Frequency tracking in subcortical structures. a-c, Frequency tracking and normalized amplitude of detected peaks in the MGB (a), IC (b), and CN (c). Data are plotted for 50 ms windows in which at least 30% of subjects had peaks that reached a 12 SNR threshold with respect to baseline. The horizontal and vertical dashed lines represent stimulus F0 and offset, respectively. Shaded bars represent the SEM.

Frequency tracking in subcortical structures. a-c, Frequency tracking and normalized amplitude of detected peaks in the MGB (a), IC (b), and CN (c). Data are plotted for 50 ms windows in which at least 30% of subjects had peaks that reached a 12 SNR threshold with respect to baseline. The horizontal and vertical dashed lines represent stimulus F0 and offset, respectively. Shaded bars represent the SEM.

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There is much debate about the existence and function of neural oscillatory mechanisms in the auditory system. The frequency- following response (FFR) is an index of neural periodicity encoding that can provide a vehicle to study entrainment in frequency ranges relevant to speech and music processing. Criteria for entrainment include the presence o...

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... the subcortical structures, the frequency tracking accuracy also increases toward the end of the stimulus, as it does for the cortex, but as the initial frequency is closer to the stimulus F0, a less pronounced pattern of convergence is observed (Fig. ...

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... DBSS uses precisely tuned auditory pulses to align brainwave activity with external stimuli (Coffey et al., 2021). By engaging key circuits in the DLPFC, ACC, and VTA, DBSS may enhance neurotransmitter balance (serotonin, dopamine) and improve cognitive and emotional regulation in OCD (Bhattacharya et al., 2021;Burke & Alvarez, 2022;Lin et al., 2023). ...
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Background: Obsessive-Compulsive Disorder (OCD) affects 1-2% of the global population, characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions) that impair daily functioning. Traditional treatments like Cognitive Behavioral Therapy (CBT) with Exposure and Response Prevention (ERP) and pharmacotherapy are effective but often limited by accessibility, cost, adherence challenges, and side effects. Objective: This study assesses the effectiveness and safety of Deep Brain Sound Stimulation (DBSS), a novel non-invasive auditory therapy, based on user-reported outcomes from individuals with OCD. Methods: We analyzed feedback from 219 users who completed DBSS therapy via the Vital Tones mobile application on the Apple App Store. Additionally, 14 participants provided detailed responses through in-app surveys evaluating symptom improvements in severity, cognitive control, and emotional regulation. Descriptive statistics were used to determine median effectiveness and satisfaction rates. Results: The therapy demonstrated a high user satisfaction rate of 99.09%, with a minimal refund rate of 0.91%. Survey respondents reported a median symptom improvement of 50% (95% CI: 22%–66%). DBSS was well-tolerated, with no severe side effects reported and only minor adverse effects in a small number of sessions. Conclusion: Preliminary findings indicate that DBSS is a promising non-invasive treatment for OCD, offering significant symptom improvement and high user satisfaction. However, the observational nature of the study, small survey sample, and reliance on self-reported data suggest that further controlled research is necessary to validate these results and establish DBSS's efficacy and safety.
... DBSS is a novel auditory neuromodulation technique that leverages the frequency-following response (FFR), a phenomenon where neural oscillations synchronize with rhythmic auditory stimuli (Chaieb et al., 2017;Krizman & Kraus, 2019;Momtaz & Bidelman, 2024). This mechanism underpins DBSS's capacity to engage targeted brain regions and modulate their activity, distinguishing it from conventional auditory therapies like binaural beats, which lack similar specificity and scalability (Coffey et al., 2021;Kraus & White-Schwoch, 2015). ...
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Background: Neurological and psychiatric conditions represent significant public health challenges, with traditional treatments such as psychotherapy and pharmacotherapy often limited by adherence issues, side effects, and variable efficacy. Deep Brain Sound Stimulation (DBSS) is a novel, non-invasive neuromodulation technique that utilizes calibrated auditory frequencies to enhance neural synchronization and plasticity through frequency-following responses (FFRs). This approach offers a targeted and scalable alternative to conventional methods like Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS). Objective: This large-scale observational study aimed to evaluate the safety, user satisfaction, and perceived therapeutic benefits of DBSS across various neurological and psychiatric conditions, including depression, anxiety, Attention-Deficit/Hyperactivity Disorder (ADHD), Post-Traumatic Stress Disorder (PTSD), and hypertension. Methods: Data were collected from 6,437 Apple App Store users who completed at least one full-treatment DBSS protocol via the Vital Tones mobile application. Additionally, 380 users participated in voluntary in-app surveys providing detailed feedback. User satisfaction was assessed through descriptive statistics of survey responses and app engagement metrics, including refund rates. Results: Among full-treatment users, 98.52% reported overall satisfaction, accompanied by a low refund rate of 1.48%. Users reported improvements in cognitive focus, emotional regulation, and motor coordination, particularly in managing anxiety, depression, ADHD, PTSD, and hypertension. Mild side effects, such as dizziness and headaches, were infrequent and transient. With over 3 million sessions administered globally since 2014, DBSS demonstrates high feasibility and potential benefits in a home-based, non-invasive setting. Conclusions: DBSS appears to be an effective and accessible non-invasive neuromodulation tool, characterized by high user satisfaction and minimal adverse events. These preliminary findings support DBSS’s potential as an alternative or complement to traditional neuromodulation treatments. However, further validation through randomized controlled trials (RCTs) and objective neurophysiological assessments is necessary to confirm its efficacy and optimize its protocols.
... • Tone Generators: High-precision tone generator software is used to produce the required monaural and isochronic tones, allowing precise frequency control and modulation necessary for effective DBSS (Coffey et al., 2021;Bhattacharya et al., 2021). ...
... Although sensory feedback has proven effective, integrating neuroimaging tools like fMRI or EEG in the future could further enhance accuracy and provide deeper insights into the neural dynamics of DBSS. Existing research supports that tailored auditory frequencies effectively modulate neural activity in targeted regions, reinforcing the scientific foundation of DBSS (Coffey et al., 2021;Bhattacharya et al., 2021). ...
... • Scientific Support: Neuroimaging studies corroborate that tailored auditory frequencies can modulate neural activity in targeted brain regions effectively (Coffey et al., 2021;Engelbregt et al., 2019). ...
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Background: Insomnia affects millions globally, significantly reducing quality of life and increasing the risk of mental and physical health issues. Traditional treatments, including Cognitive Behavioral Therapy for Insomnia (CBT-I) and pharmacotherapy, often face challenges related to accessibility, adherence, and side effects. Objective: This preliminary observational study evaluates the effectiveness and safety of Deep Brain Sound Stimulation (DBSS), a novel non-invasive auditory therapy, for individuals with insomnia and to enhance deep sleep based on user-reported outcomes. Methods: Data were collected from 358 users who completed DBSS therapy for Insomnia and Deep Sleep via the Vital Tones mobile application on the Apple App Store. Participants self-administered DBSS sessions at home and provided symptom reports through in-app surveys. User satisfaction was assessed using purchase and refund data, while symptom improvement was evaluated using descriptive statistics to determine median effectiveness and confidence intervals. Results: High user satisfaction was observed, with 99.30% of Insomnia users and 99.53% of Deep Sleep users satisfied with the treatment. Refund rates were exceptionally low, with only 0.70% (1/143) of Insomnia users and 0.47% (1/215) of Deep Sleep users requesting refunds. Among 19 survey respondents, the median symptom improvement was 80% for Insomnia (95% CI: 44.92%–85.08%) and 65% for Deep Sleep (95% CI: 35.60%–94.40%). DBSS was well-tolerated, with no severe adverse events reported and only rare mild side effects such as transient dizziness and mild headaches. Conclusion: Preliminary findings suggest that DBSS is a promising non-invasive treatment for insomnia and enhancing deep sleep, offering significant symptom reduction and high user satisfaction. Its accessibility and favorable safety profile provide advantages over traditional therapies. However, the study’s observational design, limited survey sample, and reliance on self-reported data highlight the need for further controlled research to confirm DBSS’s efficacy and safety for sleep-related disorders.
... DBSS employs precisely tuned auditory pulses to align brainwave activity with external stimuli (Coffey et al., 2021). By engaging key circuits in the dorsolateral prefrontal cortex (dlPFC), ventromedial prefrontal cortex (vmPFC), and ventral tegmental area (VTA), DBSS enhances neurotransmitter balance (dopamine, norepinephrine) and improves cognitive and behavioral regulation in ADHD (Yang et al., 2018;Engelbregt et al., 2019). ...
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Background: Attention Deficit Hyperactivity Disorder (ADHD) affects 5-10% of children and 2-5% of adults globally, characterized by inattention, hyperactivity, and impulsivity. Traditional treatments like pharmacotherapy and behavioral interventions, while effective, are often limited by side effects and accessibility issues. Objective: This study assesses the effectiveness and safety of Deep Brain Sound Stimulation (DBSS), a novel non-invasive auditory therapy, based on user-reported outcomes from individuals with ADHD. Methods: We analyzed feedback from 439 users who completed DBSS therapy via the Vital Tones mobile application on the Apple App Store. Additionally, 20 participants provided detailed responses through in-app surveys evaluating symptom improvements in attention, hyperactivity, and cognitive performance. Descriptive statistics were used to determine median effectiveness and satisfaction rates. Results: The therapy demonstrated a high user satisfaction rate of 99.32%, with a minimal refund rate of 0.68%. Survey respondents reported a median symptom improvement of 57% (95% CI: 40.33%–73.00%). DBSS was well-tolerated, with only minor side effects reported in a small number of sessions. Conclusion: Preliminary findings indicate that DBSS is a promising non-invasive treatment for ADHD, offering significant symptom improvement and high user satisfaction. However, the observational nature of the study, small survey sample, and reliance on self-reported data suggest that further controlled research is necessary to validate these results and establish DBSS's efficacy and safety.
... ulating effect lasts after the prime has ended. Previous research has provided evidence for the persistence of neural oscillations, even though they diminish in strength over time (e.g., van Bree et al., 2021;Coffey et al., 2021;Lakatos et al., 2013). A. Fiveash, N. Bedoin and B. Tillmann Journal of Experimental Child Psychology 250 (2025) 106111 Does rhythmic priming require attention? ...
... The auditory sensory modality lends itself particularly well to investigating whether spindles block sensory information, as peripheral auditory structures remain accessible during the sleep state, and the origin and timing of specific neurological responses evoked by sound within the auditory pathway are quite well understood (see Figure 1C) (25,26). Notably, recent developments in techniques to capture early responses to sound using magnetoencephalography (MEG) and electroencephalography (EEG) offer a means of measuring the effects of brain state on sensory process as sensory information ascends the central nervous system (7,(25)(26)(27)(28). ...
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Sleep spindles are transient 11-16 Hz brain oscillations generated by thalamocortical circuits. Their role in memory consolidation is well-established, but how they play a role in sleep continuity and protection of memory consolidation against interference is unclear. One theory posits that spindles or a neural refractory period following their offset act as a gating mechanism, blocking sensory information en route to the cortex at the level of the thalamus. An alternative model posits that spindles do not participate in the suppression of neural responses to sound, although they can be produced in response to sound. We present evidence from three experiments using electroencephalography and magnetoencephalography in humans that examine different evoked responses in the presence of and following sleep spindles. The results provide convergent empirical evidence suggesting that auditory processing up to cortex is maintained during sleep spindles, and their refractory periods.
... 6,11,12 Neural entrainment describes the phenomenon by which ongoing brain oscillations synchronize to the rhythmic pattern of an external stimulus, such as repetitive auditory cues, visual signals, or electrical stimulation. [13][14][15][16][17] Successful neural entrainment by an external stimulus enhanced the cognitive or motor function that was associated to the oscillatory activity being entrained. 18,19 In patients with PD, DBS is typically applied in frequencies between 90 and 180 Hz. ...
... This observation fits the hypothesis that entrainment depends on the presence of endogenous oscillatory activity belonging to physiological processes. 11,13,31 Second, increased DBS amplitudes led to an attenuation of the entrainment in three out of 15 cases (Figure 1c), a finding that confirms a non-linear response to stimulation. This attenuation of 1:2 entrainment with higher DBS intensity fits the Arnold tongue framework which suggests that entrainment . ...
... Specifically, it was shown that repetitive high-frequency stimulation enhanced local ongoing activity and that entrainment was more prominent when the stimulus was applied in frequencies closer to the intrinsic frequencies. 11,13,36 This external manipulation of ongoing oscillatory dynamics was also found to have beneficial effects in processes such as associative learning, and to improve medical conditions, such as tinnitus. 14,18 Entrainment caused by subthalamic DBS would typically appear in the gamma band around stimulation frequency (130 Hz) or its subharmonics (60-65 Hz). ...
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Finely tuned gamma oscillations have been recorded from the subthalamic nucleus and cortex in Parkinson's disease patients undergoing deep brain stimulation and are often associated with dyskinesia. More recently, it was shown that deep brain stimulation entrains finely tuned gamma to 1/2 of the stimulation frequency; however, the functional role of this signal is not yet fully understood. We recorded local field potentials from the subthalamic nucleus in 19 chronically implanted Parkinson's disease patients under effective dopaminergic medication and during deep brain stimulation with increasing stimulation amplitude, while they were at rest and during repetitive hand movements. We analyzed the effect of stimulation intensity on gamma band 1:2 entrainment and compared the entrained signal during rest and during repetitive movement. Spontaneous finely tuned gamma was present in eight out of 19 patients (peak frequency μ = 78.4 ±4.3 Hz). High-frequency deep brain stimulation induced 1:2 gamma entrainment in 15 out of 19 patients. Entrainment occurred at a mean stimulation amplitude of 2.2 ±0.75 mA and disappeared or decreased in power during higher stimulation amplitude in three patients. In patients with spontaneous finely tuned gamma, increasing the stimulation amplitude induced a progressive frequency shift of spontaneous finely tuned gamma until it locked to 1:2 entrainment. Only five out of 15 patients with entrained gamma activity showed dyskinesia during stimulation. Further, there was a significant increase in the power of 1:2 entrained gamma activity during movement in comparison to rest. Finally, patients with entrained gamma activity had faster movements as compared to those without gamma entrainment. These findings argue for a functional relevance of the stimulation-induced 1:2 gamma entrainment in Parkinson's disease patients as a prokinetic activity that, however, is not necessarily promoting dyskinesia. Previously published electrophysiological models of entrainment fit well to our results and support our findings that stimulation-induced entrainment can be a promising real-life biomarker for closed-loop deep brain stimulation.
... We used a 120 ms synthetic speech syllable (/da/, 10 ms consonant burst, a 30 ms formant transition and an 80 ms steady-state vowel with a fundamental frequency of 98 Hz), to facilitate comparison of the evoked responses in simultaneously acquired EEG and MEG with previous work (Coffey et al., 2016(Coffey et al., , 2017(Coffey et al., , 2021. The stimulus was presented binaurally through Etymotic ER-3A insert earphones with foam tips (Etymotic Research), at 55 dB SPL, which we determined through pilot testing was clearly audible but did not awaken sleeping participants. ...
... Auditory event markers were used to define epochs that started 1 s before sound onset and ended 3 s after sound onset as in the EEG analysis. Similar to previous work (Coffey et al., 2021), we used a distributed sourcemodelling approach. This process estimates activity originating throughout the brain, constrained by spatial priors derived from each subject's T1-weighted anatomic MRI scan (Baillet et al., 2001;Gross et al., 2013). ...
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Closed-loop auditory stimulation (CLAS) is a brain modulation technique in which sounds are timed to enhance or disrupt endogenous neurophysiological events. CLAS of slow oscillation up-states in sleep is becoming a popular tool to study and enhance sleep's functions, as it increases slow oscillations, evokes sleep spindles and enhances memory consolidation of certain tasks. However, few studies have examined the specific neurophysiological mechanisms involved in CLAS, in part because of practical limitations to available tools. To evaluate evidence for possible models of how sound stimulation during brain up-states alters brain activity, we simultaneously recorded electro- and magnetoencephalography in human participants who received auditory stimulation across sleep stages. We conducted a series of analyses that test different models of pathways through which CLAS of slow oscillations may affect widespread neural activity that have been suggested in literature, using spatial information, timing and phase relationships in the source-localized magnetoencephalography data. The results suggest that auditory information reaches ventral frontal lobe areas via non-lemniscal pathways. From there, a slow oscillation is created and propagated. We demonstrate that while the state of excitability of tissue in auditory cortex and frontal ventral regions shows some synchrony with the electroencephalography (EEG)-recorded up-states that are commonly used for CLAS, it is the state of ventral frontal regions that is most critical for slow oscillation generation. Our findings advance models of how CLAS leads to enhancement of slow oscillations, sleep spindles and associated cognitive benefits and offer insight into how the effectiveness of brain stimulation techniques can be improved.
... Both of these steps were taken, in part, to eliminate speech rate anomalies (typically, excessively low rate values) arising due to very short utterances or from the presence of extended pauses. In addition, listener entrainment to heard speech takes time to build up (Luo and Poeppel 2007) and is likely to be disrupted or reset after extended gaps (e.g., Coffey et al. 2021;Van Bree et al. 2021;Xu and Ye 2015). ...
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The duration of inter-speaker pauses is a pragmatically salient aspect of conversation that is affected by linguistic and non-linguistic context. Theories of conversational turn-taking imply that, due to listener entrainment to the flow of syllables, a higher speech rate will be associated with shorter turn-transition times (TTT). Previous studies have found conflicting evidence, however, some of which may be due to methodological differences. In order to test the relationship between speech rate and TTT, and how this may be modulated by other dialogue factors, we used question-answer sequences from spontaneous conversational corpora in Dutch and English. As utterance-final lengthening is a local cue to turn endings, we also examined the impact of utterance-final syllable rhyme duration on TTT. Using mixed-effect linear regression models, we observed evidence for a positive relationship between speech rate and TTT: thus, a higher speech rate is associated with longer TTT, contrary to most theoretical predictions. Moreover, for answers following a pause (“gaps”) there was a marginal interaction between speech rate and final rhyme duration, such that relatively long final rhymes are associated with shorter TTT when foregoing speech rate is high. We also found evidence that polar (yes/no) questions are responded to with shorter TTT than open questions, and that direct answers have shorter TTT than responses that do not directly answer the questions. Moreover, the effect of speech rate on TTT was modulated by question type. We found no predictors of the (negative) TTT for answers that overlap with the foregoing questions. Overall, these observations suggest that TTT is governed by multiple dialogue factors, potentially including the salience of utterance-final timing cues. Contrary to some theoretical accounts, there is no strong evidence that higher speech rates are consistently associated with shorter TTT.
... However, because this term is unable to show the integrated and experience-dependent nature of the auditory neural activity, this was replaced by the term FFR [26]. The FFR components have both subcortical and cortical origins [28][29][30][31]. ...
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Background: Auditory processing disorders (APD) may be one of the problems experienced by children with listening difficulties (LiD). The combination of auditory behavioural and electrophysiological tests could help to provide a better understanding of the abilities/disabilities of children with LiD. The current study aimed to quantify the auditory processing abilities and function in children with LiD. Methods: Twenty children, ten with LiD (age = 8.46; SD = 1.39) and ten typically developing (TD) (age = 9.45; SD = 1.57) participated in this study. All children were evaluated with auditory processing tests as well as with attention and phonemic synthesis tasks. Electrophysiological measures were also conducted with click and speech auditory brainstem responses (ABR). Results: Children with LiD performed significantly worse than TD children for most behavioural tasks, indicating shortcomings in functional auditory processing. Moreover, the click-ABR wave I amplitude was smaller, and the speech-ABR waves D and E latencies were longer for the LiD children compared to the results of TD children. No significant difference was found when evaluating neural correlates between groups. Conclusions: Combining behavioural testing with click-ABR and speech-ABR can highlight functional and neurophysiological deficiencies in children with learning and listening issues, especially at the brainstem level.