Sven Vanneste

The neural correlates of tinnitus-related distress

Tinnitus is an auditory phantom percept with a tone, hissing, or buzzing sound in the absence of any objective physical sound source. About 6% to 25% of the affected people report interference with their lives as tinnitus causes a considerable amount of distress. However, the underlying neurophysiological mechanism for the development of tinnitus-related distress remains not well understood. Hence we focus on the cortical and subcortical source differences in resting-state EEG between tinnitus patients with different grades of distress using continuous scalp EEG recordings and Low Resolution Electromagnetic Tomography (LORETA). Results show more synchronized alpha activity in the tinnitus patients with a serious amount of distress with peaks localized to various emotion-related areas. These areas include subcallosal anterior cingulate cortex, the insula, parahippocampal area and amygdala. In addition, less alpha synchronized activity was found in the posterior cingulate cortex, precuneus and DLPFC. A comparison between the tinnitus group with distress and the Nova Tech EEG (NTE) normative database demonstrated increased synchronized alpha and beta activity and less synchronized delta and theta activity in the dorsal anterior cingulate cortex in tinnitus patients with distress. It is interesting that the areas found show some overlap with the emotional component of the pain matrix and the distress related areas in asthmatic dyspnea. Unpleasantness of pain activates the anterior cingulate and prefrontal cortices, amygdala, and insula. As such, it might be that distress is related to alpha and beta activity in the dorsal anterior cingulate cortex, the amount of distress perceived to an alpha network consisting of the amygdala-anterior cingulate cortex-insula-parahippocampal area.

Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS)

A group of European experts was commissioned by the European Chapter of the International Federation of Clinical Neurophysiology to gather knowledge about the state of the art of the therapeutic use of transcranial direct current stimulation (tDCS) from studies published up until September 2016, regarding pain, Parkinsons disease, other movement disorders, motor stroke, poststroke aphasia, multiple sclerosis, epilepsy, consciousness disorders, Alzheimers disease, tinnitus, depression, schizophrenia, and craving/addiction. The evidence-based analysis included only studies based on repeated tDCS sessions with sham tDCS control procedure; 25 patients or more having received active treatment was required for Class I, while a lower number of 10-24 patients was accepted for Class II studies. Current evidence does not allow making any recommendation of Level A (definite efficacy) for any indication. Level B recommendation (probable efficacy) is proposed for: (i) anodal tDCS of the left primary motor cortex (M1) (with right orbitofrontal cathode) in fibromyalgia; (ii) anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC) (with right orbitofrontal cathode) in major depressive episode without drug resistance; (iii) anodal tDCS of the right DLPFC (with left DLPFC cathode) in addiction/craving. Level C recommendation (possible efficacy) is proposed for anodal tDCS of the left M1 (or contralateral to pain side, with right orbitofrontal cathode) in chronic lower limb neuropathic pain secondary to spinal cord lesion. Conversely, Level B recommendation (probable inefficacy) is conferred on the absence of clinical effects of: (i) anodal tDCS of the left temporal cortex (with right orbitofrontal cathode) in tinnitus; (ii) anodal tDCS of the left DLPFC (with right orbitofrontal cathode) in drug-resistant major depressive episode. It remains to be clarified whether the probable or possible therapeutic effects of tDCS are clinically meaningful and how to optimally perform tDCS in a therapeutic setting. In addition, the easy management and low cost of tDCS devices allow at home use by the patient, but this might raise ethical and legal concerns with regard to potential misuse or overuse. We must be careful to avoid inappropriate applications of this technique by ensuring rigorous training of the professionals and education of the patients.

Tinnitus Intensity Dependent Gamma Oscillations of the Contralateral Auditory Cortex

Background Non-pulsatile tinnitus is considered a subjective auditory phantom phenomenon present in 10 to 15% of the population. Tinnitus as a phantom phenomenon is related to hyperactivity and reorganization of the auditory cortex. Magnetoencephalography studies demonstrate a correlation between gamma band activity in the contralateral auditory cortex and the presence of tinnitus. The present study aims to investigate the relation between objective gamma-band activity in the contralateral auditory cortex and subjective tinnitus loudness scores. Methods and Findings In unilateral tinnitus patients (N = 15; 10 right, 5 left) source analysis of resting state electroencephalographic gamma band oscillations shows a strong positive correlation with Visual Analogue Scale loudness scores in the contralateral auditory cortex (max r = 0.73, p<0.05). Conclusion Auditory phantom percepts thus show similar sound level dependent activation of the contralateral auditory cortex as observed in normal audition. In view of recent consciousness models and tinnitus network models these results suggest tinnitus loudness is coded by gamma band activity in the contralateral auditory cortex but might not, by itself, be responsible for tinnitus perception.

Burst Spinal Cord Stimulation: Toward Paresthesia-Free Pain Suppression

INTRODUCTIONSpinal cord stimulation is commonly used for neuropathic pain modulation. The major side effect is the onset of paresthesia. The authors describe a new stimulation design that suppresses pain as well as, or even better than, the currently used stimulation, but without creating paresthesia. METHODSA spinal cord electrode (Lamitrode) for neuropathic pain was implanted in 12 patients via laminectomy: 4 at the C2 level and 7 at the T8–T9 level for cervicobrachialgia and lumboischialgia, respectively (1 at T11 at another center). During external stimulation, the patients received the classic tonic stimulation (40 or 50 Hz) and the new burst stimulation (40-Hz burst with 5 spikes at 500 Hz per burst). RESULTSPain scores were measured using a visual analog scale and the McGill Short Form preoperatively and during tonic and burst stimulation. Paresthesia was scored as present or not present. Burst stimulation was significantly better for pain suppression, by both the visual analog scale score and the McGill Short Form score. Paresthesia was present in 92% of patients during tonic stimulation, and in only 17% during burst stimulation. Average follow-up was 20.5 months. CONCLUSIONThe authors present a new method of spinal cord stimulation using bursts that suppress neuropathic pain without the mandatory paresthesia. Pain suppression seems as good as or potentially better than that achieved with the currently used stimulation. Average follow-up after nearly 2 years (20.5 months) suggests that this stimulation design is stable.

Burst Spinal Cord Stimulation for Limb and Back Pain

OBJECTIVE Spinal cord stimulation via epidurally implanted electrodes is a common treatment for medically intractable neuropathic pain of different origins. Because tonic electrical stimulation evokes paresthesias over the painful area, this method has never been proven scientifically to be superior to placebo. Recently, burst stimulation (in which closely spaced, high-frequency stimuli are delivered to the spinal cord) has been developed, which does not generate paresthesias. METHODS A randomized placebo controlled trail in which we compared three stimulation paradigms (burst, tonic, and placebo) was performed on 15 consecutive pain patients. In contrast to tonic stimulation, burst stimulation was able to provide pain relief without the generation of paresthesias, permitting us to use a double-blinded placebo controlled approach. Primary outcome measures were visual analog scale pain scores for back pain, limb pain, and general pain. Secondary outcome measures included the pain vigilance and awareness questionnaire, which is used to measure attention to pain and pain changes, and visual analog scale of the worst, least, and momentary pain. In a subgroup of five patients, a source-localized electroencephalogram was performed under four conditions: baseline, tonic, burst, and placebo stimulation. RESULTS Burst stimulation was able to improve back, limb, and general pain by 51%, 53%, and 55% and tonic stimulation by 30%, 52%, and 31%, respectively. Pain now, least, and worst pain were improved by 50%, 73%, and 36% by burst stimulation, respectively, and 26%, 46%, and 13% by tonic stimulation. In comparison with placebo, burst, corrected for multiple comparisons, was significantly better for all measurements. However, the greatest differences were obtained in the pain vigilance and awareness questionnaire measurements: burst improved the attention to pain and pain changes, whereas tonic and placebo worsened these measurements. The analysis via encephalogram demonstrates burst stimulation activates the dorsal anterior cingulate and right dorsolateral prefrontal cortex more than tonic stimulation. CONCLUSIONS The differences between tonic and burst stimulation are likely attributable to a more-selective modulation of the medial pain pathways by burst stimulation, as shown by the activation of the dorsal anterior cingulate cortex.

The neural network of phantom sound changes over time: a comparison between recent-onset and chronic tinnitus patients.

Tinnitus is characterized by an ongoing conscious perception of a sound in the absence of any external sound source. Chronic tinnitus is notoriously characterized by its resistance to treatment. In the present study the objective was to verify whether the neural generators and/or the neural tinnitus network, evaluated through EEG recordings, change over time as previously suggested by MEG. We therefore analyzed the source‐localized EEG recordings of a very homogenous group of left‐sided narrow‐band noise tinnitus patients. Results indicate that the generators involved in tinnitus of recent onset seem to change over time with increased activity in several brain areas [auditory cortex, supplementary motor area and dorsal anterior cingulate cortex (dACC) plus insula], associated with a decrease in connectivity between the different auditory and nonauditory brain structures. An exception to this general connectivity decrease is an increase in gamma‐band connectivity between the left primary and secondary auditory cortex and the left insula, and also between the auditory cortices and the right dorsal lateral prefrontal cortex. These networks are both connected to the left parahippocampal area. Thus acute and chronic tinnitus are related to differential activity and connectivity in a network comprising the auditory cortices, insula, dACC and premotor cortex.

Transient alcohol craving suppression by rTMS of dorsal anterior cingulate: An fMRI and LORETA EEG study☆

It has recently become clear that alcohol addiction might be related to a brain dysfunction, in which a genetic background and environmental factors shape brain mechanisms involved with alcohol consumption. Craving, a major component determining relapses in alcohol abuse has been linked to abnormal activity in the orbitofrontal cortex, dorsal anterior cingulated cortex (dACC) and amygdala. We report the results of a patient who underwent rTMS targeting the dACC using a double cone coil in an attempt to suppress very severe intractable alcohol craving. Functional imaging studies consisting of fMRI and resting state EEG were performed before rTMS, after successful rTMS and after unsuccessful rTMS with relapse. Craving was associated with EEG beta activity and connectivity between the dACC and PCC in the patient in comparison to a healthy population, which disappeared after successful rTMS. Cue induced worsening of craving pre-rTMS activated the ACC-vmPFC and PCC on fMRI, as well as the nucleus accumbens area, and lateral frontoparietal areas. The nucleus accumbens, ACC-vmPFC and PCC activation disappeared on fMRI following successful rTMS. Relapse was associated with recurrence of ACC and PCC EEG activity, but in gamma band, in comparison to a healthy population. On fMRI nucleus accumbens, ACC and PCC activation returned to the initial activation pattern. A pathophysiological approach is described to suppress alcohol craving temporarily by rTMS directed at the anterior cingulate. Linking functional imaging changes to craving intensity suggests this approach warrants further exploration.

The auditory and non-auditory brain areas involved in tinnitus. An emergent property of multiple parallel overlapping subnetworks

Tinnitus is the perception of a sound in the absence of an external sound source. It is characterized by sensory components such as the perceived loudness, the lateralization, the tinnitus type (pure tone, noise-like) and associated emotional components, such as distress and mood changes. Source localization of quantitative electroencephalography (qEEG) data demonstrate the involvement of auditory brain areas as well as several non-auditory brain areas such as the anterior cingulate cortex (dorsal and subgenual), auditory cortex (primary and secondary), dorsal lateral prefrontal cortex, insula, supplementary motor area, orbitofrontal cortex (including the inferior frontal gyrus), parahippocampus, posterior cingulate cortex and the precuneus, in different aspects of tinnitus. Explaining these non-auditory brain areas as constituents of separable subnetworks, each reflecting a specific aspect of the tinnitus percept increases the explanatory power of the non-auditory brain areas involvement in tinnitus. Thus, the unified percept of tinnitus can be considered an emergent property of multiple parallel dynamically changing and partially overlapping subnetworks, each with a specific spontaneous oscillatory pattern and functional connectivity signature.

Methodological aspects of clinical trials in tinnitus: A proposal for an international standard

Chronic tinnitus is a common condition with a high burden of disease. While many different treatments are used in clinical practice, the evidence for the efficacy of these treatments is low and the variance of treatment response between individuals is high. This is most likely due to the great heterogeneity of tinnitus with respect to clinical features as well as underlying pathophysiological mechanisms. There is a clear need to find effective treatment options in tinnitus, however, clinical trials differ substantially with respect to methodological quality and design. Consequently, the conclusions that can be derived from these studies are limited and jeopardize comparison between studies. Here, we discuss our view of the most important aspects of trial design in clinical studies in tinnitus and make suggestions for an international methodological standard in tinnitus trials. We hope that the proposed methodological standard will stimulate scientific discussion and will help to improve the quality of trials in tinnitus.

Bifrontal transcranial direct current stimulation modulates tinnitus intensity and tinnitus-distress-related brain activity

Bifrontal transcranial direct current stimulation (tDCS), with the anodal electrode overlying the right and the cathodal electrode overlying the left dorsolateral prefrontal cortex, has been shown to suppress tinnitus significantly in 30% of patients. The source localized resting‐state electrical activity is recorded before and after bifrontal tDCS in patients who respond to tDCS to unravel the mechanism by which tDCS suppresses tinnitus. The present electroencephalography study (N = 12) provides support for the ability of bifrontal tDCS to suppress tinnitus intensity and tinnitus‐related distress by modulation of the pregenual anterior cingulate cortex, parahippocampal area and right primary auditory cortex in resting‐state spontaneous brain activity. These findings provide direct support for tDCS having an impact not only directly on the underlying dorsolateral prefrontal cortex but also indirectly on functionally connected brain areas relevant for tinnitus distress and tinnitus intensity, respectively.