Mark Plazier

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.

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 difference between uni- and bilateral auditory phantom percept.

OBJECTIVE Tinnitus can be considered an auditory phantom percept, in which patients hear an internal sound in the absence of any external sound source, mimicking tonal memory. Tinnitus however can be perceived exclusively uni- or bilaterally. METHODS The neurophysiological differences were investigated between unilateral and bilateral tinnitus using LORETA source localized resting state EEG recordings. RESULTS The difference between unilateral and bilateral tinnitus is reflected by high frequency activity (beta and gamma) in the superior prefrontal gurus, right parahippocampus, right angular gyrus and right auditory cortex. Unilateral tinnitus is characterized by contralateral beta2 in the superior prefrontal gyrus in comparison to bilateral tinnitus, but gamma in comparison to non-tinnitus subjects. Bilateral tinnitus has delta activity in the ventrolateral prefrontal cortex in comparison to unilateral tinnitus, and bilateral beta1 in comparison to non-tinnitus subjects. Bilateral tinnitus is also characterized by bilateral frontopolar beta1 activity. CONCLUSIONS Unilateral and bilateral tinnitus can be differentiated based on their resting state oscillation patterns: beta3 and gamma-band activity in the superior premotor cortex, parahippocampal area and angular gyrus seem to form the core of a spatial localization network involved in tinnitus. SIGNIFICANCE These differences should be taken into account when evaluating functional neuroimaging data relating to tinnitus.

Theta-gamma dysrhythmia and auditory phantom perception.

Tinnitus is considered an auditory phantom percept analogous to phantom pain. Thalamocortical dysrhythmia has been proposed as a possible pathophysiological mechanism for both tinnitus and pain. Thalamocortical dysrhythmia refers to a persistent pathological resting state theta-gamma coupling that is spatially localized at an area where normally alpha oscillations predominate. Auditory cortex stimulation via implanted electrodes has been developed to treat tinnitus, targeting an area of activation on functional MR imaging elicited by tinnitus-matched sound presentation. The authors describe a case in which clinical improvement was correlated with changes in intracranial recordings. Maximal tinnitus suppression was obtained by current delivery exactly at the blood oxygen level-dependent activation hotspot, which colocalizes with increased gamma and theta activity, in contrast to the other electrode poles, which demonstrated a normal alpha peak. These spectral changes normalized when stimulation induced tinnitus suppression, both on electrode and source-localized electroencephalography recordings. These data suggest that thetagamma coupling as proposed by the thalamocortical dysrhythmia model might be causally related to a conscious auditory phantom percept.

The Differences in Brain Activity between Narrow Band Noise and Pure Tone Tinnitus

Background Tinnitus is an auditory sensation characterized by the perception of sound or noise in the absence of any external sound source. Based on neurobiological research, it is generally accepted that most forms of tinnitus are attributable to maladaptive plasticity due to damage to auditory system. Changes have been observed in auditory structures such as the inferior colliculus, the thalamus and the auditory cortex as well as in non-auditory brain areas. However, the observed changes show great variability, hence lacking a conclusive picture. One of the reasons might be the selection of inhomogeneous groups in data analysis. Methodology The aim of the present study was to delineate the differences between the neural networks involved in narrow band noise and pure tone tinnitus conducting LORETA based source analysis of resting state EEG. Conclusions Results demonstrated that narrow band noise tinnitus patients differ from pure tone tinnitus patients in the lateral frontopolar (BA 10), PCC and the parahippocampal area for delta, beta and gamma frequency bands, respectively. The parahippocampal-PCC current density differences might be load dependent, as noise-like tinnitus constitutes multiple frequencies in contrast to pure tone tinnitus. The lateral frontopolar differences might be related to pitch specific memory retrieval.

Burst stimulation of the auditory cortex: a new form of neurostimulation for noise-like tinnitus suppression: Clinical article

OBJECT Tinnitus is an auditory phantom percept related to tonic and burst hyperactivity of the auditory system. Two parallel pathways supply auditory information to the cerebral cortex: the tonotopically organized lemniscal system, and the nontonotopic extralemniscal system, which fire in tonic and burst mode, respectively. Electrical cortex stimulation is a method capable of modulating activity of the human cortex by delivering stimuli in a tonic or burst way. Burst firing is shown to be more powerful in activating the cerebral cortex than tonic firing, and bursts may activate neurons that are not activated by tonic firing. METHODS Five patients with an implanted electrode on the auditory cortex were asked to rate their tinnitus distress and intensity on a visual analog scale before and after 40-Hz tonic and 40-Hz burst (5 pulses at 500 Hz) stimulation. All patients presented with both high-pitched pure tone and white noise components in their tinnitus. RESULTS A significantly better suppression for narrowband noise tinnitus with burst stimulation in comparison with tonic stimulation (Z = -2.03, p = 0.04) was found. For pure tone tinnitus, no difference was found between tonic and burst stimulation (Z = -0.58, p = 0.56). No significant effect was obtained for stimulation amplitude (Z = -1.21, p = 0.23) and electrical charge per pulse (Z = -0.67, p = 0.50) between tonic and burst stimulation. The electrical current delivery per second was significantly different (Z = -2.02, p = 0.04). CONCLUSIONS Burst stimulation is a new form of neurostimulation that might be helpful in treating symptoms that are intractable to conventional tonic stimulation. Further exploration of this new stimulation design is warranted.

Repetitive transcranial magnetic stimulation frequency dependent tinnitus improvement by double cone coil prefrontal stimulation

Background A double cone coil (DCC) with large angled windings has been developed to modulate deeper brain areas such as the dorsal and subcallosal anterior cingulate cortex. Methods Seventy-eight tinnitus patients received transcranial magnetic stimulation (TMS) using a DCC placed over the dorsal frontal cortex. Treatment effects were assessed with visual analogue scale for intensity and distress. Results The results showed that 1 and 3 Hz of DCC frontal TMS can improve both tinnitus intensity and tinnitus distress, 5 Hz is equal to sham and 20 Hz is significantly worse than sham. Of the 78 tinnitus patients, 52 had no control response. Of these 52 placebo negative participants, 21 showed no suppressive response to stimulation and 31 patients were TMS responders. For this latter group, mean transient tinnitus suppression was obtained in 34.38% for tinnitus intensity and in 26% for tinnitus related distress. Conclusion Frontal TMS using a DCC is capable of suppressing tinnitus transiently dependent on the repetitive TMS frequency used. These data further support the idea that non-auditory areas are involved in tinnitus intensity and tinnitus distress modulation.

Dorsolateral Prefrontal Cortex Transcranial Magnetic Stimulation and Electrode Implant for Intractable Tinnitus

OBJECTIVE Tinnitus is a distressing symptom that affects up to 15% of the population; no satisfactory treatment exists. We present a novel surgical approach for the treatment of intractable tinnitus based on electrical extradural stimulation of the dorsolateral prefrontal cortex via an electrode implant. Tinnitus can be considered an auditory phantom phenomenon similar to deafferentation pain in the somatosensory system. It is characterized by gamma-band activity in the frontal cortex that can be visualized with the use of electroencephalography, magnetoencephalography, and functional magnetic resonance imaging (fMRI). CASE DESCRIPTION Transcranial magnetic stimulation (TMS) is a noninvasive technique capable of modulating the ongoing activity of the human brain. When linked with a neuronavigation system, fMRI-guided frontal cortex TMS can be performed in a placebo-controlled way. If it is successful in suppressing tinnitus, this focal and temporary effect can be maintained in perpetuity by implanting a cortical electrode. A neuronavigation-based auditory fMRI-guided frontal cortex TMS session was performed in a patient experiencing intractable tinnitus, yielding 50% tinnitus suppression. Two extradural electrodes were subsequently implanted, also based on auditory fMRI-guided navigation. Postoperatively the tinnitus has improved by 66.67% and progressively continues to improve for more than one year. CONCLUSION Focal extradural electrical stimulation of the dorsolateral prefrontal cortex at the area of cortical plasticity is capable of suppressing contralateral tinnitus partially. TMS might be a possible method for noninvasive studies of surgical candidates for implantation of stimulating electrodes for tinnitus suppression.