Silvia Kovacs

Primary and Secondary Auditory Cortex Stimulation for Intractable Tinnitus

Introduction: Recent research suggests tinnitus is a phantom phenomenon based on hyperactivity of the auditory system, which can be visualized by functional neuroimaging, and transiently modulated by transcranial magnetic stimulation (TMS). We present the results of the first implanted electrodes on the primary and secondary auditory cortex after a successful TMS suppression. Methods and Materials: Twelve patients underwent an auditory cortex implantation, 10 for unilateral and 2 for bilateral tinnitus, based on >50% suppression applying TMS. Results were analyzed for pure tone tinnitus and white noise tinnitus. Results: TMS results in 77% pure tone tinnitus and 67% white noise reduction. Electrical stimulation via an implanted electrode results in a mean of 97% pure tone tinnitus and 24% white noise suppression. Mean Visual Analogue Scale score decreases from 9.5 to 1.5 for pure tone and from 8.8 to 6.8 for white noise postoperatively. Discussion: Pure tone tinnitus might be the conscious percept of focal neuronal hyperactivity of the auditory cortex. Once visualized, this hyperactivity can be modulated by neurostimulation. Conclusion: The preliminary results of the first implantations suggest that patients with unilateral pure tone tinnitus are good surgical candidates for electrode implantation and permanent electrical stimulation of the auditory cortex, provided that the tinnitus is of recent origin and can be suppressed by TMS.

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.

Electrical stimulation of auditory and somatosensory cortices for treatment of tinnitus and pain.

The efficacy of electrical stimulation of the auditory cortex using extradural implanted electrodes for treatment of tinnitus was studied in 12 patients suffering tinnitus. The effect of similar stimulation of the somatosensory cortex for treatment of neuropathic pain was studied in five patients. It was shown that patients with pure tone type of tinnitus experienced a significant 97% suppression on average while those who had noise type tinnitus only had non-significant 24% suppression. All patients with pain experienced a significant reduction of their pain (using a visual analog scale), and in four out of five it was clinically relevant, i.e., the patient is really helped by it. It is concluded that electrical stimulation of sensory cortices can be effective treatments of severe unilateral tinnitus and unilateral neuropathic pain in selected patients. The results suggest that similar pathophysiological mechanisms underlie some forms of these phantom sensations, and therefore, similar treatment such as electrical stimulation of the respective sensory cortices can suppress tinnitus and pain.

Auditory cortex stimulation for tinnitus.

Functional imaging techniques have demonstrated a relationship between the intensity of tinnitus and the degree of reorganization of the primary auditory cortex. Studies in experimental animals and humans have revealed that tinnitus is associated with a synchronized hyperactivity in the auditory cortex and proposed that the underlying pathophysiological mechanism is thalamocortical dysrhythmia; hence, decreased auditory stimulation results in decreased firing rate, and decreased lateral inhibition. Consequently, the surrounding brain area becomes hyperactive, firing at gamma band rates; this is considered a necessary precondition of auditory consciousness, and also tinnitus. Synchronization of the gamma band activity could possibly induce a topographical reorganization based on Hebbian mechanisms. Therefore, it seems logical to try to suppress tinnitus by modifying the tinnitus-related auditory cortex reorganization and hyperactivity. This can be achieved using neuronavigation-guided transcranial magnetic stimulation (TMS), which is capable of modulating cortical activity. If TMS is capable of suppressing tinnitus, the effect should be maintained by implanting electrodes over the area of electrophysiological signal abnormality on the auditory cortex. The results in the first patients treated by auditory cortex stimulation demonstrate a statistically significant tinnitus suppression in cases of unilateral pure tone tinnitus without suppression of white or narrow band noise. Hence, auditory cortex stimulation could become a physiologically guided treatment for a selected category of patients with severe tinnitus.

Transcranial magnetic stimulation and extradural electrodes implanted on secondary auditory cortex for tinnitus suppression

OBJECT Tinnitus is a prevalent symptom, with clinical, pathophysiological, and treatment features analogous to pain. Noninvasive transcranial magnetic stimulation (TMS) and intracranial auditory cortex stimulation (ACS) via implanted electrodes into the primary or overlying the secondary auditory cortex have been developed to treat severe cases of intractable tinnitus. METHODS A series of 43 patients who benefited transiently from 2 separate placebo-controlled TMS sessions underwent implantation of auditory cortex electrodes. Targeting was based on blood oxygen level-dependent activation evoked by tinnitus-matched sound, using functional MR imaging-guided neuronavigation. RESULTS Thirty-seven percent of the patients responded to ACS with tonic stimulation. Of the 63% who were nonresponders, half benefited from burst stimulation. In total, 33% remained unaffected by the ACS. The average tinnitus reduction was 53% for the entire group. Burst stimulation was capable of suppressing tinnitus in more patients and was better than tonic stimulation, especially for noise-like tinnitus. For pure tone tinnitus, there were no differences between the 2 stimulation designs. The average pure tone tinnitus improvement was 71% versus 37% for noise-like tinnitus and 29% for a combination of both pure tone and noise-like tinnitus. Transcranial magnetic stimulation did not predict response to ACS, but in ACS responders, a correlation (r = 0.38) between the amount of TMS and ACS existed. A patients sex, age, or tinnitus duration did not influence treatment outcome. CONCLUSIONS Intracranial ACS might become a valuable treatment option for severe intractable tinnitus. Better understanding of the pathophysiological mechanisms of tinnitus, predictive functional imaging tests, new stimulation designs, and other stimulation targets are needed to improve ACS results.

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.

Activation of cortical and subcortical auditory structures at 3 T by means of a functional magnetic resonance imaging paradigm suitable for clinical use

Objectives:Visualization of functional magnetic resonance imaging (fMRI) activation of subcortical auditory structures remains challenging because of the cardiac-related pulsatile movement of both the brainstem and the cerebrospinal fluid and involved, until now, special scanning, pre- and postprocessing techniques, which are not convenient in clinical settings. The aim of this study is to examine the activation in both cortical and subcortical auditory structures by means of an fMRI paradigm, which is suitable for clinical use. Materials and Methods:Twenty subjects (13 volunteers and 7 patients) were examined on a 3 T imaging system with binaural musical stimulation. Results:Both cortical and subcortical auditory structures are successfully visualized in volunteers and patients. Conclusions:Activation of both the cortical and subcortical auditory structures can be visualized by means of an appropriate fMRI setup at 3 T. This paradigm can easily be used in patients with tumors and/or hearing disorders.

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.

Central Effects of Occipital Nerve Electrical Stimulation Studied by Functional Magnetic Resonance Imaging

Objective:  To study the central effects of occipital nerve stimulation (ONS) using functional magnetic resonance imaging (fMRI).

Resting-State Functional Magnetic Resonance Imaging for Language Preoperative Planning.

Functional magnetic resonance imaging (fMRI) is a well-known non-invasive technique for the study of brain function. One of its most common clinical applications is preoperative language mapping, essential for the preservation of function in neurosurgical patients. Typically, fMRI is used to track task-related activity, but poor task performance and movement artifacts can be critical limitations in clinical settings. Recent advances in resting-state protocols open new possibilities for pre-surgical mapping of language potentially overcoming these limitations. To test the feasibility of using resting-state fMRI instead of conventional active task-based protocols, we compared results from fifteen patients with brain lesions while performing a verb-to-noun generation task and while at rest. Task-activity was measured using a general linear model analysis and independent component analysis (ICA). Resting-state networks were extracted using ICA and further classified in two ways: manually by an expert and by using an automated template matching procedure. The results revealed that the automated classification procedure correctly identified language networks as compared to the expert manual classification. We found a good overlay between task-related activity and resting-state language maps, particularly within the language regions of interest. Furthermore, resting-state language maps were as sensitive as task-related maps, and had higher specificity. Our findings suggest that resting-state protocols may be suitable to map language networks in a quick and clinically efficient way.