Concomitant lorazepam use and antidepressive efficacy of repetitive transcranial magnetic stimulation in a naturalistic setting.

BACKGROUND/OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) has been established as an effective therapeutic intervention for the treatment of depression. Preliminary data suggest that the efficacy of rTMS is reduced in patients taking benzodiazepines (BZD). Here, we use real-world data from a large sample to investigate the influence of lorazepam on the effectiveness of rTMS. METHODS: From a retrospective cohort of clinically depressed patients that were treated with rTMS, we compared 176 patients not taking any BZD with 73 patients taking lorazepam with respect to changes in the Hamilton Depression Rating Scale (HRDS). RESULTS: Both groups improved during rTMS according to HRDS scores, but the amelioration of symptoms was significantly less pronounced in patients taking lorazepam (18% vs. 38% responders in the non-lorazepam group). We could not see any association of intake regimen of lorazepam with response in rTMS. CONCLUSION: Our observational study suggests that intake of lorazepam impedes the response to rTMS. The impact of lorazepam and other BZD on rTMS should receive more attention and be further investigated in prospective, hypothesis-based treatment studies to determine causal relationships between medication treatments and outcome. This could lead to specific recommendations for pharmacological treatment for depressed patients undergoing rTMS.

Antidepressant effect of repetitive transcranial magnetic stimulation is not impaired by intake of lithium or antiepileptic drugs.

INTRODUCTION: The effect of concomitant medication on repetitive transcranial magnetic stimulation (rTMS) outcomes in depression remains understudied. Recent analyses show attenuation of rTMS effects by antipsychotic medication and benzodiazepines, but data on the effects of antiepileptic drugs and lithium used as mood stabilizers or augmenting agents are sparse despite clinical relevance. Preclinical electrophysiological studies suggest relevant impact of the medication on treatment, but this might not translate into clinical practice. We aimed to investigate the role of lithium (Li), lamotrigine (LTG) and valproic acid (VPA) by analyzing rTMS treatment outcomes in depressed patients. METHODS: 299 patients with uni- and bipolar depression treated with rTMS were selected for analysis in respect to intake of lithium, lamotrigine and valproic acid. The majority (n = 251) were treated with high-frequency (10-20 Hz) rTMS of the lDLPFC for an average of 17 treatment sessions with a figure-of-8 coil with a MagVenture system aiming for 110% resting motor threshold, and smaller groups of patients were being treated with other protocols including intermittent theta-burst stimulation and bilateral prefrontal and medial prefrontal protocols. For group comparisons, we used analysis of variance with the between-subjects factor group or Chi-Square Test of Independence depending on the scales of measurement. For post-hoc tests, we used least significant difference (LSD). For differences in treatment effects between groups, we used an ANOVA with the between-subjects factor group (groups: no mood stabilizer, Li, LTG, VPA, Li + LTG) the within-subjects factor treatment (pre vs. post treatment with rTMS) and also Chi-Square Tests of independence for response and remission. RESULTS: Overall, patients showed an amelioration of symptoms with no significant differences for the main effect of group and for the interaction effect treatment by group. Based on direct comparisons between the single groups taking mood stabilizers against the group taking no mood stabilizers, we see a superior effect of lamotrigine, valproic acid and combination of lithium and lamotrigine for the response and remission rates. Motor threshold was significantly and markedly higher for patients taking valproic acid. CONCLUSION: Being treated with lithium, lamotrigine and valproic acid had no relevant influence on rTMS treatment outcome. The results suggest there is no reason for clinicians to withhold or withdraw these types of medication from patients who are about to undergo a course of rTMS. Prospective controlled work on the subject is encouraged.

Structural brain changes are associated with response of negative symptoms to prefrontal repetitive transcranial magnetic stimulation in patients with schizophrenia.

Impaired neural plasticity may be a core pathophysiological process underlying the symptomatology of schizophrenia. Plasticity-enhancing interventions, including repetitive transcranial magnetic stimulation (rTMS), may improve difficult-to-treat symptoms; however, efficacy in large clinical trials appears limited. The high variability of rTMS-related treatment response may be related to a comparably large variation in the ability to generate plastic neural changes. The aim of the present study was to determine whether negative symptom improvement in schizophrenia patients receiving rTMS to the left dorsolateral prefrontal cortex (DLPFC) was related to rTMS-related brain volume changes. A total of 73 schizophrenia patients with predominant negative symptoms were randomized to an active (n=34) or sham (n=39) 10-Hz rTMS intervention applied 5 days per week for 3 weeks to the left DLPFC. Local brain volume changes measured by deformation-based morphometry were correlated with changes in negative symptom severity using a repeated-measures analysis of covariance design. Volume gains in the left hippocampal, parahippocampal and precuneal cortices predicted negative symptom improvement in the active rTMS group (all r⩽-0.441, all P⩽0.009), but not the sham rTMS group (all r⩽0.211, all P⩾0.198). Further analyses comparing negative symptom responders (⩾20% improvement) and non-responders supported the primary analysis, again only in the active rTMS group (F(9, 207)=2.72, P=0.005, partial η 2=0.106). Heterogeneity in clinical response of negative symptoms in schizophrenia to prefrontal high-frequency rTMS may be related to variability in capacity for structural plasticity, particularly in the left hippocampal region and the precuneus.

[On the interdisciplinary S3 guidelines for the treatment of chronic idiopathic tinnitus]. / Zur interdisziplinären S3-Leitlinie für die Therapie des chronisch-idiopathischen Tinnitus.

INTRODUCTION: Tinnitus is a frequent symptom, which, particularly in combination with comorbidities, can result in a severe disease-related burden. Chronic idiopathic tinnitus (CIT) is the most frequent type of tinnitus. A considerable number of treatment strategies are used to treat CIT-for many of which there is no evidence of efficacy. In order to enable scientific evidence-based treatment of CIT, German interdisciplinary S3 guidelines have recently been constructed for the first time. Here we present a short form of these S3 guidelines. MATERIALS AND METHODS: The guidelines were constructed based on a meta-analysis of the treatment of chronic tinnitus performed by the authors. Additionally, a systematic literature search was performed in the PubMed and Cochrane Library databases. Furthermore, a systematic search for international guidelines was performed in Google, as well as in the Guidelines International Network and National Guideline Clearinghouse (USA) database. Evidence was classified according to the Oxford Centre for Evidence-Based Medicine system. RESULTS: According to the guidelines, alongside counselling, manualized structured tinnitus-specific cognitive behavioral therapy (tCBT) with a validated treatment manual is available as evidence-based therapy. In addition, the guidelines recommend concurrent treatment of comorbidities, including drug-based treatment, where appropriate. Particularly important is treatment of anxiety and depression. Where a psychic or psychiatric comorbidity is suspected, further diagnosis and treatment should be performed by an appropriately qualified specialist (psychiatrist, neurologist, psychosomatic medicine consultant) or psychological psychotherapist. In cases accompanied by deafness or hearing loss bordering on deafness, cochlear implants may be indicated. CONCLUSION: No recommendations can be made for drug-based treatment of CIT, audiotherapy, transcranial magnetic or electrical stimulation, specific forms of acoustic stimulation or music therapy; or such recommendations must remain open due to the lack of available evidence. Polypragmatic tinnitus treatment with therapeutic strategies for which there is no evidence of efficacy from controlled studies is to be refused.

Left prefrontal intermittent theta burst stimulation ameliorates tinnitus distress and symptoms of depression - A feasibility study.

Tinnitus remains a notoriously difficult to treat clinical entity. 1-2% of the entire population report relevant emotional distress due to tinnitus, and causal treatments are lacking. Repetitive transcranial magnetic stimulation (rTMS), most commonly of auditory cortical areas, has shown mixed results in the past. Prefrontal rTMS, including intermittent theta burst stimulation (iTBS) has shown more promising results in the treatment of depression, and clinical data suggests a meaningful overlap between tinnitus and depression. Therefore, we performed a feasibility study of 28 consecutive patients with tinnitus treated with an iTBS protocol over the left dorsolateral prefrontal cortex for three weeks. After treatment, we observed significant ameliorations of tinnitus distress as measured by the Tinnitus Handicap Inventory Questionnaire (THI), the Tinnitus Functional Index (TFI), the Mini-Tinnitus Questionnaire (Mini-TQ) and also of depression as measured by the Major Depression Inventory (MDI). Effect sizes were small to moderate and short-lived. Treatment response rates, defined as improvement of the THI of at least 7 points, were 35.7%. At follow-up twelve weeks after end of treatment, severity of tinnitus and depression returned to approximately baseline level on a descriptive level. Amelioration of depressive symptoms correlated only with TFI change, but not that of other measures of tinnitus distress. The data suggest that a prefrontal iTBS protocol might be applied in the treatment of tinnitus and open avenues for future neurostimulatory treatments other than those of auditory regions.

Treatment of depression and borderline personality disorder with 1 Hz repetitive transcranial magnetic stimulation of the orbitofrontal cortex - A pilot study.

Borderline personality disorder (BPD) is characterised by impairments in emotional regulation, impulse control and interpersonal interaction. Comorbid depression is common. The orbitofrontal cortex (OFC) plays a crucial role in the biological substrate of BPD. We investigated the effects of 1 Hz repetitive transcranial magnetic stimulation (rTMS) targeting the OFC on depressive symptoms and symptoms of BPD in 15 patients suffering from both conditions to assess feasibility and effectiveness. Target treatment intensity was 120% of resting motor threshold (RMT) and intended duration four weeks. Treatment improved both symptoms of depression as measured by the Hamilton Depression Rating Scale and of BPD as measured by Borderline Symptom List-23 and Barratt Impulsivity Scale. Drop-out rates were high with 7/15 patients not completing the full course of rTMS, but only two drop-outs were related to treatment. Only a minority of patients tolerated target treatment intensity. Despite the limitations, the results suggest efficacy of treatment and welcome further research.

Effect of 1 Hz repetitive transcranial magnetic stimulation over the auditory cortex on audiometry and otoacustic emissions.

Repetitive transcranial magnetic stimulation (rTMS) at low frequencies (≤1 Hz) delivered to the primary motor cortex for 15 min or longer has been shown to reduce motor cortex excitability. Over the visual cortex, 1 Hz rTMS led to increased phosphene thresholds and over the auditory cortex rTMS reduced auditory evoked potentials. rTMS above the auditory or temporo-parietal cortex has also been reported to reduce the severity of auditory hallucinations and the perception of tinnitus. However, possible unwanted effects on hearing function have not yet been investigated systematically. 12 right-handed normal hearing subjects (5 male, mean age 28.2 ± 4.3) received a single session of 18 min 1 Hz rTMS at 90% resting motor threshold intensity using an established coil positioning method targeting the Heschl's area of the left superior temporal gyrus. Standard pure tone audiometry and distortion-products otoacustic emissions (DPOAE) were performed before and immediately after stimulation. The main finding was that one session of 1 Hz rTMS over the temporal cortex modified neither the auditory threshold meaningfully nor the presence of DPOAE in healthy subjects. In conclusion, we found in this pilot approach no obvious indication for auditory dysfunctions due to direct electromagnetic stimulation of the superior temporal gyrus after one session of rTMS in healthy controls that may be interpreted as unwanted side effects. Nevertheless monitoring of auditory functions is strongly recommended in future clinical trials stimulating the auditory cortex, as this has not been done systematically in the past.

Surgical brain modulation for tinnitus: the past, present and future.

Tinnitus treatment has traditionally been restricted to ENT surgeons, audiologists, psychologists and psychiatrists. Recently, both basic and clinical research has focused on the brain's involvement in the generation of tinnitus, opening the tinnitus field up to neurologists and neurosurgeons specialized in the field of tinnitus. Non-pulsatile tinnitus can be considered an auditory phantom phenomenon, analogous to phantom pain, both with regards to pathophysiological mechanisms, clinical characteristics, and treatment approaches. Thus the understanding of tinnitus has benefited a lot from translating available knowledge of the somatosensory (pain) system to the auditory system. A literature review of neuromodulatory approaches to tinnitus is integrated in a single center's experience with invasive neuromodulation treatments for tinnitus. This is compared to findings from neuromodulatory treatment of chronic pain syndromes. The past, present and future options for functional neurosurgical approaches are outlined. In the past only destructive approaches were used, consisting of nerve lesions and frontal lobotomies. Presently neurostimulation trials are ongoing evaluating the effect of auditory cortex stimulation, frontal cortex stimulation, thalamic (VIM) and caudate stimulation as well as amygdalohippocampal stimulation, yielding suppression rates between 10 and 70%. Further potentially promising targets include the anterior cingulate, the medial geniculate bodies (MGB), the periaqueductal gray/ tectal longitudinal column (PAG/TLC), the dorsal cochlear nucleus, as well as the C2 and trigeminal nerve. Understanding tinnitus and its potential neuromodulation treatments is relatively simple for a neurosurgeon specialized in pain or a pain physician, based on the pathophysiological and clinical analogies. Similarly to pain a multidisciplinary approach can be advocated, and in view of the epidemiology and amount of suffering associated with this enigmatic symptom further investment in possible neuromodulation treatments is warranted.

[Hypothermia under olanzapine treatment: clinical case series and review of current literature]. / Hypothermie unter Olanzapin : Eine Fallserie mit Literaturübersicht.

BACKGROUND: Antipsychotic drugs may lead to hypothermia as well as hyperthermia. Although known for decades and clinically highly relevant, the mechanisms by which antipsychotic drugs alter thermoregulatory processes in the human body are still far from being fully understood. In clinical practice, much attention is paid to antipsychotic drug-induced elevation of body core temperature as observed in the neuroleptic malignant syndrome (NMS). But also hypothermia is a clinically highly relevant adverse reaction to antipsychotic drugs. MATERIAL AND METHODS: Here we report a case series of three patients who developed severe hypothermia after administration of olanzapine. A review of the current literature is given with a focus on risk factors for the development of antipsychotic drug-induced hypothermia and its pathophysiologic mechanisms. RESULTS: A 51-year-old female patient suffering from catatonic schizophrenia, cachectic nutritional condition and hypothyroidism developed severe hypothermia of 30.0°C body core temperature after administration of 30 mg olanzapine per day under comedication with lorazepam and L-thyroxine. A 48-year-old female patient with catatonic schizophrenia showed hypothermia of 31.0°C (rectal measurement) after single-dose administration of olanzapine 10 mg orally and a total of 3 mg lorazepam (1-1-1 mg). The third case report describes a 69-year-old male patient with acute delusional disorder exhibiting hypothermia of 33.0°C (rectal measurement) in combination with a reversible atrioventricular block grade III without any further comedication. CONCLUSION: A review of the current literature reveals that thermoregulatory disturbances as sequelae of antipsychotic drug administration depend on individual disposition as well as various independent risk factors such as environmental temperature, somatic comorbidities, endocrinological abnormalities (e.g. hypothyroidism) and structural damage of the brain. A complex interaction of dopaminergic regulatory mechanisms in the ventral hypothalamus and peripheral vaso- and sudomotor adjustments seems to be causative. Hypothermia following antipsychotic drug administration represents a serious adverse drug reaction and a potentially life-threatening event.

Rationale and study design of a trial to assess rTMS add-on value for the amelioration of negative symptoms of schizophrenia (RADOVAN).

BACKGROUND: Schizophrenia is a severe and often difficult to treat psychiatric illness. In many patients, negative symptoms dominate the clinical picture. Meta-analysis has suggested moderate, but significant effects of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on these symptoms. For treatment of depression a much shorter protocol - intermittent theta burst stimulation (iTBS) - has shown to be non-inferior to conventional high-frequency rTMS. This randomized, sham-controlled, rater-blinded clinical trial assesses the effects of conventional HF-rTMS as well as of iTBS of the left dorsolateral prefrontal cortex in comparison with sham. METHODS: The study will be conducted at two psychiatric university hospitals in Germany and at two in the Czech Republic. Assuming an effect size of 0.64 to be detected with a power of 80%, the calculated sample size is 90 patients. Primary outcome will be the difference in the Scale for the Assessment of Negative Symptoms (SANS) score between each active arm and the sham arm at end of treatment.In addition, the trial investigates effects on depressive symptoms, cognitive performance and cigarette smoking. Recording magnetic resonance imaging (MRI) and electroencephalography (EEG) data will serve to assess whether treatment success can be predicted by neural markers and is related to specific neurobiological changes. DISCUSSION: This is a clinical trial directly comparing 10 Hz-rTMS and iTBS in a sham-controlled manner in treating negative symptoms of schizophrenia. If successful, this would present an interesting treatment option for a chronic and severe condition that can be applied at most psychiatric hospitals and only takes up a few minutes per day. TRIAL REGISTRATION NUMBER: This trial has been registered at clinicaltrials.gov, Identifier: NCT04318977. DATA DISSEMINATION: Results from the trial shall be published in peer-reviewed journals and presented at meetings and conferences.

Neurophysiological correlates of residual inhibition in tinnitus: Hints for trait-like EEG power spectra.

OBJECTIVE: To investigate oscillatory brain activity changes following acoustic stimulation in tinnitus and whether these changes are associated with behavioral measures of tinnitus loudness. Moreover, differences in ongoing brain activity between individuals with and without residual inhibition (RI) are examined (responders vs. non-responders). METHODS: Three different types of noise stimuli were administered for acoustic stimulation in 45 tinnitus patients. Subjects resting state brain activity was recorded before and after stimulation via EEG alongside with subjective measurements of tinnitus loudness. RESULTS: Delta, theta and gamma band power increased, whereas alpha and beta power decreased from pre to post stimulation. Acoustic stimulation responders exhibited reduced gamma and a trend for enhanced alpha activity with the latter localized in the right inferior temporal gyrus. Post stimulation, individuals experiencing RI showed higher theta, alpha and beta power with a peak power difference in the alpha band localized in the right superior temporal gyrus. Neither correlations with behavioral tinnitus measures nor stimulus-specific changes in EEG activity were present. CONCLUSIONS: Our observations might be indicative of trait-specific forms of oscillatory signatures in different subsets of the tinnitus population related to acoustic tinnitus suppression. SIGNIFICANCE: Results and insights are not only useful to understand basic neural mechanisms behind RI but are also valuable for general neural models of tinnitus.

Transcranial Direct Current Stimulation (tDCS) for major depression - Interim analysis of cloud supervised technical data from the DepressionDC trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) of prefrontal cortex regions has been reported to exert antidepressant effects, though large scale multicenter trials in major depressive disorder (MDD) supporting this notion are still lacking. Application of tDCS in multicenter settings, however, requires measurement, storage and evaluation of technical parameters of tDCS sessions not only for safety reasons but also for quality control. To address this issue, we conducted an interim analysis of supervised technical data across study centers in order to monitor technical quality of tDCS in an ongoing multicenter RCT in MDD (DepressionDC trial). METHODS: Technical data of 818 active tDCS sessions were recorded, stored in a data cloud, and analysed without violating study blinding. Impedance, voltage and current were monitored continuously with one data point recorded every second of stimulation. RESULTS: Variability of impedance was considerable (1,42 kΩ, to 8,23 kΩ), inter-individually and even more intra-individually, but did not significantly differ between the study centre in Munich and all other sites. CONCLUSION: Measurement, centralized data storage via data cloud and remote supervision of technical parameters of tDCS are feasible and proposed for future RCTs on therapeutic tDCS in multiple settings.

Repetitive transcranial magnetic stimulation improve tinnitus in normal hearing patients: a double-blind controlled, clinical and neuroimaging outcome study.

BACKGROUND AND PURPOSE: Tinnitus is a frequent disorder which is very difficult to treat and there is compelling evidence that tinnitus is associated with functional alterations in the central nervous system. Targeted modulation of tinnitus-related cortical activity has been proposed as a promising new treatment approach. We aimed to investigate both immediate and long-term effects of low frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) in patients with tinnitus and normal hearing. METHODS: Using a parallel design, 20 patients were randomized to receive either active or placebo stimulation over the left temporoparietal cortex for five consecutive days. Treatment results were assessed by using the Tinnitus Handicap Inventory. Ethyl cysteinate dimmer-single photon emission computed tomography (SPECT) imaging was performed before and 14 days after rTMS. RESULTS: After active rTMS there was significant improvement of the tinnitus score as compared to sham rTMS for up to 6 months after stimulation. SPECT measurements demonstrated a reduction of metabolic activity in the inferior left temporal lobe after active rTMS. CONCLUSION: These results support the potential of rTMS as a new therapeutic tool for the treatment of chronic tinnitus, by demonstrating a significant reduction of tinnitus complaints over a period of at least 6 months and significant reduction of neural activity in the inferior temporal cortex, despite the stimulation applied on the superior temporal cortex.

Left temporal low-frequency rTMS for the treatment of tinnitus: clinical predictors of treatment outcome--a retrospective study.

BACKGROUND: There is increasing evidence that repetitive transcranial magnetic stimulation (rTMS) can reduce chronic tinnitus. However, treatment results are characterized by high interindividual variability. Therefore, the identification of predictors for treatment response is of high clinical relevance. METHODS: Clinical data of 194 patients with tinnitus were evaluated. All patients were treated with a standardized rTMS procedure (1 Hz, 10 days, 2000 stimuli/day, over the left temporal cortex). A potential influence on the outcome was analysed for the following parameters: age, gender, depression scores in Beck Depression Inventory (BDI) and tinnitus severity (TQ) before rTMS, lateralization, frequency and duration of tinnitus and extent of hearing loss. RESULTS: An effect of tinnitus laterality was observed. In patients with left-sided or bilateral tinnitus, rTMS resulted in a statistically significant reduction of TQ scores, whereas patients with right-sided tinnitus did not show a significant improvement after rTMS treatment. However, in correlation analyses, we found a trend which did not reach statistical significance that in the subgroup of treatment responders tinnitus duration influenced rTMS outcome. In addition, a multiple regression analysis identified the TQ score at baseline as a significant predictor for treatment outcome. For all other investigated parameters, no statistically significant effects were found. CONCLUSIONS: This study suggests that left temporal low-frequency rTMS has beneficial effects in left-sided and bilateral tinnitus, but not in right-sided tinnitus. In line with the results from earlier studies involving smaller samples, tinnitus duration was found to influence rTMS outcome.

[Cortical plasticity and changes in tinnitus: treatment options]. / Kortikale Plastizität und Veränderungen bei Tinnitus: Therapeutische Optionen.

A growing consensus in current tinnitus research suggests central nervous changes as the cause of tinnitus. Several animal and human experimental studies were able to show altered tonotopic representations as well as spontaneous activity in the auditory cortex. However, a causal relationship between altered neurophysiological processes and aspects of tinnitus are still missing. Furthermore, it is likely that the importance of diverse processes changes with continuing duration of tinnitus. These open questions complicate the development of effective treatments. Nevertheless, today several neuroscientifically motivated treatments are available, or treatments that can be integrated into a neuroscientific framework. This article gives an overview of current neuroscientific developments in tinnitus research and discusses their implications for the treatment of tinnitus.

Repetitive transcranial magnetic stimulation for the treatment of negative symptoms in residual schizophrenia: rationale and design of a sham-controlled, randomized multicenter study.

Current meta-analysis revealed small, but significant effects of repetitive transcranial magnetic stimulation (rTMS) on negative symptoms in patients with schizophrenia. There is a need for further controlled, multicenter trials to assess the clinical efficacy of rTMS on negative symptoms in schizophrenia in a larger sample of patients. The objective of this multicenter, randomized, sham-controlled, rater- and patient-blind clinical trial is to investigate the efficacy of 3-week 10-Hz high frequency rTMS add on to antipsychotic therapy, 15 sessions per 3 weeks, 1,000 stimuli per session, stimulation intensity 110% of the individual motor threshold) of the left dorsolateral prefrontal cortex for treating negative symptoms in schizophrenia, and to evaluate the effect during a 12 weeks of follow-up. The primary efficacy endpoint is a reduction of negative symptoms as assessed by the negative sum score of the positive and negative symptom score (PANSS). A sample size of 63 in each group will have 80% power to detect an effect size of 0.50. Data analysis will be based on the intention to treat population. The study will be conducted at three university hospitals in Germany. This study will provide information about the efficacy of rTMS in the treatment of negative symptoms. In addition to psychopathology, other outcome measures such as neurocognition, social functioning, quality of life and neurobiological parameters will be assessed to investigate basic mechanisms of rTMS in schizophrenia. Main limitations of the trial are the potential influence of antipsychotic dosage changes and the difficulty to ensure adequate blinding.

Modulating cerebello-thalamocortical pathways by neuronavigated cerebellar repetitive transcranial stimulation (rTMS).

OBJECTIVES: Increasing evidence suggests that dysfunctions of the cortico-cerebello-thalamocortical circuit are involved in the pathophysiology of neuropsychiatric disorders. This study explores the effects of cerebellar repetitive transcranial magnetic stimulation (rTMS) on cerebello-thalamocortical pathways. METHODS: Ten healthy volunteers received MRI-guided rTMS in four separate sessions (120% motor threshold, 1000 stimuli) over either the medial or the right lateral cerebellum using frequencies of 1 and 10 Hz. Motor cortex excitability was assessed before and after the intervention by paired-pulse transcranial magnetic stimulation. RESULTS: Depending on stimulation frequency, cerebellar rTMS differentially modified intracortical inhibition. Low frequency rTMS increased short intracortical inhibition (SICI), whereas high frequency rTMS had no significant effect on SICI. CONCLUSIONS: These results suggest that rTMS over the cerebellum can modulate cerebello-thalamocortical pathways in a frequency-specific manner.

Genetics of chronic tinnitus.

Susceptibility to chronic tinnitus is highly variable and of particular interest when it comes to defining strategies for prevention and treatment. While several rare monogenic disorders have been described that are associated with tinnitus, the genetic underpinnings of the more common forms of the syndrome are still poorly understood. The present article incorporates recent advancements in the field, including the epidemiology of tinnitus in subjects with neuropsychiatric illness, and highlights pilot studies of candidate genes.

Transcranial magnetic stimulation (TMS) for treatment of chronic tinnitus: clinical effects.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method used to induce electrical current in the brain through impulses of strong magnetic fields applied externally. The technique can relieve tinnitus by modulating the excitability of neurons in the auditory cortex to decrease the hyperexcitability that is associated with generating the neural activity that causes some form of tinnitus. This chapter will review clinical studies using rTMS for the treatment of tinnitus.

Functional imaging of chronic tinnitus: the use of positron emission tomography.

Recent advances in functional imaging have opened new possibilities for understanding tinnitus. Especially, positron emission tomography (PET) has been increasingly used in the last two decades to identify cortical networks, which are involved in the generation of various forms of chronic tinnitus. PET studies have confirmed that the anatomical location of the anomalies that cause many forms of tinnitus are regions of the brain that are normally involved in auditory processing as well as regions engaged in emotional processing. These findings have contributed to the development of new more causally oriented treatment strategies. In particular, identification of increased activity of the auditory cortex by PET has prompted the use of focal brain stimulation techniques such as electrical or transcranial magnetic stimulation in treatment of tinnitus. PET studies that map distinct neurochemical pathways and receptors by the use of specific ligands may in the future provide new possibilities for pharmacologically based treatment of some forms of tinnitus.