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BACKGROUND: Despite the high frequency of tinnitus and its impact on wellbeing, little is known about its economic burden and no data to our knowledge are available on out-of-pocket (OOP) expenses. METHODS: In 2022 a survey was conducted on OOP costs of tinnitus. We enrolled 679 participants with slight, moderate and severe tinnitus in Italy, United Kingdom, Netherlands, Germany and Spain. We estimated annual OOP expenses for tinnitus-related healthcare visits, treatments, medications and alternative medicine practices. Prevalence of tinnitus in the general population, obtained from a representative survey we conducted in Europe in 2017-2018, was used to generalise costs for people with any tinnitus at the national level. RESULTS: OOP expenses were 368 (95% confidence intervals (CI), 78-690), 728 (95% CI, 316-1,288), and 1,492 (95% CI, 760-2,688) for slight, moderate, and severe tinnitus, respectively, with annual expenditure of 565 for people with any tinnitus: 209 for healthcare visits, 93 for treatments, 16 for drugs, 64 for hearing supporting systems and 183 for acupuncture, homeopathy and osteopathy. Individuals with slight, moderate, and severe tinnitus expressed a willingness to invest 1.6, 4.3, and 7.0 times their monthly income, respectively, to achieve complete relief from tinnitus. CONCLUSIONS: This study offers for the first time insights into the OOP expenses incurred by individuals with tinnitus. OOP expenses exhibited substantial variations based on severity status, accounting for more than 17 thousand million in the countries considered. In terms of financial burden, these findings align tinnitus to the recognised leading disabilities, including back pain and migraine.
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BACKGROUND: Low frequency repetitive transcranial magnetic stimulation (rTMS) is commonly used to inhibit pathological hyperactivity of the auditory cortex in tinnitus. Novel and supposedly superior and faster inhibitory protocols such as continuous theta burst stimulation (cTBS) were examined as well, but so far there is not sufficient evidence for a treatment application in chronic tinnitus. rTMS effects in general are dependent on the brain state immediate before stimulation. This feasibility study was designed based on the concept to shift the pathological intrinsic brain state of tinnitus patients via acoustic stimulation ("activate") and induce inhibitory effects via cTBS ("fire"). METHODS: Seven tinnitus patients with response in residual inhibition received 10 consecutive daily sessions of a combinatory treatment comprised of 3-minute acoustic stimulation with white noise followed by 600 pulses of cTBS over the left temporo-parietal cortex (activate & fire). A control group of 5 patients was treated parallel to the activate & fire data collection with 10 sessions á 3000 pulses of 1 Hz rTMS over the left temporo-parietal cortex. RESULTS: The activate & fire protocol was well tolerated except in one patient with tinnitus loudness increase. This patient was excluded from analyses. No statistical superiority of the activate & fire treatment approach in alleviating tinnitus-related symptoms was evident. Power calculations showed an effect size of 0.706 and a needed sample size of 66 for statistical significant group differences. On a descriptive level the activate & fire group demonstrated a stronger decrease in tinnitus-related symptoms. CONCLUSION: The present feasibility study showed that combining acoustic stimulation with magnetic brain stimulation may be well-tolerable in the majority of patients and represents a promising treatment approach for tinnitus by hypothetically alter the intrinsic state prior to brain stimulation.
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Zumbido , Humanos , Zumbido/terapia , Zumbido/etiologia , Estimulação Magnética Transcraniana/métodos , Estimulação Acústica , Estudos de Viabilidade , Inquéritos e Questionários , Resultado do TratamentoRESUMO
OBJECTIVES: Transcranial direct current stimulation (tDCS) of the right dorsolateral prefrontal cortex has been hypothesized to reduce tinnitus severity by modifying cortical activity in brain regions associated with the perception of tinnitus. However, individual response to tDCS has proven to be variable. We investigated the feasibility of using random forest classification to predict the response to high-definition (HD) tDCS for tinnitus relief. DESIGN: A retrospective analysis was performed on a dataset consisting of 99 patients with subjective tinnitus receiving six consecutive sessions of HD-tDCS at the Antwerp University Hospital. A baseline assessment consisted of pure-tone audiometry and a set of questionnaires including the Tinnitus Functional Index (TFI), Hospital Anxiety and Depression Scale, and Edinburgh Handedness Inventory. Random forest classification was applied to predict, based on baseline questionnaire scores and hearing levels, whether each individual responded positively to the treatment (defined as a decrease of at least 13 points on the TFI). Further testing of the model was performed on an independent cohort of 32 patients obtained from the tinnitus center at the University of Regensburg. RESULTS: Twenty-four participants responded positively to the HD-tDCS treatment. The random forest classifier predicted treatment response with an accuracy of 85.71% (100% sensitivity, 81.48% specificity), significantly outperforming a more traditional logistic regression approach. Performance of the classifier on an independent cohort was slightly but not significantly above chance level (71.88% accuracy, 66.67% sensitivity, 73.08% specificity). Feature importance analyses revealed that baseline tinnitus severity, co-occurrence of depressive symptoms and handedness were the most important predictors of treatment response. Baseline TFI scores were significantly higher in responders than in nonresponders. CONCLUSIONS: The proposed random forest classifier predicted treatment response with a high accuracy, significantly outperforming a more traditional statistical approach. Machine learning methods to predict treatment response might ultimately be used in a clinical setting to guide targeted treatment recommendations for individual tinnitus patients.
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Zumbido , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Zumbido/terapia , Estudos de Viabilidade , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
Previous studies in human subjects reported that the parieto-insular vestibular cortex (PIVC), a core area of the vestibular cortex, is inhibited when visual processing is prioritized. However, it has remained unclear which networks in the brain modulate this inhibition of PIVC. Based on previous results showing that the inhibition of PIVC is strongly influenced by visual attention, we here examined whether attention networks in the parietooccipital cortex modulate the inhibition of PIVC. Using diffusion-weighted and resting-state fMRI in a group of female and male subjects, we found structural and functional connections between PIVC and the posterior parietal cortex (PPC), a major brain region of the cortical attention network. We then temporarily inhibited PPC by repetitive transcranial magnetic stimulation (rTMS) and hypothesized that the modulatory influence of PPC over PIVC would be reduced; and, as a result, PIVC would be less inhibited. Subjects performed a visual attentional tracking task immediately after rTMS, and the inhibition of PIVC during attentive tracking was measured with fMRI. The results showed that the inhibition of PIVC during attentive tracking was less pronounced compared with sham rTMS. We also examined the effects of inhibitory rTMS over the occipital cortex and found that the visual-vestibular posterior insular cortex area was less activated during attentive tracking compared with sham rTMS or rTMS over PPC. Together, these results suggest that attention networks in the parietooccipital cortex modulate activity in core areas of the vestibular cortex during attentive visual processing.SIGNIFICANCE STATEMENT Although multisensory integration is generally considered beneficial, it can become detrimental when cues from different senses are in conflict. The occurrence of such multisensory conflicts can be minimized by inhibiting core cortical areas of the subordinate sensory system (e.g., vestibular), thus reducing potential conflict with ongoing processing of the prevailing sensory (e.g., visual) cues. However, it has remained unclear which networks in the brain modulate the magnitude of inhibition of the subordinate sensory system. Here, by investigating the inhibition of the vestibular sensory system when visual processing is prioritized, we show that attention networks in the parietooccipital cortex modulate the magnitude of inhibition of the vestibular cortex.
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Atenção/fisiologia , Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Percepção Visual/fisiologia , Adulto , Mapeamento Encefálico , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/fisiologia , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Masculino , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Lobo Occipital/anatomia & histologia , Lobo Occipital/fisiologia , Lobo Parietal/anatomia & histologia , Lobo Parietal/fisiologia , Estimulação Magnética Transcraniana , Adulto JovemRESUMO
BACKGROUND: Hypersexuality and hyposexuality occur frequently, often in a variety of psychiatric disorders, and are difficult to treat. While there is meta-analytic evidence for the significant effect of non-invasive brain stimulation on drug and food craving, no study has investigated the potential of this technique to modulate sexual behavior. AIM: Here, we tested the hypothesis that a single session of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) would reduce sexual arousal. METHODS: We employed a randomized, double-blind, sham-controlled crossover study design. 19 healthy male participants received high-frequency rTMS over the left DLPFC, high-frequency rTMS over the right DLPFC, and sham rTMS (each 10 Hz; 110% resting motor threshold; 60 trains with 50 pulses) in randomized and counterbalanced order with a 1-week interval between stimulation sessions to avoid carryover effects. Participants were exposed to neutral and sexual cues before and after each intervention and rated their sexual arousal after each block of cue presentation. MAIN OUTCOME MEASURE: Efficacy of the respective intervention was operationalized by the change of subjective sexual arousal according to a rating scale. RESULTS: rTMS of the right DLPFC significantly reduced subjective sexual arousal (t18 = 2.282, P = .035). In contrast, neither sham rTMS nor rTMS of the left DLPFC affected sexual arousal (P > .389). Greater rTMS-induced reduction of subjective sexual arousal was observed in participants with higher trait-based dyadic sexual desire within the last 12 months (r = -0.417, P = .038). CLINICAL IMPLICATION: Non-invasive brain stimulation might hold potential for influencing hypersexual behavior. STRENGTH & LIMITATION: This was a randomized, double-blind, sham-controlled crossover study with subjective but no physiological measures of sexual arousal. CONCLUSION: The results indicate that 1 session of high-frequency rTMS (10 Hz) of the right DLPFC could significantly reduce subjective sexual arousal induced by visual stimuli in healthy subjects. On this basis, future studies with larger sample sizes and more stimulation sessions are needed to explore the therapeutic potential of rTMS in hypersexual behavior. Schecklmann M, Sakreida K, Oblinger B, et al. Repetitive Transcranial Magnetic Stimulation as a Potential Tool to Reduce Sexual Arousal: A Roof of Concept Study. J Sex Med 2020;17:1553-1559.
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Excitação Sexual , Estimulação Magnética Transcraniana , Fissura , Estudos Cross-Over , Humanos , Masculino , Córtex Pré-Frontal , Estudo de Prova de Conceito , Resultado do TratamentoRESUMO
The aim of this study is to elucidate the role of repetitive transcranial magnetic stimulation (rTMS) for treating depression during pregnancy. The treatment of depression in pregnant women poses a number of therapeutic challenges. Psychotherapy can be beneficial but is associated with limited availability and possibly an onset of effect which may be too long to be acceptable. Pharmacotherapy is limited by concerns of fetotoxicity, both real and possibly exaggerated in the view of patients and caregivers alike. While efficacy and safety of rTMS are well established for the treatment of depression, the available data for use in pregnancy is still sparse. We reviewed the available literature on the topic on PubMed. In addition to a number of case reports, three studies concerning the treatment of depressed pregnant women with rTMS are available. According to the data, rTMS seems to be safe for both the pregnant woman and her unborn offspring. No obstetric complications or adverse postnatal effects on development have been reported. rTMS alleviated depressive symptoms better than sham treatment in one study. rTMS seems to be safe and effective in treating depression in pregnant women. Further studies with larger numbers of participants are warranted to further clarify the significance of rTMS for the treatment of depression in pregnancy.
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Depressão/terapia , Transtorno Depressivo Maior/terapia , Complicações na Gravidez/terapia , Estimulação Magnética Transcraniana , Feminino , Humanos , Gravidez , Resultado do TratamentoRESUMO
Paired associative stimulation (PAS), a form of non-invasive cortical stimulation pairing transcranial magnetic stimulation (TMS) with a peripheral sensory stimulus, has been shown to induce neuroplastic effects in the human motor, somatosensory and auditory cortex. The current study investigated the effects of acoustic PAS on late auditory evoked potentials (LAEP) and the influence of tone duration and placebo stimulation. In two experiments, 18 participants underwent a PAS with a 4 kHz paired tone of 400 ms duration using 200 pairs of stimuli (TMS-pulse over the left auditory cortex 45 ms after tone-onset) presented at 0.1 Hz. In Experiment 1 this protocol was contrasted with a protocol using a short paired tone of 23 ms duration (PAS-23 ms vs. PAS-400 ms). In Experiment 2 this PAS protocol was contrasted with sham stimulation (PAS-400 ms-sham vs. PAS-400 ms). Before and after PAS, LAEP were recorded for tones of 4 kHz (same carrier frequency as the paired tone) and 1 kHz as control tone. In Experiment 1, there was a significant difference between LAEP amplitudes of the 4 kHz tone after PAS-23 ms and PAS-400 ms with higher LAEP amplitudes after PAS-23 ms. Before both conditions, no difference could be detected. In Experiment 2 we observed a significant overall decrease in LAEP amplitudes pre to post PAS. Unspecific decreases of LAEP following PAS with a long paired tone (PAS-400 ms) might be related to habituation effects due to repeated presentation of sound stimuli which are not evident for PAS with a short paired tone (PAS-23 ms). Interpreting this result using the concept of temporal integration time allows us to discuss it in the context of spike-timing dependent plasticity.
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Estimulação Acústica , Associação , Potenciais Evocados Auditivos/fisiologia , Plasticidade Neuronal/fisiologia , Estimulação Magnética Transcraniana , Adulto , Córtex Auditivo , Feminino , Humanos , Masculino , Adulto JovemRESUMO
BACKGROUND: The phenomenon of short-term tinnitus suppression by different forms of acoustic stimulation is referred to as residual inhibition (RI). RI can be triggered in the majority of tinnitus cases and was found to be depending on the used intensity, length or types of sounds. Past research already stressed the impact of noise stimulation as well as the superiority of amplitude modulated (AM) pure tones at the individual tinnitus frequency for RI in tonal tinnitus. Recently a novel approach for the determination of noise-like tinnitus characteristics was proposed. OBJECTIVES: The aim of the present study was to investigate whether in participants with noise-like tinnitus RI can be increased by AM noise stimuli according to the individual tinnitus frequency range. METHODS: For this purpose the individual tinnitus characteristics (noise-like and tonal tinnitus) of 29 people affected by tinnitus (mean age = 55.59, 7 females, mean tinnitus duration = 159.97 months) were assessed via customizable noise-band matching. The objective was to generate bandpass filtered stimuli according to the individual tinnitus sound (individualized bandpass filtered [IBP] sounds). Subsequently, various stimuli differing in bandpass filtering and AM were tested with respect to their potential to induce RI. Participants were acoustically stimulated with 7 different types of stimuli for 3 min each and had to rate the loudness of their tinnitus after each stimuli. RESULTS: Results indicate a general efficacy of noise stimuli for the temporary suppression of tinnitus, but no significant differences between AM and unmodulated IBP. Significantly better effects were observed for the subgroup with noise-like tinnitus (n = 14), especially directly after stimulation offset. CONCLUSIONS: The study at hand provides further insights in potential mechanisms behind RI for different types of tinnitus. Beyond that, derived principles may qualify for new or extend current tinnitus sound therapies.
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Estimulação Acústica/métodos , Ruído , Zumbido/terapia , Adulto , Idoso , Audiometria , Audiometria de Tons Puros , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Som , Zumbido/fisiopatologia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has become increasingly popular during the last decades mainly driven by the antidepressant effects of dorsolateral prefrontal cortex stimulation with "butterfly" coils. Only recently, alternative targets such as the dorsomedial prefrontal cortex (dmPFC) have been brought into focus and innovative coil designs such as the angled geometry of the double cone coil (DCC) have raised hope to reach even deeper located targets. OBJECTIVE: To provide a systematic and comprehensive review on the application of rTMS stimulation of the dmPFC using the DCC in neuropathological and healthy samples. METHODS: We systematically searched the MEDLINE® database (http://www.ncbi.nlm.nih.gov/pubmed/). Due to the heterogeneous naming of DCC stimulation over the dmPFC a variety of search terms was applied resulting in a numeral quantity of 340 hits. RESULTS: DCC stimulation over the dmPFC has been proven to be safe and feasible in various neuropsychiatric disorders and in healthy subjects. Clinical results are encouraging, but have to be considered as preliminary as data from sham-controlled clinical trials and knowledge about the neurobiological underpinnings are still scarce. CONCLUSION: DCC stimulation over the dmPFC represents a promising approach in the fast evolving noninvasive brain stimulation techniques aiming at the functional modulation of brain areas vitally involved in affect, sensory autonomic, cognitive, and salience regulation. This may hold potential for both neuroscientific research and clinical applications in the treatment of psychiatric disorders.
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Transtorno Depressivo/terapia , Córtex Pré-Frontal , Estimulação Magnética Transcraniana/métodos , Transtorno Depressivo/psicologia , Humanos , Estimulação Magnética Transcraniana/instrumentação , Resultado do TratamentoRESUMO
Noninvasive brain stimulation can modify phantom sounds for longer periods by modulating neural activity and putatively inducing regional neuroplastic changes. However, treatment response is limited and there are no good demographic or clinical predictors for treatment outcome. We used state-of-the-art voxel-based morphometry (VBM) to investigate whether transcranial magnetic stimulation-induced neuroplasticity determines therapeutic outcome. Sixty subjects chronically experiencing phantom sounds (i.e., tinnitus) received repetitive transcranial magnetic stimulation (rTMS) of left dorsolateral prefrontal and temporal cortex according to a protocol that has been shown to yield a significantly higher number of treatment responders than sham stimulation and previous stimulation protocols. Structural magnetic resonance imaging was performed before and after rTMS. In VBM whole-brain analyses (P < 0.05, FWE corrected), we assessed longitudinal gray matter changes as well as structural connectivity between the ensuing regions. We observed longitudinal mesoscopic gray matter changes of left dorsolateral prefontal (DLPFC), left operculo-insular, and right inferior temporal cortex (ITC) in responders (N = 22) but not nonresponders (N = 38), as indicated by a group × time interaction and post-hoc tests. These results were neither influenced by age, sex, hearing loss nor by tinnitus laterality, duration, and severity at baseline. Furthermore, we found robust DLPFC-insula and insula-ITC connectivity in responders, while only relatively weak DLPFC-insula connectivity and no insula-ITC connectivity could be demonstrated in nonresponders. Our results reinforce the implication of nonauditory brain regions in phantom sounds and suggest the dependence of therapeutic response on their neuroplastic capabilities. The latter in turn may depend on (differences in) their individual structural connectivity. Hum Brain Mapp 39:554-562, 2018. © 2017 Wiley Periodicals, Inc.
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Encéfalo/diagnóstico por imagem , Plasticidade Neuronal , Zumbido/diagnóstico por imagem , Zumbido/terapia , Estimulação Magnética Transcraniana , Percepção Auditiva/fisiologia , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Resultado do TratamentoAssuntos
Transtorno Depressivo Resistente a Tratamento , Eletroconvulsoterapia , Epilepsia , Estimulação do Nervo Vago , Humanos , Transtorno Depressivo Resistente a Tratamento/complicações , Transtorno Depressivo Resistente a Tratamento/terapia , Estimulação Magnética Transcraniana , Epilepsia/complicações , Epilepsia/terapia , Nervo Vago , Resultado do Tratamento , Eletrodos ImplantadosRESUMO
BACKGROUND: Hyperacusis is intolerance of certain everyday sounds that causes significant distress and impairment in social, occupational, recreational, and other day-to-day activities. OBJECTIVE: The aim of this report is to summarize the key findings and conclusions from the Third International Conference on Hyperacusis. TOPICS COVERED: The main topics discussed comprise (1) diagnosis of hyperacusis and audiological evaluations, (2) neurobiological aspect of hyperacusis, (3) misophonia, (4) hyperacusis in autism spectrum disorder, (5) noise sensitivity, (6) hyperacusis-related distress and comorbid psychiatric illness, and (7) audiologist-delivered cognitive behavioral therapy for hyperacusis. CONCLUSIONS: Implications for research and clinical practice are summarised.
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Hiperacusia/diagnóstico , Hiperacusia/terapia , Audiometria/métodos , Transtorno do Espectro Autista/complicações , Terapia Cognitivo-Comportamental/métodos , Congressos como Assunto , Feminino , Humanos , Hiperacusia/etiologia , MasculinoRESUMO
Interference of ongoing neuronal activity and brain stimulation motivated this study to combine repetitive transcranial magnetic stimulation (rTMS) and relaxation techniques in tinnitus patients. Forty-two patients were enrolled in this one-arm proof-of-concept study to receive ten sessions of rTMS applied to the left dorsolateral prefrontal cortex and temporo-parietal cortex. During stimulation, patients listened to five different kinds of relaxation audios. Variables of interest were tinnitus questionnaires, tinnitus numeric rating scales, depressivity, and quality of life. Results were compared to results of historical control groups having received the same rTMS protocol (active control) and sham treatment (placebo) without relaxation techniques. Thirty-eight patients completed the treatment, drop-out rates and adverse events were low. Responder rates (reduction in tinnitus questionnaire (TQ) score ≥5 points 10 weeks after treatment) were 44.7 % in the study, 27.8 % in the active control group, and 21.7 % in the placebo group, differing between groups on a near significant level. For the tinnitus handicap inventory (THI), the main effect of group was not significant. However, linear mixed model analyses showed that the relaxation/rTMS group differed significantly from the active control group showing steeper negative THI trend for the relaxation/rTMS group indicating better amelioration over the course of the trial. Deepness of relaxation during rTMS and selection of active relaxation vs. passive listening to music predicted larger TQ. All remaining secondary outcomes turned out non-significant. This combined treatment proved to be a safe, feasible and promising approach to enhance rTMS treatment effects in chronic tinnitus.
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Córtex Pré-Frontal/fisiologia , Terapia de Relaxamento/métodos , Zumbido/terapia , Estimulação Magnética Transcraniana/métodos , Adolescente , Adulto , Idoso , Doença Crônica/terapia , Terapia Combinada , Método Duplo-Cego , Eletroencefalografia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Inquéritos e Questionários , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Motor cortex excitability was found to be changed after repetitive transcranial magnetic stimulation (rTMS) of the temporal cortex highlighting the occurrence of cross-modal plasticity in non-invasive brain stimulation. Here, we investigated the effects of temporal low-frequency rTMS on motor cortex plasticity in a large sample of tinnitus patients. In 116 patients with chronic tinnitus different parameters of cortical excitability were assessed before and after ten rTMS treatment sessions. Patients received one of three different protocols all including 1 Hz rTMS over the left temporal cortex. Treatment response was defined as improvement by at least five points in the tinnitus questionnaire (TQ). Variables of interest were resting motor threshold (RMT), short-interval intra-cortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP). RESULTS: After rTMS treatment RMT was decreased by about 1% of stimulator output near-significantly in the whole group of patients. SICI was associated with significant changes with respect to treatment response. The group of treatment responders showed a decrease of SICI over the course of treatment, the group of non-responders the reverse pattern. CONCLUSIONS: Minor RMT changes during rTMS treatment do not necessarily suggest the need for systematic re-examination of the RMT for safety and efficacy issues. Treatment response to rTMS was shown to be related to changes in SICI that might reflect modulation of GABAergic mechanisms directly or indirectly related to rTMS treatment effects.
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Córtex Motor/fisiopatologia , Inibição Neural , Plasticidade Neuronal , Zumbido/fisiopatologia , Zumbido/terapia , Estimulação Magnética Transcraniana/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Zumbido/diagnóstico , Resultado do Tratamento , Adulto JovemRESUMO
Schizophrenia is a severe, debilitating, chronic disease that is accompanied by morphologic changes within the brain. However, it is unclear to what extent alterations of grey and white matter in schizophrenia are linked to the disease itself, or whether they are a consequence of neuroleptic treatment. Typical and atypical antipsychotics exert differential effects on brain structure. Moreover, atypical antipsychotics may have distinct profiles with respect to grey matter in schizophrenic patients. Findings on drug-induced grey matter changes are heterogeneous due to variation in stage of illness, duration of treatment and use of multiple antipsychotics. Using voxel-based morphometry applied to high-resolution magnetic resonance images, we show that monotherapy with the atypical agent quetiapine (mean daily dose = 445 mg ± 200 s.d.) may induce structural brain changes in first-episode schizophrenia patients (N = 20) within 21 d of treatment. Specifically, we demonstrate longitudinal macroscopic changes (i.e. grey matter increases) in the left amygdalohippocampal region that were predicted by drug plasma levels but not daily doses. These structural alterations were accompanied by a clinical improvement of schizophrenic symptoms. Comparison with healthy controls (n = 30) showed that grey matter amount in the respective amygdalar region was significantly reduced in unmedicated first-episode schizophrenia patients. These findings suggest that drug-induced neuroplastic changes in schizophrenia can occur quickly and are dependent on pharmacokinetics.
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Tonsila do Cerebelo/efeitos dos fármacos , Antipsicóticos/uso terapêutico , Dibenzotiazepinas/uso terapêutico , Hipocampo/efeitos dos fármacos , Esquizofrenia/tratamento farmacológico , Adolescente , Adulto , Idoso , Tonsila do Cerebelo/patologia , Feminino , Seguimentos , Substância Cinzenta/efeitos dos fármacos , Substância Cinzenta/patologia , Hipocampo/patologia , Humanos , Processamento de Imagem Assistida por Computador , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Plasticidade Neuronal/efeitos dos fármacos , Fumarato de Quetiapina , Esquizofrenia/patologia , Adulto JovemRESUMO
Findings from molecular genetic studies and analyses of postmortem and peripheral tissue led to the hypothesis that neurotrophins-as crucial moderators of neuroplasticity-impact on the pathophysiology of autism spectrum disorder (ASD). The study projects aimed to complement former results on the role of brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family with fundamental impact on brain development and function. The purpose of this work was to investigate peripheral BDNF mRNA expression and BDNF protein concentrations in ASD as potential surrogates for the effects observed in the central nervous system. In a BDNF protein quantification study, serum concentrations were analyzed using Enzyme-Linked Immunosorbent Assays in 24 male patients with ASD, all with an IQ > 70 (age 13.9 ± 3.0 years) and 20 age- and gender-matched healthy control subjects (age 14.4 ± 2.1 years; p = 0.522). In a further independent project, a BDNF mRNA expression analysis, mRNA levels from total blood were assessed by quantitative real-time polymerase chain reaction in a sample of 16 male ASD patients (age 10.8 ± 2.2), 15 age- and gender-matched healthy controls (age 12.1 ± 2.2) and 15 patients with attention deficit hyperactivity disorder as a clinical control group (age 11.8 ± 2.2; p = 0.207). In the protein quantification project, significantly decreased BDNF serum concentrations were found in ASD cases compared to healthy control children (t = -2.123, df = 42, p < 0.05). Analysis of covariance (ANCOVA) revealed this result in accordance with significant reductions in BDNF mRNA expression in ASD, observed in the mRNA expression study (F = 3.65; df = 2.43; p < 0.05); neither age nor IQ confounded the result, as indicated by ANCOVA (F = 3.961; df = 2.41; p < 0.05, η (2) = 0.162). Our study projects supported the notion that neurotrophins are involved in the pathophysiology of ASD. Further studies may eventually contribute to the identification of distinct peripheral mRNA expression and protein concentration patterns possibly supporting diagnostic and therapeutic processes.
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Fator Neurotrófico Derivado do Encéfalo/sangue , Transtornos Globais do Desenvolvimento Infantil/sangue , Adolescente , Fatores Etários , Análise de Variância , Transtorno do Deficit de Atenção com Hiperatividade/sangue , Criança , Ensaio de Imunoadsorção Enzimática , Humanos , Inteligência , Testes de Inteligência , Masculino , Reação em Cadeia da Polimerase , RNA Mensageiro/sangueRESUMO
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.
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Encéfalo/patologia , Zumbido/patologia , Zumbido/terapia , Estimulação Magnética Transcraniana , Adulto , Idoso , Córtex Cerebral/patologia , Interpretação Estatística de Dados , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Zumbido/diagnóstico , Resultado do TratamentoRESUMO
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.
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Ritmo alfa/fisiologia , Zumbido/fisiopatologia , Estimulação Acústica , Adulto , Idoso , Algoritmos , Doença Crônica , Interpretação Estatística de Dados , Potenciais Evocados Auditivos/fisiologia , Feminino , Humanos , Magnetoencefalografia , Masculino , Pessoa de Meia-Idade , Plasticidade Neuronal/fisiologia , Adulto JovemRESUMO
OBJECTIVE: Several neuroscience tools showed the involvement of auditory cortex in chronic tinnitus. In this proof-of-principle study we probed the capability of functional near-infrared spectroscopy (fNIRS) for the measurement of brain oxygenation in auditory cortex in dependence from chronic tinnitus and from intervention with transcranial magnetic stimulation. METHODS: Twenty-three patients received continuous theta burst stimulation over the left primary auditory cortex in a randomized sham-controlled neuronavigated trial (verum = 12; placebo = 11). Before and after treatment, sound-evoked brain oxygenation in temporal areas was measured with fNIRS. Brain oxygenation was measured once in healthy controls (n = 12). RESULTS: Sound-evoked activity in right temporal areas was increased in the patients in contrast to healthy controls. Left-sided temporal activity under the stimulated area changed over the course of the trial; high baseline oxygenation was reduced and vice versa. CONCLUSIONS: By demonstrating that rTMS interacts with auditory evoked brain activity, our results confirm earlier electrophysiological findings and indicate the sensitivity of fNIRS for detecting rTMS induced changes in brain activity. Moreover, our findings of trait- and state-related oxygenation changes indicate the potential of fNIRS for the investigation of tinnitus pathophysiology and treatment response.
Assuntos
Córtex Auditivo/fisiopatologia , Espectroscopia de Luz Próxima ao Infravermelho , Zumbido/fisiopatologia , Estimulação Magnética Transcraniana , Estimulação Acústica , Adulto , Doença Crônica , Potenciais Evocados Auditivos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Tinnitus, the perception of sound without an external source, affects 15% of the population, with 2.4% experiencing significant distress. In this review, we summarize the current state of knowledge about tinnitus management with a particular focus on the translation into clinical practice. In the first section, we analyze shortcomings, knowledge gaps, and challenges in the field of tinnitus research. Then, we highlight the relevance of the diagnostic process to account for tinnitus heterogeneity and to identify all relevant aspects of the tinnitus in an individual patient, such as etiological aspects, pathophysiological mechanisms, factors that contribute most to suffering, and comorbidities. In the next section, we review available treatment options, including counselling, cognitive-behavioral therapy (CBT), hearing aids and cochlear implants for patients with a relevant hearing loss, sound generators, novel auditory stimulation approaches, tinnitus retraining therapy (TRT), pharmacological treatment, neurofeedback, brain stimulation, bimodal stimulation, Internet- and app-based digital approaches, and alternative treatment approaches. The evidence for the effectiveness of the various treatment interventions varies considerably. We also discuss differences in current respective guideline recommendations and close with a discussion of how current pathophysiological knowledge, latest scientific evidence, and patient perspectives can be translated in patient-centered care.