Exploring block construction and mental imagery: Evidence of atypical orientation discrimination in Williams syndrome

The visuo-spatial perceptual abilities of individuals with Williams syndrome (WS) were investigated in two experiments. Experiment 1 measured the ability of participants to discriminate between oblique and between nonoblique orientations. Individuals with WS showed a smaller effect of obliqueness in response time, when compared to controls matched for non-verbal mental age. Experiment 2 investigated the possibility that this deviant pattern of orientation discrimination accounts for the poor ability to perform mental rotation in WS (Farran et al., 2001). A size transformation task was employed, which shares the image transformation requirements of mental rotation, but not the orientation discrimination demands. Individuals with WS performed at the same level as controls. The results suggest a deviance at the perceptual level in WS, in processing orientation, which fractionates from the ability to mentally transform images

Tinnitus: network pathophysiology-network pharmacology

Tinnitus, the phantom perception of sound, is a prevalent disorder. One in 10 adults has clinically significant subjective tinnitus, and for one in 100, tinnitus severely affects their quality of life. Despite the significant unmet clinical need for a safe and effective drug targeting tinnitus relief, there is currently not a single Food and Drug Administration (FDA)-approved drug on the market. The search for drugs that target tinnitus is hampered by the lack of a deep knowledge of the underlying neural substrates of this pathology. Recent studies are increasingly demonstrating that, as described for other central nervous system (CNS) disorders, tinnitus is a pathology of brain networks. The application of graph theoretical analysis to brain networks has recently provided new information concerning their topology, their robustness and their vulnerability to attacks. Moreover, the philosophy behind drug design and pharmacotherapy in CNS pathologies is changing from that of “magic bullets” that target individual chemoreceptors or “disease-causing genes” into that of “magic shotguns,” “promiscuous” or “dirty drugs” that target “disease-causing networks,” also known as network pharmacology. In the present work we provide some insight into how this knowledge could be applied to tinnitus pathophysiology and pharmacotherapy

Temporomandibular Joint Disorder Complaints in Tinnitus: Further Hints for a Putative Tinnitus Subtype

OBJECTIVE: Tinnitus is considered to be highly heterogeneous with respect to its etiology, its comorbidities and the response to specific interventions. Subtyping is recommended, but it remains to be determined which criteria are useful, since it has not yet been clearly demonstrated whether and to which extent etiologic factors, comorbid states and interventional response are related to each other and are thus applicable for subtyping tinnitus. Analyzing the Tinnitus Research Initiative Database we differentiated patients according to presence or absence of comorbid temporomandibular joint (TMJ) disorder complaints and compared the two groups with respect to etiologic factors. METHODS: 1204 Tinnitus patients from the Tinnitus Research Initiative (TRI) Database with and without subjective TMJ complaints were compared with respect to demographic, tinnitus and audiological characteristics, questionnaires, and numeric ratings. Data were analysed according to a predefined statistical analysis plan. RESULTS: Tinnitus patients with TMJ complaints (22% of the whole group) were significantly younger, had a lower age at tinnitus onset, and were more frequently female. They could modulate or mask their tinnitus more frequently by somatic maneuvers and by music or sound stimulation. Groups did not significantly differ for tinnitus duration, type of onset (gradual/abrupt), onset related events (whiplash etc.), character (pulsatile or not), hyperacusis, hearing impairment, tinnitus distress, depression, quality of life and subjective ratings (loudness etc.). CONCLUSION: Replicating previous work in tinnitus patients with TMJ complaints, classical risk factors for tinnitus like older age and male gender are less relevant in tinnitus patients with TMJ complaints. By demonstrating group differences for modulation of tinnitus by movements and sounds our data further support the notion that tinnitus with TMJ complaints represents a subgroup of tinnitus with clinical features that are highly relevant for specific therapeutic management

Identifying Tinnitus-Related Genes Based on a Side-Effect Network Analysis

Tinnitus, phantom sound perception, is a worldwide highly prevalent disorder for which no clear underlying pathology has been established and for which no approved drug is on the market. Thus, there is an urgent need for new approaches to understand this condition. We used a network pharmacology side-effect analysis to search for genes that are involved in tinnitus generation. We analyzed a network of 1,313 drug–target pairs, based on 275 compounds that elicit tinnitus as side effect and their targets reported in databases, and used a quantitative score to identify emergent significant targets that were more common than expected at random. Cyclooxigenase 1 and 2 were significant, which validates our approach, since salicylate is a known tinnitus generator. More importantly, we predict previously unknown tinnitus-related targets. The present results have important implications toward understanding tinnitus pathophysiology and might pave the way toward the design of novel pharmacotherapies.Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; ArgentinaFil: Langguth, B.. University of Regensburg. Interdisciplinary Tinnitus Clinic. Department of Psychiatry and Psychotherapy; AlemaniaFil: Nowak, Wanda. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; ArgentinaFil: Schecklmann, M.. University of Regensburg. Interdisciplinary Tinnitus Clinic. Department of Psychiatry and Psychotherapy; AlemaniaFil: de Ridder, D.. University of Otago. Dunedin School of Medicine. Unit of Neurosurgery. Department of Surgical Sciences; Nueva ZelandaFil: Vanneste, S.. University of Texas at Dallas. School of Behavioral and Brain Sciences. Laboratory for Auditory & Integrative Neuroscience; Estados Unido

Sexual motivation is reflected by stimulus-dependent motor cortex excitability

Sexual behavior involves motivational processes. Findings from both animal models and neuroimaging in humans suggest that the recruitment of neural motor networks is an integral part of the sexual response. However, no study so far has directly linked sexual motivation to physiologically measurable changes in cerebral motor systems in humans. Using transcranial magnetic stimulation in hetero- and homosexual men, we here show that sexual motivation modulates cortical excitability. More specifically, our results demonstrate that visual sexual stimuli corresponding with one's sexual orientation, compared with non-corresponding visual sexual stimuli, increase the excitability of the motor cortex. The reflection of sexual motivation in motor cortex excitability provides evidence for motor preparation processes in sexual behavior in humans. Moreover, such interrelationship links theoretical models and previous neuroimaging findings of sexual behavio

Meeting report: International workshop on implementation of biowaivers based on the biopharmaceutics classification system (BCS)

Even though the pivotal article stating the theoretical basis for a biopharmaceutics drug classification (1) was published almost 20 years ago, the extension of BCS-based biowaiver decisions to drugs belonging to BCS classes other than those showing high solubility and high permeability has not yet reached a consensus among regulators, industrial scientists, and academics. Also, within some jurisdictions, BCS principles have not yet been incorporated into legal frameworks and thus have not been used to allow science- and risk-based regulatory flexibility. This report provides a brief description of the presentations from the International Workshop on Implementation of Biowaivers based on the BCS in Buenos Aires, Argentina, that took place on March 5–6, 2015. The meeting was cosponsored by National University of La Plata, Confederación Farmacéutica Argentina, International Pharmaceutical Federation (FIP), and the American Association of Pharmaceutical Scientists (AAPS). The main objectives of the meeting were to describe the state of the art with respect to in vitro and in silico tools to support waiving in vivo bioequivalence studies and to foster discussion about implementing BCS-based biowaiver decisions to support generic drug registration in South America. Two hundred and fifteen scientists from universities, the pharmaceutical industry, and regulatory authorities took part in this meetingFacultad de Ciencias Exacta

Meeting report: International workshop on implementation of biowaivers based on the biopharmaceutics classification system (BCS)

Even though the pivotal article stating the theoretical basis for a biopharmaceutics drug classification (1) was published almost 20 years ago, the extension of BCS-based biowaiver decisions to drugs belonging to BCS classes other than those showing high solubility and high permeability has not yet reached a consensus among regulators, industrial scientists, and academics. Also, within some jurisdictions, BCS principles have not yet been incorporated into legal frameworks and thus have not been used to allow science- and risk-based regulatory flexibility. This report provides a brief description of the presentations from the International Workshop on Implementation of Biowaivers based on the BCS in Buenos Aires, Argentina, that took place on March 5–6, 2015. The meeting was cosponsored by National University of La Plata, Confederación Farmacéutica Argentina, International Pharmaceutical Federation (FIP), and the American Association of Pharmaceutical Scientists (AAPS). The main objectives of the meeting were to describe the state of the art with respect to in vitro and in silico tools to support waiving in vivo bioequivalence studies and to foster discussion about implementing BCS-based biowaiver decisions to support generic drug registration in South America. Two hundred and fifteen scientists from universities, the pharmaceutical industry, and regulatory authorities took part in this meetingFacultad de Ciencias Exacta

Anti-Suicidal Efficacy of Repetitive Transcranial Magnetic Stimulation in Depressive Patients: A Retrospective Analysis of a Large Sample

Background: Suicide is a major public health problem. About 90% of suicide victims have one or more major psychiatric disorder, with a reported 20-fold increased risk for suicide in patients with affective disorders in comparison with healthy subjects. Repetitive transcranial magnetic stimulation (rTMS) has been established as an effective alternative or adjunctive treatment option for patients with depressive disorders, but little is known about its effects on suicide risk. Objective: For the assessment of the effectiveness of rTMS on suicidal ideation and behaviors, we performed a retrospective analysis of a large sample of patients with depressive disorders, who were treated with rTMS. Methods: We analyzed the records of 711 TMS in- and out-patients with depressive affective disorders in a tertiary referral hospital between 2002 and 2017. Out of these patients we were able to collect Hamilton depression rating scale (HAMD) data of 332 patients (180 females, 152 males; age range 20 to 79 years; mean age 47.3 ± 12.3) for which we analyzed the change of suicidal ideation by using item 3 (suicidality) of HAMD. Results: Out of all 711 patients treated with rTMS for their depression, one patient (0.1%) committed suicide during the TMS treatment. In the statistical analysis of the subsample with 332 patients there was an overall amelioration of depressive symptoms accompanied by a significant decrease in the suicidality item with a medium effect size. Decrease in suicidality was not inferior to changes in other items as indicated by effect sizes. Forty-seven percent of patients showed an amelioration in suicidality, 41.3% of patients did not show a change in their suicidality’s scores, and 11.7% of patients showed an increase in suicidality’s scores from baseline to final rating. Correlation of item 3 (suicidality) and item 7 (drive) demonstrated a significant positive association, revealing improved drive with a parallel decreased suicidality. Conclusion: Based on the proposed data, there is no evidence that rTMS increases the risk for suicide during the course of the treatment. Conversely, rTMS tends to reduce suicidal ideation. Our findings call for further rTMS controlled studies using large sample sizes and specific suicidality assessment measures to obtain more conclusive results

Emerging pharmacotherapy of tinnitus

Tinnitus, the perception of sound in the absence of an auditory stimulus, is perceived by about 1 in 10 adults, and for at least 1 in 100, tinnitus severely affects their quality of life. Because tinnitus is frequently associated with irritability, agitation, stress, insomnia, anxiety and depression, the social and economic burdens of tinnitus can be enormous. No curative treatments are available. However, tinnitus symptoms can be alleviated to some extent. The most widespread management therapies consist of auditory stimulation and cognitive behavioral treatment, aiming at improving habituation and coping strategies. Available clinical trials vary in methodological rigor and have been performed for a considerable number of different drugs. None of the investigated drugs have demonstrated providing replicable long-term reduction of tinnitus impact in the majority of patients in excess of placebo effects. Accordingly, there are no FDA or European Medicines Agency approved drugs for the treatment of tinnitus. However, in spite of the lack of evidence, a large variety of different compounds are prescribed off-label. Therefore, more effective pharmacotherapies for this huge and still growing market are desperately needed and even a drug that produces only a small but significant effect would have an enormous therapeutic impact. This review describes current and emerging pharmacotherapies with current difficulties and limitations. In addition, it provides an estimate of the tinnitus market. Finally, it describes recent advances in the tinnitus field which may help overcome obstacles faced in the pharmacological treatment of tinnitus. These include incomplete knowledge of tinnitus pathophysiology, lack of well-established animal models, heterogeneity of different forms of tinnitus, difficulties in tinnitus assessment and outcome measurement and variability in clinical trial methodology. © 2009 Informa UK Ltd.Fil: Langguth, Berthold. Universitat Regensburg; AlemaniaFil: Salvi, Richard. State University of New York; Estados UnidosFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentin