Neural Plasticity The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Cytokines in Bipolar Disorder: Paving the Way for Neuroprogression Tue, 09 Sep 2014 00:00:00 +0000 Bipolar disorder (BD) is a severe, chronic, and recurrent psychiatric illness. It has been associated with high prevalence of medical comorbidities and cognitive impairment. Its neurobiology is not completely understood, but recent evidence has shown a wide range of immune changes. Cytokines are proteins involved in the regulation and the orchestration of the immune response. We performed a review on the involvement of cytokines in BD. We also discuss the cytokines involvement in the neuroprogression of BD. It has been demonstrated that increased expression of cytokines in the central nervous system in postmortem studies is in line with the elevated circulating levels of proinflammatory cytokines in BD patients. The proinflammatory profile and the immune imbalance in BD might be regarded as potential targets to the development of new therapeutic strategies. Izabela Guimarães Barbosa, Moisés Evandro Bauer, Rodrigo Machado-Vieira, and Antonio Lucio Teixeira Copyright © 2014 Izabela Guimarães Barbosa et al. All rights reserved. Plasticity of Neural Systems in Tinnitus Mon, 08 Sep 2014 09:07:31 +0000 Martin Meyer, Berthold Langguth, Tobias Kleinjung, and Aage R. Møller Copyright © 2014 Martin Meyer et al. All rights reserved. Blockade of Lysosomal Acid Ceramidase Induces GluN2B-Dependent Tau Phosphorylation in Rat Hippocampal Slices Mon, 08 Sep 2014 05:23:30 +0000 The lysosomal acid ceramidase, an enzyme known to limit intracellular ceramide accumulation, has been reported to be defective in neurodegenerative disorders. We show here that rat hippocampal slices, preincubated with the acid ceramidase inhibitor (ACI) d-NMAPPD, exhibit increased N-methyl-D-aspartate (NMDA) receptor-mediated field excitatory postsynaptic potentials (fEPSPs) in CA1 synapses. The ACI by itself did not interfere with either paired pulse facilitation or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor-mediated fEPSPs, indicating that its influence on synaptic transmission is postsynaptic in origin and specific to the NMDA subtype of glutamate receptors. From a biochemical perspective, we observed that Tau phosphorylation at the Ser262 epitope was highly increased in hippocampal slices preincubated with the ACI, an effect totally prevented by the global NMDA receptor antagonist D/L(−)-2-amino-5-phosphonovaleric acid (AP-5), the calcium chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA), and the GluN2B (but not the GluN2A) receptor antagonist RO25-6981. On the other hand, preincubation of hippocampal slices with the compound KN-62, an inhibitor known to interfere with calcium/calmodulin-dependent protein kinase II (CaMKII), totally abolished the effect of ACI on Tau phosphorylation at Ser262 epitopes. Collectively, these results provide experimental evidence that ceramides play an important role in regulating Tau phosphorylation in the hippocampus via a mechanism dependent on GluN2B receptor subunits and CaMKII activation. Marie-Elaine Laurier-Laurin, Audrée De Montigny, Suzanne Attiori Essis, Michel Cyr, and Guy Massicotte Copyright © 2014 Marie-Elaine Laurier-Laurin et al. All rights reserved. Abeta(1-42) Enhances Neuronal Excitability in the CA1 via NR2B Subunit-Containing NMDA Receptors Wed, 03 Sep 2014 11:39:33 +0000 Neuronal hyperexcitability is a phenomenon associated with early Alzheimer’s disease. The underlying mechanism is considered to involve excessive activation of glutamate receptors; however, the exact molecular pathway remains to be determined. Extracellular recording from the CA1 of hippocampal slices is a long-standing standard for a range of studies both in basic research and in neuropharmacology. Evoked field potentials (fEPSPs) are regarded as the input, while spiking rate is regarded as the output of the neuronal network; however, the relationship between these two phenomena is not fully clear. We investigated the relationship between spontaneous spiking and evoked fEPSPs using mouse hippocampal slices. Blocking AMPA receptors (AMPARs) with CNQX abolished fEPSPs, but left firing rate unchanged. NMDA receptor (NMDAR) blockade with MK801 decreased neuronal spiking dose dependently without altering fEPSPs. Activating NMDARs by small concentration of NMDA induced a trend of increased firing. These results suggest that fEPSPs are mediated by synaptic activation of AMPARs, while spontaneous firing is regulated by the activation of extrasynaptic NMDARs. Synaptotoxic Abeta(1-42) increased firing activity without modifying evoked fEPSPs. This hyperexcitation was prevented by ifenprodil, an antagonist of the NR2B NMDARs. Overall, these results suggest that Abeta(1-42) induced neuronal overactivity is not dependent on AMPARs but requires NR2B. Edina Varga, Gábor Juhász, Zsolt Bozsó, Botond Penke, Lívia Fülöp, and Viktor Szegedi Copyright © 2014 Edina Varga et al. All rights reserved. Disentangling Tinnitus Distress and Tinnitus Presence by Means of EEG Power Analysis Wed, 03 Sep 2014 09:27:05 +0000 The present study investigated 24 individuals suffering from chronic tinnitus (TI) and 24 nonaffected controls (CO). We recorded resting-state EEG and collected psychometric data to obtain information about how chronic tinnitus experience affects the cognitive and emotional state of TI. The study was meant to disentangle TI with high distress from those who suffer less from persistent tinnitus based on both neurophysiological and behavioral data. A principal component analysis of psychometric data uncovers two distinct independent dimensions characterizing the individual tinnitus experience. These independent states are distress and presence, the latter is described as the perceived intensity of sound experience that increases with tinnitus duration devoid of any considerable emotional burden. Neuroplastic changes correlate with the two independent components. TI with high distress display increased EEG activity in the oscillatory range around 25 Hz (upper β-band) that agglomerates over frontal recording sites. TI with high presence show enhanced EEG signal strength in the δ-, α-, and lower γ-bands (30–40 Hz) over bilateral temporal and left perisylvian electrodes. Based on these differential patterns we suggest that the two dimensions, namely, distress and presence, should be considered as independent dimensions of chronic subjective tinnitus. Martin Meyer, Matthias S. Luethi, Patrick Neff, Nicolas Langer, and Stefan Büchi Copyright © 2014 Martin Meyer et al. All rights reserved. Proliferation in the Alzheimer Hippocampus Is due to Microglia, Not Astroglia, and Occurs at Sites of Amyloid Deposition Tue, 19 Aug 2014 09:11:07 +0000 Microglia and astrocytes contribute to Alzheimer’s disease (AD) etiology and may mediate early neuroinflammatory responses. Despite their possible role in disease progression and despite the fact that they can respond to amyloid deposition in model systems, little is known about whether astro- or microglia can undergo proliferation in AD and whether this is related to the clinical symptoms or to local neuropathological changes. Previously, proliferation was found to be increased in glia-rich regions of the presenile hippocampus. Since their phenotype was unknown, we here used two novel triple-immunohistochemical protocols to study proliferation in astro- or microglia in relation to amyloid pathology. We selected different age-matched cohorts to study whether proliferative changes relate to clinical severity or to neuropathological changes. Proliferating cells were found across the hippocampus but never in mature neurons or astrocytes. Almost all proliferating cells were colabeled with Iba1+, indicating that particularly microglia contribute to proliferation in AD. Proliferating Iba1+ cells was specifically seen within the borders of amyloid plaques, indicative of an active involvement in, or response to, plaque accumulation. Thus, consistent with animal studies, proliferation in the AD hippocampus is due to microglia, occurs in close proximity of plaque pathology, and may contribute to the neuroinflammation common in AD. Michael W. Marlatt, Jan Bauer, Eleonora Aronica, Elise S. van Haastert, Jeroen J. M. Hoozemans, Marian Joels, and Paul J. Lucassen Copyright © 2014 Michael W. Marlatt et al. All rights reserved. Hippocampal Proliferation Is Increased in Presymptomatic Parkinson’s Disease and due to Microglia Thu, 14 Aug 2014 00:00:00 +0000 Besides dopamine-deficiency related motor symptoms, nonmotor symptoms, including cognitive changes occur in Parkinson's disease (PD) patients, that may relate to accumulation of α-synuclein in the hippocampus (HC). This brain region also contains stem cells that can proliferate. This is a well-regulated process that can, for example, be altered by neurodegenerative conditions. In contrast to proliferation in the substantia nigra and subventricular zone, little is known about the HC in PD. In addition, glial cells contribute to neurodegenerative processes and may proliferate in response to PD pathology. In the present study, we questioned whether microglial cells proliferate in the HC of established PD patients versus control subjects or incidental Lewy body disease (iLBD) cases as a prodromal state of PD. To this end, proliferation was assessed using the immunocytochemical marker minichromosome maintenance protein 2 (MCM2). Colocalization with Iba1 was performed to determine microglial proliferation. MCM2-positive cells were present in the HC of controls and were significantly increased in the presymptomatic iLBD cases, but not in established PD patients. Microglia represented the majority of the proliferating cells in the HC. This suggests an early microglial response to developing PD pathology in the HC and further indicates that neuroinflammatory processes play an important role in the development of PD pathology. Karlijn J. Doorn, Benjamin Drukarch, Anne-Marie van Dam, and Paul J. Lucassen Copyright © 2014 Karlijn J. Doorn et al. All rights reserved. Neurological Disorders Related Neuronal Network Impairment: Function and Mechanism Wed, 23 Jul 2014 08:37:36 +0000 Sheng-tian Li, Yun Wang, and Masayuki Matsushita Copyright © 2014 Sheng-tian Li et al. All rights reserved. The Interplay between Reproductive Social Stimuli and Adult Olfactory Bulb Neurogenesis Tue, 22 Jul 2014 00:00:00 +0000 Adult neurogenesis is a striking form of structural plasticity that adapts the brain to the changing world. Accordingly, new neuron production is involved in cognitive functions, such as memory, learning, and pattern separation. Recent data in rodents indicate a close link between adult neurogenesis and reproductive social behavior. This provides a key to unravel the functional meaning of adult neurogenesis in biological relevant contexts and, in parallel, opens new perspectives to explore the way the brain is processing social stimuli. In this paper we will summarize some of the major achievements on cues and mechanisms modulating adult neurogenesis during social behaviors related to reproduction and possible role/s played by olfactory newborn neurons in this context. We will point out that newborn interneurons in the accessory olfactory bulb (AOB) represent a privileged cellular target for social stimuli that elicit reproductive behaviors and that such cues modulate adult neurogenesis at two different levels increasing both proliferation of neuronal progenitors in the germinative regions and integration of newborn neurons into functional circuits. This dual mechanism provides fresh neurons that can be involved in critical activities for the individual fitness, that is, the processing of social stimuli driving the parental behavior and partner recognition. Paolo Peretto, Roberta Schellino, Silvia De Marchis, and Aldo Fasolo Copyright © 2014 Paolo Peretto et al. All rights reserved. Combination of Acellular Nerve Graft and Schwann Cells-Like Cells for Rat Sciatic Nerve Regeneration Wed, 09 Jul 2014 11:07:08 +0000 Objective. To investigate the effect of tissue engineering nerve on repair of rat sciatic nerve defect. Methods. Forty-five rats with defective sciatic nerve were randomly divided into three groups. Rats in group A were repaired by acellular nerve grafts only. Rats in group B were repaired by tissue engineering nerve. In group C, rats were repaired by autogenous nerve grafts. After six and twelve weeks, sciatic nerve functional index (SFI), neural electrophysiology (NEP), histological and transmission electron microscope observation, recovery ratio of wet weight of gastrocnemius muscle, regenerated myelinated nerve fibers number, nerve fiber diameter, and thickness of the myelin sheath were measured to assess the effect. Results. After six and twelve weeks, the recovery ratio of SFI and wet weight of gastrocnemius muscle, NEP, and the result of regenerated myelinated nerve fibers in groups B and C were superior to that of group A (), and the difference between groups B and C was not statistically significant (). Conclusion. The tissue engineering nerve composed of acellular allogenic nerve scaffold and Schwann cells-like cells can effectively repair the nerve defect in rats and its effect was similar to that of the autogenous nerve grafts. Songtao Gao, Yan Zheng, Qiqing Cai, Zhansheng Deng, Weitao Yao, Jiaqiang Wang, Xin Wang, and Peng Zhang Copyright © 2014 Songtao Gao et al. All rights reserved. Tinnitus-Related Distress and the Personality Characteristic Resilience Tue, 08 Jul 2014 00:00:00 +0000 It has been suggested that personality traits may be prognostic for the severity of suffering from tinnitus. Resilience as measured with the Wagnild and Young resilience scale represents a positive personality characteristic that promotes adaptation to adverse life conditions including chronic health conditions. Aim of the study was to explore the relation between resilience and tinnitus severity. In a cross-sectional study with a self-report questionnaire, information on tinnitus-related distress and subjective tinnitus loudness was recorded together with the personality characteristic resilience and emotional health, a measure generated from depression, anxiety, and somatic symptom severity scales. Data from 4705 individuals with tinnitus indicate that tinnitus-related distress and to a lesser extent the experienced loudness of the tinnitus show an inverse correlation with resilience. A mediation analysis revealed that the relationship between resilience and tinnitus-related distress is mediated by emotional health. This indirect effect indicates that high resilience is associated with better emotional health or less depression, anxiety, and somatic symptom severity, which in turn is associated with a less distressing tinnitus. Validity of resilience as a predictor for tinnitus-related distress is supported but needs to be explored further in longitudinal studies including acute tinnitus patients. Elisabeth Wallhäusser-Franke, Wolfgang Delb, Tobias Balkenhol, Wolfgang Hiller, and Karl Hörmann Copyright © 2014 Elisabeth Wallhäusser-Franke et al. All rights reserved. The Enigma of the Tinnitus-Free Dream State in a Bayesian World Sun, 06 Jul 2014 07:37:56 +0000 There are pathophysiological, clinical, and treatment analogies between phantom limb pain and phantom sound (i.e., tinnitus). Phantom limb pain commonly is absent in dreams, and the question arises whether this is also the case for tinnitus. A questionnaire was given to 78 consecutive tinnitus patients seen at a specialized tinnitus clinic. Seventy-six patients remembered their dreams and of these 74 claim not to perceive tinnitus during their dreams (97%). This can be most easily explained by a predictive Bayesian brain model. That is, during the awake state the brain constantly makes predictions about the environment. Tinnitus is hypothesized to be the result of a prediction error due to deafferentation, and missing input is filled in by the brain. The heuristic explanation then is that in the dream state there is no interaction with the environment and therefore no updating of the prediction error, resulting in the absence of tinnitus. Dirk De Ridder, Kathleen Joos, and Sven Vanneste Copyright © 2014 Dirk De Ridder et al. All rights reserved. Behavioral Improvement and Regulation of Molecules Related to Neuroplasticity in Ischemic Rat Spinal Cord Treated with PEDF Thu, 03 Jul 2014 14:17:00 +0000 Pigment epithelium derived factor (PEDF) exerts trophic actions to motoneurons and modulates nonneuronal restorative events, but its effects on neuroplasticity responses after spinal cord (SC) injury are unknown. Rats received a low thoracic SC photothrombotic ischemia and local injection of PEDF and were evaluated behaviorally six weeks later. PEDF actions were detailed in SC ventral horn (motor) in the levels of the lumbar central pattern generator (CPG), far from the injury site. Molecules related to neuroplasticity (MAP-2), those that are able to modulate such event, for instance, neurotrophic factors (NT-3, GDNF, BDNF, and FGF-2), chondroitin sulfate proteoglycans (CSPG), and those associated with angiogenesis and antiapoptosis (laminin and Bcl-2) and Eph (receptor)/ephrin system were evaluated at cellular or molecular levels. PEDF injection improved motor behavioral performance and increased MAP-2 levels and dendritic processes in the region of lumbar CPG. Treatment also elevated GDNF and decreased NT-3, laminin, and CSPG. Injury elevated EphA4 and ephrin-B1 levels, and PEDF treatment increased ephrin A2 and ephrins B1, B2, and B3. Eph receptors and ephrins were found in specific populations of neurons and astrocytes. PEDF treatment to SC injury triggered neuroplasticity in lumbar CPG and regulation of neurotrophic factors, extracellular matrix molecules, and ephrins. Chary Marquez Batista, Leonardo Luis Torres Bianqui, Bruno Bonganha Zanon, Mauricio Menezes Aben Athar Ivo, Gabriela Pintar de Oliveira, Jessica Ruivo Maximino, and Gerson Chadi Copyright © 2014 Chary Marquez Batista et al. All rights reserved. Adult Hippocampal Neurogenesis in Parkinson’s Disease: Impact on Neuronal Survival and Plasticity Thu, 03 Jul 2014 12:01:40 +0000 In Parkinson’s disease (PD) and other synucleinopathies, chronic neurodegeneration occurs within different areas of the central nervous system leading to progressive motor and nonmotor symptoms. The symptomatic treatment options that are currently available do not slow or halt disease progression. This highlights the need of a better understanding of disease mechanisms and disease models. The generation of newborn neurons in the adult hippocampus and in the subventricular zone/olfactory bulb system is affected by many different regulators and possibly involved in memory processing, depression, and olfaction, symptoms which commonly occur in PD. The pathology of the adult neurogenic niches in human PD patients is still mostly elusive, but different preclinical models have shown profound alterations of adult neurogenesis. Alterations in stem cell proliferation, differentiation, and survival as well as neurite outgrowth and spine formation have been related to different aspects in PD pathogenesis. Therefore, neurogenesis in the adult brain provides an ideal model to study disease mechanisms and compounds. In addition, adult newborn neurons have been proposed as a source of endogenous repair. Herein, we review current knowledge about the adult neurogenic niches in PD and highlight areas of future research. Martin Regensburger, Iryna Prots, and Beate Winner Copyright © 2014 Martin Regensburger et al. All rights reserved. Diffusion Imaging of Auditory and Auditory-Limbic Connectivity in Tinnitus: Preliminary Evidence and Methodological Challenges Sun, 22 Jun 2014 09:39:05 +0000 Subjective tinnitus, or “ringing in the ears,” is perceived by 10 to 15 percent of the adult population and causes significant suffering in a subset of patients. While it was originally thought of as a purely auditory phenomenon, there is increasing evidence that the limbic system influences whether and how tinnitus is perceived, far beyond merely determining the patient’s emotional reaction to the phantom sound. Based on functional imaging and electrophysiological data, recent articles frame tinnitus as a “network problem” arising from abnormalities in auditory-limbic interactions. Diffusion-weighted magnetic resonance imaging is a noninvasive method for investigating anatomical connections in vivo. It thus has the potential to provide anatomical evidence for the proposed changes in auditory-limbic connectivity. However, the few diffusion imaging studies of tinnitus performed to date have inconsistent results. In the present paper, we briefly summarize the results of previous studies, aiming to reconcile their results. After detailing analysis methods, we then report findings from a new dataset. We conclude that while there is some evidence for tinnitus-related increases in auditory and auditory-limbic connectivity that counteract hearing-loss related decreases in auditory connectivity, these results should be considered preliminary until several technical challenges have been overcome. Anna Seydell-Greenwald, Erika P. Raven, Amber M. Leaver, Ted K. Turesky, and Josef P. Rauschecker Copyright © 2014 Anna Seydell-Greenwald et al. All rights reserved. Spinal fMRI of Interoceptive Attention/Awareness in Experts and Novices Tue, 17 Jun 2014 06:03:43 +0000 Many disciplines/traditions that promote interoceptive (inner sensation of body parts) attention/awareness (IAA) train practitioners to both attend to and be aware of interoceptive sensory experiences in body parts. The effect of such practices has been investigated in previous imaging studies but limited to cerebral neural activity. Here, for the first time, we studied the impact of these practices on the spinal neural activity of experts and novices. We also attempted to clarify the effect of constant and deep breathing, a paradigm utilized in concentration practices to avoid mind wandering, on IAA-related spinal neural activity. Subjects performed IAA tasks with and without a deep and constant breathing pattern in two sessions. Results showed that neural activity in the spinal segment innervating the attended-to body area increased in experts () when they performed IAA and that this increase was significantly larger for experts versus novices in each of the sessions (). The significant effects of IAA and expertise on spinal neural activity are consistent with and elaborate on previous reports showing similar effects on cerebral neural activity. As the spinal cord directly innervates body parts, the results might indicate that IAA has an instantaneous (possibly beneficial) effect on the physical body after extended training. Keyvan Kashkouli Nejad, Motoaki Sugiura, Benjamin Thyreau, Takayuki Nozawa, Yuka Kotozaki, Yoshihito Furusawa, Kozo Nishino, Toshohiro Nukiwa, and Ryuta Kawashima Copyright © 2014 Keyvan Kashkouli Nejad et al. All rights reserved. Protective Effects of Ginkgo biloba Extract EGb 761 against Noise Trauma-Induced Hearing Loss and Tinnitus Development Tue, 17 Jun 2014 00:00:00 +0000 Noise-induced hearing loss (NIHL) and resulting comorbidities like subjective tinnitus are common diseases in modern societies. A substance shown to be effective against NIHL in an animal model is the Ginkgo biloba extract EGb 761. Further effects of the extract on the cellular and systemic levels of the nervous system make it a promising candidate not only for protection against NIHL but also for its secondary comorbidities like tinnitus. Following an earlier study we here tested the potential effectiveness of prophylactic EGb 761 treatment against NIHL and tinnitus development in the Mongolian gerbil. We monitored the effects of EGb 761 and noise trauma-induced changes on signal processing within the auditory system by means of behavioral and electrophysiological approaches. We found significantly reduced NIHL and tinnitus development upon EGb 761 application, compared to vehicle treated animals. These protective effects of EGb 761 were correlated with changes in auditory processing, both at peripheral and central levels. We propose a model with two main effects of EGb 761 on auditory processing, first, an increase of auditory brainstem activity leading to an increased thalamic input to the primary auditory cortex (AI) and second, an asymmetric effect on lateral inhibition in AI. Konstantin Tziridis, Sabine Korn, Sönke Ahlf, and Holger Schulze Copyright © 2014 Konstantin Tziridis et al. All rights reserved. Modulation of Electrocortical Brain Activity by Attention in Individuals with and without Tinnitus Thu, 12 Jun 2014 08:11:42 +0000 Age and hearing-level matched tinnitus and control groups were presented with a 40 Hz AM sound using a carrier frequency of either 5 kHz (in the tinnitus frequency region of the tinnitus subjects) or 500 Hz (below this region). On attended blocks subjects pressed a button after each sound indicating whether a single 40 Hz AM pulse of variable increased amplitude (target, probability 0.67) had or had not occurred. On passive blocks subjects rested and ignored the sounds. The amplitude of the 40 Hz auditory steady-state response (ASSR) localizing to primary auditory cortex (A1) increased with attention in control groups probed at 500 Hz and 5 kHz and in the tinnitus group probed at 500 Hz, but not in the tinnitus group probed at 5 kHz (128 channel EEG). N1 amplitude (this response localizing to nonprimary cortex, A2) increased with attention at both sound frequencies in controls but at neither frequency in tinnitus. We suggest that tinnitus-related neural activity occurring in the 5 kHz but not the 500 Hz region of tonotopic A1 disrupted attentional modulation of the 5 kHz ASSR in tinnitus subjects, while tinnitus-related activity in A1 distributing nontonotopically in A2 impaired modulation of N1 at both sound frequencies. Brandon T. Paul, Ian C. Bruce, Daniel J. Bosnyak, David C. Thompson, and Larry E. Roberts Copyright © 2014 Brandon T. Paul et al. All rights reserved. A Brain Centred View of Psychiatric Comorbidity in Tinnitus: From Otology to Hodology Wed, 11 Jun 2014 07:50:22 +0000 Introduction. Comorbid psychiatric disorders are frequent among patients affected by tinnitus. There are mutual clinical influences between tinnitus and psychiatric disorders, as well as neurobiological relations based on partially overlapping hodological and neuroplastic phenomena. The aim of the present paper is to review the evidence of alterations in brain networks underlying tinnitus physiopathology and to discuss them in light of the current knowledge of the neurobiology of psychiatric disorders. Methods. Relevant literature was identified through a search on Medline and PubMed; search terms included tinnitus, brain, plasticity, cortex, network, and pathways. Results. Tinnitus phenomenon results from systemic-neurootological triggers followed by neuronal remapping within several auditory and nonauditory pathways. Plastic reorganization and white matter alterations within limbic system, arcuate fasciculus, insula, salience network, dorsolateral prefrontal cortex, auditory pathways, ffrontocortical, and thalamocortical networks are discussed. Discussion. Several overlapping brain network alterations do exist between tinnitus and psychiatric disorders. Tinnitus, initially related to a clinicoanatomical approach based on a cortical localizationism, could be better explained by an holistic or associationist approach considering psychic functions and tinnitus as emergent properties of partially overlapping large-scale neural networks. Massimo Salviati, Francesco Saverio Bersani, Giuseppe Valeriani, Amedeo Minichino, Roberta Panico, Graziella Francesca Romano, Filippo Mazzei, Valeria Testugini, Giancarlo Altissimi, and Giancarlo Cianfrone Copyright © 2014 Massimo Salviati et al. All rights reserved. Structural Brain Changes Following Left Temporal Low-Frequency rTMS in Patients with Subjective Tinnitus Tue, 03 Jun 2014 12:02:56 +0000 Repetitive transcranial magnetic stimulation (rTMS) of the temporal cortex has been used to treat patients with subjective tinnitus. While rTMS is known to induce morphological changes in healthy subjects, no study has investigated yet whether rTMS treatment induces grey matter (GM) changes in tinnitus patients as well, whether these changes are correlated with treatment success, and whether GM at baseline is a useful predictor for treatment outcome. Therefore, we examined magnetic resonance images of 77 tinnitus patients who were treated with rTMS of the left temporal cortex (10 days, 2000 stimuli/day, 1 Hz). At baseline and after the last treatment session high-resolution structural images of the brain were acquired and tinnitus severity was assessed. For a subgroup of 41 patients, additional brain scans were done after a follow-up period of 90 days. GM changes were analysed by means of voxel based morphometry. Transient GM decreases were detectable in several brain regions, especially in the insula and the inferior frontal cortex. These changes were not related to treatment outcome though. Baseline images correlated with change in tinnitus severity in the frontal cortex and the lingual gyrus, suggesting that GM at baseline might hold potential as a possible predictor for treatment outcome. Astrid Lehner, Berthold Langguth, Timm B. Poeppl, Rainer Rupprecht, Göran Hajak, Michael Landgrebe, and Martin Schecklmann Copyright © 2014 Astrid Lehner et al. All rights reserved. Paving the Way for Speech: Voice-Training-Induced Plasticity in Chronic Aphasia and Apraxia of Speech—Three Single Cases Sun, 25 May 2014 07:11:57 +0000 Difficulties with temporal coordination or sequencing of speech movements are frequently reported in aphasia patients with concomitant apraxia of speech (AOS). Our major objective was to investigate the effects of specific rhythmic-melodic voice training on brain activation of those patients. Three patients with severe chronic nonfluent aphasia and AOS were included in this study. Before and after therapy, patients underwent the same fMRI procedure as 30 healthy control subjects in our prestudy, which investigated the neural substrates of sung vowel changes in untrained rhythm sequences. A main finding was that post-minus pretreatment imaging data yielded significant perilesional activations in all patients for example, in the left superior temporal gyrus, whereas the reverse subtraction revealed either no significant activation or right hemisphere activation. Likewise, pre- and posttreatment assessments of patients’ vocal rhythm production, language, and speech motor performance yielded significant improvements for all patients. Our results suggest that changes in brain activation due to the applied training might indicate specific processes of reorganization, for example, improved temporal sequencing of sublexical speech components. In this context, a training that focuses on rhythmic singing with differently demanding complexity levels as concerns motor and cognitive capabilities seems to support paving the way for speech. Monika Jungblut, Walter Huber, Christiane Mais, and Ralph Schnitker Copyright © 2014 Monika Jungblut et al. All rights reserved. Hippocampal Neurogenesis and Antidepressive Therapy: Shocking Relations Thu, 22 May 2014 06:11:50 +0000 Speculations on the involvement of hippocampal neurogenesis, a form of neuronal plasticity, in the aetiology of depression and the mode of action of antidepressive therapies, started to arise more than a decade ago. But still, conclusive evidence that adult neurogenesis contributes to antidepressive effects of pharmacological and physical therapies has not been generated yet. This review revisits recent findings on the close relation between the mode(s) of action of electroconvulsive therapy (ECT), a powerful intervention used as second-line treatment of major depression disorders, and the neurogenic response to ECT. Following application of electroconvulsive shocks, intricate interactions between neurogenesis, angiogenesis, and microglia activation, the hypothalamic-pituitary-adrenal axis and the secretion of neurotrophic factors have been documented. Furthermore, considering the fact that neurogenesis strongly diminishes along aging, we investigated the response to electroconvulsive shocks in young as well as in aged cohorts of mice. Peter Rotheneichner, Simona Lange, Anna O’Sullivan, Julia Marschallinger, Pia Zaunmair, Christian Geretsegger, Ludwig Aigner, and Sebastien Couillard-Despres Copyright © 2014 Peter Rotheneichner et al. All rights reserved. Reduced Variability of Auditory Alpha Activity in Chronic Tinnitus Mon, 19 May 2014 11:17:35 +0000 Subjective tinnitus is characterized by the conscious perception of a phantom sound which is usually more prominent under silence. Resting state recordings without any auditory stimulation demonstrated a decrease of cortical alpha activity in temporal areas of subjects with an ongoing tinnitus perception. This is often interpreted as an indicator for enhanced excitability of the auditory cortex in tinnitus. In this study we want to further investigate this effect by analysing the moment-to-moment variability of the alpha activity in temporal areas. Magnetoencephalographic resting state recordings of 21 tinnitus subjects and 21 healthy controls were analysed with respect to the mean and the variability of spectral power in the alpha frequency band over temporal areas. A significant decrease of auditory alpha activity was detected for the low alpha frequency band (8–10 Hz) but not for the upper alpha band (10–12 Hz). Furthermore, we found a significant decrease of alpha variability for the tinnitus group. This result was significant for the lower alpha frequency range and not significant for the upper alpha frequencies. Tinnitus subjects with a longer history of tinnitus showed less variability of their auditory alpha activity which might be an indicator for reduced adaptability of the auditory cortex in chronic tinnitus. Winfried Schlee, Martin Schecklmann, Astrid Lehner, Peter M. Kreuzer, Veronika Vielsmeier, Timm B. Poeppl, and Berthold Langguth Copyright © 2014 Winfried Schlee et al. All rights reserved. BACE1 Is Necessary for Experience-Dependent Homeostatic Synaptic Plasticity in Visual Cortex Wed, 14 May 2014 00:00:00 +0000 Alzheimer’s disease (AD) is the most common form of age-related dementia, which is thought to result from overproduction and/or reduced clearance of amyloid-beta (Aβ) peptides. Studies over the past few decades suggest that Aβ is produced in an activity-dependent manner and has physiological relevance to normal brain functions. Similarly, physiological functions for β- and γ-secretases, the two key enzymes that produce Aβ by sequentially processing the amyloid precursor protein (APP), have been discovered over recent years. In particular, activity-dependent production of Aβ has been suggested to play a role in homeostatic regulation of excitatory synaptic function. There is accumulating evidence that activity-dependent immediate early gene Arc is an activity “sensor,” which acts upstream of Aβ production and triggers AMPA receptor endocytosis to homeostatically downregulate the strength of excitatory synaptic transmission. We previously reported that Arc is critical for sensory experience-dependent homeostatic reduction of excitatory synaptic transmission in the superficial layers of visual cortex. Here we demonstrate that mice lacking the major neuronal β-secretase, BACE1, exhibit a similar phenotype: stronger basal excitatory synaptic transmission and failure to adapt to changes in visual experience. Our results indicate that BACE1 plays an essential role in sensory experience-dependent homeostatic synaptic plasticity in the neocortex. Emily Petrus and Hey-Kyoung Lee Copyright © 2014 Emily Petrus and Hey-Kyoung Lee. All rights reserved. Effects of Diet on Brain Plasticity in Animal and Human Studies: Mind the Gap Mon, 12 May 2014 07:45:24 +0000 Dietary interventions have emerged as effective environmental inducers of brain plasticity. Among these dietary interventions, we here highlight the impact of caloric restriction (CR: a consistent reduction of total daily food intake), intermittent fasting (IF, every-other-day feeding), and diet supplementation with polyphenols and polyunsaturated fatty acids (PUFAs) on markers of brain plasticity in animal studies. Moreover, we also discuss epidemiological and intervention studies reporting the effects of CR, IF and dietary polyphenols and PUFAs on learning, memory, and mood. In particular, we evaluate the gap in mechanistic understanding between recent findings from animal studies and those human studies reporting that these dietary factors can benefit cognition, mood, and anxiety, aging, and Alzheimer’s disease—with focus on the enhancement of structural and functional plasticity markers in the hippocampus, such as increased expression of neurotrophic factors, synaptic function and adult neurogenesis. Lastly, we discuss some of the obstacles to harnessing the promising effects of diet on brain plasticity in animal studies into effective recommendations and interventions to promote healthy brain function in humans. Together, these data reinforce the important translational concept that diet, a modifiable lifestyle factor, holds the ability to modulate brain health and function. Tytus Murphy, Gisele Pereira Dias, and Sandrine Thuret Copyright © 2014 Tytus Murphy et al. All rights reserved. Playing and Listening to Tailor-Made Notched Music: Cortical Plasticity Induced by Unimodal and Multimodal Training in Tinnitus Patients Thu, 08 May 2014 07:00:51 +0000 Background. The generation and maintenance of tinnitus are assumed to be based on maladaptive functional cortical reorganization. Listening to modified music, which contains no energy in the range of the individual tinnitus frequency, can inhibit the corresponding neuronal activity in the auditory cortex. Music making has been shown to be a powerful stimulator for brain plasticity, inducing changes in multiple sensory systems. Using magnetoencephalographic (MEG) and behavioral measurements we evaluated the cortical plasticity effects of two months of (a) active listening to (unisensory) versus (b) learning to play (multisensory) tailor-made notched music in nonmusician tinnitus patients. Taking into account the fact that uni- and multisensory trainings induce different patterns of cortical plasticity we hypothesized that these two protocols will have different affects. Results. Only the active listening (unisensory) group showed significant reduction of tinnitus related activity of the middle temporal cortex and an increase in the activity of a tinnitus-coping related posterior parietal area. Conclusions. These findings indicate that active listening to tailor-made notched music induces greater neuroplastic changes in the maladaptively reorganized cortical network of tinnitus patients while additional integration of other sensory modalities during training reduces these neuroplastic effects. Janna Pape, Evangelos Paraskevopoulos, Maximilian Bruchmann, Andreas Wollbrink, Claudia Rudack, and Christo Pantev Copyright © 2014 Janna Pape et al. All rights reserved. Salicylate-Induced Auditory Perceptual Disorders and Plastic Changes in Nonclassical Auditory Centers in Rats Wed, 07 May 2014 16:21:07 +0000 Previous studies have shown that sodium salicylate (SS) activates not only central auditory structures, but also nonauditory regions associated with emotion and memory. To identify electrophysiological changes in the nonauditory regions, we recorded sound-evoked local field potentials and multiunit discharges from the striatum, amygdala, hippocampus, and cingulate cortex after SS-treatment. The SS-treatment produced behavioral evidence of tinnitus and hyperacusis. Physiologically, the treatment significantly enhanced sound-evoked neural activity in the striatum, amygdala, and hippocampus, but not in the cingulate. The enhanced sound evoked response could be linked to the hyperacusis-like behavior. Further analysis showed that the enhancement of sound-evoked activity occurred predominantly at the midfrequencies, likely reflecting shifts of neurons towards the midfrequency range after SS-treatment as observed in our previous studies in the auditory cortex and amygdala. The increased number of midfrequency neurons would lead to a relative higher number of total spontaneous discharges in the midfrequency region, even though the mean discharge rate of each neuron may not increase. The tonotopical overactivity in the midfrequency region in quiet may potentially lead to tonal sensation of midfrequency (the tinnitus). The neural changes in the amygdala and hippocampus may also contribute to the negative effect that patients associate with their tinnitus. Guang-Di Chen, Kelly E. Radziwon, Nina Kashanian, Senthilvelan Manohar, and Richard Salvi Copyright © 2014 Guang-Di Chen et al. All rights reserved. Modulation of Adult Hippocampal Neurogenesis by Early-Life Environmental Challenges Triggering Immune Activation Wed, 07 May 2014 08:24:23 +0000 The immune system plays an important role in the communication between the human body and the environment, in early development as well as in adulthood. Per se, research has shown that factors such as maternal stress and nutrition as well as maternal infections can activate the immune system in the infant. A rising number of research studies have shown that activation of the immune system in early life can augment the risk of some psychiatric disorders in adulthood, such as schizophrenia and depression. The mechanisms of such a developmental programming effect are unknown; however some preliminary evidence is emerging in the literature, which suggests that adult hippocampal neurogenesis may be involved. A growing number of studies have shown that pre- and postnatal exposure to an inflammatory stimulus can modulate the number of proliferating and differentiating neural progenitors in the adult hippocampus, and this can have an effect on behaviours of relevance to psychiatric disorders. This review provides a summary of these studies and highlights the evidence supporting a neurogenic hypothesis of immune developmental programming. Ksenia Musaelyan, Martin Egeland, Cathy Fernandes, Carmine M. Pariante, Patricia A. Zunszain, and Sandrine Thuret Copyright © 2014 Ksenia Musaelyan et al. All rights reserved. The Maternal Brain: An Organ with Peripartal Plasticity Sun, 04 May 2014 16:10:54 +0000 The time of pregnancy, birth, and lactation, is characterized by numerous specific alterations in several systems of the maternal body. Peripartum-associated changes in physiology and behavior, as well as their underlying molecular mechanisms, have been the focus of research since decades, but are still far from being entirely understood. Also, there is growing evidence that pregnancy and lactation are associated with a variety of alterations in neural plasticity, including adult neurogenesis, functional and structural synaptic plasticity, and dendritic remodeling in different brain regions. All of the mentioned changes are not only believed to be a prerequisite for the proper fetal and neonatal development, but moreover to be crucial for the physiological and mental health of the mother. The underlying mechanisms apparently need to be under tight control, since in cases of dysregulation, a certain percentage of women develop disorders like preeclampsia or postpartum mood and anxiety disorders during the course of pregnancy and lactation. This review describes common peripartum adaptations in physiology and behavior. Moreover, it concentrates on different forms of peripartum-associated plasticity including changes in neurogenesis and their possible underlying molecular mechanisms. Finally, consequences of malfunction in those systems are discussed. Katharina Maria Hillerer, Volker Rudolf Jacobs, Thorsten Fischer, and Ludwig Aigner Copyright © 2014 Katharina Maria Hillerer et al. All rights reserved. Adult Neuroplasticity: More Than 40 Years of Research Sun, 04 May 2014 13:01:37 +0000 Within the last four decades, our view of the mature vertebrate brain has changed significantly. Today it is generally accepted that the adult brain is far from being fixed. A number of factors such as stress, adrenal and gonadal hormones, neurotransmitters, growth factors, certain drugs, environmental stimulation, learning, and aging change neuronal structures and functions. The processes that these factors may induce are morphological alterations in brain areas, changes in neuron morphology, network alterations including changes in neuronal connectivity, the generation of new neurons (neurogenesis), and neurobiochemical changes. Here we review several aspects of neuroplasticity and discuss the functional implications of the neuroplastic capacities of the adult and differentiated brain with reference to the history of their discovery. Eberhard Fuchs and Gabriele Flügge Copyright © 2014 Eberhard Fuchs and Gabriele Flügge. All rights reserved.