Prefrontal and auditory tRNS in sequence for treating chronic tinnitus: a modified multisite protocol

Van der Groen, O., Potok, W., Wenderoth, N., Edwards, G., Mattingley, J.B. and Edwards, D. Using noise for the better: The effects of transcranial random noise stimulation on the brain and behavior. NEUROSCI BIOBEHAV REV X (X) XXX-XXX 2021.- Transcranial random noise stimulation (tRNS) is a non-invasive electrical brain stimulation method that is increasingly employed in studies of human brain function and behavior, in health and disease. tRNS is effective in modulating perception acutely and can improve learning. By contrast, its effectiveness for modulating higher cognitive processes is variable. Prolonged stimulation with tRNS, either as one longer application, or multiple shorter applications, may engage plasticity mechanisms that can result in long-term benefits. Here we provide an overview of the current understanding of the effects of tRNS on the brain and behavior and provide some specific recommendations for future research.

Tinnitus is a common disorder in which auditory and non-auditory areas are involved as a network. Therefore, the multisite protocol of brain stimulation (tRNS) seems effective in relieving tinnitus symptoms. This study aimed to verify the modulatory effects of multisite tRNS on the tinnitus network. Thirty-two tinnitus-suffering patients received two consecutive sessions of tRNS (SHAM+ REAL) applied over the T3, T4 (the auditory cortex group) and F4, FP1 followed by T3, T4 (the multisite group). A 3-min resting-state EEG was recorded before and immediately after each session. After the multisite-tRNS real session, there was a significantly increased power in the alpha-1 band at the auditory and prefrontal cortex accompanied by decreased power in the delta and beta-2 bands in the prefrontal cortex. Standardized low-resolution brain electromagnetic tomography (sLORETA) showed a significant decrease in beta-2 activity in the prefrontal cortex, anterior cingulate cortex, and the parahippocampus and decreased alpha connectivity between the right prefrontal cortex and the left auditory cortex. No significant effects were noticed for the sham session. This study showed that tRNS has modulatory effects on the electrical activity of the brain and that targeting prefrontal and auditory areas in sequence could modulate the distress network and multiple hubs in the tinnitus network.

Random noise stimulation was reported as the more effective and safer type of electrical stimulation techniques in relieving tinnitus symptoms. The multisite protocol of transcranial random noise stimulation has shown additional favorable effects.

Here we will discuss the role of applying eight sessions of multisite transcranial random noise stimulation in decreasing tinnitus loudness and annoyance without exerting additional adverse effects.

Twenty-nine subjects (8 female), the mean age of (45.34 ± 9.57) with chronic tinnitus received transcranial random noise stimulation in the multisite protocol, 10 min of auditory-transcranial random noise stimulation applied over the T3, T4 preceded by 10 min of prefrontal-transcranial random noise stimulation applied over F4, FP1. In the first group, only one session was applied and the multiple-sessions group contained eight repeated sessions. Visual analog scale scores for loudness and distress were recorded before and immediately after the treatment. Multivariate repeated measure ANOVA test was used and minimal detectable change calculated.

There was a statistically and clinically significant reduction in tinnitus loudness and annoyance in both groups (p < 0.05, effect size (η²) > 0.8), while the amount of annoyance suppression in the multiple-sessions group was significantly greater than the single-session group. The patients of the multiple-sessions transcranial random noise stimulation group reported an improvement in their sleep and lower tinnitus handicap inventory scores without experiencing any additional adverse effects of the intervention.

The results of this study showed a substantial improvement in tinnitus symptoms by using the multiple sessions of transcranial random noise stimulation in the multisite protocol without producing any additional side effects. We suggest further clinical trials with long-term follow-up be investigated.

Tem sido relatado que a estimulação transcraniana por ruído aleatório é um tipo mais eficaz e seguro de técnica de estimulação elétrica no alívio dos sintomas do zumbido. O protocolo multissítio da estimulação transcraniana por ruído aleatório mostrou efeitos favoráveis adicionais.

Discutir o papel da aplicação de oito sessões de estimulação transcraniana por ruído aleatório multissítio na diminuição da intensidade (loudness) do som e incômodo (annoyance) do zumbido sem causar efeitos adversos adicionais.

Vinte e nove indivíduos com zumbido crônico (oito do sexo feminino), com média de 45,34 ± 9,57 anos, receberam estimulação transcraniana por ruído aleatório no protocolo multissítio, 10 minutos de estimulação transcraniana por ruído aleatório-auditivo aplicado no T3, T4 precedido por 10 min de estimulação transcraniana por ruído aleatório pré-frontal aplicado sobre F4, FP1. No primeiro grupo, apenas uma sessão foi aplicada e o grupo de múltiplas sessões recebeu oito sessões. Os escores da escala visual analógica para a intensidade do som (loudness) e incômodo (annoyance) do zumbido foram registrados antes e imediatamente após o tratamento. O teste Anova multivariada para medidas repetidas foi utilizado e a mudança mínima detectável foi calculada.

Houve uma redução estatisticamente e clinicamente significante na intensidade e incômodo do zumbido em ambos os grupos (p < 0,05; tamanho do efeito (η2) > 0,8), embora o nível de supressão do incômodo no grupo de sessões múltiplas tenha sido significantemente maior do que no grupo de sessão única. Os pacientes do grupo estimulação transcraniana por ruído aleatório com múltiplas sessões relataram uma melhoria no sono e menores escores no tinnitus handicap inventory, sem experimentar quaisquer efeitos adversos adicionais da intervenção.

Os resultados deste estudo mostraram uma melhora substancial nos sintomas do zumbido utilizando múltiplas sessões de estimulação transcraniana por ruído aleatório no protocolo multissítio sem produzir quaisquer efeitos colaterais adicionais. Sugerimos que novos ensaios clínicos com seguimento de longo prazo sejam realizados.