VMR), acoustic-masseteric (AMR), vestibulo-collic (VCR) and trigemino-collic (TCR) reflexes in patients with multiple sclerosis (MS); to relate abnormalities of brainstem reflexes (BSRs) to multimodal evoked potentials (EPs), clinical and Magnetic Resonance Imaging (MRI) findings. Click-evoked VMR, AMR and VCR were recorded from active masseter and sternocleidomastoid muscles, respectively; TCR was recorded from active sternocleidomastoid muscles, following electrical stimulation of the infraorbital nerve. EPs and MRI were performed with standard techniques. Frequencies of abnormal BSRs were: VMR 62.1%, AMR 55.1%, VCR 25.9%, TCR 58.6%. Brainstem dysfunction was identified by these tests, combined into a four-reflex battery, in 86.9% of cases, by EPs in 82.7%, MRI in 71.7% and clinical examination in 37.7% of cases. The sensitivity of paired BSRs/EPs (93.3%) was significantly higher than combined MRI/clinical testing (70%) in patients with disease duration ⩽6.4years. BSR alterations significantly correlated with clinical, EP and MRI findings. The four-BSR battery effectively increases the performance of standard EPs in early detection of brainstem impairment, otherwise undetected by clinical examination and neuroimaging. Multiple BSR assessment usefully supplements conventional testing and monitoring of brainstem function in MS, especially in newly diagnosed patients. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Enterovirus 71 can directly infect the brainstem via cranial nerves and infection can be ameliorated by passive immunization.

PubMed

Tan, Soon Hao; Ong, Kien Chai; Wong, Kum Thong

2014-11-01

Enterovirus 71 (EV71)-associated hand, foot, and mouth disease may be complicated by encephalomyelitis. We investigated EV71 brainstem infection and whether this infection could be ameliorated by passive immunization in a mouse model. Enterovirus 71 was injected into unilateral jaw/facial muscles of 2-week-old mice, and hyperimmune sera were given before or after infection. Harvested tissues were studied by light microscopy, immunohistochemistry, in situ hybridization, and viral titration. In unimmunized mice, viral antigen and RNA were detected within 24 hours after infection only in ipsilateral cranial nerves, motor trigeminal nucleus, reticular formation, and facial nucleus; viral titers were significantly higher in the brainstem than in the spinal cord samples. Mice given preinfection hyperimmune serum showed a marked reduction of ipsilateral viral antigen/RNA and viral titers in the brainstem in a dose-dependent manner. With optimum hyperimmune serum given after infection, brainstem infection was significantly reduced in a time-dependent manner. A delay in disease onset and a reduction of disease severity and mortality were also observed. Thus, EV71 can directly infect the brainstem, including the medulla, via cranial nerves, most likely by retrograde axonal transport. This may explain the sudden cardiorespiratory collapse in human patients with fatal encephalomyelitis. Moreover, our results suggest that passive immunization may still benefit EV71-infected patients who have neurologic complications.

Expression of cholinergic, insulin, vitamin D receptors and GLUT 3 in the brainstem of streptozotocin induced diabetic rats: effect of treatment with vitamin D₃.

PubMed

Peeyush Kumar, T; Paul, Jes; Antony, Sherin; Paulose, C S

2011-11-01

Complications arising from diabetes mellitus include cognitive deficits, neurophysiological and structural changes in the brain. The current study investigated the expression of cholinergic, insulin, Vitamin D receptor and GLUT 3 in the brainstem of streptozotocin-induced diabetic rats. Radioreceptor binding assays and gene expression were done in the brainstem of male Wistar rats. Our results showed that B(max) of total muscarinic, muscarinic M3 receptors was increased and muscarinic M1 receptor was decreased in diabetic rats compared to control. A significant increase in gene expression of muscarinic M3, α7 nicotinic acetylcholine, insulin, Vitamin D₃ receptors, acetylcholine esterase, choline acetyl transferase and GLUT 3 were observed in the brainstem of diabetic rats. Immunohistochemistry studies of muscarinic M1, M3 and α7 nicotinic acetylcholine receptors confirmed the gene expression at protein level. Vitamin D₃ and insulin treatment reversed diabetes-induced alterations to near control. This study provides an evidence that diabetes can alter the expression of cholinergic, insulin, Vitamin D receptors and GLUT 3 in brainstem. We found that Vitamin D₃ treatment could modulate the Vitamin D receptors and plays a pivotal role in maintaining the glucose transport and expressional level of cholinergic receptors in the brainstem of diabetic rats. Thus, our results suggest a therapeutic role of Vitamin D₃ in managing neurological disorders associated with diabetes.

Opiate-induced Changes in Brain Adenosine Levels and Narcotic Drug Responses

PubMed Central

Wu, Manhong; Sahbaie, Peyman; Zheng, Ming; Lobato, Robert; Boison, Detlev; Clark, J. David; Peltz, Gary

2012-01-01

We have very little information about the metabolomic changes that mediate neurobehavioral responses, including addiction. It was possible that opioid-induced metabolomic changes in brain could mediate some of the pharmacodynamic effects of opioids. To investigate this, opiate-induced brain metabolomic responses were profiled using a semi-targeted method in C57BL/6 and 129Sv1 mice, which exhibit extreme differences in their tendency to become opiate dependent. Escalating morphine doses (10–40 mg/kg) administered over a 4-day period selectively induced a two-fold decrease (p<0.00005) in adenosine abundance in the brainstem of C57BL/6 mice, which exhibited symptoms of narcotic drug dependence; but did not decrease adenosine abundance in 129Sv1 mice, which do not exhibit symptoms of dependence. Based on this finding, the effect of adenosine on dependence was investigated in genetically engineered mice with alterations in adenosine tone in the brain and in pharmacologic experiments. Morphine withdrawal behaviors were significantly diminished (P<0.0004) in genetically engineered mice with reduced adenosine tone in the brainstem, and by treatment with an adenosine receptor1 (A1) agonist (2-chloro-N6-cyclopentyladenosine, 0.5 mg/kg) or an A2a receptor (A2a) antagonist (SCH 58261 1 mg/kg). These results indicate that adenosine homeostasis plays a crucial role in narcotic drug responses. Opiate-induced changes in brain adenosine levels may explain many important neurobehavioral features associated with opiate addiction and withdrawal. PMID:23098802

Plasticity of vagal brainstem circuits in the control of gastrointestinal function

PubMed Central

Browning, Kirsteen N; Travagli, R. Alberto

2010-01-01

The afferent vagus transmits sensory information from the gastrointestinal (GI) tract and other viscera to the brainstem via a glutamatergic synapse at the level of the nucleus of the solitary tract (NTS). Second order NTS neurons integrate this sensory information with inputs from other CNS regions that regulate autonomic functions and homeostasis. Glutamatergic and GABAergic neurons are responsible for conveying the integrated response to other nuclei, including the adjacent dorsal motor nucleus of the vagus (DMV). The preganglionic neurons in the DMV are the source of the parasympathetic motor response back to the GI tract. The glutamatergic synapse between the NTS and DMV is unlikely to be tonically active in regulating gastric motility and tone although almost all neurotransmitters tested so far modulate transmission at this synapse. In contrast, the tonic inhibitory GABAergic input from the NTS to the DMV appears to be critical in setting the tone of gastric motility and, under basal conditions, is unaffected by many neurotransmitters or neurohormones. This review is based, in part, on a presentation by Dr Browning at the 2009 ISAN meeting in Sydney, Australia and discusses how neurohormones and macronutrients modulate glutamatergic transmission to NTS neurons and GABAergic transmission to DMV neurons in relation to sensory information that is received from the GI tract. These neurohormones and macronutrients appear to exert efficient “on-demand” control of the motor output from the DMV in response to ever-changing demands required to maintain homeostasis. PMID:21147043

Prediction of permanent hearing loss in high-risk preterm infants at term age.

PubMed

Valkama, A M; Laitakari, K T; Tolonen, E U; Väyrynen, M R; Vainionpää, L K; Koivisto, M E

2000-06-01

The aim of this series was to assess hearing screenings; auditory brainstem responses (ABR), transient evoked otoacoustic emissions (TEOAE) and free field auditory responses (FF) for the prediction of permanent bilateral hearing loss in high-risk preterm infants at term post-conceptional age. A total of 51 preterm infants (gestational age < 34 weeks, birth weight < 1500 g) underwent examinations at term and hearing, speech and neurological development were followed up until a corrected age of 18 months. Significant hearing defects were verified by broader ABR examinations under sedation and by clinical ward observation including responsiveness to sounds and enhancement of hearing using an amplification device. Seven bilateral fails in ABR were found, together with nine bilateral fails in TEOAE and four fails in FF screening at term age. Six preterm infants were later confirmed to have a significant permanent bilateral hearing loss, four of whom had also cerebral palsy. Bilateral failure in ABR screening predicted hearing loss with a sensitivity of 100% and a specificity of 98%, TEOAE with a sensitivity of 50% and a specificity of 84% and in the FF examination at the levels of 50% and 98%, respectively. Transient evoked otoacoustic emissions alone seem not to be so applicable to the neonatal screening of hearing in high-risk preterm infants as shown earlier in full-term infants, possibly because a hearing defect may be due to retrocochlear damage. Consequently, auditory brainstem response screening seems to be more suitable for very low birth weight preterm infants.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trifiletti, Daniel M., E-mail: daniel.trifiletti@gmail.com; Lee, Cheng-Chia; Kano, Hideyuki

Purpose: To pool data across multiple institutions internationally and report on the cumulative experience of brainstem stereotactic radiosurgery (SRS). Methods and Materials: Data on patients with brainstem metastases treated with SRS were collected through the International Gamma Knife Research Foundation. Clinical, radiographic, and dosimetric characteristics were compared for factors prognostic for local control (LC) and overall survival (OS) using univariate and multivariate analyses. Results: Of 547 patients with 596 brainstem metastases treated with SRS, treatment of 7.4% of tumors resulted in severe SRS-induced toxicity (grade ≥3, increased odds with increasing tumor volume, margin dose, and whole-brain irradiation). Local control at 12 monthsmore » after SRS was 81.8% and was improved with increasing margin dose and maximum dose. Overall survival at 12 months after SRS was 32.7% and impacted by age, gender, number of metastases, tumor histology, and performance score. Conclusions: Our study provides additional evidence that SRS has become an option for patients with brainstem metastases, with an excellent benefit-to-risk ratio in the hands of experienced clinicians. Prior whole-brain irradiation increases the risk of severe toxicity in brainstem metastasis patients undergoing SRS.« less

Kavalactones and dihydrokavain modulate GABAergic activity in a rat gastric-brainstem preparation.

PubMed

Yuan, Chun-Su; Dey, Lucy; Wang, Anbao; Mehendale, Sangeeta; Xie, Jing-Tian; Aung, Han H; Ang-Lee, Michael K

2002-12-01

Using an in vitro neonatal rat gastric-brainstem preparation, the activity of majority neurons recorded in the nucleus tractus solitarius (NTS) of the brainstem were significantly inhibited by GABA A receptor agonist, muscimol (30 microM), and this inhibition was reversed by selective GABA A receptor antagonist, bicuculline (10 microM). Application of kavalactones (300 microg/ml) and dihydrokavain (300 microM) into the brainstem compartment of the preparation also significantly reduced the discharge rate of these NTS neurons (39 % and 32 %, respectively, compared to the control level), and this reduction was partially reversed by bicuculline (10 microM). Kavalactones or dihydrokavain induced inhibitory effects were not reduced after co-application of saclofen (10 microM; a selective GABA B receptor antagonist) or naloxone (100 nM; an opioid receptor antagonist). Pretreatment with kavalactones (300 microg/ml) or dihydrokavain (300 microM) significantly decreased the NTS inhibitory effects induced by muscimol (30 microM), approximately from 51 % to 36 %. Our results demonstrated modulation of brainstem GABAergic mechanism by kavalactones and dihydrokavain, and suggested that these compounds may play an important role in regulation of GABAergic neurotransmission.

Vertigo in brainstem and cerebellar strokes.

PubMed

Choi, Kwang-Dong; Lee, Hyung; Kim, Ji-Soo

2013-02-01

The aim of this study is to review the recent findings on the prevalence, clinical features, and diagnosis of vertigo from brainstem and cerebellar strokes. Patients with isolated vertigo are at higher risk for stroke than the general population. Strokes involving the brainstem and cerebellum may manifest as acute vestibular syndrome, and acute isolated audiovestibular loss may herald impending infarction in the territory of the anterior inferior cerebellar artery. Appropriate bedside evaluation is superior to MRI for detecting central vestibular syndromes. Recording of vestibular-evoked myogenic potentials is useful for evaluation of the central otolithic pathways in brainstem and cerebellar strokes. Accurate identification of isolated vascular vertigo is very important since misdiagnosis of acute stroke may result in significant morbidity and mortality, whereas overdiagnosis of vascular vertigo would lead to unnecessary costly work-ups and medication.

IFNγ inhibits G-CSF induced neutrophil expansion and invasion of the CNS to prevent viral encephalitis.

PubMed

Ramakrishna, Chandran; Cantin, Edouard M

2018-01-01

Emergency hematopoiesis facilitates the rapid expansion of inflammatory immune cells in response to infections by pathogens, a process that must be carefully regulated to prevent potentially life threatening inflammatory responses. Here, we describe a novel regulatory role for the cytokine IFNγ that is critical for preventing fatal encephalitis after viral infection. HSV1 encephalitis (HSE) is triggered by the invasion of the brainstem by inflammatory monocytes and neutrophils. In mice lacking IFNγ (GKO), we observed unrestrained increases in G-CSF levels but not in GM-CSF or IL-17. This resulted in uncontrolled expansion and infiltration of apoptosis-resistant, degranulating neutrophils into the brainstem, causing fatal HSE in GKO but not WT mice. Excessive G-CSF in GKO mice also induced granulocyte derived suppressor cells, which inhibited T-cell proliferation and function, including production of the anti-inflammatory cytokine IL-10. Unexpectedly, we found that IFNγ suppressed G-CSF signaling by increasing SOCS3 expression in neutrophils, resulting in apoptosis. Depletion of G-CSF, but not GM-CSF, in GKO mice induced neutrophil apoptosis and reinstated IL-10 secretion by T cells, which restored their ability to limit innate inflammatory responses resulting in protection from HSE. Our studies reveals a novel, complex interplay among IFNγ, G-CSF and IL-10, which highlights the opposing roles of G-CSF and IFNγ in regulation of innate inflammatory responses in a murine viral encephalitis model and reveals G-CSF as a potential therapeutic target. Thus, the antagonistic G-CSF-IFNγ interactions emerge as a key regulatory node in control of CNS inflammatory responses to virus infection.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hua Chiaho, E-mail: Chia-Ho.Hua@stjude.org; Merchant, Thomas E.; Gajjar, Amar

Purpose: To characterize therapy-induced changes in normal-appearing brainstems of childhood brain tumor patients by serial diffusion tensor imaging (DTI). Methods and Materials: We analyzed 109 DTI studies from 20 brain tumor patients, aged 4 to 23 years, with normal-appearing brainstems included in the treatment fields. Those with medulloblastomas, supratentorial primitive neuroectodermal tumors, and atypical teratoid rhabdoid tumors (n = 10) received postoperative craniospinal irradiation (23.4-39.6 Gy) and a cumulative dose of 55.8 Gy to the primary site, followed by four cycles of high-dose chemotherapy. Patients with high-grade gliomas (n = 10) received erlotinib during and after irradiation (54-59.4 Gy). Parametricmore » maps of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were computed and spatially registered to three-dimensional radiation dose data. Volumes of interest included corticospinal tracts, medial lemnisci, and the pons. Serving as an age-related benchmark for comparison, 37 DTI studies from 20 healthy volunteers, aged 6 to 25 years, were included in the analysis. Results: The median DTI follow-up time was 3.5 years (range, 1.6-5.0 years). The median mean dose to the pons was 56 Gy (range, 7-59 Gy). Three patterns were seen in longitudinal FA and apparent diffusion coefficient changes: (1) a stable or normal developing time trend, (2) initial deviation from normal with subsequent recovery, and (3) progressive deviation without evidence of complete recovery. The maximal decline in FA often occurred 1.5 to 3.5 years after the start of radiation therapy. A full recovery time trend could be observed within 4 years. Patients with incomplete recovery often had a larger decline in FA within the first year. Radiation dose alone did not predict long-term recovery patterns. Conclusions: Variations existed among individual patients after therapy in longitudinal evolution of brainstem white matter injury and recovery. Early response in brainstem anisotropy may serve as an indicator of the recovery time trend over 5 years after radiation therapy.« less

Coma in fatal adult human malaria is not caused by cerebral oedema

PubMed Central

2011-01-01

Background The role of brain oedema in the pathophysiology of cerebral malaria is controversial. Coma associated with severe Plasmodium falciparum malaria is multifactorial, but associated with histological evidence of parasitized erythrocyte sequestration and resultant microvascular congestion in cerebral vessels. To determine whether these changes cause breakdown of the blood-brain barrier and resultant perivascular or parenchymal cerebral oedema, histology, immunohistochemistry and image analysis were used to define the prevalence of histological patterns of oedema and the expression of specific molecular pathways involved in water balance in the brain in adults with fatal falciparum malaria. Methods The brains of 20 adult Vietnamese patients who died of severe malaria were examined for evidence of disrupted vascular integrity. Immunohistochemistry and image analysis was performed on brainstem sections for activation of the vascular endothelial growth factor (VEGF) receptor 2 and expression of the aquaporin 4 (AQP4) water channel protein. Fibrinogen immunostaining was assessed as evidence of blood-brain barrier leakage and perivascular oedema formation. Correlations were performed with clinical, biochemical and neuropathological parameters of severe malaria infection. Results The presence of oedema, plasma protein leakage and evidence of VEGF signalling were heterogeneous in fatal falciparum malaria and did not correlate with pre-mortem coma. Differences in vascular integrity were observed between brain regions with the greatest prevalence of disruption in the brainstem, compared to the cortex or midbrain. There was a statistically non-significant trend towards higher AQP4 staining in the brainstem of cases that presented with coma (P = .02). Conclusions Histological evidence of cerebral oedema or immunohistochemical evidence of localised loss of vascular integrity did not correlate with the occurrence of pre-mortem coma in adults with fatal falciparum malaria. Enhanced expression of AQP4 water channels in the brainstem may, therefore, reflect a mix of both neuropathological or attempted neuroprotective responses to oedema formation. PMID:21923924

Phase locked neural activity in the human brainstem predicts preference for musical consonance.

PubMed

Bones, Oliver; Hopkins, Kathryn; Krishnan, Ananthanarayan; Plack, Christopher J

2014-05-01

When musical notes are combined to make a chord, the closeness of fit of the combined spectrum to a single harmonic series (the 'harmonicity' of the chord) predicts the perceived consonance (how pleasant and stable the chord sounds; McDermott, Lehr, & Oxenham, 2010). The distinction between consonance and dissonance is central to Western musical form. Harmonicity is represented in the temporal firing patterns of populations of brainstem neurons. The current study investigates the role of brainstem temporal coding of harmonicity in the perception of consonance. Individual preference for consonant over dissonant chords was measured using a rating scale for pairs of simultaneous notes. In order to investigate the effects of cochlear interactions, notes were presented in two ways: both notes to both ears or each note to different ears. The electrophysiological frequency following response (FFR), reflecting sustained neural activity in the brainstem synchronised to the stimulus, was also measured. When both notes were presented to both ears the perceptual distinction between consonant and dissonant chords was stronger than when the notes were presented to different ears. In the condition in which both notes were presented to the both ears additional low-frequency components, corresponding to difference tones resulting from nonlinear cochlear processing, were observable in the FFR effectively enhancing the neural harmonicity of consonant chords but not dissonant chords. Suppressing the cochlear envelope component of the FFR also suppressed the additional frequency components. This suggests that, in the case of consonant chords, difference tones generated by interactions between notes in the cochlea enhance the perception of consonance. Furthermore, individuals with a greater distinction between consonant and dissonant chords in the FFR to individual harmonics had a stronger preference for consonant over dissonant chords. Overall, the results provide compelling evidence for the role of neural temporal coding in the perception of consonance, and suggest that the representation of harmonicity in phase locked neural firing drives the perception of consonance. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Coma in fatal adult human malaria is not caused by cerebral oedema.

PubMed

Medana, Isabelle M; Day, Nicholas P J; Sachanonta, Navakanit; Mai, Nguyen T H; Dondorp, Arjen M; Pongponratn, Emsri; Hien, Tran T; White, Nicholas J; Turner, Gareth D H

2011-09-17

The role of brain oedema in the pathophysiology of cerebral malaria is controversial. Coma associated with severe Plasmodium falciparum malaria is multifactorial, but associated with histological evidence of parasitized erythrocyte sequestration and resultant microvascular congestion in cerebral vessels. To determine whether these changes cause breakdown of the blood-brain barrier and resultant perivascular or parenchymal cerebral oedema, histology, immunohistochemistry and image analysis were used to define the prevalence of histological patterns of oedema and the expression of specific molecular pathways involved in water balance in the brain in adults with fatal falciparum malaria. The brains of 20 adult Vietnamese patients who died of severe malaria were examined for evidence of disrupted vascular integrity. Immunohistochemistry and image analysis was performed on brainstem sections for activation of the vascular endothelial growth factor (VEGF) receptor 2 and expression of the aquaporin 4 (AQP4) water channel protein. Fibrinogen immunostaining was assessed as evidence of blood-brain barrier leakage and perivascular oedema formation. Correlations were performed with clinical, biochemical and neuropathological parameters of severe malaria infection. The presence of oedema, plasma protein leakage and evidence of VEGF signalling were heterogeneous in fatal falciparum malaria and did not correlate with pre-mortem coma. Differences in vascular integrity were observed between brain regions with the greatest prevalence of disruption in the brainstem, compared to the cortex or midbrain. There was a statistically non-significant trend towards higher AQP4 staining in the brainstem of cases that presented with coma (P = .02). Histological evidence of cerebral oedema or immunohistochemical evidence of localised loss of vascular integrity did not correlate with the occurrence of pre-mortem coma in adults with fatal falciparum malaria. Enhanced expression of AQP4 water channels in the brainstem may, therefore, reflect a mix of both neuropathological or attempted neuroprotective responses to oedema formation.

A BDNF loop-domain mimetic acutely reverses spontaneous apneas and respiratory abnormalities during behavioral arousal in a mouse model of Rett syndrome

PubMed Central

Kron, Miriam; Lang, Min; Adams, Ian T.; Sceniak, Michael; Longo, Frank; Katz, David M.

2014-01-01

Reduced levels of brain-derived neurotrophic factor (BDNF) are thought to contribute to the pathophysiology of Rett syndrome (RTT), a severe neurodevelopmental disorder caused by loss-of-function mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). In Mecp2 mutant mice, BDNF deficits have been associated with breathing abnormalities, a core feature of RTT, as well as with synaptic hyperexcitability within the brainstem respiratory network. Application of BDNF can reverse hyperexcitability in acute brainstem slices from Mecp2-null mice, suggesting that therapies targeting BDNF or its receptor, TrkB, could be effective at acute reversal of respiratory abnormalities in RTT. Therefore, we examined the ability of LM22A-4, a small-molecule BDNF loop-domain mimetic and TrkB partial agonist, to modulate synaptic excitability within respiratory cell groups in the brainstem nucleus tractus solitarius (nTS) and to acutely reverse abnormalities in breathing at rest and during behavioral arousal in Mecp2 mutants. Patch-clamp recordings in Mecp2-null brainstem slices demonstrated that LM22A-4 decreases excitability at primary afferent synapses in the nTS by reducing the amplitude of evoked excitatory postsynaptic currents and the frequency of spontaneous and miniature excitatory postsynaptic currents. In vivo, acute treatment of Mecp2-null and -heterozygous mutants with LM22A-4 completely eliminated spontaneous apneas in resting animals, without sedation. Moreover, we demonstrate that respiratory dysregulation during behavioral arousal, a feature of human RTT, is also reversed in Mecp2 mutants by acute treatment with LM22A-4. Together, these data support the hypothesis that reduced BDNF signaling and respiratory dysfunction in RTT are linked, and establish the proof-of-concept that treatment with a small-molecule structural mimetic of a BDNF loop domain and a TrkB partial agonist can acutely reverse abnormal breathing at rest and in response to behavioral arousal in symptomatic RTT mice. PMID:25147297

Interactive effects of toluene and hexane on behavior and neurophysiologic responses in Fischer-344 rats.

PubMed

Pryor, G T; Rebert, C S

1992-01-01

Solvent mixtures are ubiquitous in industrialized environments and are used frequently for recreational purposes. Toluene and hexane are common components of many solvent mixtures and have characteristic, but different, neurotoxic consequences. Interestingly, Takeuchi et al., (1981) reported that toluene attenuated the peripheral neuropathy caused by n-hexane, possibly by blocking its metabolism to 2,5-hexanedione (Perbellini, et al., 1982). To confirm such effects at higher concentrations and to examine effects on the central nervous system (CNS), four groups of 12 rats each were exposed to air, toluene (1200 ppm), hexane (4000 ppm), or a mixture of toluene (1200 ppm) and hexane (4,000 ppm) 14 hr/day for 9 weeks. A battery of behavioral and electrophysiologic tests was used to assess the functional consequences of their exposures. The battery consisted of measures of grip strength, locomotor gait and landing splay, sensory sensitivities during conditioned avoidance performance, the action potential of the ventral caudal nerve, and the brainstem auditory evoked response. Measures of peripheral nervous system functions (e.g., grip strength and conduction velocity) showed interactive effects like those reported by Takeuchi et al. Toluene greatly reduced the neuropathy caused by hexane. Hexane-induced abnormalities in central components of the brainstem response were much less reduced in the presence of toluene. There was no reciprocal action of hexane on the motor syndrome and hearing loss caused by toluene.

Short term total sleep deprivation in the rat increases antioxidant responses in multiple brain regions without impairing spontaneous alternation behavior

PubMed Central

Ramanathan, Lalini; Hu, Shuxin; Frautschy, Sally A.; Siegel, Jerome M.

2009-01-01

Total sleep deprivation (TSD) induces a broad spectrum of cognitive, behavioral and cellular changes. We previously reported that long term (5–11 days) TSD in the rat, by the disk-over-water method, decreases the activity of the antioxidant enzyme superoxide dismutase (SOD) in the brainstem and hippocampus. To gain insight into the mechanisms causing cognitive impairment, here we explore the early associations between metabolic activity, antioxidant responses and working memory (one form of cognitive impairment). Specifically we investigated the impact of short term (6 h) TSD, by gentle handling, on the levels of the endogenous antioxidant, total glutathione (GSHt), and the activities of the antioxidative enzymes, SOD and glutathione peroxidase (GPx). Short term TSD had no significant impact on SOD activity, but increased GSHt levels in the rat cortex, brainstem and basal forebrain, and GPx activity in the rat hippocampus and cerebellum. We also observed increased activity of hexokinase, (HK), the rate limiting enzyme of glucose metabolism, in the rat cortex and hypothalamus. We further showed that 6h of TSD leads to increased exploratory behavior to a new environment, without impairing spontaneous alternation behavior (SAB) in the Y maze. We conclude that acute (6h) sleep loss may trigger compensatory mechanisms (like increased antioxidant responses) that prevent initial deterioration in working memory. PMID:19850085

Interpersonal violence in posttraumatic women: brain networks triggered by trauma-related pictures.

PubMed

Neumeister, Paula; Feldker, Katharina; Heitmann, Carina Y; Helmich, Ruth; Gathmann, Bettina; Becker, Michael P I; Straube, Thomas

2017-04-01

Interpersonal violence (IPV) is one of the most frequent causes for the development of posttraumatic stress disorder (PTSD) in women. Trauma-related triggers have been proposed to evoke automatic emotional responses in PTSD. The present functional magnetic resonance study investigated the neural basis of trauma-related picture processing in women with IPV-PTSD (n = 18) relative to healthy controls (n = 18) using a newly standardized trauma-related picture set and a non-emotional vigilance task. We aimed to identify brain activation and connectivity evoked by trauma-related pictures, and associations with PTSD symptom severity. We found hyperactivation during trauma-related vs neutral picture processing in both subcortical [basolateral amygdala (BLA), thalamus, brainstem] and cortical [anterior cingulate cortex (ACC), medial prefrontal cortex (mPFC), insula, occipital cortex] regions in IPV-PTSD. In patients, brain activation in amygdala, ACC, insula, occipital cortex and brainstem correlated positively with symptom severity. Furthermore, connectivity analyses revealed hyperconnectivity between BLA and dorsal ACC/mPFC. Results show symptom severity-dependent brain activation and hyperconnectivity in response to trauma-related pictures in brain regions related to fear and visual processing in women suffering from IPV-PTSD. These brain mechanisms appear to be associated with immediate responses to trauma-related triggers presented in a non-emotional context in this PTSD subgroup. © The Author (2016). Published by Oxford University Press.

A novel method of brainstem auditory evoked potentials using complex verbal stimuli.

PubMed

Kouni, Sophia N; Koutsojannis, Constantinos; Ziavra, Nausika; Giannopoulos, Sotirios

2014-08-01

The click and tone-evoked auditory brainstem responses are widely used in clinical practice due to their consistency and predictability. More recently, the speech-evoked responses have been used to evaluate subcortical processing of complex signals, not revealed by responses to clicks and tones. Disyllable stimuli corresponding to familiar words can induce a pattern of voltage fluctuations in the brain stem resulting in a familiar waveform, and they can yield better information about brain stem nuclei along the ascending central auditory pathway. We describe a new method with the use of the disyllable word "baba" corresponding to English "daddy" that is commonly used in many other ethnic languages spanning from West Africa to the Eastern Mediterranean all the way to the East Asia. This method was applied in 20 young adults institutionally diagnosed as dyslexic (10 subjects) or light dyslexic (10 subjects) who were matched with 20 sex, age, education, hearing sensitivity, and IQ-matched normal subjects. The absolute peak latencies of the negative wave C and the interpeak latencies of A-C elicited by verbal stimuli "baba" were found to be significantly increased in the dyslexic group in comparison with the control group. The method is easy and helpful to diagnose abnormalities affecting the auditory pathway, to identify subjects with early perception and cortical representation abnormalities, and to apply the suitable therapeutic and rehabilitation management.

Hemifacial Spasm

MedlinePlus

... nerve at the place where it exits the brainstem. × Definition Hemifacial spasm is a neuromuscular disorder characterized ... nerve at the place where it exits the brainstem. View Full Definition Treatment Surgical treatment in the ...

Clinical Correlates of Brainstem Dysfunction in Autistic Children.

ERIC Educational Resources Information Center

Fein, Deborah; And Others

1981-01-01

It is suggested that social and attentional pathology may be more specifically associated with the brainstem pathology that may characterize autism than are symptoms in other developmental areas. (Author)

An adult case of mumps brainstem encephalitis.

PubMed

Koyama, S; Morita, K; Yamaguchi, S; Fujikane, T; Sasaki, N; Aizawa, H; Kikuchi, K

2000-06-01

We present an adult case of mumps brainstem encephalitis. He was successfully treated with steroid pulse therapy and recovered completely except for persistent dysuria. He had not been vaccinated and had no history of acute mumps infection. We consider that encephalitis in this case was caused by a reversible autoimmune process triggered by mumps infection. We emphasize the usefulness of pulse therapy for the treatment of some cases of mumps brainstem encephalitis in addition to the importance of mumps vaccination to prevent such a severe complication as encephalitis.

Learning to Encode Timing: Mechanisms of Plasticity in the Auditory Brainstem

PubMed Central

Tzounopoulos, Thanos; Kraus, Nina

2009-01-01

Mechanisms of plasticity have traditionally been ascribed to higher-order sensory processing areas such as the cortex, whereas early sensory processing centers have been considered largely hard-wired. In agreement with this view, the auditory brainstem has been viewed as a nonplastic site, important for preserving temporal information and minimizing transmission delays. However, recent groundbreaking results from animal models and human studies have revealed remarkable evidence for cellular and behavioral mechanisms for learning and memory in the auditory brainstem. PMID:19477149

Influence of cochlear traveling wave and neural adaptation on auditory brainstem responses.

PubMed

Junius, Dirk; Dau, Torsten

2005-07-01

The present study investigates the relationship between evoked responses to transient broadband chirps and responses to the same chirps when embedded in longer-duration stimuli. It examines to what extent the responses to the composite stimuli can be explained by a linear superposition of the responses to the single components, as a function of stimulus level. In the first experiment, a single rising chirp was temporally and spectrally embedded in two steady-state tones. In the second experiment, the stimulus consisted of a continuous alternating train of chirps: each rising chirp was followed by the temporally reversed (falling) chirp. In both experiments, the transitions between stimulus components were continuous. For stimulation levels up to approximately 70 dB SPL, the responses to the embedded chirp corresponded to the responses to the single chirp. At high stimulus levels (80-100 dB SPL), disparities occurred between the responses, reflecting a nonlinearity in the processing when neural activity is integrated across frequency. In the third experiment, the effect of within-train rate on wave-V response was investigated. The response to the chirp presented at a within-train rate of 95 Hz exhibited the same amplitude as that to the chirp presented in the traditional single-stimulus paradigm at a rate of 13 Hz. For a corresponding experiment with bandlimited chirps of 4 ms duration, where the within-train rate was 250 Hz, a clear reduction of the response amplitude was observed. This nonlinearity in terms of temporal processing most likely reflects effects of short-term adaptation. Overall, the results of the present study further demonstrate the importance of cochlear processing for the formation of brainstem potentials. The data may provide constraints on future models of peripheral processing in the human auditory system. The findings might also be useful for the development of effective stimulation paradigms in clinical applications.

Modeling Cerebral Vascular Injury

DTIC Science & Technology

2016-01-01

vessels to inform the material response of the surrounding brain tissue. 15. SUBJECT TERMS traumatic brain injury, vasculature, injury biomechanics ...Margulies SS. A fiber-reinforced composite model of the viscoelastic behavior of the brainstem in shear. Journal of Biomechanics . 1999;32:865– 870...RH, McDowell K, Vettel J. High rate computational brain injury biomechanics . ARL Ballistic Technology Workshop; 2010 May 24–26; Herndon, VA. Kraft

Enhanced Auditory Brainstem Response and Parental Bonding Style in Children with Gastrointestinal Symptoms

PubMed Central

Seino, Shizuka; Watanabe, Satoshi; Ito, Namiko; Sasaki, Konosuke; Shoji, Kaori; Miura, Shoko; Kozawa, Kanoko; Nakai, Kunihiko; Sato, Hiroshi; Kanazawa, Motoyori; Fukudo, Shin

2012-01-01

Background The electrophysiological properties of the brain and influence of parental bonding in childhood irritable bowel syndrome (IBS) are unclear. We hypothesized that children with chronic gastrointestinal (GI) symptoms like IBS may show exaggerated brainstem auditory evoked potential (BAEP) responses and receive more inadequate parental bonding. Methodology/Principal Findings Children aged seven and their mothers (141 pairs) participated. BAEP was measured by summation of 1,000 waves of the electroencephalogram triggered by 75 dB click sounds. The mothers completed their Children's Somatization Inventory (CSI) and Parental Bonding Instrument (PBI). CSI results revealed 66 (42%) children without GI symptoms (controls) and 75 (58%) children with one or more GI symptoms (GI group). The III wave in the GI group (median 4.10 interquartile range [3.95–4.24] ms right, 4.04 [3.90–4.18] ms left) had a significantly shorter peak latency than controls (4.18 [4.06–4.34] ms right, p = 0.032, 4.13 [4.02–4.24] ms left, p = 0.018). The female GI group showed a significantly shorter peak latency of the III wave (4.00 [3.90–4.18] ms) than controls (4.18 [3.97–4.31] ms, p = 0.034) in the right side. BAEP in the male GI group did not significantly differ from that in controls. GI scores showed a significant correlation with the peak latency of the III wave in the left side (rho = −0.192, p = 0.025). The maternal care PBI scores in the GI group (29 [26]–[33]) were significantly lower than controls (31 [28.5–33], p = 0.010), while the maternal over-protection PBI scores were significantly higher in the GI group (16 [12]–[17]) than controls (13 [10.5–16], p = 0.024). Multiple regression analysis in females also supported these findings. Conclusions It is suggested that children with chronic GI symptoms have exaggerated brainstem responses to environmental stimuli and inadequate parental behaviors aggravate these symptoms. PMID:22470430

Focal traumatic brain stem injury is a rare type of head injury resulting from assault: a forensic neuropathological study.

PubMed

Al-Sarraj, Safa; Fegan-Earl, Ashley; Ugbade, Antonia; Bodi, Istvan; Chapman, Rob; Poole, Simon; Swift, Ben; Jerreat, Peter; Cary, Nat

2012-04-01

Brainstem haemorrhage is common in cases of head injury when it is associated with space-occupying lesion and increases in the intracranial pressure (duret haemorrhage), in cases of diffuse axonal injury (in dorso-lateral quadrant) and diffuses vascular injury (in the periventricular tissue). However focal traumatic brainstem injury is rare. We identified 12 cases of focal traumatic brainstem injury from review of 319 case of head injury. The head trauma had been caused by different mechanisms of complex fall from height and assault. 10/12 are associated with skull fracture, 11/12 with contre coup contusions in the frontal and temporal lobes, 5/12 direct contusions to cerebellum, 5/12 haemorrhage in corpus callosum and 2/11 have gliding contusions. None of the cases had pathological evidence of increase in the intracranial pressure. The bleeding in the pons was at the edge in 2/12 and cross the section in 10/12. The majority of patients were unconscious immediately after the incident (10/12) and 9/12 died within one day. Focal traumatic brainstem injury occurs most likely due to direct impact at the back of the head or stretching forces affecting the brainstem in cases of complex fall from height and after assault, particularly those associated with kicks. It is a serious and commonly fatal brain damage, which needed to be differentiated from other causes of brainstem haemorrhages. Copyright © 2012 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

A single dose of a neuron-binding human monoclonal antibody improves brainstem NAA concentrations, a biomarker for density of spinal cord axons, in a model of progressive multiple sclerosis.

PubMed

Wootla, Bharath; Denic, Aleksandar; Watzlawik, Jens O; Warrington, Arthur E; Rodriguez, Moses

2015-04-29

Intracerebral infection of susceptible mouse strains with Theiler's murine encephalomyelitis virus (TMEV) results in chronic demyelinating disease with progressive axonal loss and neurologic dysfunction similar to progressive forms of multiple sclerosis (MS). We previously showed that as the disease progresses, a marked decrease in brainstem N-acetyl aspartate (NAA; metabolite associated with neuronal integrity) concentrations, reflecting axon health, is measured. We also demonstrated stimulation of neurite outgrowth by a neuron-binding natural human antibody, IgM12. Treatment with either the serum-derived or recombinant human immunoglobulin M 12 (HIgM12) preserved functional motor activity in the TMEV model. In this study, we examined IgM-mediated changes in brainstem NAA concentrations and central nervous system (CNS) pathology. (1)H-magnetic resonance spectroscopy (MRS) showed that treatment with HIgM12 significantly increased brainstem NAA concentrations compared to controls in TMEV-infected mice. Pathologic analysis demonstrated a significant preservation of axons in the spinal cord of animals treated with HIgM12. This study links drug efficacy of slowing deficits with axon preservation and NAA concentrations in the brainstem in a model of progressive MS. HIgM12-mediated changes of NAA concentrations in the brainstem are a surrogate marker of axon injury/preservation throughout the spinal cord. This study provides proof-of-concept that a neuron-reactive human IgM can be therapeutic and provides a biomarker for clinical trials.

Convection-Enhanced Delivery for Diffuse Intrinsic Pontine Glioma Treatment.

PubMed

Zhou, Zhiping; Singh, Ranjodh; Souweidane, Mark M

2017-01-01

Convection-enhanced delivery (CED) is a technique designed to deliver drugs directly into the brain or tumors. Its ability to bypass the blood-brain barrier (BBB), one of the major hurdles in delivering drugs to the brain, has made it a promising drug delivery method for the treatment of primary brain tumors. A number of clinical trials utilizing CED of various therapeutic agents have been conducted to treat patients with supratentorial high-grade gliomas. Significant responses have been observed in certain patients in all of these trials. However, the insufficient ability to monitor drug distribution and pharmacokinetics hampers CED from achieving its potentials on a larger scale. Brainstem CED for diffuse intrinsic pontine glioma (DIPG) treatment is appealing because this tumor is compact and has no definitive treatment. The safety of brainstem CED has been established in small and large animals, and recently in early stage clinical trials. There are a few current clinical trials of brainstem CED in treating DIPG patients using targeted macromolecules such as antibodies and immunotoxins. Future advances for CED in DIPG treatment will come from several directions including: choosing the right agents for infusion; developing better agents and regimen for DIPG infusion; improving instruments and technique for easier and accurate surgical targeting and for allowing multisession or prolonged infusion to implement optimal time sequence; and better understanding and control of drug distribution, clearance and time sequence. CED-based therapies for DIPG will continue to evolve with new understanding of the technique and the disease.

Convection-Enhanced Delivery for Diffuse Intrinsic Pontine Glioma Treatment

PubMed Central

Zhou, Zhiping; Singh, Ranjodh; Souweidane, Mark M.

2017-01-01

Convection-enhanced delivery (CED) is a technique designed to deliver drugs directly into the brain or tumors. Its ability to bypass the blood-brain barrier (BBB), one of the major hurdles in delivering drugs to the brain, has made it a promising drug delivery method for the treatment of primary brain tumors. A number of clinical trials utilizing CED of various therapeutic agents have been conducted to treat patients with supratentorial high-grade gliomas. Significant responses have been observed in certain patients in all of these trials. However, the insufficient ability to monitor drug distribution and pharmacokinetics hampers CED from achieving its potentials on a larger scale. Brainstem CED for diffuse intrinsic pontine glioma (DIPG) treatment is appealing because this tumor is compact and has no definitive treatment. The safety of brainstem CED has been established in small and large animals, and recently in early stage clinical trials. There are a few current clinical trials of brainstem CED in treating DIPG patients using targeted macromolecules such as antibodies and immunotoxins. Future advances for CED in DIPG treatment will come from several directions including: choosing the right agents for infusion; developing better agents and regimen for DIPG infusion; improving instruments and technique for easier and accurate surgical targeting and for allowing multisession or prolonged infusion to implement optimal time sequence; and better understanding and control of drug distribution, clearance and time sequence. CED-based therapies for DIPG will continue to evolve with new understanding of the technique and the disease. PMID:27306036

A developmental classification of malformations of the brainstem.

PubMed

Barkovich, A James; Millen, Kathleen J; Dobyns, William B

2007-12-01

With advances in imaging and genetics, malformations of the brainstem are being more commonly identified. We describe and classify brainstem anomalies in 138 patients ascertained over a period of 10 years Magnetic resonance imaging studies and, where available, clinical records of the patients were retrospectively reviewed. Malformations were segregated according to magnetic resonance findings and classified when possible by embryological mechanisms The most common location for anomalies was the pons, which was involved in 114 patients. The midbrain was involved in 45 patients, whereas the medulla was involved in 14. In 53 patients, more than 1 region was affected (all 3 regions in 6 patients, midbrain and pons in 39, and medulla and pons in 8). The malformations were divided into four groups: (1) malformations with abnormal brainstem segmentation, (2) malformations with segmental hypoplasia, (3) postsegmentation malformations, and (4) malformations associated with abnormal cortical organization The malformations of the brainstem identified in this study were diverse and complex. This proposed classification organizes them into groupings based on known genetics and embryological events. Use of this system will help clinicians and scientists to better understand these disorders and, ultimately, to better counsel families of affected patients.

Impaired brainstem and thalamic high-frequency oscillatory EEG activity in migraine between attacks.

PubMed

Porcaro, Camillo; Di Lorenzo, Giorgio; Seri, Stefano; Pierelli, Francesco; Tecchio, Franca; Coppola, Gianluca

2017-09-01

Introduction We investigated whether interictal thalamic dysfunction in migraine without aura (MO) patients is a primary determinant or the expression of its functional disconnection from proximal or distal areas along the somatosensory pathway. Methods Twenty MO patients and twenty healthy volunteers (HVs) underwent an electroencephalographic (EEG) recording during electrical stimulation of the median nerve at the wrist. We used the functional source separation algorithm to extract four functionally constrained nodes (brainstem, thalamus, primary sensory radial, and primary sensory motor tangential parietal sources) along the somatosensory pathway. Two digital filters (1-400 Hz and 450-750 Hz) were applied in order to extract low- (LFO) and high- frequency (HFO) oscillatory activity from the broadband signal. Results Compared to HVs, patients presented significantly lower brainstem (BS) and thalamic (Th) HFO activation bilaterally. No difference between the two cortical HFO as well as in LFO peak activations between the two groups was seen. The age of onset of the headache was positively correlated with HFO power in the right brainstem and thalamus. Conclusions This study provides evidence for complex dysfunction of brainstem and thalamocortical networks under the control of genetic factors that might act by modulating the severity of migraine phenotype.

Distribution of Neurotensin and Somatostatin-28 (1-12) in the Minipig Brainstem.

PubMed

Sánchez, M L; Vecino, E; Coveñas, R

2016-08-01

Using an indirect immunoperoxidase technique, an in depth study has been carried out for the first time on the distribution of fibres and cell bodies containing neurotensin and somatostatin-28 (1-12) (SOM) in the minipig brainstem. The animals used were not treated with colchicine. The distribution of neurotensin- and SOM-immunoreactive fibres was seen to be quite similar and was moderate in the minipig brainstem: a close anatomical relationship between both neuropeptides was observed. The distribution of cell bodies containing neurotensin or SOM was quite different and restricted. Cell bodies containing neurotensin were found in four brainstem nuclei: nucleus centralis raphae, nucleus dorsalis raphae, in the pars centralis of the nucleus tractus spinalis nervi trigemini and in the nucleus ventralis raphae. Cell bodies containing SOM were found in six nuclei/regions of the brainstem: nucleus ambiguus, nucleus dorsalis motorius nervi vagus, formatio reticularis, nucleus parabrachialis medialis, nucleus reticularis lateralis and nucleus ventralis raphae. According to the observed anatomical distribution of the immunoreactive structures containing neurotensin or SOM, the peptides could be involved in sleep-waking, nociceptive, gustatory, motor, respiratory and autonomic mechanisms. © 2015 Blackwell Verlag GmbH.

Stereotactic radiosurgery for deep intracranial arteriovenous malformations, part 1: Brainstem arteriovenous malformations.

PubMed

Cohen-Inbar, Or; Ding, Dale; Chen, Ching-Jen; Sheehan, Jason P

2016-02-01

The management of brainstem arteriovenous malformations (AVM) are one of the greatest challenges encountered by neurosurgeons. Brainstem AVM have a higher risk of hemorrhage compared to AVM in other locations, and rupture of these lesions commonly results in devastating neurological morbidity and mortality. The potential morbidity associated with currently available treatment modalities further compounds the complexity of decision making for affected patients. Stereotactic radiosurgery (SRS) has an important role in the management of brainstem AVM. SRS offers acceptable obliteration rates with lower risks of hemorrhage occurring during the latency period. Complex nidal architecture requires a multi-disciplinary treatment approach. Nidi partly involving subpial/epipial regions of the dorsal midbrain or cerebellopontine angle should be considered for a combination of endovascular embolization, micro-surgical resection and SRS. Considering the fact that incompletely obliterated lesions (even when reduced in size) could still cause lethal hemorrhages, additional treatment, including repeat SRS and surgical resection should be considered when complete obliteration is not achieved by first SRS. Patients with brainstem AVM require continued clinical and radiological observation and follow-up after SRS, well after angiographic obliteration has been confirmed. Copyright © 2015 Elsevier Ltd. All rights reserved.

A pathway in the brainstem for roll-tilt of the subjective visual vertical: evidence from a lesion-behavior mapping study.

PubMed

Baier, Bernhard; Thömke, Frank; Wilting, Janine; Heinze, Caroline; Geber, Christian; Dieterich, Marianne

2012-10-24

The perceived subjective visual vertical (SVV) is an important sign of a vestibular otolith tone imbalance in the roll plane. Previous studies suggested that unilateral pontomedullary brainstem lesions cause ipsiversive roll-tilt of SVV, whereas pontomesencephalic lesions cause contraversive roll-tilts of SVV. However, previous data were of limited quality and lacked a statistical approach. We therefore tested roll-tilt of the SVV in 79 human patients with acute unilateral brainstem lesions due to stroke by applying modern statistical lesion-behavior mapping analysis. Roll-tilt of the SVV was verified to be a brainstem sign, and for the first time it was confirmed statistically that lesions of the medial longitudinal fasciculus (MLF) and the medial vestibular nucleus are associated with ipsiversive tilt of the SVV, whereas contraversive tilts are associated with lesions affecting the rostral interstitial nucleus of the MLF, the superior cerebellar peduncle, the oculomotor nucleus, and the interstitial nucleus of Cajal. Thus, these structures constitute the anatomical pathway in the brainstem for verticality perception. Present data indicate that graviceptive otolith signals present a predominant role in the multisensory system of verticality perception.

The nucleus parvocellularis reticularis regulates submandibular-sublingual salivary secretion in the rat: a pharmacological study.

PubMed

Ramos, J M; Puerto, A

1988-09-01

This experiment shows that activation of the nucleus parvocellularis reticularis in the rat brainstem provokes salivary hypersecretion by the submandibular-sublingual glands. The secretory effect is mediated by cholinergic mechanisms, as the administration of atropine blocked the flow of saliva evoked by stimulation of the nucleus parvocellularis. In contrast, injection of dihydroergotamine (an alpha-blocker) and/or propranolol (a beta-blocker) failed to significantly reduce submandibular and sublingual salivary secretion when compared to a control group injected with distilled water. The cholinergic nature of the salivary response suggests that the nucleus parvocellularis reticularis exerts its secretory effect on the salivary glands parasympathetically rather than through mechanisms associated with sympathetic pathways. The area of the brainstem activated in the present study closely overlaps the region in which cell bodies of superior salivatory neurons have recently been identified with retrograde transport of peroxidase. The data presented herein represent functional proof in support of the location of the superior salivatory nucleus within the parvocellularis reticular formation.

Long-term treatment with haloperidol affects neuropeptide S and NPSR mRNA levels in the rat brain.

PubMed

Palasz, Artur; Rojczyk, Ewa; Golyszny, Milosz; Filipczyk, Lukasz; Worthington, John J; Wiaderkiewicz, Ryszard

2016-04-01

The brainstem-derived neuropeptide S (NPS) has a multidirectional regulatory activity, especially as a potent anxiolytic factor. Accumulating data suggests that neuroleptics affect peptidergic signalling in various brain structures. However, there is no information regarding the influence of haloperidol on NPS and NPS receptor (NPSR) expression. We assessed NPS and NPSR mRNA levels in brains of rats treated with haloperidol using quantitative real-time polymerase chain reaction. Chronic haloperidol treatment (4 weeks) led to a striking upregulation of NPS and NPSR expression in the rat brainstem. Conversely, the NPSR mRNA expression was decreased in the hippocampus and striatum. This stark increase of NPS in response to haloperidol treatment supports the hypothesis that this neuropeptide is involved in the dopamine-dependent anxiolytic actions of neuroleptics and possibly also in the pathophysiology of mental disorders. Furthermore, our findings underline the complex nature of potential interactions between dopamine receptors and brain peptidergic pathways, which has potential clinical applications.

Workshop: Tuning the ‘cough center’

PubMed Central

Widdicombe, J.; Tatar, M.; Fontana, G.; Hanacek, J.; Davenport, P.; Lavorini, F.; Bolser, D.

2011-01-01

The Workshop considered the mechanisms whereby the ‘cough center’ could be tuned by various afferent inputs. There were particular presentations on the effects of inputs from the nose, mouth, respiratory tract and lungs, cerebral cortex, somatic tissues and the pharynx. From all these sites cough induced from the lungs could be increased or decreased in its strength or modified in its pattern. Thus ‘tuning’ of cough could be due to the interaction of afferent inputs, or to the sensitization or desensitization of brainstem neural pathways. The pattern of response depended on the ‘type’ of cough being studied and, in some instances, on the timing of the sensory input into the brainstem. Cough inputs could also affect various ‘non-cough’ motor outputs from the brain, although this was not the main theme of the Workshop. The main conclusion was that cough is not a stereotyped output from the medullary ‘cough center’, but that its pattern and strength depend on many afferent inputs acting on the ‘cough center’. PMID:21215322

Atoh1-lineal neurons are required for hearing and for the survival of neurons in the spiral ganglion and brainstem accessory auditory nuclei

PubMed Central

Maricich, Stephen M.; Xia, Anping; Mathes, Erin L.; Wang, Vincent Y.; Oghalai, John S.; Fritzsch, Bernd; Zoghbi, Huda Y.

2009-01-01

Atoh1 is a basic helix-loop-helix transcription factor necessary for the specification of inner ear hair cells and central auditory system neurons derived from the rhombic lip. We used the Cre-loxP system and two Cre-driver lines (Egr2Cre and Hoxb1Cre) to delete Atoh1 from different regions of the cochlear nucleus (CN) and accessory auditory nuclei (AAN). Adult Atoh1-conditional knockout mice (Atoh1CKO) are behaviorally deaf, have diminished auditory brainstem evoked responses and disrupted CN and AAN morphology and connectivity. In addition, Egr2; Atoh1CKO mice lose spiral ganglion neurons in the cochlea and AAN neurons during the first 3 days of life, revealing a novel critical period in the development of these neurons. These new mouse models of predominantly central deafness illuminate the importance of the CN for support of a subset of peripheral and central auditory neurons. PMID:19741118

Identification of Dynamic Patterns of Speech-Evoked Auditory Brainstem Response Based on Ensemble Empirical Mode Decomposition and Nonlinear Time Series Analysis Methods

NASA Astrophysics Data System (ADS)

Mozaffarilegha, Marjan; Esteki, Ali; Ahadi, Mohsen; Nazeri, Ahmadreza

The speech-evoked auditory brainstem response (sABR) shows how complex sounds such as speech and music are processed in the auditory system. Speech-ABR could be used to evaluate particular impairments and improvements in auditory processing system. Many researchers used linear approaches for characterizing different components of sABR signal, whereas nonlinear techniques are not applied so commonly. The primary aim of the present study is to examine the underlying dynamics of normal sABR signals. The secondary goal is to evaluate whether some chaotic features exist in this signal. We have presented a methodology for determining various components of sABR signals, by performing Ensemble Empirical Mode Decomposition (EEMD) to get the intrinsic mode functions (IMFs). Then, composite multiscale entropy (CMSE), the largest Lyapunov exponent (LLE) and deterministic nonlinear prediction are computed for each extracted IMF. EEMD decomposes sABR signal into five modes and a residue. The CMSE results of sABR signals obtained from 40 healthy people showed that 1st, and 2nd IMFs were similar to the white noise, IMF-3 with synthetic chaotic time series and 4th, and 5th IMFs with sine waveform. LLE analysis showed positive values for 3rd IMFs. Moreover, 1st, and 2nd IMFs showed overlaps with surrogate data and 3rd, 4th and 5th IMFs showed no overlap with corresponding surrogate data. Results showed the presence of noisy, chaotic and deterministic components in the signal which respectively corresponded to 1st, and 2nd IMFs, IMF-3, and 4th and 5th IMFs. While these findings provide supportive evidence of the chaos conjecture for the 3rd IMF, they do not confirm any such claims. However, they provide a first step towards an understanding of nonlinear behavior of auditory system dynamics in brainstem level.

Auditory Brainstem Responses for Click and CE-chirp Stimuli in Individuals with and without Occupational Noise Exposure

PubMed Central

Pushpalatha, Zeena Venkatacheluvaiah; Konadath, Sreeraj

2016-01-01

Introduction: Encoding of CE-chirp and click stimuli in auditory system was studied using auditory brainstem responses (ABRs) among individuals with and without noise exposure. Materials and Methods: The study consisted of two groups. Group 1 (experimental group) consisted of 20 (40 ears) individuals exposed to occupational noise with hearing thresholds within 25 dB HL. They were further divided into three subgroups based on duration of noise exposure (0–5 years of exposure-T1, 5–10 years of exposure-T2, and >10 years of exposure-T3). Group 2 (control group) consisted of 20 individuals (40 ears). Absolute latency and amplitude of waves I, III, and V were compared between the two groups for both click and CE-chirp stimuli. T1, T2, and T3 groups were compared for the same parameters to see the effect of noise exposure duration on CE-chirp and click ABR. Result: In Click ABR, while both the parameters for wave III were significantly poorer for the experimental group, wave V showed a significant decline in terms of amplitude only. There was no significant difference obtained for any of the parameters for wave I. In CE-Chirp ABR, the latencies for all three waves were significantly prolonged in the experimental group. However, there was a significant decrease in terms of amplitude in only wave V for the same group. Discussion: Compared to click evoked ABR, CE-Chirp ABR was found to be more sensitive in comparison of latency parameters in individuals with occupational noise exposure. Monitoring of early pathological changes at the brainstem level can be studied effectively by using CE-Chirp stimulus in comparison to click stimulus. Conclusion: This study indicates that ABR's obtained with CE-chirp stimuli serves as an effective tool to identify the early pathological changes due to occupational noise exposure when compared to click evoked ABR. PMID:27762255

[Effects of electromagnetic fields emitted by cellular phone on auditory and vestibular labyrinth].

PubMed

Sievert, U; Eggert, S; Goltz, S; Pau, H W

2007-04-01

It is the subject of this study to investigate the biological effect of the HF radiation produced by the Global System for Mobile Communications-( GSM)-mobile phone on the inner ear with its sensors of the vestibular and auditive systems. Thermographic investigations made on various model materials and on the human temporal bone should show whether mobile phone does induce any increases of temperature which would lead to a relevant stimulus for the auditive and vestibular system or not. We carried out video-nystagmographic recordings of 13 subjects, brainstem electric response audiometry of 24 ears, and recordings of distorsion products of otoacoustic emissions of 20 ears. All tests were made with and without a mobile phone in use. The data was then analyzed for variation patterns in the functional parameters of the hearing and balance system that are subject to the (non)existence of electromagnetic radiation from the mobile phone. The thermographic investigations suggest that the mobile phone does not induce any increases of temperature which would lead to a relevant stimulus for the auditive and vestibular system. Video-nystagmographic recordings under field effect do not furnish any indication of vestibular reactions generated by field effects. Compared with the recording without field, the brainstem electric response audiometry under field effect did not reveal any changes of the parameters investigated, i. e. absolute latency of the peaks I, III, V and the interpeak latency between the peaks I and V. The distorsion products of otoacoustic emissions do not indicate, comparing the three measuring situations, i. e. before field effect, pulsed field and continuous field, any possible impacts of the HF field on the spectrum or levels of emissions for none of the probands. The investigations made show that the electromagnetic fields generated in using the mobile phone do not have an effect on the inner ear and auditive system to the colliculus inferior in the brainstem and on the vestibular receptors in the inner ear and the vestibular system.

Comparison of the Full Outline of UnResponsiveness score and the Glasgow Coma Scale in predicting mortality in critically ill patients*.

PubMed

Wijdicks, Eelco F M; Kramer, Andrew A; Rohs, Thomas; Hanna, Susan; Sadaka, Farid; O'Brien, Jacklyn; Bible, Shonna; Dickess, Stacy M; Foss, Michelle

2015-02-01

Impaired consciousness has been incorporated in prediction models that are used in the ICU. The Glasgow Coma Scale has value but is incomplete and cannot be assessed in intubated patients accurately. The Full Outline of UnResponsiveness score may be a better predictor of mortality in critically ill patients. Thirteen ICUs at five U.S. hospitals. One thousand six hundred ninety-five consecutive unselected ICU admissions during a six-month period in 2012. Glasgow Coma Scale and Full Outline of UnResponsiveness score were recorded within 1 hour of admission. Baseline characteristics and physiologic components of the Acute Physiology and Chronic Health Evaluation system, as well as mortality were linked to Glasgow Coma Scale/Full Outline of UnResponsiveness score information. None. We recruited 1,695 critically ill patients, of which 1,645 with complete data could be linked to data in the Acute Physiology and Chronic Health Evaluation system. The area under the receiver operating characteristic curve of predicting ICU mortality using the Glasgow Coma Scale was 0.715 (95% CI, 0.663-0.768) and using the Full Outline of UnResponsiveness score was 0.742 (95% CI, 0.694-0.790), statistically different (p = 0.001). A similar but nonsignificant difference was found for predicting hospital mortality (p = 0.078). The respiratory and brainstem reflex components of the Full Outline of UnResponsiveness score showed a much wider range of mortality than the verbal component of Glasgow Coma Scale. In multivariable models, the Full Outline of UnResponsiveness score was more useful than the Glasgow Coma Scale for predicting mortality. The Full Outline of UnResponsiveness score might be a better prognostic tool of ICU mortality than the Glasgow Coma Scale in critically ill patients, most likely a result of incorporating brainstem reflexes and respiration into the Full Outline of UnResponsiveness score.

Recovery of Dysphagia in Lateral Medullary Stroke

PubMed Central

Gupta, Hitesh; Banerjee, Alakananda

2014-01-01

Lateral medullary stroke is typically associated with increased likelihood of occurrence of dysphagia and exhibits the most severe and persistent form. Worldwide little research exists on dysphagia in brainstem stroke. An estimated 15% of all patients admitted to stroke rehabilitation units experience a brainstem stroke out of which about 47% suffer from dysphagia. In India, a study showed that 22.3% of posterior circulation stroke patients develop dysphagia. Dearth of literature on dysphagia and its outcome in brainstem stroke particularly lateral medullary stroke motivated the author to present an actual case study of a patient who had dysphagia following a lateral medullary infarct. This paper documents the severity and management approach of dysphagia in brainstem stroke, with traditional dysphagia therapy and VitalStim therapy. Despite being diagnosed with a severe form of dysphagia followed by late treatment intervention, the patient had complete recovery of the swallowing function. PMID:25045555

Recovery of Dysphagia in lateral medullary stroke.

PubMed

Gupta, Hitesh; Banerjee, Alakananda

2014-01-01

Lateral medullary stroke is typically associated with increased likelihood of occurrence of dysphagia and exhibits the most severe and persistent form. Worldwide little research exists on dysphagia in brainstem stroke. An estimated 15% of all patients admitted to stroke rehabilitation units experience a brainstem stroke out of which about 47% suffer from dysphagia. In India, a study showed that 22.3% of posterior circulation stroke patients develop dysphagia. Dearth of literature on dysphagia and its outcome in brainstem stroke particularly lateral medullary stroke motivated the author to present an actual case study of a patient who had dysphagia following a lateral medullary infarct. This paper documents the severity and management approach of dysphagia in brainstem stroke, with traditional dysphagia therapy and VitalStim therapy. Despite being diagnosed with a severe form of dysphagia followed by late treatment intervention, the patient had complete recovery of the swallowing function.

A Stem Cell-Seeded Nanofibrous Scaffold for Auditory Nerve Replacement

DTIC Science & Technology

2015-10-01

guinea pigs . Initial results show improved electrically-evoked auditory brainstem responses in cell-seeded implants compared to control, cell-free...scaffold’s conduit, but the IAM of the guinea pig and limits imposed by the surgical approach make this difficult. Alternatives are being pursued...transplantation of the seeded nanofibrous scaffold Task 13. Group 1: Pilot deafening. Confirm efficacy of ß-bungarotoxin in guinea pig and time point of

Audiological and electrophysiological assessment of professional pop/rock musicians.

PubMed

Samelli, Alessandra G; Matas, Carla G; Carvallo, Renata M M; Gomes, Raquel F; de Beija, Carolina S; Magliaro, Fernanda C L; Rabelo, Camila M

2012-01-01

In the present study, we evaluated peripheral and central auditory pathways in professional musicians (with and without hearing loss) compared to non-musicians. The goal was to verify if music exposure could affect auditory pathways as a whole. This is a prospective study that compared the results obtained between three groups (musicians with and without hearing loss and non-musicians). Thirty-two male individuals participated and they were assessed by: Immittance measurements, pure-tone air conduction thresholds at all frequencies from 0.25 to 20 kHz, Transient Evoked Otoacoustic Emissions, Auditory Brainstem Response (ABR), and Cognitive Potential. The musicians showed worse hearing thresholds in both conventional and high frequency audiometry when compared to the non-musicians; the mean amplitude of Transient Evoked Otoacoustic Emissions was smaller in the musicians group, but the mean latencies of Auditory Brainstem Response and Cognitive Potential were diminished in the musicians when compared to the non-musicians. Our findings suggest that the population of musicians is at risk for developing music-induced hearing loss. However, the electrophysiological evaluation showed that latency waves of ABR and P300 were diminished in musicians, which may suggest that the auditory training to which these musicians are exposed acts as a facilitator of the acoustic signal transmission to the cortex.

A comparison of auditory brainstem responses across diving bird species

USGS Publications Warehouse

Crowell, Sara E.; Berlin, Alicia; Carr, Catherine E.; Olsen, Glenn H.; Therrien, Ronald E.; Yannuzzi, Sally E.; Ketten, Darlene R.

2015-01-01

There is little biological data available for diving birds because many live in hard-to-study, remote habitats. Only one species of diving bird, the black-footed penguin (Spheniscus demersus), has been studied in respect to auditory capabilities (Wever et al., Proc Natl Acad Sci USA 63:676–680, 1969). We, therefore, measured in-air auditory threshold in ten species of diving birds, using the auditory brainstem response (ABR). The average audiogram obtained for each species followed the U-shape typical of birds and many other animals. All species tested shared a common region of the greatest sensitivity, from 1000 to 3000 Hz, although audiograms differed significantly across species. Thresholds of all duck species tested were more similar to each other than to the two non-duck species tested. The red-throated loon (Gavia stellata) and northern gannet (Morus bassanus) exhibited the highest thresholds while the lowest thresholds belonged to the duck species, specifically the lesser scaup (Aythya affinis) and ruddy duck (Oxyura jamaicensis). Vocalization parameters were also measured for each species, and showed that with the exception of the common eider (Somateria mollisima), the peak frequency, i.e., frequency at the greatest intensity, of all species' vocalizations measured here fell between 1000 and 3000 Hz, matching the bandwidth of the most sensitive hearing range.

Notched-noise embedded frequency specific chirps for objective audiometry using auditory brainstem responses

PubMed Central

Corona-Strauss, Farah I.; Schick, Bernhard; Delb, Wolfgang; Strauss, Daniel J.

2012-01-01

It has been shown recently that chirp-evoked auditory brainstem responses (ABRs) show better performance than click stimulations, especially at low intensity levels. In this paper we present the development, test, and evaluation of a series of notched-noise embedded frequency specific chirps. ABRs were collected in healthy young control subjects using the developed stimuli. Results of the analysis of the corresponding ABRs using a time-scale phase synchronization stability (PSS) measure are also reported. The resultant wave V amplitude and latency measures showed a similar behavior as for values reported in literature. The PSS of frequency specific chirp-evoked ABRs reflected the presence of the wave V for all stimulation intensities. The scales that resulted in higher PSS are in line with previous findings, where ABRs evoked by broadband chirps were analyzed, and which stated that low frequency channels are better for the recognition and analysis of chirp-evoked ABRs. We conclude that the development and test of the series of notched-noise embedded frequency specific chirps allowed the assessment of frequency specific ABRs, showing an identifiable wave V for different intensity levels. Future work may include the development of a faster automatic recognition scheme for these frequency specific ABRs. PMID:26557336

A comparison of auditory brainstem responses across diving bird species

PubMed Central

Crowell, Sara E.; Wells-Berlin, Alicia M.; Carr, Catherine E.; Olsen, Glenn H.; Therrien, Ronald E.; Yannuzzi, Sally E.; Ketten, Darlene R.

2015-01-01

There is little biological data available for diving birds because many live in hard-to-study, remote habitats. Only one species of diving bird, the black-footed penguin (Spheniscus demersus), has been studied in respect to auditory capabilities (Wever et al. 1969). We therefore measured in-air auditory threshold in ten species of diving birds, using the auditory brainstem response (ABR). The average audiogram obtained for each species followed the U-shape typical of birds and many other animals. All species tested shared a common region of greatest sensitivity, from 1000 to 3000 Hz, although audiograms differed significantly across species. Thresholds of all duck species tested were more similar to each other than to the two non-duck species tested. The red-throated loon (Gavia stellata) and northern gannet (Morus bassanus) exhibited the highest thresholds while the lowest thresholds belonged to the duck species, specifically the lesser scaup (Aythya affinis) and ruddy duck (Oxyura jamaicensis). Vocalization parameters were also measured for each species, and showed that with the exception of the common eider (Somateria mollisima), the peak frequency, i.e. frequency at the greatest intensity, of all species’ vocalizations measured here fell between 1000 and 3000 Hz, matching the bandwidth of the most sensitive hearing range. PMID:26156644

A circuit for detection of interaural time differences in the nucleus laminaris of turtles.

PubMed

Willis, Katie L; Carr, Catherine E

2017-11-15

The physiological hearing range of turtles is approximately 50-1000 Hz, as determined by cochlear microphonics ( Wever and Vernon, 1956a). These low frequencies can constrain sound localization, particularly in red-eared slider turtles, which are freshwater turtles with small heads and isolated middle ears. To determine if these turtles were sensitive to interaural time differences (ITDs), we investigated the connections and physiology of their auditory brainstem nuclei. Tract tracing experiments showed that cranial nerve VIII bifurcated to terminate in the first-order nucleus magnocellularis (NM) and nucleus angularis (NA), and the NM projected bilaterally to the nucleus laminaris (NL). As the NL received inputs from each side, we developed an isolated head preparation to examine responses to binaural auditory stimulation. Magnocellularis and laminaris units responded to frequencies from 100 to 600 Hz, and phase-locked reliably to the auditory stimulus. Responses from the NL were binaural, and sensitive to ITD. Measures of characteristic delay revealed best ITDs around ±200 μs, and NL neurons typically had characteristic phases close to 0, consistent with binaural excitation. Thus, turtles encode ITDs within their physiological range, and their auditory brainstem nuclei have similar connections and cell types to other reptiles. © 2017. Published by The Company of Biologists Ltd.

Comparison of distortion product otoacoustic emissions with auditory brain-stem response for clinical use in neonatal intensive care unit.

PubMed

Ochi, A; Yasuhara, A; Kobayashi, Y

1998-11-01

This study compares the clinical usefulness of distortion product otoacoustic emissions (DPOAEs) with the auditory brain-stem response (ABR) for neonates in the neonatal intensive care unit for the evaluation of hearing impairment. Both DPOAEs and ABR were performed on 36 neonates (67 ears) on the same day. We defined neonates as having normal hearing when the thresholds of wave V of ABR were < or =45 dB hearing level. (1) We could not obtain DPOAEs at f2 = 977 Hz in neonates with normal hearing because of high noise floors. DPOAE recording time was 36 min shorter than that of ABR. (2) We defined as normal DPOAEs, the number of frequencies which showed the DPgram-noise floor > or =4 dB was > or =4 at 6 f2 frequencies, from 1416 Hz to 7959 Hz. (3) Normal thresholds of ABR and normal DPOAEs showed the same percentages, i.e. 68.7%, but the percentage of different results between ABR and DPOAEs was 6.0%. Our study indicates that DPOAEs represent a simple procedure, which can be easily performed in the NICU to obtain reliable results in high-risk neonates. Results obtained by DPOAEs were comparable to those obtained by the more complex procedure of ABR.

Auditory brainstem responses to stop consonants predict literacy.

PubMed

Neef, Nicole E; Schaadt, Gesa; Friederici, Angela D

2017-03-01

Precise temporal coding of speech plays a pivotal role in sound processing throughout the central auditory system, which, in turn, influences literacy acquisition. The current study tests whether an electrophysiological measure of this precision predicts literacy skills. Complex auditory brainstem responses were analysed from 62 native German-speaking children aged 11-13years. We employed the cross-phaseogram approach to compute the quality of the electrophysiological stimulus contrast [da] and [ba]. Phase shifts were expected to vary with literacy. Receiver operating curves demonstrated a feasible sensitivity and specificity of the electrophysiological measure. A multiple regression analysis resulted in a significant prediction of literacy by delta cross-phase as well as phonological awareness. A further commonality analysis separated a unique variance that was explained by the physiological measure, from a unique variance that was explained by the behavioral measure, and common effects of both. Despite multicollinearities between literacy, phonological awareness, and subcortical differentiation of stop consonants, a combined assessment of behavior and physiology strongly increases the ability to predict literacy skills. The strong link between the neurophysiological signature of sound encoding and literacy outcome suggests that the delta cross-phase could indicate the risk of dyslexia and thereby complement subjective psychometric measures for early diagnoses. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

The Relationship between the Behavioral Hearing Thresholds and Maximum Bilirubin Levels at Birth in Children with a History of Neonatal Hyperbilirubinemia

PubMed Central

Panahi, Rasool; Jafari, Zahra; Sheibanizade, Abdoreza; Salehi, Masoud; Esteghamati, Abdoreza; Hasani, Sara

2013-01-01

Introduction: Neonatal hyperbilirubinemia is one of the most important factors affecting the auditory system and can cause sensorineural hearing loss. This study investigated the relationship between behavioral hearing thresholds in children with a history of jaundice and the maximum level of bilirubin concentration in the blood. Materials and Methods: This study was performed on 18 children with a mean age of 5.6 years and with a history of neonatal hyperbilirubinemia. Behavioral hearing thresholds, transient evoked emissions and brainstem evoked responses were evaluated in all children. Results: Six children (33.3%) had normal hearing thresholds and the remaining (66.7%) had some degree of hearing loss. There was no significant relationship (r=-0.28, P=0.09) between the mean total bilirubin levels and behavioral hearing thresholds in all samples. A transient evoked emission was seen only in children with normal hearing thresholds however in eight cases brainstem evoked responses had not detected. Conclusion: Increased blood levels of bilirubin at the neonatal period were potentially one of the causes of hearing loss. There was a lack of a direct relationship between neonatal bilirubin levels and the average hearing thresholds which emphasizes on the necessity of monitoring the various amounts of bilirubin levels. PMID:24303432

Age-dependent plasticity in endocannabinoid modulation of pain processing through postnatal development.

PubMed

Kwok, Charlie H-T; Devonshire, Ian M; Imraish, Amer; Greenspon, Charles M; Lockwood, Stevie; Fielden, Catherine; Cooper, Andrew; Woodhams, Stephen; Sarmad, Sarir; Ortori, Catherine A; Barrett, David A; Kendall, David; Bennett, Andrew J; Chapman, Victoria; Hathway, Gareth J

2017-11-01

Significant age- and experience-dependent remodelling of spinal and supraspinal neural networks occur, resulting in altered pain responses in early life. In adults, endogenous opioid peptide and endocannabinoid (ECs) pain control systems exist which modify pain responses, but the role they play in acute responses to pain and postnatal neurodevelopment is unknown. Here, we have studied the changing role of the ECs in the brainstem nuclei essential for the control of nociception from birth to adulthood in both rats and humans. Using in vivo electrophysiology, we show that substantial functional changes occur in the effect of microinjection of ECs receptor agonists and antagonists in the periaqueductal grey (PAG) and rostroventral medulla (RVM), both of which play central roles in the supraspinal control of pain and the maintenance of chronic pain states in adulthood. We show that in immature PAG and RVM, the orphan receptor, GPR55, is able to mediate profound analgesia which is absent in adults. We show that tissue levels of endocannabinoid neurotransmitters, anandamide and 2-arachidonoylglycerol, within the PAG and RVM are developmentally regulated (using mass spectrometry). The expression patterns and levels of ECs enzymes and receptors were assessed using quantitative PCR and immunohistochemistry. In human brainstem, we show age-related alterations in the expression of key enzymes and receptors involved in ECs function using PCR and in situ hybridisation. These data reveal that significant changes on ECs that to this point have been unknown and which shed new light into the complex neurochemical changes that permit normal, mature responses to pain.

Survey of the Knowledge of Brainstem Death and Attitude Toward Organ Donation Among Relations of Neurosurgical Patients in Nigeria.

PubMed

Rabiu, T B; Oshola, H A; Adebayo, B O

2016-01-01

Organ transplantation is a developing field in Nigeria, and availability of organs for donation would be a determining factor of the success of the transplant programs. Patients with brainstem death (BSD) are a major source of organs for transplantation. The level of knowledge of BSD as well as attitudes toward organ donation are very important determinants of people's willingness or otherwise to donate organs. We conducted a survey of relations of our in-service neurosurgical patients to assess their knowledge of brainstem death and attitude toward organ donation. To our knowledge, this is the first study of its kind among the growing Nigerian neurosurgery patient and patient-relations population. Convenience sampling of randomly selected relations of neurosurgical patients on admission using interviewer-administered questionnaires was performed. Demographic information and information about brainstem death, attitude toward brainstem death, knowledge of organ donation, and attitude toward organ donation were obtained. The study comprised 127 respondents with a mean age of 36 years (range, 19-72). The majority of the respondents (87, 62.4%) were Christians, 122 (96.1%) were Yorubas, and 66 (52.0%) were women. Eighty-five (66.9%) of the respondents had at least a secondary level of education, and 77 (60.6%) were of low socioeconomic status. Twenty-eight (22.2%) of the respondents had heard of brainstem death. Twenty-six (92.9%) of those who had heard of brainstem death believed that the brain could die long before life finally ceases. One hundred twenty-five (98.4%) of the respondents believed that death only occurs when both breathing and heartbeat stop, and 107 (83.6%) would agree with the physician on a diagnosis of brainstem death in the relation. Sixty-five (51.2%) would want such patients put on a ventilator, and, of these, 43 (66.2%) would want such patients on the ventilator in hope that he or she may recover. One hundred twelve (88.2%) of the relations were aware of organ donation, 109 (85.8%) knew that the kidney can be transplanted, and 27 (21.6%) and 17 (13.4%), respectively, were aware of heart and cornea transplant. One hundred five (82.7%) supported organ transplantation, 85 (66.9%) would donate an organ, and 97 (76.4%) would accept a transplanted organ. The majority of the respondents (76, 59.8%) would generally not allow an organ to be taken from their relation, although 70 (55.1%) would allow organ(s) to be harvested from their relation if the person had consented to it before death. More men are likely to donate organs and allow organs to be harvested from their relations than were women. Likewise, respondents with at least a secondary level of education had better awareness of brainstem death and were more likely to donate organs and allow organs to be harvested from their relations than were their less-educated counterparts. The knowledge of brainstem death was low among respondents, although most of them would agree with the physician if such diagnosis was made for their relation. Most of the respondents were aware of organ donation and supported it, but the majority would not allow an organ to be harvested from their relations. Hence, education of the Nigerian people about brainstem death and organ donation is essential to increase the pool of available organs for transplantation in our community. Copyright © 2016 Elsevier Inc. All rights reserved.

Long-term outcome after resection of brainstem hemangioblastomas in von Hippel-Lindau disease

PubMed Central

Wind, Joshua J.; Bakhtian, Kamran D.; Sweet, Jennifer A.; Mehta, Gautam U.; Thawani, Jayesh P.; Asthagiri, Ashok R.; Oldfield, Edward H.; Lonser, Russell R.

2016-01-01

Object Brainstem hemangioblastomas are frequently encountered in patients with von Hippel-Lindau (VHL) disease. These tumors can cause significant morbidity, and their optimal management has not been defined. To better define the outcome and management of these tumors, the authors analyzed the long-term results in patients who underwent resection of brainstem hemangioblastomas. Methods Consecutive patients with VHL disease who underwent resection of brainstem hemangioblastomas with a follow-up of 12 months or more were included in this study. Serial functional assessments, radiographic examinations, and operative records were analyzed. Results Forty-four patients (17 male and 27 female) underwent 51 operations for resection of 71 brainstem hemangioblastomas. The most common presenting symptoms were headache, swallowing difficulties, singultus, gait difficulties, and sensory abnormalities. The mean follow-up was 5.9 ± 5.0 years (range 1.0–20.8 years). Immediately after 34 operations (66.7%), the patients remained at their preoperative functional status; they improved after 8 operations (15.7%) and worsened after 9 operations (17.6%) as measured by the McCormick scale. Eight (88.9%) of the 9 patients who were worse immediately after resection returned to their preoperative status within 6 months. Two patients experienced functional decline during long-term follow-up (beginning at 2.5 and 5 years postoperatively) caused by extensive VHL disease–associated CNS disease. Conclusions Generally, resection of symptomatic brainstem hemangioblastomas is a safe and effective management strategy in patients with VHL disease. Most patients maintain their preoperative functional status, although long-term decline in functional status may occur due to VHL disease–associated progression. PMID:20932100

7 Tesla 22-channel wrap-around coil array for cervical spinal cord and brainstem imaging.

PubMed

Zhang, Bei; Seifert, Alan C; Kim, Joo-Won; Borrello, Joseph; Xu, Junqian

2017-10-01

Increased signal-to-noise ratio and blood oxygenation level-dependent sensitivity at 7 Tesla (T) have the potential to enable high-resolution imaging of the human cervical spinal cord and brainstem. We propose a new two-panel radiofrequency coil design for these regions to fully exploit the advantages of ultra-high field. A two-panel array, containing four transmit/receive and 18 receive-only elements fully encircling the head and neck, was constructed following simulations demonstrating the B1+ and specific absorption rate (SAR) benefits of two-panel over one-panel arrays. This array was compared with a previously reported posterior-only array and tested for safety using a phantom. Its anatomical, functional, and diffusion MRI performance was demonstrated in vivo. The two-panel array produced more uniform B1+ across the brainstem and cervical spinal cord without compromising SAR, and achieved 70% greater receive sensitivity than the posterior-only array. The two-panel design enabled acceleration of R = 2 × 2 in two dimensions or R = 3 in a single dimension. High quality in vivo anatomical, functional, and diffusion images of the human cervical spinal cord and brainstem were acquired. We have designed and constructed a wrap-around coil array with excellent performance for cervical spinal cord and brainstem MRI at 7T, which enables simultaneous human cervical spinal cord and brainstem functional MRI. Magn Reson Med 78:1623-1634, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakaya, Kotaro; Department of Neurosurgery, Tokyo Women's Medical University, Tokyo; Niranjan, Ajay

Purpose: This study evaluated the role of radiosurgery in the management of symptomatic patients with brainstem compression from benign basal tumors. Methods and Materials: Over a 17-year, period 246 patients (202 vestibular schwannomas and 44 meningiomas) with brainstem compression from benign skull-base tumors were managed with Gamma Knife radiosurgery. Median tumor volumes were 3.9 cm{sup 3} (range, 0.8-39.0 mL) and 6.6 mL (range, 1.6-25.1 mL) for vestibular schwannomas and meningiomas, respectively. For both tumors, a median marginal dose of 13 Gy was prescribed. Median follow-up of patients was 65 months for vestibular schwannomas and 60 months for meningiomas. Patients weremore » categorized into four groups on the basis of the tumor-brainstem relationship on neuroimaging. Results: Preservation of function was stratified according to grade of brainstem compression. We analyzed the effect of radiosurgery on symptoms of brainstem compression. The tumor control rate was 100 % for meningioma and 97% for vestibular schwannomas (although 5% required an additional procedure such as a ventriculoperitoneal shunt). In patients with vestibular schwannoma, serviceable hearing was preserved in 72.0%. Balance improved in 31.9%, remained unchanged in 56.5%, and deteriorated in 11.6% of patients who had imbalance at presentation. Balance improved significantly in patients who had less tumor compression (p = 0.0357) after radiosurgery. Symptoms improved in 43.2% of patients with meningioma. Conclusion: Radiosurgery is a minimally invasive option for patients with benign basal tumors that indent or distort the brainstem. A high tumor growth control rate and satisfactory rate of neurological preservation and symptom control can be obtained with radiosurgery.« less

Macrovascular Decompression of the Brainstem and Cranial Nerves: Evolution of an Anteromedial Vertebrobasilar Artery Transposition Technique.

PubMed

Choudhri, Omar; Connolly, Ian D; Lawton, Michael T

2017-08-01

Tortuous and dolichoectatic vertebrobasilar arteries can impinge on the brainstem and cranial nerves to cause compression syndromes. Transposition techniques are often required to decompress the brainstem with dolichoectatic pathology. We describe our evolution of an anteromedial transposition technique and its efficacy in decompressing the brainstem and relieving symptoms. To present the anteromedial vertebrobasilar artery transposition technique for macrovascular decompression of the brainstem and cranial nerves. All patients who underwent vertebrobasilar artery transposition were identified from the prospectively maintained database of the Vascular Neurosurgery service, and their medical records were reviewed retrospectively. The extent of arterial displacement was measured pre- and postoperatively on imaging. Vertebrobasilar arterial transposition and macrovascular decompression was performed in 12 patients. Evolution in technique was characterized by gradual preference for the far-lateral approach, use of a sling technique with muslin wrap, and an anteromedial direction of pull on the vertebrobasilar artery with clip-assisted tethering to the clival dura. With this technique, mean lateral displacement decreased from 6.6 mm in the first half of the series to 3.8 mm in the last half of the series, and mean anterior displacement increased from 0.8 to 2.5 mm, with corresponding increases in satisfaction and relief of symptoms. Compressive dolichoectatic pathology directed laterally into cranial nerves and posteriorly into the brainstem can be corrected with anteromedial transposition towards the clivus. Our technique accomplishes this anteromedial transposition from an inferolateral surgical approach through the vagoaccessory triangle, with sling fixation to clival dura using aneurysm clips. Copyright © 2017 by the Congress of Neurological Surgeons

IFNγ inhibits G-CSF induced neutrophil expansion and invasion of the CNS to prevent viral encephalitis

PubMed Central

Ramakrishna, Chandran

2018-01-01

Emergency hematopoiesis facilitates the rapid expansion of inflammatory immune cells in response to infections by pathogens, a process that must be carefully regulated to prevent potentially life threatening inflammatory responses. Here, we describe a novel regulatory role for the cytokine IFNγ that is critical for preventing fatal encephalitis after viral infection. HSV1 encephalitis (HSE) is triggered by the invasion of the brainstem by inflammatory monocytes and neutrophils. In mice lacking IFNγ (GKO), we observed unrestrained increases in G-CSF levels but not in GM-CSF or IL-17. This resulted in uncontrolled expansion and infiltration of apoptosis-resistant, degranulating neutrophils into the brainstem, causing fatal HSE in GKO but not WT mice. Excessive G-CSF in GKO mice also induced granulocyte derived suppressor cells, which inhibited T-cell proliferation and function, including production of the anti-inflammatory cytokine IL-10. Unexpectedly, we found that IFNγ suppressed G-CSF signaling by increasing SOCS3 expression in neutrophils, resulting in apoptosis. Depletion of G-CSF, but not GM-CSF, in GKO mice induced neutrophil apoptosis and reinstated IL-10 secretion by T cells, which restored their ability to limit innate inflammatory responses resulting in protection from HSE. Our studies reveals a novel, complex interplay among IFNγ, G-CSF and IL-10, which highlights the opposing roles of G-CSF and IFNγ in regulation of innate inflammatory responses in a murine viral encephalitis model and reveals G-CSF as a potential therapeutic target. Thus, the antagonistic G-CSF-IFNγ interactions emerge as a key regulatory node in control of CNS inflammatory responses to virus infection. PMID:29352287

The Influence of Traumatic Axonal Injury in Thalamus and Brainstem on Level of Consciousness at Scene or Admission: A Clinical Magnetic Resonance Imaging Study

PubMed Central

Moen, Kent Gøran; Skandsen, Toril; Kvistad, Kjell Arne; Laureys, Steven; Håberg, Asta; Vik, Anne

2018-01-01

Abstract The aim of this study was to investigate how traumatic axonal injury (TAI) lesions in the thalamus, basal ganglia, and brainstem on clinical brain magnetic resonance imaging (MRI) are associated with level of consciousness in the acute phase in patients with moderate to severe traumatic brain injury (TBI). There were 158 patients with moderate to severe TBI (7–70 years) with early 1.5T MRI (median 7 days, range 0–35) without mass lesion included prospectively. Glasgow Coma Scale (GCS) scores were registered before intubation or at admission. The TAI lesions were identified in T2*gradient echo, fluid attenuated inversion recovery, and diffusion weighted imaging scans. In addition to registering TAI lesions in hemispheric white matter and the corpus callosum, TAI lesions in the thalamus, basal ganglia, and brainstem were classified as uni- or bilateral. Twenty percent of patients had TAI lesions in the thalamus (7% bilateral), 18% in basal ganglia (2% bilateral), and 29% in the brainstem (9% bilateral). One of 26 bilateral lesions in the thalamus or brainstem was found on computed tomography. The GCS scores were lower in patients with bilateral lesions in the thalamus (median four) and brainstem (median five) than in those with corresponding unilateral lesions (median six and eight, p = 0.002 and 0.022). The TAI locations most associated with low GCS scores in univariable ordinal regression analyses were bilateral TAI lesions in the thalamus (odds ratio [OR] 35.8; confidence interval [CI: 10.5−121.8], p < 0.001), followed by bilateral lesions in basal ganglia (OR 13.1 [CI: 2.0–88.2], p = 0.008) and bilateral lesions in the brainstem (OR 11.4 [CI: 4.0–32.2], p < 0.001). This Trondheim TBI study showed that patients with bilateral TAI lesions in the thalamus, basal ganglia, or brainstem had particularly low consciousness at admission. We suggest these bilateral lesions should be evaluated further as possible biomarkers in a new TAI-MRI classification as a worst grade, because they could explain low consciousness in patients without mass lesions. PMID:29334825

Disruption of Glucagon-Like Peptide 1 Signaling in Sim1 Neurons Reduces Physiological and Behavioral Reactivity to Acute and Chronic Stress.

PubMed

Ghosal, Sriparna; Packard, Amy E B; Mahbod, Parinaz; McKlveen, Jessica M; Seeley, Randy J; Myers, Brent; Ulrich-Lai, Yvonne; Smith, Eric P; D'Alessio, David A; Herman, James P

2017-01-04

Organismal stress initiates a tightly orchestrated set of responses involving complex physiological and neurocognitive systems. Here, we present evidence for glucagon-like peptide 1 (GLP-1)-mediated paraventricular hypothalamic circuit coordinating the global stress response. The GLP-1 receptor (Glp1r) in mice was knocked down in neurons expressing single-minded 1, a transcription factor abundantly expressed in the paraventricular nucleus (PVN) of the hypothalamus. Mice with single-minded 1-mediated Glp1r knockdown had reduced hypothalamic-pituitary-adrenal axis responses to both acute and chronic stress and were protected against weight loss associated with chronic stress. In addition, regional Glp1r knockdown attenuated stress-induced cardiovascular responses accompanied by decreased sympathetic drive to the heart. Finally, Glp1r knockdown reduced anxiety-like behavior, implicating PVN GLP-1 signaling in behavioral stress reactivity. Collectively, these findings support a circuit whereby brainstem GLP-1 activates PVN signaling to mount an appropriate whole-organism response to stress. These results raise the possibility that dysfunction of this system may contribute to stress-related pathologies, and thereby provide a novel target for intervention. Dysfunctional stress responses are linked to a number of somatic and psychiatric diseases, emphasizing the importance of precise neuronal control of effector pathways. Pharmacological evidence suggests a role for glucagon-like peptide-1 (GLP-1) in modulating stress responses. Using a targeted knockdown of the GLP-1 receptor in the single-minded 1 neurons, we show dependence of paraventricular nucleus GLP-1 signaling in the coordination of neuroendocrine, autonomic, and behavioral responses to acute and chronic stress. To our knowledge, this is the first direct demonstration of an obligate brainstem-to-hypothalamus circuit orchestrating general stress excitation across multiple effector systems. These findings provide novel information regarding signaling pathways coordinating central control of whole-body stress reactivity. Copyright © 2017 the authors 0270-6474/17/370184-10$15.00/0.

The Binaural Interaction Component in Barn Owl (Tyto alba) Presents few Differences to Mammalian Data.

PubMed

Palanca-Castan, Nicolas; Laumen, Geneviève; Reed, Darrin; Köppl, Christine

2016-12-01

The auditory brainstem response (ABR) is an evoked potential that reflects the responses to sound by brainstem neural centers. The binaural interaction component (BIC) is obtained by subtracting the sum of the monaural ABR responses from the binaural response. Its latency and amplitude change in response to variations in binaural cues. The BIC is thus thought to reflect the activity of binaural nuclei and is used to non-invasively test binaural processing. However, any conclusions are limited by a lack of knowledge of the relevant processes at the level of individual neurons. The aim of this study was to characterize the ABR and BIC in the barn owl, an animal where the ITD-processing neural circuits are known in great detail. We recorded ABR responses to chirps and to 1 and 4 kHz tones from anesthetized barn owls. General characteristics of the barn owl ABR were similar to those observed in other bird species. The most prominent peak of the BIC was associated with nucleus laminaris and is thus likely to reflect the known processes of ITD computation in this nucleus. However, the properties of the BIC were very similar to previously published mammalian data and did not reveal any specific diagnostic features. For example, the polarity of the BIC was negative, which indicates a smaller response to binaural stimulation than predicted by the sum of monaural responses. This is contrary to previous predictions for an excitatory-excitatory system such as nucleus laminaris. Similarly, the change in BIC latency with varying ITD was not distinguishable from mammalian data. Contrary to previous predictions, this behavior appears unrelated to the known underlying neural delay-line circuitry. In conclusion, the generation of the BIC is currently inadequately understood and common assumptions about the BIC need to be reconsidered when interpreting such measurements.

Clinical analysis of anti-Ma2-associated encephalitis.

PubMed

Dalmau, Josep; Graus, Francesc; Villarejo, Alberto; Posner, Jerome B; Blumenthal, Deborah; Thiessen, Brian; Saiz, Albert; Meneses, Patricio; Rosenfeld, Myrna R

2004-08-01

Increasing experience indicates that anti-Ma2-associated encephalitis differs from classical paraneoplastic limbic or brainstem encephalitis, and therefore may be unrecognized. To facilitate its diagnosis we report a comprehensive clinical analysis of 38 patients with anti-Ma2 encephalitis. Thirty-four (89%) patients presented with isolated or combined limbic, diencephalic or brainstem dysfunction, and four with other syndromes. Considering the clinical and MRI follow-up, 95% of the patients developed limbic, diencephalic or brainstem encephalopathy. Only 26% had classical limbic encephalitis. Excessive daytime sleepiness affected 32% of the patients, sometimes with narcolepsy-cataplexy and low CSF hypocretin. Additional hormonal or MRI abnormalities indicated diencephalic-hypothalamic involvement in 34% of the patients. Eye movement abnormalities were prominent in 92% of the patients with brainstem dysfunction, but those with additional limbic or diencephalic deficits were most affected; 60% of these patients had vertical gaze paresis that sometimes evolved to total external ophthalmoplegia. Three patients developed atypical parkinsonism, and two a severe hypokinetic syndrome with a tendency to eye closure and dramatic reduction of verbal output. Neurological symptoms preceded the tumour diagnosis in 62% of the patients. Brain MRI abnormalities were present in 74% of all patients and 89% of those with limbic or diencephalic dysfunction. Among the 34 patients with cancer, 53% had testicular germ-cell tumours. Two patients without evidence of cancer had testicular microcalcification and one cryptorchidism, risk factors for testicular germ-cell tumours. After neurological syndrome development, 17 of 33 patients received oncological treatment (nine also immunotherapy), 10 immunotherapy alone, and six no treatment. Overall, 33% of the patients had neurological improvement, three with complete recovery; 21% had long-term stabilization, and 46% deteriorated. Features significantly associated with improvement or stabilization included, male gender, age <45 years, testicular tumour with complete response to treatment, absence of anti-Ma1 antibodies and limited CNS involvement. Immunosuppression was not found to be associated with improvement but was clearly effective in some patients. Fifteen patients (10 women, five men) had additional antibodies to Ma1. These patients were more likely to have tumours other than testicular cancer and to develop ataxia, and had a worse prognosis than patients with only anti-Ma2 antibodies (two women, 21 men); 67% of deceased patients had anti-Ma1 antibodies. Anti-Ma2 encephalitis (with or without anti-Ma1 antibodies) should be suspected in patients with limbic, diencephalic or brainstem dysfunction, MRI abnormalities in these regions, and inflammatory changes in the CSF. In young male patients, the primary tumour is usually in the testis, in other patients the leading neoplasm is lung cancer.

Evaluation of the occurrence of canine congenital sensorineural deafness in puppies of predisposed dog breeds using the brainstem auditory evoked response.

PubMed

Płonek, Marta; Giza, Elżbieta; Niedźwiedź, Artur; Kubiak, Krzysztof; Nicpoń, Józef; Wrzosek, Marcin

2016-12-01

Canine congenital sensorineural deafness (CCSD) affects predisposed breeds of dogs and is primarily caused by an atrophy of the stria vascularis of the organ of Corti. The analysis of the brainstem auditory evoked response (BAER) is a reliable method for the evaluation of hearing in animals as it allows an accurate detection of unilateral or bilateral deafness. The occurrence of unilateral and bilateral deafness using the BAER was determined in a representative group of dogs in Poland, including Bull Terriers (n = 117), Australian Cattle Dogs (n = 62), English Setters (n = 32) and the Dogo Argentino (n = 32). Overall deafness, deafness in each dog breed and an association between deafness and phenotype were studied. Among the 243 dogs tested, 156 (81%) had a normal BAER, 27 (11%) were unilaterally deaf, and 12 (5%) were bilaterally deaf. The amplitudes and latencies of waves I, II, III, V, the V/I wave amplitude ratio, and wave I-V, I-III and III-V inter-peak intervals were recorded for each dog. Unilaterally and bilaterally deaf dogs were present in all the dog breeds studied. There were 17 (14.5%) deaf Bull Terriers, three (4.8%) deaf Australian Cattle Dogs, seven (21.9%) deaf English Setters, and 12 (37.5%) deaf Dogos Argentinos. Preventive BAER screening should be routinely performed in these four breeds to prevent the spread of genes responsible for deafness.

Neonate Auditory Brainstem Responses to CE-Chirp and CE-Chirp Octave Band Stimuli I: Versus Click and Tone Burst Stimuli.

PubMed

Cobb, Kensi M; Stuart, Andrew

The purpose of the study was to generate normative auditory brainstem response (ABR) wave component peak latency and amplitude values for neonates with air- and bone-conducted CE-Chirps and air-conducted CE-Chirp octave band stimuli (i.e., 500, 1000, 2000, and 4000 Hz). A second objective was to compare neonate ABRs to CE-Chirp stimuli with ABR responses to traditional click and tone burst stimuli with the same stimulus parameters. Participants were 168 healthy neonates. ABRs were obtained to air- and bone-conducted CE-Chirp and click stimuli and air-conducted CE-Chirp octave band and tone burst stimuli. The effects of stimulus level, rate, and polarity were examined with air-conducted CE-Chirps and clicks. The effect of stimulus level was also examined with bone-conducted CE-Chirps and clicks and air-conducted CE-Chirp octave band stimuli. In general, ABR wave V amplitudes to air- and bone-conducted CE-Chirp stimuli were significantly larger (p < 0.05) than those evoked to traditional click and tone burst stimuli. Systematic statistically significant (p < 0.05) wave V latency differences existed between the air- and bone-conducted CE-Chirp and CE-Chirp octave band stimuli relative to traditional click and tone burst stimuli. ABRs to air- and bone-conducted CE-Chirps and CE-Chirp octave band stimuli may be valuable in the assessment of newborn infants. However, the prognostic value of such stimuli needs to be validated.

The rostral medulla of bullfrog tadpoles contains critical lung rhythmogenic and chemosensitive regions across metamorphosis.

PubMed

Reed, Mitchell D; Iceman, Kimberly E; Harris, Michael B; Taylor, Barbara E

2018-06-08

The development of amphibian breathing provides insight into vertebrate respiratory control mechanisms. Neural oscillators in the rostral and caudal medulla drive ventilation in amphibians, and previous reports describe ventilatory oscillators and CO 2 sensitive regions arise during different stages of amphibian metamorphosis. However, inconsistent findings have been enigmatic, and make comparisons to potential mammalian counterparts challenging. In the current study we assessed amphibian central CO 2 responsiveness and respiratory rhythm generation during two different developmental stages. Whole-nerve recordings of respiratory burst activity in cranial and spinal nerves were made from intact or transected brainstems isolated from tadpoles during early or late stages of metamorphosis. Brainstems were transected at the level of the trigeminal nerve, removing rostral structures including the nucleus isthmi, midbrain, and locus coeruleus, or transected at the level of the glossopharyngeal nerve, removing the putative buccal oscillator and caudal medulla. Removal of caudal structures stimulated the frequency of lung ventilatory bursts and revealed a hypercapnic response in normally unresponsive preparations derived from early stage tadpoles. In preparations derived from late stage tadpoles, removal of rostral or caudal structures reduced lung burst frequency, while CO 2 responsiveness was retained. Our results illustrate that structures within the rostral medulla are capable of sensing CO 2 throughout metamorphic development. Similarly, the region controlling lung ventilation appears to be contained in the rostral medulla throughout metamorphosis. This work offers insight into the consistency of rhythmic respiratory and chemosensitive capacities during metamorphosis. Copyright © 2018. Published by Elsevier Inc.

A Novel Method of Brainstem Auditory Evoked Potentials Using Complex Verbal Stimuli

PubMed Central

Kouni, Sophia N; Koutsojannis, Constantinos; Ziavra, Nausika; Giannopoulos, Sotirios

2014-01-01

Background: The click and tone-evoked auditory brainstem responses are widely used in clinical practice due to their consistency and predictability. More recently, the speech-evoked responses have been used to evaluate subcortical processing of complex signals, not revealed by responses to clicks and tones. Aims: Disyllable stimuli corresponding to familiar words can induce a pattern of voltage fluctuations in the brain stem resulting in a familiar waveform, and they can yield better information about brain stem nuclei along the ascending central auditory pathway. Materials and Methods: We describe a new method with the use of the disyllable word “baba” corresponding to English “daddy” that is commonly used in many other ethnic languages spanning from West Africa to the Eastern Mediterranean all the way to the East Asia. Results: This method was applied in 20 young adults institutionally diagnosed as dyslexic (10 subjects) or light dyslexic (10 subjects) who were matched with 20 sex, age, education, hearing sensitivity, and IQ-matched normal subjects. The absolute peak latencies of the negative wave C and the interpeak latencies of A-C elicited by verbal stimuli “baba” were found to be significantly increased in the dyslexic group in comparison with the control group. Conclusions: The method is easy and helpful to diagnose abnormalities affecting the auditory pathway, to identify subjects with early perception and cortical representation abnormalities, and to apply the suitable therapeutic and rehabilitation management. PMID:25210677

[Brainstem auditory evoked potentials (BAEPs) and assessment of personality test in patients with migraine].

PubMed

Yang, Y; Li, P; Ye, H C

2000-02-28

To explore personality test and brainstem auditory potentials (BAEPs) in patients with migraine. BAEPs and eysenck personality scale were recorded in 30 patients with migraine. The abnormal rate of BAEPs was 53%. The latency of individual wave I, III and V were prolonged, so did the interval of the wave III and wave V. The results of personality test showed that 3 patients(10%) manifested introvert personality, 12 patients (40%) extravert personality, and 17 patients (56%) the intermediate personality. It is indicated that migraine may be related to the disturbance of brainstem disfunction and personality of patients.

Differential diagnosis of ventriculomegaly and brainstem kinking on fetal MRI.

PubMed

Amir, Tali; Poretti, Andrea; Boltshauser, Eugen; Huisman, Thierry A G M

2016-01-01

Fetal ventriculomegaly is a common and frequently leading neuroimaging finding in complex brain malformations. Here we report on pre- and postnatal neuroimaging findings in three fetuses with prenatal ventriculomegaly and brainstem kinking. We aim to identify key neuroimaging features that may allow the prenatal differentiation between diseases associated with fetal ventriculomegaly and brainstem kinking. All pre- and postnatal magnetic resonance imaging (MRI) data were qualitatively evaluated for infra- and supratentorial abnormalities. Data about clinical features and genetic findings were collected from clinical histories. In all three patients, fetal MRI showed ventriculomegaly and brainstem kinking. In two patients, postnatal MRI also showed supratentorial migration abnormalities and eye abnormalities were found. In these children, the diagnosis of α-dystroglycanopathy was genetically confirmed. In the third patient, basal ganglia had an abnormal shape on MRI suggesting a tubulinopathy. The differential diagnosis of prenatal ventriculomegaly and brainstem kinking includes α-dystroglycanopathies, X-linked hydrocephalus due to mutations in L1CAM, and tubulinopathies. The prenatal differentiation between these diseases may be difficult. The presence of ocular abnormalities on prenatal neuroimaging may favor α-dystroglycanopathies, while dysplastic basal ganglia may suggest a tubulinopathy. However, in some patients the final differentiation between these diseases is possible only postnatally. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Spinal cord stress injury assessment (SCOSIA): clinical applications of mechanical modeling of the spinal cord and brainstem

NASA Astrophysics Data System (ADS)

Wong, Kenneth H.; Choi, Jae; Wilson, William; Berry, Joel; Henderson, Fraser C., Sr.

2009-02-01

Abnormal stretch and strain is a major cause of injury to the spinal cord and brainstem. Such forces can develop from age-related degeneration, congenital malformations, occupational exposure, or trauma such as sporting accidents, whiplash and blast injury. While current imaging technologies provide excellent morphology and anatomy of the spinal cord, there is no validated diagnostic tool to assess mechanical stresses exerted upon the spinal cord and brainstem. Furthermore, there is no current means to correlate these stress patterns with known spinal cord injuries and other clinical metrics such as neurological impairment. We have therefore developed the spinal cord stress injury assessment (SCOSIA) system, which uses imaging and finite element analysis to predict stretch injury. This system was tested on a small cohort of neurosurgery patients. Initial results show that the calculated stress values decreased following surgery, and that this decrease was accompanied by a significant decrease in neurological symptoms. Regression analysis identified modest correlations between stress values and clinical metrics. The strongest correlations were seen with the Brainstem Disability Index (BDI) and the Karnofsky Performance Score (KPS), whereas the weakest correlations were seen with the American Spinal Injury Association (ASIA) scale. SCOSIA therefore shows encouraging initial results and may have wide applicability to trauma and degenerative disease involving the spinal cord and brainstem.

Morphometric analysis of astrocytes in brainstem respiratory regions.

PubMed

Sheikhbahaei, Shahriar; Morris, Brian; Collina, Jared; Anjum, Sommer; Znati, Sami; Gamarra, Julio; Zhang, Ruli; Gourine, Alexander V; Smith, Jeffrey C

2018-06-11

Astrocytes, the most abundant and structurally complex glial cells of the central nervous system, are proposed to play an important role in modulating the activities of neuronal networks, including respiratory rhythm-generating circuits of the preBötzinger complex (preBötC) located in the ventrolateral medulla of the brainstem. However, structural properties of astrocytes residing within different brainstem regions are unknown. In this study astrocytes in the preBötC, an intermediate reticular formation (IRF) region with respiratory-related function, and a region of the nucleus tractus solitarius (NTS) in adult rats were reconstructed and their morphological features were compared. Detailed morphological analysis revealed that preBötC astrocytes are structurally more complex than those residing within the functionally distinct neighboring IRF region, or the NTS, located at the dorsal aspect of the medulla oblongata. Structural analyses of the brainstem microvasculature indicated no significant regional differences in vascular properties. We hypothesize that high morphological complexity of preBötC astrocytes reflects their functional role in providing structural/metabolic support and modulation of the key neuronal circuits essential for breathing, as well as constraints imposed by arrangements of associated neurons and/or other local structural features of the brainstem parenchyma. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Relation between cognition and neural connection from injured cingulum to brainstem cholinergic nuclei in chronic patients with traumatic brain injury.

PubMed

Yoo, Jin-Sun; Kim, Oh Lyong; Kim, Seong Ho; Kim, Min Su; Jang, Sung Ho

2014-01-01

This study investigated the relation between cognition and the neural connection from injured cingulum to brainstem cholinergic nuclei in patients with traumatic brain injury (TBI), using diffusion tensor tractography (DTT). Among 353 patients with TBI, 20 chronic patients who showed discontinuation of both anterior cingulums from the basal forebrain on DTT were recruited for this study. The Wechsler Intelligence Scale and the Memory Assessment Scale (MAS; short-term, verbal, visual and total memory) were used for assessment of cognition. Patients were divided into two groups according to the presence of a neural connection between injured cingulum and brainstem cholinergic nuclei. Eight patients who had a neural connection between injured cingulum and brainstem cholinergic nuclei showed better short-term memory on MAS than 12 patients who did not (p < 0.05). However, other results of neuropsychological testing showed no significant difference (p > 0.05). Better short-term memory in patients who had the neural connection between injured cingulum and brainstem cholinergic nuclei appears to have been attributed to the presence of cholinergic innervation to the cerebral cortex through the neural connection instead of the injured anterior cingulum. The neural connection appears to compensate for the injured anterior cingulum in obtaining cholinergic innervation.

Immediate, irreversible, posttraumatic coma: a review indicating that bilateral brainstem injury rather than widespread hemispheric damage is essential for its production.

PubMed

Rosenblum, William I

2015-03-01

Traumatic brain injury may result in immediate long-lasting coma. Much attention has been given to predicting this outcome from the initial examination because these predictions can guide future treatment and interactions with the patient's family. Reports of diffuse axonal injury in these cases have ascribed the coma to widespread damage in the deep white matter that disconnects the hemispheres from the ascending arousal system (AAS). However, brainstem lesions are also present in such cases, and the AAS may be interrupted at the brainstem level. This review examines autopsy and imaging literature that assesses the presence, extent, and predictive value of lesions in both sites. The evidence suggests that diffuse injury to the deep white matter is not the usual cause of immediate long-lasting posttraumatic coma. Instead, brainstem lesions in the rostral pons or midbrain are almost always the cause but only if the lesions are bilateral. Moreover, recovery is possible if critical brainstem inputs to the AAS are spared. The precise localization of the latter is subject to ongoing investigation with advanced imaging techniques using magnets of very high magnetic gradients. Limited availability of this equipment plus the need to verify the findings continue to require meticulous autopsy examination.

Combined preoperative traction with instrumented posterior occipitocervical fusion for severe ventral brainstem compression secondary to displaced os odontoideum: technical report of 2 cases.

PubMed

Abd-El-Barr, Muhammad M; Snyder, Brian D; Emans, John B; Proctor, Mark R; Hedequist, Daniel

2016-12-01

Severe os odontoideum causing ventral brainstem compression is a rare and difficult entity to treat. It is generally accepted that severe os odontoideum causing ventral brainstem compression and neurological deficits warrants surgical treatment. This often requires both anterior and posterior procedures. Anterior approaches to the craniocervical junction are fraught with complications, including infection and risk of injury to neurovascular structures. External traction systems traditionally require long-term bedrest. The authors report 2 cases of severe ventral brainstem compression secondary to displaced os odontoideum and describe their use of extended preoperative halo vest traction to reduce the severe kyphosis and improve neurological function, followed by posterior occipitocervical fusion. Postoperatively both patients showed remarkable improvements in their neurological function and kyphotic deformity. Preoperative halo vest traction combined with posterior occipitocervical fusion appears to be a safe and effective method to treat brainstem compression by severe os odontoideum. It allows for adequate decompression of ventral neural structures and improvement of neurological function, but it is not hindered by the risks of anterior surgical approaches and does not restrict patients to strict bedrest as traditional traction systems. This method of halo vest traction and posterior-only approaches may be transferable to other cervical instability issues with both anterior and posterior pathologies.

Consciousness and the Brainstem.

ERIC Educational Resources Information Center

Parvizi, Josef; Damasio, Antonio

2001-01-01

Summarizes a theoretical framework and set of hypotheses aimed at accounting for consciousness in neurobiological terms. Discusses the functional neuroanatomy of nuclei in the brainstem reticular formation. Notes that the views presented are compatible with the idea that the reticular formation modulates the electrophysiological activity of the…

The enigma of the dorsolateral pons as a migraine generator

PubMed Central

Borsook, D; Burstein, R

2013-01-01

In this editorial, we integrate improved understanding of functional and structural brain stem anatomy with lessons learned from other disciplines on brainstem function to provide an alternative interpretation to the data used to support the brainstem migraine generator theory. PMID:22798640

Cerebral Proliferative Angiopathy (CPA): Imaging Findings and Response to Therapy.

PubMed

Lopci, Egesta; Olivari, Laura; Bello, Lorenzo; Navarria, Pierina; Chiti, Arturo

2016-12-01

We report the case of a 55-year-old woman with cerebral proliferative angiopathy (CPA). Her medical history included brain surgery for small vascular lesions and suspicion of cerebral malignancy. C methionine PET (C-METH PET) demonstrated a diffusely increased uptake on the right hemisphere. Contrast-enhanced MRI documented a massive lesion with a diffuse "nidus" appearance, involving the right cerebral hemisphere (sparing the inferior frontal gyrus and the anterior frontal lobe), the brainstem, and the middle cerebellar peduncle. Pathology confirmed the diagnosis of CPA and, after radiation treatment, the patient presented with clinical and radiological response.

Advancing functional dysconnectivity and atrophy in progressive supranuclear palsy.

PubMed

Brown, Jesse A; Hua, Alice Y; Trujllo, Andrew; Attygalle, Suneth; Binney, Richard J; Spina, Salvatore; Lee, Suzee E; Kramer, Joel H; Miller, Bruce L; Rosen, Howard J; Boxer, Adam L; Seeley, William W

2017-01-01

Progressive supranuclear palsy syndrome (PSP-S) results from neurodegeneration within a network of brainstem, subcortical, frontal and parietal cortical brain regions. It is unclear how network dysfunction progresses and relates to longitudinal atrophy and clinical decline. In this study, we evaluated patients with PSP-S (n = 12) and healthy control subjects (n = 20) at baseline and 6 months later. Subjects underwent structural MRI and task-free functional MRI (tf-fMRI) scans and clinical evaluations at both time points. At baseline, voxel based morphometry (VBM) revealed that patients with mild-to-moderate clinical symptoms showed structural atrophy in subcortex and brainstem, prefrontal cortex (PFC; supplementary motor area, paracingulate, dorsal and ventral medial PFC), and parietal cortex (precuneus). Tf-fMRI functional connectivity (FC) was examined in a rostral midbrain tegmentum (rMT)-anchored intrinsic connectivity network that is compromised in PSP-S. In healthy controls, this network contained a medial parietal module, a prefrontal-paralimbic module, and a subcortical-brainstem module. Baseline FC deficits in PSP-S were most severe in rMT network integrative hubs in the prefrontal-paralimbic and subcortical-brainstem modules. Longitudinally, patients with PSP-S had declining intermodular FC between the subcortical-brainstem and parietal modules, while progressive atrophy was observed in subcortical-brainstem regions (midbrain, pallidum) and posterior frontal (perirolandic) cortex. This suggested that later-stage subcortical-posterior cortical change may follow an earlier-stage subcortical-anterior cortical disease process. Clinically, patients with more severe baseline impairment showed greater subsequent prefrontal-parietal cortical FC declines and posterior frontal atrophy rates, while patients with more rapid longitudinal clinical decline showed coupled prefrontal-paralimbic FC decline. VBM and FC can augment disease monitoring in PSP-S by tracking the disease through stages while detecting changes that accompany heterogeneous clinical progression.

A case study of IMRT planning (Plan B) subsequent to a previously treated IMRT plan (Plan A)

NASA Astrophysics Data System (ADS)

Cao, F.; Leong, C.; Schroeder, J.; Lee, B.

2014-03-01

Background and purpose: Treatment of the contralateral neck after previous ipsilateral intensity modulated radiation therapy (IMRT) for head and neck cancer is a challenging problem. We have developed a technique that limits the cumulative dose to the spinal cord and brainstem while maximizing coverage of a planning target volume (PTV) in the contralateral neck. Our case involves a patient with right tonsil carcinoma who was given ipsilateral IMRT with 70Gy in 35 fractions (Plan A). A left neck recurrence was detected 14 months later. The patient underwent a neck dissection followed by postoperative left neck radiation to a dose of 66 Gy in 33 fractions (Plan B). Materials and Methods: The spinal cord-brainstem margin (SCBM) was defined as the spinal cord and brainstem with a 1.0 cm margin. Plan A was recalculated on the postoperative CT scan but the fluence outside of SCBM was deleted. A further modification of Plan A resulted in a base plan that was summed with Plan B to evaluate the cumulative dose received by the spinal cord and brainstem. Plan B alone was used to evaluate for coverage of the contralateral neck PTV. Results: The maximum cumulative doses to the spinal cord with 0.5cm margin and brainstem with 0.5cm margin were 51.96 Gy and 45.60 Gy respectively. For Plan B, 100% of the prescribed dose covered 95% of PTVb1. Conclusion: The use of a modified ipsilateral IMRT plan as a base plan is an effective way to limit the cumulative dose to the spinal cord and brainstem while enabling coverage of a PTV in the contralateral neck.

The Structural, Functional, and Molecular Organization of the Brainstem

PubMed Central

Nieuwenhuys, Rudolf

2011-01-01

According to His (1891, 1893) the brainstem consists of two longitudinal zones, the dorsal alar plate (sensory in nature) and the ventral basal plate (motor in nature). Johnston and Herrick indicated that both plates can be subdivided into separate somatic and visceral zones, distinguishing somatosensory and viscerosensory zones within the alar plate, and visceromotor and somatomotor zones within the basal plate. To test the validity of this “four-functional-zones” concept, I developed a topological procedure, surveying the spatial relationships of the various cell masses in the brainstem in a single figure. Brainstems of 16 different anamniote species were analyzed, and revealed that the brainstems are clearly divisible into four morphological zones, which correspond largely with the functional zones of Johnston and Herrick. Exceptions include (1) the magnocellular vestibular nucleus situated in the viscerosensory zone; (2) the basal plate containing a number of evidently non-motor centers (superior and inferior olives). Nevertheless the “functional zonal model” has explanatory value. Thus, it is possible to interpret certain brain specializations related to particular behavioral profiles, as “local hypertrophies” of one or two functional columns. Recent developmental molecular studies on brains of birds and mammals confirmed the presence of longitudinal zones, and also showed molecularly defined transverse bands or neuromeres throughout development. The intersecting boundaries of the longitudinal zones and the transverse bands appeared to delimit radially arranged histogenetic domains. Because neuromeres have been observed in embryonic and larval stages of numerous anamniote species, it may be hypothesized that the brainstems of all vertebrates share a basic organizational plan, in which intersecting longitudinal and transverse zones form fundamental histogenetic and genoarchitectonic units. PMID:21738499

Utility of Brainstem Trigeminal Evoked Potentials in Patients With Primary Trigeminal Neuralgia Treated by Microvascular Decompression.

PubMed

Zhu, Jin; Zhang, Xin; Zhao, Hua; Tang, Yin-Da; Ying, Ting-Ting; Li, Shi-Ting

2017-09-01

To investigate the characteristics of brainstem trigeminal evoked potentials (BTEP) waveform in patients with and without trigeminal neuralgia (TN), and to discuss the utility of BTEP in patients with primary TN treated by microvascular decompression (MVD). A retrospective review of 43 patients who underwent BTEP between January 2016 and June 2016, including 33 patients with TN who underwent MVD and 10 patients without TN. Brainstem trigeminal evoked potentials characteristics of TN and non-TN were summarized, in particular to compare the BTEP changes between pre- and post-MVD, and to discover the relationship between BTEP changes and surgical outcome. Brainstem trigeminal evoked potentials can be recorded in patients without trigeminal neuralgia. Abnormal BTEP could be recorded when different branches were stimulated. After decompression, the original W2, W3 disappeared and then replaced by a large wave in most patients, or original wave poorly differentiated improved in some patients, showed as shorter latency and (or) amplitude increased. Brainstem trigeminal evoked potentials waveform of healthy side in patients with trigeminal neuralgia was similar to the waveform of patients without TN. In 3 patients, after decompression the W2, W3 peaks increased, and the latency, duration, IPLD did not change significantly. Until discharge, 87.9% (29/33) of the patients presented complete absence of pain without medication (BNI I) and 93.9% (31/33) had good pain control without medication (BNI I-II). Brainstem trigeminal evoked potentials can reflect the conduction function of the trigeminal nerve to evaluate the functional level of the trigeminal nerve conduction pathway. The improvement and restoration of BTEP waveforms are closely related to the postoperative curative effect.

Population calcium imaging of spontaneous respiratory and novel motor activity in the facial nucleus and ventral brainstem in newborn mice

PubMed Central

Persson, Karin; Rekling, Jens C

2011-01-01

Abstract The brainstem contains rhythm and pattern forming circuits, which drive cranial and spinal motor pools to produce respiratory and other motor patterns. Here we used calcium imaging combined with nerve recordings in newborn mice to reveal spontaneous population activity in the ventral brainstem and in the facial nucleus. In Fluo-8 AM loaded brainstem–spinal cord preparations, respiratory activity on cervical nerves was synchronized with calcium signals at the ventrolateral brainstem surface. Individual ventrolateral neurons at the level of the parafacial respiratory group showed perfect or partial synchrony with respiratory nerve bursts. In brainstem–spinal cord preparations, cut at the level of the mid-facial nucleus, calcium signals were recorded in the dorsal, lateral and medial facial subnuclei during respiratory activity. Strong activity initiated in the dorsal subnucleus, followed by activity in lateral and medial subnuclei. Whole-cell recordings from facial motoneurons showed weak respiratory drives, and electrical field potential recordings confirmed respiratory drive to particularly the dorsal and lateral subnuclei. Putative facial premotoneurons showed respiratory-related calcium signals, and were predominantly located dorsomedial to the facial nucleus. A novel motor activity on facial, cervical and thoracic nerves was synchronized with calcium signals at the ventromedial brainstem extending from the level of the facial nucleus to the medulla–spinal cord border. Cervical dorsal root stimulation induced similar ventromedial activity. The medial facial subnucleus showed calcium signals synchronized with this novel motor activity on cervical nerves, and cervical dorsal root stimulation induced similar medial facial subnucleus activity. In conclusion, the dorsal and lateral facial subnuclei are strongly respiratory-modulated, and the brainstem contains a novel pattern forming circuit that drives the medial facial subnucleus and cervical motor pools. PMID:21486812

Survival, migration, and differentiation of Sox1-GFP embryonic stem cells in coculture with an auditory brainstem slice preparation.

PubMed

Glavaski-Joksimovic, Aleksandra; Thonabulsombat, Charoensri; Wendt, Malin; Eriksson, Mikael; Palmgren, Björn; Jonsson, Anna; Olivius, Petri

2008-03-01

The poor regeneration capability of the mammalian hearing organ has initiated different approaches to enhance its functionality after injury. To evaluate a potential neuronal repair paradigm in the inner ear and cochlear nerve we have previously used embryonic neuronal tissue and stem cells for implantation in vivo and in vitro. At present, we have used in vitro techniques to study the survival and differentiation of Sox1-green fluorescent protein (GFP) mouse embryonic stem (ES) cells as a monoculture or as a coculture with rat auditory brainstem slices. For the coculture, 300 microm-thick brainstem slices encompassing the cochlear nucleus and cochlear nerve were prepared from postnatal SD rats. The slices were propagated using the membrane interface method and the cochlear nuclei were prelabeled with DiI. After some days in culture a suspension of Sox1 cells was deposited next to the brainstem slice. Following deposition Sox1 cells migrated toward the brainstem and onto the cochlear nucleus. GFP was not detectable in undifferentiated ES cells but became evident during neural differentiation. Up to 2 weeks after transplantation the cocultures were fixed. The undifferentiated cells were evaluated with antibodies against progenitor cells whereas the differentiated cells were determined with neuronal and glial markers. The morphological and immunohistochemical data indicated that Sox1 cells in monoculture differentiated into a higher percentage of glial cells than neurons. However, when a coculture was used a significantly lower percentage of Sox1 cells differentiated into glial cells. The results demonstrate that a coculture of Sox1 cells and auditory brainstem present a useful model to study stem cell differentiation.

Effect of neonatal nociceptin or nocistatin imprinting on the brain concentration of biogenic amines and their metabolites.

PubMed

Tekes, Kornélia; Gyenge, Melinda; Sótonyi, Péter; Csaba, György

2009-04-01

Noradrenaline (NA), dopamine (DA), homovanillic acid (HA), serotonin (5HT) and 5-hydroxyindole acetic acid (5HIAA) content of five brain regions (hypothalamus, hippocampus, brainstem, striatum and frontal cortex) and the cerebrospinal fluid (CSF) was measured in adult (three months old) male and female rats treated neonatally with a single dose of 10 microg nociceptin (NC) or 10 microg nocistatin (NS) for hormonal imprinting. The biogenic amine and metabolite content of cerebrospinal fluid was also determined. In NC treated animals the serotonergic, dopaminergic as well as noradrenergic systems were influenced by the imprinting. The 5HT level increased in hypothalamus, the 5HIAA tissue levels were found increased in hypothalamus. Hippocampus and striatum and the HVA levels increased highly significantly in brainstem. Dopamine level decreased significantly in striatum, however in frontal cortex both noradrenalin and 5HIAA level decreased. Nevertheless, in NS-treated rats decreased NA tissue levels were found in hypothalamus, brainstem and frontal cortex. Decreased DA levels were found in the hypothalamus, brainstem and striatum. NS imprinting resulted in decreased HVA level, but increased one in the brainstem. The 5HT levels decreased in the hypothalamus, brainstem, striatum and frontal cortex, while 5HIAA content of CSF, and frontal cortex decreased, and that of hypothalamus, hippocampus and striatum increased. There was no significant difference between genders except in the 5HT tissue levels of NC treated rats. Data presented show that neonatal imprinting both by NC and NS have long-lasting and brain area specific effects. In earlier experiments endorphin imprinting also influenced the serotonergic system suggesting that during labour release of pain-related substances may durably affect the serotonergic (dopaminergic, adrenergic) system which can impress the animals' later behavior.

FOOD-INTAKE DYSREGULATION IN TYPE 2 DIABETIC GOTO-KAKIZAKI RATS: HYPOTHESIZED ROLE OF DYSFUNCTIONAL BRAINSTEM THYROTROPIN-RELEASING HORMONE AND IMPAIRED VAGAL OUTPUT

PubMed Central

Zhao, K.; Ao, Y.; Harper, R.M.; Go, V. L.W.; Yang, H.

2013-01-01

Thyrotropin-releasing hormone (TRH), a neuropeptide contained in neural terminals innervating brainstem vagal motor neurons, enhances vagal outflow to modify multisystemic visceral functions and food intake. Type 2 diabetes (T2D) and obesity are accompanied by impaired vagal functioning. We examined the possibility that impaired brainstem TRH action may contribute to the vagal dysregulation of food intake in Goto-Kakizaki (GK) rats, a T2D model with hyperglycemia and impaired central vagal activation by TRH. Food intake induced by intracisternal injection of TRH analog was reduced significantly by 50% in GK rats, compared to Wistar rats. Similarly, natural food intake in the dark phase or food intake after an overnight fast was reduced by 56–81% in GK rats. Fasting (48 h) and refeeding (2 h)-associated changes in serum ghrelin, insulin, peptide YY, pancreatic polypeptide and leptin, and the concomitant changes in orexigenic or anorexigenic peptide expression in the brainstem and hypothalamus, all apparent in Wistar rats, were absent or markedly reduced in GK rats, with hormone release stimulated by vagal activation, such as ghrelin and pancreatic polypeptide, decreased substantially. Fasting-induced Fos expression accompanying endogenous brainstem TRH action decreased by 66% and 91%, respectively, in the nucleus tractus solitarius (NTS) and the dorsal motor nucleus of the vagus (DMV) in GK rats, compared to Wistar rats. Refeeding abolished fasting-induced Fos-expression in the NTS, while that in the DMV remained in Wistar but not GK rats. These findings indicate that dysfunctional brainstem TRH-elicited vagal impairment contributes to the disturbed food intake in T2D GK rats, and may provide a pathophysiological mechanism which prevents further weight gain in T2D and obesity. PMID:23701881

Food-intake dysregulation in type 2 diabetic Goto-Kakizaki rats: hypothesized role of dysfunctional brainstem thyrotropin-releasing hormone and impaired vagal output.

PubMed

Zhao, K; Ao, Y; Harper, R M; Go, V L W; Yang, H

2013-09-05

Thyrotropin-releasing hormone (TRH), a neuropeptide contained in neural terminals innervating brainstem vagal motor neurons, enhances vagal outflow to modify multisystemic visceral functions and food intake. Type 2 diabetes (T2D) and obesity are accompanied by impaired vagal functioning. We examined the possibility that impaired brainstem TRH action may contribute to the vagal dysregulation of food intake in Goto-Kakizaki (GK) rats, a T2D model with hyperglycemia and impaired central vagal activation by TRH. Food intake induced by intracisternal injection of TRH analog was reduced significantly by 50% in GK rats, compared to Wistar rats. Similarly, natural food intake in the dark phase or food intake after an overnight fast was reduced by 56-81% in GK rats. Fasting (48h) and refeeding (2h)-associated changes in serum ghrelin, insulin, peptide YY, pancreatic polypeptide and leptin, and the concomitant changes in orexigenic or anorexigenic peptide expression in the brainstem and hypothalamus, all apparent in Wistar rats, were absent or markedly reduced in GK rats, with hormone release stimulated by vagal activation, such as ghrelin and pancreatic polypeptide, decreased substantially. Fasting-induced Fos expression accompanying endogenous brainstem TRH action decreased by 66% and 91%, respectively, in the nucleus tractus solitarius (NTS) and the dorsal motor nucleus of the vagus (DMV) in GK rats, compared to Wistar rats. Refeeding abolished fasting-induced Fos-expression in the NTS, while that in the DMV remained in Wistar but not GK rats. These findings indicate that dysfunctional brainstem TRH-elicited vagal impairment contributes to the disturbed food intake in T2D GK rats, and may provide a pathophysiological mechanism which prevents further weight gain in T2D and obesity. Published by Elsevier Ltd.

Plasticity and Activation of Spared Intraspinal Respiratory Circuits Following Spinal Cord Injury

DTIC Science & Technology

2015-10-01

scheduled to present these data at the Spring 2016 Experimental Biology Meeting in San Diego, CA, and thus fully anticipate that analysis will be...that had been deprived of descending drive from the brainstem from an acute cervical spinal cord injury in an endogenous rhythmic manner. To address...epidural stimulation. Major Task 3: Analysis of Tissue Responses to Microwire Implantation These experiments, which were incorporated into the revised

Acute hyperbilirubinaemia induces presynaptic neurodegeneration at a central glutamatergic synapse

PubMed Central

Haustein, Martin D; Read, David J; Steinert, Joern R; Pilati, Nadia; Dinsdale, David; Forsythe, Ian D

2010-01-01

There is a well-established link between hyperbilirubinaemia and hearing loss in paediatrics, but the cellular mechanisms have not been elucidated. Here we used the Gunn rat model of hyperbilirubinaemia to investigate bilirubin-induced hearing loss. In vivo auditory brainstem responses revealed that Gunn rats have severe auditory deficits within 18 h of exposure to high bilirubin levels. Using an in vitro preparation of the auditory brainstem from these rats, extracellular multi-electrode array recording from the medial nucleus of the trapezoid body (MNTB) showed longer latency and decreased amplitude of evoked field potentials following bilirubin exposure, suggestive of transmission failure at this synaptic relay. Whole-cell patch-clamp recordings confirmed that the electrophysiological properties of the postsynaptic MNTB neurons were unaffected by bilirubin, with no change in action potential waveforms or current–voltage relationships. However, stimulation of the trapezoid body was unable to elicit large calyceal EPSCs in MNTB neurons of hyperbilirubinaemic rats, indicative of damage at a presynaptic site. Multi-photon imaging of anterograde-labelled calyceal projections revealed axonal staining and presynaptic profiles around MNTB principal neuron somata. Following induction of hyperbilirubinaemia the giant synapses were largely destroyed. Electron microscopy confirmed loss of presynaptic calyceal terminals and supported the electrophysiological evidence for healthy postsynaptic neurons. MNTB neurons express high levels of neuronal nitric oxide synthase (nNOS). Nitric oxide has been implicated in mechanisms of bilirubin toxicity elsewhere in the brain, and antagonism of nNOS by 7-nitroindazole protected hearing during bilirubin exposure. We conclude that bilirubin-induced deafness is caused by degeneration of excitatory synaptic terminals in the auditory brainstem. PMID:20937712

Acute hyperbilirubinaemia induces presynaptic neurodegeneration at a central glutamatergic synapse.

PubMed

Haustein, Martin D; Read, David J; Steinert, Joern R; Pilati, Nadia; Dinsdale, David; Forsythe, Ian D

2010-12-01

There is a well-established link between hyperbilirubinaemia and hearing loss in paediatrics, but the cellular mechanisms have not been elucidated. Here we used the Gunn rat model of hyperbilirubinaemia to investigate bilirubin-induced hearing loss. In vivo auditory brainstem responses revealed that Gunn rats have severe auditory deficits within 18 h of exposure to high bilirubin levels. Using an in vitro preparation of the auditory brainstem from these rats, extracellular multi-electrode array recording from the medial nucleus of the trapezoid body (MNTB) showed longer latency and decreased amplitude of evoked field potentials following bilirubin exposure, suggestive of transmission failure at this synaptic relay. Whole-cell patch-clamp recordings confirmed that the electrophysiological properties of the postsynaptic MNTB neurons were unaffected by bilirubin, with no change in action potential waveforms or current-voltage relationships. However, stimulation of the trapezoid body was unable to elicit large calyceal EPSCs in MNTB neurons of hyperbilirubinaemic rats, indicative of damage at a presynaptic site. Multi-photon imaging of anterograde-labelled calyceal projections revealed axonal staining and presynaptic profiles around MNTB principal neuron somata. Following induction of hyperbilirubinaemia the giant synapses were largely destroyed. Electron microscopy confirmed loss of presynaptic calyceal terminals and supported the electrophysiological evidence for healthy postsynaptic neurons. MNTB neurons express high levels of neuronal nitric oxide synthase (nNOS). Nitric oxide has been implicated in mechanisms of bilirubin toxicity elsewhere in the brain, and antagonism of nNOS by 7-nitroindazole protected hearing during bilirubin exposure. We conclude that bilirubin-induced deafness is caused by degeneration of excitatory synaptic terminals in the auditory brainstem.

Visualization of Oxytocin Release that Mediates Paired Pulse Facilitation in Hypothalamic Pathways to Brainstem Autonomic Neurons

PubMed Central

Piñol, Ramón A.; Jameson, Heather; Popratiloff, Anastas; Lee, Norman H.; Mendelowitz, David

2014-01-01

Recent work has shown that oxytocin is involved in more than lactation and uterine contraction. The paraventricular nucleus of the hypothalamus (PVN) contains neuroendocrine neurons that control the release of hormones, including vasopressin and oxytocin. Other populations of PVN neurons do not release hormones, but rather project to and release neurotransmitters onto other neurons in the CNS involved in fluid retention, thermoregulation, sexual behavior and responses to stress. Activation of oxytocin receptors can be cardioprotective and reduces the adverse cardiovascular consequences of anxiety and stress, yet how oxytocin can affect heart rate and cardiac function is unknown. While anatomical work has shown the presence of peptides, including oxytocin, in the projections from the PVN to parasympathetic nuclei, electrophysiological studies to date have only demonstrated release of glutamate and activation of fast ligand gated receptors in these pathways. In this study, using rats, we directly show, using sniffer CHO cells that express oxytocin receptors and the Ca2+ indicator R-GECO, that optogenetic activation of channelrhodopsin-2 (ChR2) expressing PVN fibers in the brainstem activates oxytocin receptors in the dorsomotor nucleus of the vagus (DMNV). We also demonstrate that while a single photoactivation of PVN terminals only activates glutamatergic receptors in brainstem cardiac vagal neurons (CVNs), neurons that dominate the neural control of heart rate, both the paired pulse facilitation, and sustained enhancement of glutamate release in this pathway is mediated by activation of oxytocin receptors. Our results provide direct evidence that a pathway from the PVN likely releases oxytocin and enhances short-term plasticity of this critical autonomic connection. PMID:25379676

The Role of the Auditory Brainstem in Processing Musically Relevant Pitch

PubMed Central

Bidelman, Gavin M.

2013-01-01

Neuroimaging work has shed light on the cerebral architecture involved in processing the melodic and harmonic aspects of music. Here, recent evidence is reviewed illustrating that subcortical auditory structures contribute to the early formation and processing of musically relevant pitch. Electrophysiological recordings from the human brainstem and population responses from the auditory nerve reveal that nascent features of tonal music (e.g., consonance/dissonance, pitch salience, harmonic sonority) are evident at early, subcortical levels of the auditory pathway. The salience and harmonicity of brainstem activity is strongly correlated with listeners’ perceptual preferences and perceived consonance for the tonal relationships of music. Moreover, the hierarchical ordering of pitch intervals/chords described by the Western music practice and their perceptual consonance is well-predicted by the salience with which pitch combinations are encoded in subcortical auditory structures. While the neural correlates of consonance can be tuned and exaggerated with musical training, they persist even in the absence of musicianship or long-term enculturation. As such, it is posited that the structural foundations of musical pitch might result from innate processing performed by the central auditory system. A neurobiological predisposition for consonant, pleasant sounding pitch relationships may be one reason why these pitch combinations have been favored by composers and listeners for centuries. It is suggested that important perceptual dimensions of music emerge well before the auditory signal reaches cerebral cortex and prior to attentional engagement. While cortical mechanisms are no doubt critical to the perception, production, and enjoyment of music, the contribution of subcortical structures implicates a more integrated, hierarchically organized network underlying music processing within the brain. PMID:23717294

Neuronal Basis of Crossed Actions from the Reticular Formation on Feline Hindlimb Motoneurons

PubMed Central

Jankowska, Elzbieta; Hammar, Ingela; Slawinska, Urszula; Maleszak, Katarzyna; Edgley, Stephen A.

2007-01-01

Pathways through which reticulospinal neurons can influence contralateral limb movements were investigated by recording from mo-toneurons innervating hindlimb muscles. Reticulospinal tract fibers were stimulated within the brainstem or in the lateral funiculus of the thoracic spinal cord contralateral to the motoneurons. Effects evoked by ipsilaterally descending reticulospinal tract fibers were eliminated by a spinal hemisection at an upper lumbar level. Stimuli applied in the brainstem evoked EPSPs, IPSPs, or both at latencies of 1.42 ± 0.03 and 1.53 ± 0.04 msec, respectively, from the first components of the descending volleys and with properties indicating a disynaptic linkage, in most contralateral motoneurons: EPSPs in 76% and IPSPs in 26%. EPSPs with characteristics of monosynaptically evoked responses, attributable to direct actions of crossed axon collaterals of reticulospinal fibers, were found in a small proportion of the motoneurons, whether evoked from the brainstem (9%) or from the thoracic cord (12.5%). Commissural neurons, which might mediate the crossed disynaptic actions (i.e., were antidromically activated from contralateral motor nuclei and monosynaptically excited from the ipsilateral reticular formation), were found in Rexed’s lamina VIII in the midlumbar segments (L3–L5). The results reveal that although direct actions of reticulospinal fibers are much more potent on ipsilateral motoneurons, interneuronally mediated actions are as potent contralaterally as ipsilaterally, and midlumbar commissural neurons are likely to contribute to them. They indicate a close coupling between the spinal interneuronal systems used by the reticulospinal neurons to coordinate muscle contractions ipsilaterally and contralaterally. PMID:12629191

Brainstem cavernous malformations: Natural history versus surgical management.

PubMed

Walcott, Brian P; Choudhri, Omar; Lawton, Michael T

2016-10-01

While brainstem cavernous malformations were once considered inoperable, improvements in patient selection, surgical exposures, intraoperative MRI-guidance, MR tractography, and neurophysiologic monitoring have resulted in good outcomes in the majority of operated patients. In a consecutive series of 104 patients with brainstem cavernous malformations, only 14% of patients experienced cranial nerve or motor dysfunction that was worse at late follow-up, relative to their preoperative condition. Outcomes were predicted by several factors, including larger lesion size, lesions that crossed the midline, the presence of a developmental venous anomaly, older age, and greater time interval from lesion hemorrhage to surgery. The 14% of patients who experienced a persistent neurological deficit as a result of surgery, while substantial from any perspective, compares favorably with the risks of observation based on a recent meta-analysis. Curative resection is a safe and effective treatment for brainstem cavernous malformations that will prevent re-hemorrhage in symptomatic patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prospective Characterization of Cognitive Function in Typical and 'Brainstem Predominant'Progressive Supranuclear Palsy Phenotypes.

PubMed

Lee, Young-Eun C; Williams, David R; Anderson, Jacqueline F I

2018-05-01

Clinicopathological studies over the last decade have broadened the clinical spectrum of progressive supranuclear palsy (PSP) to include several distinct clinical syndromes. We examined the cognitive profiles of patients with PSP-Richardson's syndrome (PSP-RS) and two atypical 'brainstem predominant' PSP phenotypes (PSP-parkinsonism, PSP-P; and PSP-pure akinesia with gait freezing, PSP-PAGF) using a comprehensive neuropsychological battery. Fourteen patients diagnosed as PSP-RS, three patients with PSP-P and four patients with PSP-PAGF were assessed using a comprehensive battery of neuropsychological tests. The typical PSP-RS subgroup demonstrated greater impairments in processing speed [t(19) = -4.10, p = 0.001 (d =1.66)] and executive function [t(19) = -2.63, p = 0.02 (d = 1.20)] compared to the 'brainstem predominant' PSP phenotype. This is the first prospective study to demonstrate that PSP-RS and 'brainstem predominant' PSP phenotypes can be differentiated on cognitive grounds. These differences correspond with variations in pathological profiles reported in the literature.

Narcolepsy: regional cerebral blood flow during sleep and wakefulness

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakai, F.; Meyer, J.S.; Karacan, I.

Serial measurements of regional cerebral blood flow were made by the 135Xe inhalation method during the early stages of sleep and wakefulness in eight normal volunteers and 12 patients with narcolepsy. Electroencephalogram, electro-oculogram, and submental electromyogram were recorded simultaneously. In normals, mean hemispheric gray matter blood flow (Fg) during stages I and II sleep was significantly less than waking values. Maximum regional blood flow decreases during sleep occurred in the brainstem-cerebellar, right inferior temporal, and bilateral frontal regions. In patients with narcolepsy, mean hemispheric Fg while awake was 80.5 +- 13 ml per 100 gm brain per minute. During REMmore » sleep, mean hemispheric Fg increased concurrently with large increases in brainstem-cerebellar region flow. During stages I and II sleep without REM, there were significant increases in mean hemispheric Fg and brainstem-cerebellar Fg, just the opposite of changes in normals. In narcolepsy, there appears to be a reversal of normal cerebral deactivation patterns, particularly involving the brainstem, during stages I and II sleep.« less

Abnormal oxygen homeostasis in the nucleus tractus solitarii of the spontaneously hypertensive rat.

PubMed

Hosford, Patrick S; Millar, Julian; Ramage, Andrew G; Marina, Nephtali

2017-04-01

What is the central question of this study? Arterial hypertension is associated with impaired neurovascular coupling in the somatosensory cortex. Abnormalities in activity-dependent oxygen consumption in brainstem regions involved in the control of cardiovascular reflexes have not been explored previously. What is the main finding and its importance? Using fast-cyclic voltammetry, we found that changes in local tissue PO2 in the nucleus tractus solitarii induced by electrical stimulation of the vagus nerve are significantly impaired in spontaneously hypertensive rats. This is consistent with previous observations showing that brainstem hypoxia plays an important role in the pathogenesis of arterial hypertension. The effects of arterial hypertension on cerebral blood flow remain poorly understood. Haemodynamic responses within the somatosensory cortex have been shown to be impaired in the spontaneously hypertensive rat (SHR) model. However, it is unknown whether arterial hypertension affects oxygen homeostasis in vital brainstem areas that control cardiovascular reflexes. In this study, we assessed vagus nerve stimulation-induced changes in local tissue PO2 (PtO2) in the caudal nucleus tractus solitarii (cNTS) of SHRs and normotensive Wistar rats. Measurements of PtO2 were performed using a novel application of fast-cyclic voltammetry, which allows higher temporal resolution of O 2 changes than traditional optical fluorescence techniques. Electrical stimulation of the central cut end of the vagus nerve (ESVN) caused profound reductions in arterial blood pressure along with biphasic changes in PtO2 in the cNTS, characterized by a rapid decrease in PtO2 ('initial dip') followed by a post-stimulus overshoot above baseline. The initial dip was found to be significantly smaller in SHRs compared with normotensive Wistar rats even after ganglionic blockade. The post-ESVN overshoot was similar in both groups but was reduced in Wistar rats after ganglionic blockade. In conclusion, neural activity-dependent changes in tissue oxygen in brainstem cardiovascular autonomic centres are significantly impaired in animals with arterial hypertension. © 2017 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Functional neuroanatomy of human cortex cerebri in relation to wanting sex and having it.

PubMed

Georgiadis, Janniko R

2015-04-01

Neuroanatomical textbooks typically restrict the central nervous system control of sexual responsiveness to the hypothalamus, brainstem and spinal cord. However, for all its primitive functions human sex is surprisingly complex and versatile. This review aims to extend the neuroanatomy of sexual responsiveness by providing a comprehensive overview of the empirical evidence for cerebral cortical involvement. To this end I will structure relevant human brain research data to fit the sexual pleasure cycle template-wanting sex, having sex, inhibiting sex-arguing that going through these sexual response phases requires adequate shifting between functional cortical networks. The relevance of this notion for understanding certain sexual dysfunctions is discussed. © 2015 Wiley Periodicals, Inc.

Diffusion tensor imaging of the brainstem in children with achondroplasia

PubMed Central

BOSEMANI, THANGAMADHAN; ORMAN, GUNES; CARSON, KATHRYN A; MEODED, AVNER; HUISMAN, THIERRY A G M; PORETTI, ANDREA

2014-01-01

Aim The aims of this study were to compare, using diffusion tensor imaging (DTI) of the brainstem, microstructural integrity of the white matter in children with achondroplasia and age-matched participants and to correlate the severity of craniocervical junction (CCJ) narrowing and neurological findings with DTI scalars in children with achondroplasia. This study also aimed to assess the potential role of fibroblast growth factor receptor type 3 on white matter microstructure. Method Diffusion tensor imaging was performed using a 1.5T magnetic resonance scanner and balanced pairs of diffusion gradients along 20 non-collinear directions. Measurements were obtained from regions of interest, sampled in each pontine corticospinal tract (CST), medial lemniscus, and middle cerebellar peduncle, as well as in the lower brainstem and centrum semiovale, for fractional anisotropy and for mean, axial and radial diffusivity. In addition, a severity score for achondroplasia was assessed by measuring CCJ narrowing. Result Eight patients with achondroplasia (seven males, one female; mean age 5y 6mo, range 1y 1mo–15y 1mo) and eight age- and sex-matched comparison participants (mean age 5y 2mo, range 1y 1mo–14y 11mo) were included in this study. Fractional anisotropy was lower and mean diffusivity and radial diffusivity were higher in the lower brainstem of patients with achondroplasia than in age-matched comparison participants. The CST and middle cerebellar peduncle of the participants showed increases in mean, axial, and radial diffusivity. Fractional anisotropy in the lower brainstem was negatively correlated with the degree of CCJ narrowing. No differences in the DTI metrics of the centrum semiovale were observed between the two groups. Interpretation The reduction in fractional anisotropy and increase in diffusivities in the lower brainstem of participants with achondroplasia may reflect secondary encephalomalacic degeneration and cavitation of the affected white matter tracts as shown by histology. In children with achondroplasia, DTI may serve as a potential biomarker for brainstem white matter injury and aid in the care and management of these patients. PMID:24825324

Diffusion tensor imaging of the brainstem in children with achondroplasia.

PubMed

Bosemani, Thangamadhan; Orman, Gunes; Carson, Kathryn A; Meoded, Avner; Huisman, Thierry A G M; Poretti, Andrea

2014-11-01

The aims of this study were to compare, using diffusion tensor imaging (DTI) of the brainstem, microstructural integrity of the white matter in children with achondroplasia and age-matched participants and to correlate the severity of craniocervical junction (CCJ) narrowing and neurological findings with DTI scalars in children with achondroplasia. This study also aimed to assess the potential role of fibroblast growth factor receptor type 3 on white matter microstructure. Diffusion tensor imaging was performed using a 1.5T magnetic resonance scanner and balanced pairs of diffusion gradients along 20 non-collinear directions. Measurements were obtained from regions of interest, sampled in each pontine corticospinal tract (CST), medial lemniscus, and middle cerebellar peduncle, as well as in the lower brainstem and centrum semiovale, for fractional anisotropy and for mean, axial, and radial diffusivity. In addition, a severity score for achondroplasia was assessed by measuring CCJ narrowing. Eight patients with achondroplasia (seven males, one female; mean age 5y 6mo, range 1y 1mo-15y 1mo) and eight age- and sex-matched comparison participants (mean age 5y 2mo, range 1y 1mo-14y 11mo) were included in this study. Fractional anisotropy was lower and mean diffusivity and radial diffusivity were higher in the lower brainstem of patients with achondroplasia than in age-matched comparison participants. The CST and middle cerebellar peduncle of the participants showed increases in mean, axial, and radial diffusivity. Fractional anisotropy in the lower brainstem was negatively correlated with the degree of CCJ narrowing. No differences in the DTI metrics of the centrum semiovale were observed between the two groups. The reduction in fractional anisotropy and increase in diffusivities in the lower brainstem of participants with achondroplasia may reflect secondary encephalomalacic degeneration and cavitation of the affected white matter tracts as shown by histology. In children with achondroplasia, DTI may serve as a potential biomarker for brainstem white matter injury and aid in the care and management of these patients. © 2014 Mac Keith Press.

Mechanical Characterization of Immature Porcine Brainstem in Tension at Dynamic Strain Rates.

PubMed

Zhao, Hui; Yin, Zhiyong; Li, Kui; Liao, Zhikang; Xiang, Hongyi; Zhu, Feng

2016-01-21

Many brain injury cases involve pediatric road traffic accidents, and among these, brainstem injury causes disastrous outcomes. A thorough understanding of the tensile characterization of immature brainstem tissue is crucial in modeling traumatic brain injury sustained by children, but limited experimental data in tension is available for the immature brain tissue at dynamic strain rates. We harvested brainstem tissue from immature pigs (about 4 weeks old, and at a developmental stage similar to that of human toddlers) as a byproduct from a local slaughter house and very carefully prepared the samples. Tensile tests were performed on specimens at dynamic strain rates of 2/s, 20/s, and 100/s using a biological material instrument. The constitutive models, Fung, Ogden, Gent, and exponential function, for immature brainstem tissue material property were developed for the recorded experimental data using OriginPro 8.0 software. The t test was performed for infinitesimal shear modules. The curves of stress-versus-stretch ratio were convex in shape, and inflection points were found in all the test groups at the strain of about 2.5%. The average Lagrange stress of the immature brainstem specimen at the 30% strain at the strain rates of 2, 20, and 100/s was 273±114, 515±107, and 1121±197 Pa, respectively. The adjusted R-Square (R2) of Fung, Ogden, Gent, and exponential model was 0.820≤R2≤0.933, 0.774≤R2≤0.940, 0.650≤R2≤0.922, and 0.852≤R2≤0.981, respectively. The infinitesimal shear modulus of the strain energy functions showed a significant association with the strain rate (p<0.01). The immature brainstem is a rate-dependent material in dynamic tensile tests, and the tissue becomes stiffer with increased strain rate. The reported results may be useful in the study of brain injuries in children who sustain injuries in road traffic accidents. Further research in more detail should be performed in the future.

Ontogeny of cholecystokinin-like immunoreactivity in the Brazilian opossum brain.

PubMed

Fox, C A; Jeyapalan, M; Ross, L R; Jacobson, C D

1991-12-17

We have studied the anatomical distribution of cholecystokinin-like immunoreactive (CCK-IR) somata and fibers in the brain of the adult and developing Brazilian short-tailed opossum, Monodelphis domestica. Animals ranged in age from the day of birth (1PN) to young adulthood (180PN). A nickel enhanced, avidin-biotin, indirect immunohistochemical technique was used to identify CCK-IR structures. Somata containing CCK immunoreactivity were observed in the cerebral cortex, hippocampus, hypothalamus, thalamus, midbrain, and brainstem in the adult. Cholecystokinin immunoreactive fibers had a wide distribution in the adult Monodelphis brain. The only major region of the brain that did not contain CCK-IR fibers was the cerebellum. The earliest expression of CCK immunoreactivity was found in fibers in the dorsal brainstem of 5-day-old opossum pups. It is possible that the CCK-IR fibers in the brainstem at 5PN are of vagal origin. Cholecystokinin immunoreactive somata were observed in the brainstem on 10PN. The CCK-IR cell bodies observed in the brainstem at 10PN may mark the first expression of CCK-IR elements intrinsic to the brain. A broad spectrum of patterns of onset of CCK expression was observed in the opossum brain. The early occurrence and varied ontogenesis of CCK-IR structures indicates CCK may be involved in the function of a variety of circuits from the brainstem to the cerebral cortex. The early expression of CCK-IR structures in the dorsal brainstem suggests that CCK may modulate feeding behavior in the Monodelphis neonate. Cholecystokinin immunoreactivity in forebrain structures such as the suprachiasmatic nucleus, medial preoptic area, thalamus and cortical structures indicates that CCK may also be involved in circadian rhythmicity, reproductive functions, as well as the state of arousal of the Brazilian opossum. The ontogenic timing of CCK immunoreactivity in specific circuitry also indicates that CCK expression does not occur simultaneously throughout the brain. This pattern of CCK onset may relate to the temporal need for CCK in specific circuits of the central nervous system (CNS) during development.

Clinical anatomy and imaging of the cranial nerves and skull base.

PubMed

Jha, Ruchira M; Klein, Joshua P

2012-09-01

Evaluation of patients with cranial neuropathies requires an understanding of brainstem anatomy and nerve pathways. Advances in neuroimaging, particularly high spatial resolution magnetic resonance imaging (MRI), have enabled visualization of these tiny structures and their related pathology. This review provides an approach toward using imaging in the evaluation of cranial nerve (CN) and skull base anatomy and pathology. Because brainstem nuclei are inextricably linked to the information contained within CNs, they are briefly mentioned whenever relevant; however, a comprehensive discussion of brainstem syndromes is beyond the scope of this review. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Boxing sparring complicated by an acute subdural haematoma and brainstem haemorrhage.

PubMed

Hart, Michael G; Trivedi, Rikin A; Hutchinson, Peter J

2012-10-01

A professional boxer developed an acute subdural haematoma after boxing sparring. Despite timely surgical decompression, he had a poor overall outcome predominantly from a delayed brainstem haematoma. Magnetic resonance imaging (MRI) was used to elucidate the pathophysiology of the patients' injury and clinical condition.

Immunohistochemical localization of calcium-binding proteins in the brainstem vestibular nuclei of the jaundiced Gunn rat.

PubMed

Shaia, Wayne T; Shapiro, Steven M; Heller, Andrew J; Galiani, David L; Sismanis, Aristides; Spencer, Robert F

2002-11-01

Vestibular gaze and postural abnormalities are major sequelae of neonatal hyperbilirubinemia. The sites and cellular effects of bilirubin toxicity in the brainstem vestibular pathway are not easily detected. Since altered intracellular calcium homeostasis may play a role in neuronal cell death, we hypothesized that altered expression of calcium-binding proteins may occur in brainstem vestibular nuclei of the classic animal model of bilirubin neurotoxicity. The expression of the calcium-binding proteins calbindin-D28k and parvalbumin in the brainstem vestibular pathways and cerebellum of homozygous recessive jaundiced (jj) Gunn rats was examined by light microscopy and immunohistochemistry at 18 days postnatally and compared to the findings obtained from age-matched non-jaundiced heterozygous (Nj) littermate controls. Jaundiced animals exhibited decreased parvalbumin immunoreactivity specifically in synaptic inputs to superior, medial, and inferior vestibular nuclei, and to oculomotor and trochlear nuclei, whereas the neurons retained their normal immunoreactivity. Jaundiced animals also demonstrated a decrease in calbindin expression in the lateral vestibular nuclei and a paucity of calbindin-immunoreactive synaptic endings on the somata of Deiters' neurons. The involved regions are related to the control of the vestibulo-ocular and vestibulospinal reflexes. Decreased expression of calcium-binding proteins in brainstem vestibular neurons may relate to the vestibulo-ocular and vestibulospinal dysfunction seen with clinical kernicterus, and may provide a sensitive new way to assess bilirubin toxicity in the vestibular system.

Changes of neurotransmitters in the brainstem of patients with respiratory-pattern disorders during childhood.

PubMed

Saito, Y; Ito, M; Ozawa, Y; Obonai, T; Kobayashi, Y; Washizawa, K; Ohsone, Y; Takami, T; Oku, K; Takashima, S

1999-06-01

We examined neuropathologically and immunohistochemically the respiratory centers in the brainstem of two patients with Joubert syndrome (JS), three patients with congenital central hypoventilation syndrome (CCHS) and a patient with apneustic breathing (prolonged inspiratory pause) due to unknown etiology. Immunoreactivity (IR) of tryptophan hydroxylase (TPH) was decreased in the dorsal raphe nuclei of two patients with JS compared with age-matched controls, as well as in two patients with Dandy-Walker malformation. The two JS patients showed vermian defect and elongated cerebellar peduncles, and peculiar vascularities in the midline of the whole brainstem were also noted in one of these patients. These findings, as a whole, confirm that the midline structures of brainstem are disordered both structurally and functionally in JS, conceivably resulting in respiratory patterns and psychomotor deficits. IR of serotonin 1A receptor showed no significant changes in the medulla oblongata of these patients, however. In the parabrachial complex, IR of substance P was increased in two patients with CCHS, and one with apneustic breathing. IR of tyrosine hydroxylase was also increased in the latter. The brainstem of these patients showed reactive astrogliosis. These findings suggest preceding hypoxic episodes as well as an increased activity in the parabrachial complex which plays an important role in conducting the driving force to the medullary respiratory neurons from ascending sensory pathways.

Developmental study of vitamin C distribution in children's brainstems by immunohistochemistry.

PubMed

Coveñas, R; González-Fuentes, J; Rivas-Infante, E; Lagartos-Donate, M J; Mangas, A; Geffard, M; Arroyo-Jiménez, M M; Cebada-Sánchez, S; Insausti, R; Marcos, P

2015-09-01

Vitamin C (Vit C) is an important antioxidant, exerts powerful neuroprotective brain effects and plays a role in neuronal development and maturation. Vit C is present in brain tissue at higher concentrations than in other organs, but its detailed distribution in brain is unknown. Immunohistochemical detection of this vitamin has been performed by using a highly specific antibody against Vit C. The aim of the present work was to analyze the distribution of Vit C in children's brainstems during postnatal development, comparing two groups of ages: younger and older than one year of life. In general, the same areas showing neurons with Vit C in young cases are also immunostained at older ages. The distribution of neurons containing Vit C was broader in the brainstems of older children, suggesting that brainstem neurons maintain or even increase their ability to retain Vit C along the life span. Immunohistochemical labeling revealed only cell bodies containing this vitamin, and no immunoreactive fibers were observed. The distribution pattern of Vit C in children's brainstems suggests a possible role of Vit C in brain homeostatic regulation. In addition, the constant presence of Vit C in neurons of locus coeruleus supports the important role of Vit C in noradrenaline synthesis, which seemed to be maintained along postnatal development. Copyright © 2015 Elsevier GmbH. All rights reserved.

Activity of Tachykinin1-Expressing Pet1 Raphe Neurons Modulates the Respiratory Chemoreflex

PubMed Central

Corcoran, Andrea E.; Brust, Rachael D.; Chang, YoonJeung; Nattie, Eugene E.

2017-01-01

Homeostatic control of breathing, heart rate, and body temperature relies on circuits within the brainstem modulated by the neurotransmitter serotonin (5-HT). Mounting evidence points to specialized neuronal subtypes within the serotonergic neuronal system, borne out in functional studies, for the modulation of distinct facets of homeostasis. Such functional differences, read out at the organismal level, are likely subserved by differences among 5-HT neuron subtypes at the cellular and molecular levels, including differences in the capacity to coexpress other neurotransmitters such as glutamate, GABA, thyrotropin releasing hormone, and substance P encoded by the Tachykinin-1 (Tac1) gene. Here, we characterize in mice a 5-HT neuron subtype identified by expression of Tac1 and the serotonergic transcription factor gene Pet1, referred to as the Tac1-Pet1 neuron subtype. Transgenic cell labeling showed Tac1-Pet1 soma resident largely in the caudal medulla. Chemogenetic [clozapine-N-oxide (CNO)-hM4Di] perturbation of Tac1-Pet1 neuron activity blunted the ventilatory response of the respiratory CO2 chemoreflex, which normally augments ventilation in response to hypercapnic acidosis to restore normal pH and PCO2. Tac1-Pet1 axonal boutons were found localized to brainstem areas implicated in respiratory modulation, with highest density in motor regions. These findings demonstrate that the activity of a Pet1 neuron subtype with the potential to release both 5-HT and substance P is necessary for normal respiratory dynamics, perhaps via motor outputs that engage muscles of respiration and maintain airway patency. These Tac1-Pet1 neurons may act downstream of Egr2-Pet1 serotonergic neurons, which were previously established in respiratory chemoreception, but do not innervate respiratory motor nuclei. SIGNIFICANCE STATEMENT Serotonin (5-HT) neurons modulate physiological processes and behaviors as diverse as body temperature, respiration, aggression, and mood. Using genetic tools, we characterize a 5-HT neuron subtype defined by expression of Tachykinin1 and Pet1 (Tac1-Pet1 neurons), mapping soma localization to the caudal medulla primarily and axonal projections to brainstem motor nuclei most prominently, and, when silenced, observed blunting of the ventilatory response to inhaled CO2. Tac1-Pet1 neurons thus appear distinct from and contrast previously described Egr2-Pet1 neurons, which project primarily to chemosensory integration centers and are themselves chemosensitive. PMID:28073937

Familial auditory neuropathy.

PubMed

Wang, Qiuju; Gu, Rui; Han, Dongyi; Yang, Weiyan

2003-09-01

Auditory neuropathy is a sensorineural hearing disorder characterized by absent or abnormal auditory brainstem responses and normal cochlear outer hair cell function as measured by otoacoustic emission recordings. Many risk factors are thought to be involved in its etiology and pathophysiology. Four Chinese pedigrees with familial auditory neuropathy were presented to demonstrate involvement of genetic factors in the etiology of auditory neuropathy. Probands of the above-mentioned pedigrees, who had been diagnosed with auditory neuropathy, were evaluated and followed in the Department of Otolaryngology-Head and Neck Surgery, China People Liberation Army General Hospital (Beijing, China). Their family members were studied, and the pedigree maps established. History of illness, physical examination, pure-tone audiometry, acoustic reflex, auditory brainstem responses, and transient evoked and distortion-product otoacoustic emissions were obtained from members of these families. Some subjects received vestibular caloric testing, computed tomography scan of the temporal bone, and electrocardiography to exclude other possible neuropathic disorders. In most affected patients, hearing loss of various degrees and speech discrimination difficulties started at 10 to 16 years of age. Their audiological evaluation showed absence of acoustic reflex and auditory brainstem responses. As expected in auditory neuropathy, these patients exhibited near-normal cochlear outer hair cell function as shown in distortion product otoacoustic emission recordings. Pure-tone audiometry revealed hearing loss ranging from mild to profound in these patients. Different inheritance patterns were observed in the four families. In Pedigree I, 7 male patients were identified among 43 family members, exhibiting an X-linked recessive pattern. Affected brothers were found in Pedigrees II and III, whereas in pedigree IV, two sisters were affected. All the patients were otherwise normal without evidence of peripheral neuropathy at the time of writing. Patients with characteristics of nonsyndromic hereditary auditory neuropathy were identified in one large and three smaller Chinese families. Pedigree analysis suggested an X-linked, recessive hereditary pattern in one pedigree and autosomal recessive inheritances in the other three pedigrees. The phenotypes in the study were typical of auditory neuropathy; they were transmitted in different inheritance patterns, indicating clinical and genetic heterogeneity of this disorder. The observed inheritance and clinical audiological findings are different from those previously described for nonsyndromic low-frequency sensorineural hearing loss. This information should facilitate future molecular linkage analyses and positional cloning for the relative genes contributing to auditory neuropathy.

Click-evoked auditory brainstem responses and autism spectrum disorder: A meta-analytic review.

PubMed

Talge, Nicole M; Tudor, Brooke M; Kileny, Paul R

2018-06-01

Behavior does not differentiate ASD risk prior to 12 months of age, but biomarkers may inform risk before symptoms emerge. Click-evoked auditory brainstem responses (ABRs) may be worth consideration due to their measurement properties (noninvasiveness; reliability) and conceptual features (well-characterized neural generators), but participant characteristics and assessment protocols vary considerably across studies. Our goal is to perform a meta-analysis of the association between ABRs and ASD. Following an electronic database search (PubMed, Medline, PsycInfo, PsycArticles), we included papers that were written in English, included ASD and typically-developing (TD) groups, and reported the information needed to calculate standardized mean differences (Hedges's g) for at least one ABR latency component (I, III, V, I-III, III-V, I-V). We weighted and averaged effect sizes across conditions and subsets of participants to yield one estimate per component per study. We then performed random-effects regressions to generate component-specific estimates. ASD was associated with longer ABR latencies for Waves III (g = 0.5, 95% CI 0.1, 0.9), V (g = 0.7, 95% CI 0.3, 1.1), I-III (g = 0.7, 95% CI 0.2, 1.2), and I-V (g = 0.6, 95% CI 0.2, 1.0). All components showed significant heterogeneity. Associations were strongest among participants ≤8 years of age and those without middle ear abnormalities or elevated auditory thresholds. In sum, associations between ABRs and ASD are medium-to-large in size, but exhibit heterogeneity. Identifying sources of heterogeneity is challenging, however, due to power limitations and co-occurrence of sample/design characteristics across studies. Research addressing the above limitations is crucial to determining the etiologic and/or prognostic value of ABRs for ASD. Autism Res 2018, 11: 916-927. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. Auditory brainstem responses (ABR) may be associated with ASD, but participant characteristics and assessment protocols vary considerably across individual studies. Our goal is to combine the results across these studies to facilitate clarity on the topic. Doing so represents a first step in evaluating whether ABRs yield potential for informing the etiology of ASD risk and/or ASD symptom profiles. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.