Cortical Centers Research Articles

Speech in Noise Perception as a Marker of Cognitive Impairment in HIV Infection.

Human immunodeficiency virus positive (HIV+) individuals report hearing difficulties, but standard audiological tests show no, or small, changes in peripheral hearing ability. The hearing complaints may reflect central nervous system (CNS) auditory processing deficits, rather than middle or inner ear problems, and may result from CNS damage due to HIV infection or treatment. If central auditory task performance and cognitive deficits in HIV+ individuals are shown to be related, then central auditory tests might serve as a "window" into CNS function in these patients. We measured cognitive performance (Mandarin Montreal Cognitive Assessment [MoCA]) and speech in noise perception (Mandarin hearing-in-noise test [HINT]) in 166 normal-hearing HIV+ individuals (158 men, 8 women, average age 36 years) at the Shanghai Public Health Clinical Center in Shanghai, China. Data collection included audiometry, tympanometry, and the Amsterdam Inventory of Auditory Handicap (AIAH), which assesses the subjective ability to understand speech and localize sound. Subjects had no middle ear disease and met criteria for normal-hearing sensitivity (all thresholds 20 dB HL or less). A significant negative relationship between speech reception thresholds (SRT) and MoCA scores (r = 0.15, F = 28.2, p < 0.001) existed. Stepwise linear regression showed that when the factors of age, MoCA scores, hearing thresholds, and education level were considered, only age and MoCA scores contributed independently to the SRT results (overall model r = 0.30, F = 38.8, p < 0.001). Subjective hearing complaints from the AIAH supported the HINT results. AIAH and MoCA scores were also related (r = 0.05, F = 8.5, p = 0.004), with those with worse MoCA scores having more problems on the AIAH. When the cohort was divided into those with normal and abnormal performance on the MoCA, those with abnormal performance on the MoCA had significantly higher average SRTs (p < 0.001). Understanding speech in noise measured both objectively with the HINT and subjectively with the AIAH was inversely related to cognitive abilities despite a normal ability to hear soft sounds determined by audiometry. Although age was also an important independent factor affecting speech perception, the age relationship within the speech findings in this study may represent more than just age-related declines in speech in noise understanding. Although reliable data on disease duration are not available, the older members of this cohort likely had HIV longer and probably had more severe symptoms at presentation than the younger members because early detection and treatment of HIV in Shanghai has improved over time. Therefore, the age relationship may also include elements of disease duration and severity. Speech perception, especially in challenging listening conditions, involves cortical and subcortical centers and is a demanding neurological task. The problems interpreting speech in noise HIV+ individuals have may reflect HIV-related or HIV treatment-related, central nervous damage, suggesting that CNS complications in HIV+ individuals could potentially be diagnosed and monitored using central auditory tests.

Deciphering the Neural Signature of Human Blood Pressure Control

The aim of this study was to measure the activity of hypothalamic and brainstem centers regulating blood pressure in humansThe human body has several systems to regulate blood pressure, one of which is the baroreflex. It is mediated by a number of nuclei in the brainstem and hypothalamus that via autonomic efferents adjust the mean arterial pressure by altering both the force and speed of the heart's contractions, as well as systemic vascular resistance. While cortical centers influencing the baroreflex have been studied in humans using functional magnetic resonance imaging (fMRI), the brainstem region suffers from strong physiological noise that makes detection more difficult. Here, we combined high‐resolution fMRI with lower body negative pressure (LBNP) and concomitant autonomic recordings hypothesizing that such an approach would make it possible to detect hypothalamic and brainstem nuclei controlling the baroreflex in humans.15 healthy subjects were scanned using a 3T MR scanner. The protocol involved SMS‐EPI functional scans (voxel size=2×2×2 mm3) as well as T1‐weighted structural scans (voxel size=1*1*1.2 mm3). LBNP stimulation was delivered using a custom‐made MR‐compatible pressure chamber and a vacuum cleaner that was controlled by a digital pressure gauge. FMRI data were minimally preprocessed using tools from FMRIB Software Library (FSL v5.0) including motion correction, unwarping, temporal high‐pass filtering and normalization to a study template. The data were masked to retain only the brainstem and hypothalamus, excluding the adjacent areas with high physiological noise. Statistical analysis was conducted using masked independent component analysis (mICA), spectral analysis, and network modelling.We found activations related to the LBNP paradigm in multiple nuclei known to be involved in baroreflex regulation. These included the nucleus of the solitary tract and the caudal ventrolateral medulla in the lower brainstem as well as the paraventricular hypothalamic nucleus and lateral hypothalamus. We further observed significant activity changes on the lower ventral medullary surface. Frequency analysis revealed that the BOLD signal in the rostroventrolateral medulla showed spectral changes in the Mayer band (0.1 ± 0.035 Hz) during LBNP.Being able to measure baroreflex nuclei in vivo is an important step towards the understanding of this system in humans. Our results show the importance of selected nuclei in the hypothalamus and brainstem.Support or Funding InformationFunding: Horst Goertz FoundationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Univariate and multivariate conditional entropy measures for the characterization of short-term cardiovascular complexity under physiological stress

Objective: A defining feature of physiological systems under the neuroautonomic regulation is their dynamical complexity. The most common approach to assess physiological complexity from short-term recordings, i.e. to compute the rate of entropy generation of an individual system by means of measures of conditional entropy (CE), does not consider that complexity may change when the investigated system is part of a network of physiological interactions. This study aims at extending the concept of short-term complexity towards the perspective of network physiology, defining multivariate CE measures whereby multiple physiological processes are accounted for in the computation of entropy rates. Approach: Univariate and multivariate CE measures are computed using state-of-the-art methods for entropy estimation and applied to time series of heart period (H), systolic (S) and diastolic (D) arterial pressure, and respiration (R) variability measured in healthy subjects monitored in a resting state and during conditions of postural and mental stress. Main results: Compared with the traditional univariate metric of short-term complexity, multivariate measures provide additional information with plausible physiological interpretation, such as (i) the dampening of respiratory sinus arrhythmia and activation of the baroreflex control during postural stress; (ii) the increased complexity of heart period and blood pressure variability during mental stress, reflecting the effect of respiratory influences and upper cortical centers; (iii) the strong influence of D on S, mediated by left ventricular ejection fraction and vascular properties; (iv) the role of H in reducing the complexity of D, related to cardiac run-off effects; and (v) the unidirectional role of R in influencing cardiovascular variability. Significance: Our results document the importance of employing a network perspective in the evaluation of the short-term complexity of cardiovascular and respiratory dynamics across different physiological states.

Evaluation of vascular reactivity to overcome limitations of neurovascular uncoupling in BOLD fMRI of malignant brain tumors

The sensitivity of fMRI in identification of eloquent cortical centers in the case of large infiltrative growing tumors and pronounced peritumoral edema may be reduced or significantly limited in some cases. The main cause is an attenuated Blood-Oxygen-Level-Dependent response (BOLD) caused by pathological vascular reactivity and subsequent neurovascular uncoupling of fMRI. In our study, we attempted to overcome these limitations and increase the sensitivity of this technique in identification of eloquent cortical areas adjacent to brain tumors by using vasoreactivity features of a breath-holding test and including these data in the BOLD analysis. Local vasoreactivity using a breath-holding paradigm with the same block design of both motor and speech tests was determined in 5 healthy volunteers and 3 patients in the preoperative period (two patients with high grade gliomas and one patient with single metastasis). A coherence-based model was developed for analysis of BOLD fMRI, which took into account altered hemodynamics in peritumoral zones. Obtained coherence maps demonstrated clinically more significant activation zones that were not seen with standard methods of fMRI processing. Thus, neurovascular uncoupling that is known to affect the accuracy of the BOLD fMRI response adjacent to brain tumors may be partially overcome by including an independent measurement of vasoreactivity using a breath-holding test in the BOLD analysis.

Methods in Rodent Chemosensory Cognition.

Olfactory information processing and learning are highly developed computational abilities of rodents. These attributes can be exploited to ask questions at several levels of complexity, from aspects of odorant binding by olfactory receptors to higher order learning about the predictive consequences of odorant stimulus presentation. Quantitative understanding of rodent odorant sampling patterns, both baseline nasal breathing and odorant-stimulated sniffing, is critical to elucidating mechanisms of olfactory information processing, from primary olfactory receptors to cortical centers that synthesize olfactory percepts from preprocessed multimodal inputs. This chapter outlines an innovative new method for measuring breathing and sniffing rates in unrestrained mice while the mice are performing odor-guided tasks in a computer controlled olfactometer.The method described here involves implantation of a wireless pressure sensor in the mouse that reports on thoracic pressure transients caused by breathing and sniffing. Recordings of pressure sensor outputs are made simultaneously with optically-sensed nose pokes by the mouse into an odor delivery port or a water delivery port. Odorant delivery timing and water reward delivery are also recorded simultaneously. This method allows for breathing and sniffing dependent thoracic pressure transients to be recorded with high temporal precision before, during, and after the mouse approaches an odor delivery port, samples the delivered odor, and obtains a water reward contingent on the identity of the odor that was presented and sampled.

Different contributions of primary motor cortex, reticular formation, and spinal cord to fractionated muscle activation

Coordinated movement requires patterned activation of muscles. In this study, we examined differences in selective activation of primate upper limb muscles by cortical and subcortical regions. Five macaque monkeys were trained to perform a reach and grasp task, and electromyogram (EMG) was recorded from 10 to 24 muscles while weak single-pulse stimuli were delivered through microelectrodes inserted in the motor cortex (M1), reticular formation (RF), or cervical spinal cord (SC). Stimulus intensity was adjusted to a level just above threshold. Stimulus-evoked effects were assessed from averages of rectified EMG. M1, RF, and SC activated 1.5 ± 0.9, 1.9 ± 0.8, and 2.5 ± 1.6 muscles per site (means ± SD); only M1 and SC differed significantly. In between recording sessions, natural muscle activity in the home cage was recorded using a miniature data logger. A novel analysis assessed how well natural activity could be reconstructed by stimulus-evoked responses. This provided two measures: normalized vector length L, reflecting how closely aligned natural and stimulus-evoked activity were, and normalized residual R, measuring the fraction of natural activity not reachable using stimulus-evoked patterns. Average values for M1, RF, and SC were L = 119.1 ± 9.6, 105.9 ± 6.2, and 109.3 ± 8.4% and R = 50.3 ± 4.9, 56.4 ± 3.5, and 51.5 ± 4.8%, respectively. RF was significantly different from M1 and SC on both measurements. RF is thus able to generate an approximation to the motor output with less activation than required by M1 and SC, but M1 and SC are more precise in reaching the exact activation pattern required. Cortical, brainstem, and spinal centers likely play distinct roles, as they cooperate to generate voluntary movements.NEW & NOTEWORTHY Brainstem reticular formation, primary motor cortex, and cervical spinal cord intermediate zone can all activate primate upper limb muscles. However, brainstem output is more efficient but less precise in producing natural patterns of motor output than motor cortex or spinal cord. We suggest that gross muscle synergies from the reticular formation are sculpted and refined by motor cortex and spinal circuits to reach the finely fractionated output characteristic of dexterous primate upper limb movements.

Modulation of Glycine-Mediated Spinal Neurotransmission for the Treatment of Chronic Pain.

Chronic pain constitutes a significant and expanding worldwide health crisis. Currently available analgesics poorly serve individuals suffering from chronic pain, and new therapeutic agents that are more effective, safer, and devoid of abuse liabilities are desperately needed. Among the myriad of cellular and molecular processes contributing to chronic pain, spinal disinhibition of pain signaling to higher cortical centers plays a critical role. Accumulating evidence shows that glycinergic inhibitory neurotransmission in the spinal cord dorsal horn gates nociceptive signaling, is essential in maintaining physiological pain sensitivity, and is diminished in pathological pain states. Thus, it is hypothesized that agents capable of enhancing glycinergic tone within the dorsal horn could obtund nociceptor signaling to the brain and serve as analgesics for persistent pain. This Perspective highlights the potential that pharmacotherapies capable of increasing inhibitory spinal glycinergic neurotransmission hold in providing new and transformative analgesic therapies for the treatment of chronic pain.

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BACKGROUND: Of the ~50 million cases of epilepsy worldwide, an estimated 80% originate from cortical areas implicated in language. Although the precise language loci can vary significantly across individuals, electrical stimulation mapping for eloquent areas has become standard of care in resective surgery for frontotemporal epilepsies. Although considerable work has been done to establish the minimum necessary resection distance from these sites to preserve language, no previous work has shown how these representations are affected by proximal resections. METHODS: Between 1967 and 2005, 22 patients [seizure onset (y): 11.5 (0.2–33); age at initial resection (y): 27.7 (10–39); time between operations (y): 8.4 (1–20.3); sex: 14 females; hemisphere: 21 left] underwent repeated perisylvian resective epilepsy surgeries of the language-dominant hemisphere. Each set of operations comprised intraoperative language mapping and cortical photographs. Using this data, a Bayesian hierarchical model was used to estimate the variability of language localization pre-resection Versus post-resection. RESULTS: The statistical model shows the posterior median difference in cortical location of language sites preresection Versus postresection is 0.6 cm, with a posterior 95% CI of 0.4 cm, 0.9 cm. CONCLUSION: This work suggests permanence in cortical language centers following resection of infringing cortex, while providing a reasonable statistical method to impute unobserved sites during the mappings, and confirming the validity of using proximity sites defined by shortest distance in the current literature.

Francisco de Castro: Localizationism, intelligence and the frontal lobe.

ABSTRACTThis article addresses the largely unknown legacy of Francisco de Castro regarding the neurological sciences. His essay "Psychogenic Cortical Centers", written in 1881 for his admission to the Imperial Academy of Medicine in Rio de Janeiro, is a refined appreciation of the theory of localized cortical functions that was in evidence in Europe in the second half of the nineteenth century.

A reduced somatosensory gating response in individuals with multiple sclerosis is related to walking impairment.

When identical stimuli are presented in rapid temporal succession, neural responses to the second stimulation are often weaker than those observed for the first. This phenomenon is termed sensory gating and is believed to be an adaptive feature that helps prevent higher-order cortical centers from being flooded with unnecessary information. Recently, sensory gating in the somatosensory system has been linked to deficits in tactile discrimination. Additionally, studies have linked poor tactile discrimination with impaired walking and balance in individuals with multiple sclerosis (MS). In this study, we examine the neural basis of somatosensory gating in patients with MS and healthy controls and assess the relationship between somatosensory gating and walking performance. We used magnetoencephalography to record neural responses to paired-pulse electrical stimulation applied to the right posterior tibial nerve. All participants also walked across a digital mat, which recorded their spatiotemporal gait kinematics. Our results showed the amplitude of the response to the second stimulation was sharply reduced only in controls, resulting in a significantly reduced somatosensory gating in the patients with MS. No group differences were observed in the amplitude of the response to the first stimulation nor the latency of the neural response to either the first or second stimulation. Interestingly, the altered somatosensory gating responses were correlated with aberrant spatiotemporal gait kinematics in the patients with MS. These results suggest that inhibitory GABA circuits may be altered in patients with MS, which impacts somatosensory gating and contributes to the motor performance deficits seen in these patients.NEW & NOTEWORTHY We aimed to determine whether somatosensory gating in patients with multiple sclerosis (MS) differed compared with healthy controls and whether a relationship exists between somatosensory gating and walking performance. We found reduced somatosensory gating responses in patients with MS, and these altered somatosensory gating responses were correlated with the mobility impairments. These novel findings show that somatosensory gating is impaired in patients with MS and is related to the mobility impairments seen in these patients.

Does Muscle Fatigue Alter EEG Bands of Brain Hemispheres?

Background: Muscle fatigue has been known to influence brain activity, but very little is known about how cortical centers respond to muscle fatigue.Objective: This study was conducted to investigate the effects of muscle contraction and fatigue induced by two different percents of maximal voluntary contraction (MVC) on Electroencephalography (EEG) signals.Material and Methods: In this quasi-experimental study, EEG signals were recorded from twenty-one healthy human subjects during three phases (rest, pre fatigue and post fatigue) contraction of Adductor pollicis muscle (APM) at 30% and 70% MVC. The mean powers of EEG bands (alpha, beta and gamma) were computed offline in the frequency domain.Results: None of the three phases with each percent of MVC revealed significant differences for all bands (p>0.05). Comparison of two hemispheres showed that right hemisphere gamma band activity was enhanced during pre-fatigue state at 30% MVC (p= 0.042) and post-fatigue state at 70% MVC (p= 0.028). Right hemisphere beta band activity also increased prominently at 70% MVC in post-fatigue condition (p = 0.030).Conclusion: These results suggest muscle contraction and fatigue at 30% and 70% MVC have no significant effect on EEG activity, but the trends of beta and gamma band activities are almost similar in each percent of 30% and 70% MVC. Right brain hemisphere shows more activity than left hemisphere in beta and gamma rhythm after fatigue state at 70% MVC.

PATHOPHYSIOLOGY AND PRINCIPLES OF THERAPY OF A NEUROGENIC HYPERACTIVE URINARY BLADDER IN PATIENTS AFTER CEREBROVASCULAR ACCIDENT

Neurogenic hyperactiv e bladder in different clinical variations is a characteristic com plication of restorativ e and residual periods of ischemic stroke and an important diagnostic criterion in vascular dementia. Mechanisms of formation of individual symptoms included in this syndrome is due to ischemic damage to cortical, subcortical and brainstem (the nucleus of Barrington) centres of urination and associative areas of the brain, and the functional dissociation of these structures due to demyelination of the Central conductors of the afferent and efferent impulses. As a result of deficit of cerebral effects (such as brake and activating), is a violation of the implementation of the reflexes of urination (including carrying out continence), ongoing spinal (sympathetic, parasympathetic and somatic). The article presents a new concept of formation of the syndrome of hyperactive bladder on the basis of violations of the implementation of the 4 reflexes of urination, which provides the normal retention of urine and are responsible for the accumulation function of the bladder. First we analyzed the main point of application of drugs of anticholinergic and sympathomimetic actions in the reflexes of urination and mechanisms of restoration of function of the lower urinary tract in patients with acute and chronic v ascular diseases of the brain.

Endothelial basement membrane laminin 511 is essential for shear stress response.

Corrigendum15 May 2017free access Endothelial basement membrane laminin 511 is essential for shear stress response Jacopo Di Russo orcid.org/0000-0001-6731-9612 Search for more papers by this author Anna-Liisa Luik orcid.org/0000-0003-0389-5850 Search for more papers by this author Lema Yousif Search for more papers by this author Sigmund Budny Search for more papers by this author Hans Oberleithner Search for more papers by this author Verena Hofschröer Search for more papers by this author Juergen Klingauf Search for more papers by this author Ed van Bavel Search for more papers by this author Erik NTP Bakker Search for more papers by this author Per Hellstrand Search for more papers by this author Anirban Bhattachariya Search for more papers by this author Sebastian Albinsson Search for more papers by this author Frederic Pincet Search for more papers by this author Rupert Hallmann Search for more papers by this author Lydia M Sorokin orcid.org/0000-0001-7704-7921 Search for more papers by this author Jacopo Di Russo orcid.org/0000-0001-6731-9612 Search for more papers by this author Anna-Liisa Luik orcid.org/0000-0003-0389-5850 Search for more papers by this author Lema Yousif Search for more papers by this author Sigmund Budny Search for more papers by this author Hans Oberleithner Search for more papers by this author Verena Hofschröer Search for more papers by this author Juergen Klingauf Search for more papers by this author Ed van Bavel Search for more papers by this author Erik NTP Bakker Search for more papers by this author Per Hellstrand Search for more papers by this author Anirban Bhattachariya Search for more papers by this author Sebastian Albinsson Search for more papers by this author Frederic Pincet Search for more papers by this author Rupert Hallmann Search for more papers by this author Lydia M Sorokin orcid.org/0000-0001-7704-7921 Search for more papers by this author Author Information Jacopo Di Russo, Anna-Liisa Luik, Lema Yousif, Sigmund Budny, Hans Oberleithner, Verena Hofschröer, Juergen Klingauf, Ed Bavel, Erik NTP Bakker, Per Hellstrand, Anirban Bhattachariya, Sebastian Albinsson, Frederic Pincet, Rupert Hallmann and Lydia M Sorokin EMBO J (2017)36:1464-1464https://doi.org/10.15252/embj.201797000 This article corrects the following: Endothelial basement membrane laminin 511 is essential for shear stress response09 December 2016 ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info Editorial Note J. Di Russo and L. Sorokin were co-authors on another recent paper on laminin 511 in endothelial junctions in leukocyte extravasation (Song et al, 2017). Song et al (2017) was not made available for assessment by the editors and referees of this journal. While there is no reuse of specific text or figures between the two papers, it was an oversight to omit the citation to Song et al (2017). L. Sorokin, J. Di Russo and the Faculty of Medicine of Münster University, represented by Mathias Herrmann, agree with this statement. References Song J, Zhang X, Buscher K, Wang Y, Wang H, Di Russo J, Li L, Lütke-Enking S, Zarbock A, Stadtmann A, Striewski P, Wirth B, Kuzmanov I, Wiendl H, Schulte D, Vestweber D, Sorokin L (2017) Endothelial basement membrane laminin 511 contributes to endothelial junctional tightness and thereby inhibits leukocyte transmigration. Cell Rep 18: 1256–1269CrossrefCASPubMedWeb of Science®Google Scholar Next ArticlePrevious Article Read MoreAbout the coverClose modalView large imageVolume 36,Issue 10,15 May 2017Cover: The balance of brain organoid differentiation. This drawing illustrates the remarkable self-organization capacity of cerebral organoids that allows them to recapitulate human brain development in vitro. The authors show that organizing centers induce the formation of dorsal and ventral progenitor zones separated by a defined boundary – like a yin-yang symbolizing the balance between distinct but complementary entities. Color code: Dark red = Cortical hem signaling center Red = Pax6 positive radial glia progenitors in the dorsal forebrain Magenta = TBR2 positive intermediate progenitor cells in the dorsal forebrain Yellow-green = GSX2 positive progenitors in the ventral forebrain Green = DLX2 progenitors and young neurons in the ventral forebrain Cyan = VGAT positive interneurons migrating from ventral to dorsal forebrain Purple = Excitatory neurons generated in the dorsal forebrain From Magdalena Renner, Madeline A Lancaster, Jürgen A Knoblich and colleagues: Self-organized developmental patterning and differentiation in cerebral organoids. For details, see the Article on p 1316, also highlighted by Dias and Guillemot on p 1299. Artwork by Beata Edyta Mierzwa, Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), Vienna, Austria; (beatascienceart.com). Volume 36Issue 1015 May 2017In this issue ReferencesRelatedDetailsLoading ...

Osteopontin attenuates aging-associated phenotypes of hematopoietic stem cells.

Corrigendum15 May 2017free access Osteopontin attenuates aging-associated phenotypes of hematopoietic stem cells Novella Guidi Novella Guidi Search for more papers by this author Mehmet Sacma Mehmet Sacma Search for more papers by this author Ludger Ständker Ludger Ständker Search for more papers by this author Karin Soller Karin Soller Search for more papers by this author Gina Marka Gina Marka Search for more papers by this author Karina Eiwen Karina Eiwen Search for more papers by this author Johannes M Weiss Johannes M Weiss Search for more papers by this author Frank Kirchhoff Frank Kirchhoff Search for more papers by this author Tanja Weil Tanja Weil Search for more papers by this author Jose A Cancelas Jose A Cancelas Search for more papers by this author Maria Carolina Florian Maria Carolina Florian Search for more papers by this author Hartmut Geiger Hartmut Geiger orcid.org/0000-0001-7314-9891 Search for more papers by this author Novella Guidi Novella Guidi Search for more papers by this author Mehmet Sacma Mehmet Sacma Search for more papers by this author Ludger Ständker Ludger Ständker Search for more papers by this author Karin Soller Karin Soller Search for more papers by this author Gina Marka Gina Marka Search for more papers by this author Karina Eiwen Karina Eiwen Search for more papers by this author Johannes M Weiss Johannes M Weiss Search for more papers by this author Frank Kirchhoff Frank Kirchhoff Search for more papers by this author Tanja Weil Tanja Weil Search for more papers by this author Jose A Cancelas Jose A Cancelas Search for more papers by this author Maria Carolina Florian Maria Carolina Florian Search for more papers by this author Hartmut Geiger Hartmut Geiger orcid.org/0000-0001-7314-9891 Search for more papers by this author Author Information Novella Guidi, Mehmet Sacma, Ludger Ständker, Karin Soller, Gina Marka, Karina Eiwen, Johannes M Weiss, Frank Kirchhoff, Tanja Weil, Jose A Cancelas, Maria Carolina Florian and Hartmut Geiger The EMBO Journal (2017)36:1463-1463https://doi.org/10.15252/embj.201796968 This article corrects the following: Osteopontin attenuates aging-associated phenotypes of hematopoietic stem cells02 March 2017 ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info We have found that panel A in Figure 5 (subpanel Old + C) is mistakenly a duplication of panel H in Figure 4 (subpanel Old + FL). According to our inspection of the original data sets, this is due to a mistake during the assembly of the panels. We show here the amended correct images for Figure 5, panel A (Old + C). Figure 5.Figure 5A, with correct panel Old + C. Download figure Download PowerPoint The change does not affect the original conclusions presented. We apologize for this mistake. All authors approve of this correction. Related Source data for Figure 5A, panel Old + C. Red: AcH4K16; Green: tubulin; Blue: DAPI. Previous ArticleNext Article Read MoreAbout the coverClose modalView large imageVolume 36,Issue 10,15 May 2017Cover: The balance of brain organoid differentiation. This drawing illustrates the remarkable self-organization capacity of cerebral organoids that allows them to recapitulate human brain development in vitro. The authors show that organizing centers induce the formation of dorsal and ventral progenitor zones separated by a defined boundary – like a yin-yang symbolizing the balance between distinct but complementary entities. Color code: Dark red = Cortical hem signaling center Red = Pax6 positive radial glia progenitors in the dorsal forebrain Magenta = TBR2 positive intermediate progenitor cells in the dorsal forebrain Yellow-green = GSX2 positive progenitors in the ventral forebrain Green = DLX2 progenitors and young neurons in the ventral forebrain Cyan = VGAT positive interneurons migrating from ventral to dorsal forebrain Purple = Excitatory neurons generated in the dorsal forebrain From Magdalena Renner, Madeline A Lancaster, Jürgen A Knoblich and colleagues: Self-organized developmental patterning and differentiation in cerebral organoids. For details, see the Article on p 1316, also highlighted by Dias and Guillemot on p 1299. Artwork by Beata Edyta Mierzwa, Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), Vienna, Austria; (beatascienceart.com). Volume 36Issue 1015 May 2017In this issue FiguresRelatedDetailsLoading ...

Signaling in the Auditory System: Implications in Hair Cell Regeneration and Hearing Function.

Ear is a sensitive organ involved in hearing and balance function. The complex signaling network in the auditory system plays a crucial role in maintaining normal physiological function of the ear. The inner ear comprises a variety of host signaling pathways working in synergy to deliver clear sensory messages. Any disruption, as minor as it can be, has the potential to affect this finely tuned system with temporary or permanent sequelae including vestibular deficits and hearing loss. Mutations linked to auditory symptoms, whether inherited or acquired, are being actively researched for ways to reverse, silence, or suppress them. In this article, we discuss recent advancements in understanding the pathways involved in auditory system signaling, from hair cell development through transmission to cortical centers. Our review discusses Notch and Wnt signaling, cell to cell communication through connexin and pannexin channels, and the detrimental effects of reactive oxygen species on the auditory system. There has been an increased interest in the auditory community to explore the signaling system in the ear for hair cell regeneration. Understanding signaling pathways in the auditory system will pave the way for the novel avenues to regenerate sensory hair cells and restore hearing function. J. Cell. Physiol. 232: 2710-2721, 2017. © 2016 Wiley Periodicals, Inc.

The cortical connectivity of the periaqueductal gray and the conditioned response to the threat of breathlessness.

Previously we observed differential activation in individual columns of the periaqueductal grey (PAG) during breathlessness and its conditioned anticipation (Faull et al., 2016b). Here, we have extended this work by determining how the individual columns of the PAG interact with higher cortical centres, both at rest and in the context of breathlessness threat. Activation was observed in ventrolateral PAG (vlPAG) and lateral PAG (lPAG), where activity scaled with breathlessness intensity ratings, revealing a potential interface between sensation and cognition during breathlessness. At rest the lPAG was functionally correlated with cortical sensorimotor areas, conducive to facilitating fight/flight responses, and demonstrated increased synchronicity with the amygdala during breathlessness. The vlPAG showed fronto-limbic correlations at rest, whereas during breathlessness anticipation, reduced functional synchronicity was seen to both lPAG and motor structures, conducive to freezing behaviours. These results move us towards understanding how the PAG might be intricately involved in human responses to threat.

DMRT5 Together with DMRT3 Directly Controls Hippocampus Development and Neocortical Area Map Formation.

Mice that are constitutively null for the zinc finger doublesex and mab-3 related (Dmrt) gene, Dmrt5/Dmrta2, show a variety of patterning abnormalities in the cerebral cortex, including the loss of the cortical hem, a powerful cortical signaling center. In conditional Dmrt5 gain of function and loss of function mouse models, we generated bidirectional changes in the neocortical area map without affecting the hem. Analysis indicated that DMRT5, independent of the hem, directs the rostral-to-caudal pattern of the neocortical area map. Thus, DMRT5 joins a small number of transcription factors shown to control directly area size and position in the neocortex. Dmrt5 deletion after hem formation also reduced hippocampal size and shifted the position of the neocortical/paleocortical boundary. Dmrt3, like Dmrt5, is expressed in a gradient across the cortical primordium. Mice lacking Dmrt3 show cortical patterning defects akin to but milder than those in Dmrt5 mutants, perhaps in part because Dmrt5 expression increases in the absence of Dmrt3. DMRT5 upregulates Dmrt3 expression and negatively regulates its own expression, which may stabilize the level of DMRT5. Together, our findings indicate that finely tuned levels of DMRT5, together with DMRT3, regulate patterning of the cerebral cortex.

Supraspinal Control Predicts Locomotor Function and Forecasts Responsiveness to Training after Spinal Cord Injury.

Restoration of walking ability is an area of great interest in the rehabilitation of persons with spinal cord injury. Because many cortical, subcortical, and spinal neural centers contribute to locomotor function, it is important that intervention strategies be designed to target neural elements at all levels of the neuraxis that are important for walking ability. While to date most strategies have focused on activation of spinal circuits, more recent studies are investigating the value of engaging supraspinal circuits. Despite the apparent potential of pharmacological, biological, and genetic approaches, as yet none has proved more effective than physical therapeutic rehabilitation strategies. By making optimal use of the potential of the nervous system to respond to training, strategies can be developed that meet the unique needs of each person. To complement the development of optimal training interventions, it is valuable to have the ability to predict future walking function based on early clinical presentation, and to forecast responsiveness to training. A number of clinical prediction rules and association models based on common clinical measures have been developed with the intent, respectively, to predict future walking function based on early clinical presentation, and to delineate characteristics associated with responsiveness to training. Further, a number of variables that are correlated with walking function have been identified. Not surprisingly, most of these prediction rules, association models, and correlated variables incorporate measures of volitional lower extremity strength, illustrating the important influence of supraspinal centers in the production of walking behavior in humans.

Differential activation of the frontal pole to high vs low calorie foods: The neural basis of food preference in Anorexia Nervosa?

Neuroimaging studies in anorexia nervosa (AN) suggest that altered food reward processing may result from dysfunction in both limbic reward and cortical control centers of the brain. This fMRI study aimed to index the neural correlates of food reward in a subsample of individuals with restrictive AN: twelve currently ill, fourteen recovered individuals and sixteen healthy controls. Participants were shown pictures of high and low-calorie foods and asked to evaluate how much they wanted to eat each one following a four hour fast. Whole-brain task-activated analysis was followed by psychophysiological interaction analysis (PPI) of the amygdala and caudate. In the AN group, we observed a differential pattern of activation in the lateral frontal pole: increasing following presentation of high-calorie stimuli and decreasing in during presentation of low-calorie food pictures, the opposite of which was seen in the healthy control (HC) group. In addition, decreased activation to food pictures was observed in somatosensory regions in the AN group. PPI analyses suggested hypo-connectivity in reward pathways, and between the caudate and both somatosensory and visual processing regions in the AN group. No significant between-group differences were observed between the recovered group and the currently ill and healthy controls in the PPI analysis. Taken together, these findings further our understanding of the neural processes which may underpin the avoidance of high-calorie foods in those with AN and might exacerbate the development of compulsive weight-loss behavior, despite emaciation.

Ictal bradyarrhythmias and asystole requiring pacemaker implantation: Combined EEG-ECG analysis of 5 cases.

Seizures can lead to cardiac arrhythmias by a number of mechanisms including activation/inhibition of cortical autonomic centers, increase in vagal tone through activation of brainstem reflex centers, and respiratory failure. Ictal asystole (IA) is a potential mechanism underlying sudden unexpected death in epilepsy (SUDEP). We analyzed the clinical features of 5 patients who developed IA requiring pacemaker implantation. Patients with ictal arrhythmias were identified from the video-telemetry and ambulatory EEG database at Greater Manchester Neurosciences Centre, as well as an independent epilepsy residential care facility. Only those who had IA requiring pacemaker implantation were included in the analysis. A total of 5 patients were identified. Of the 5 patients with IA, 4 were female. All 5 patients had focal epilepsy, and four had temporal lobe epilepsy. Ictal asystole occurred with focal seizures with impairment of awareness. Seizure onset was left-sided in 2 patients, right-sided in one, left-sided onset with switch of lateralization in one, and nonlateralized in one patient. Three patients had hippocampal sclerosis, one of whom had undergone epilepsy surgery, one had traumatic encephalomalacia of the temporal lobe, and one patient had no lesions detected on MRI. Interictal epileptiform activity was more pronounced during sleep in all patients. Asystole occurred in association with sleep-related seizures in 4 of 5 patients. Ictal asystole (IA) occurred in association with sleep-related seizures in 4 out of 5 cases, predominantly in patients with temporal lobe epilepsy. These findings may be of relevance to SUDEP.