UC Berkeley Press Release

Neuro Endocrinol Lett. 2007 Oct 8;28(5)

Pre-treatment anterior cingulate activity as a predictor of antidepressant response to repetitive transcranial magnetic stimulation (rTMS).

Langguth B , Wiegand R , Kharraz A , Landgrebe M , Marienhagen J , Frick U , Hajak G , Eichhammer P .

Department of Psychiatry, Psychosomatics and Psychotherapy, University of Regensburg , Germany . Berthold.Langguth@medbo.de.

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) is a brain stimulation technique which has received increasing attention as an antidepressant treatment. However available studies are characterized by a substantial variability in response. We hypothesized that individual patients' characteristics might contribute to such heterogeneity. Therefore we investigated whether either alterations of regional cerebral blood flow (rCBF) or clinical characteristics may predict antidepressant response to rTMS. DESIGN: 24 patients with major depression and stable medication received high frequency (10 Hz) rTMS over the left dorsolateral prefrontal cortex (DLPFC) for two weeks as add-on treatment. ECD-Single photon emission computed tomographay (SPECT) imaging was performed 1 to 2 days before rTMS. SETTING: Tertial referral center RESULTS: After two weeks of rTMS a mean reduction of 30% of the initial Hamilton Depression Rating Score (HAMD) was observed. Using a multivariate regression model with simultaneous evaluation of the relative impact of a-priori chosen potential factors influencing treatment outcome, two variables, the pretreatment anterior cingulate rCBF and the former response to antidepressant agents proved significant. High pretreatment anterior cingulate activity and low treatment resistance to pharmacologic therapy were positive predictors for treatment response to rTMS. CONCLUSIONS: Pretreatment anterior cingulate activity seems to be a useful prognostic marker of rTMS treatment response, which is in line with other treatment strategies, like sleep deprivation, electroconvulsive therapy or antidepressant medication



Encephale. 2007 Mar-Apr;33(2):126-34.

[Efficacy of repetitive transcranial magnetic stimulation (rTMS) in major depression: a review]

[Article in French]

Brunelin J , Poulet E , Boeuve C , Zeroug-vial H , d'Amato T , Saoud M .

EA 3092, UCBL, Professeur J. Daléry, CH Le Vinatier, 95 boulevard Pinel, 69677 Bron cedex.

INTRODUCTION: In 1985, Barker et al. showed that it was possible to stimulate both nerves and brain using external magnetic stimulation without significant pain. During the past 10 years, therapeutic effects of repeated Transcranial Magnetic Stimulation (rTMS) have been widely studied in psychiatry and its efficacy has been demonstrated in the treatment of major depressive disorders, particularly as an alternative to electroconvulsivotherapy (ECT). Facing the large range of studies, we found necessary to propose an up-to-date review in French of the methodological and therapeutic variations among them. METHOD: Based on an exhaustive consultation of Medline data and the Avery-George-Holtzheimer Database of rTMS Depression-Studies, supplemented by a manual research, only works evaluating the therapeutic efficacy of rTMS on depressive symptoms were retained, excluding all studies exclusively investigating the stimulation parameters or the tolerance as well as case reports. RESULTS: Out the 66 available reports we retained 30 studies. After a description of the main results of these 30 studies, several elements of the 66 will be discussed. Open studies demonstrated that short courses rTMS (5 to 10 sessions) produced a decrease in the mean Hamilton Depression Ratting Scale (HDRS) scores, although significant remission of depression in individuals was rare. Most authors had used high frequency rTMS applied to the left Dorso Lateral Prefrontal Cortex (left DLPFC). However, low frequency rTMS applied to the right DLPFC was also followed by significant reduction of HDRS scores. Parallel arm, double blind versus placebo studies are designed to clarify the therapeutic efficacy of rTMS therapy but conclude in contradicting results. Literature data globally confirms a greater efficacy of rTMS compared to placebo (37% responders in the active group vs 20% in the sham). This efficacy could in fact be even greater because the sham procedure is disputable in most studies. Indeed, positioning rTMS coil at 45 or 90 from the scalp may not represent an accurate sham procedure and the use of real sham coil is to be recommended. Only one study has suggested that associating rTMS and ECT could decrease the number of general anesthesia required. Therapeutic efficacy has been shown by either inhibiting the right DLPFC or by stimulating the left DLPFC, although some patients exhibit paradoxical responses. High frequency rTMS (>5 Hz) increases cortical excitability and metabolism, while low-frequency rTMS stimulation ( 1 Hz) has the opposite effect. Other parameters are: relevant: intensity (from 80 to 110% of motor threshold), total number of stimulations (from 120 to 2 000) and total number of rTMS sessions (from 5 to 20). As suggested in most recent studies, higher-intensity pulses, higher number of stimulation or longer treatment courses may be more effective. Greater responsiveness to rTMS may be predicted by several patients' factors, including the absence of psychosis, younger age and previous response to rTMS therapy. DISCUSSION: Conclusions on these factors and others, such as the importance of anatomically accurate coil placement and the distance from the coil to the brain, await further investigation. Despite heterogeneity of these reports according to methodology and treatment parameters, the antidepressive properties of rTMS now appear obvious, opening interesting prospects, in particular in the treatment of pharmacoresistant major depressive patients and, we hope, administered as adjuvant therapy in non-resistant depression. CONCLUSION: Thus, many questions remain unanswered concerning the optimal stimulation parameters, privileged indications and maintenance sessions. This justifies the development of structured evaluation trials on larger samples.


Prog Brain Res. 2007;166:369-75.

TMS for treatment of chronic tinnitus - neurobiological effects.

Eichhammer P , Kleinjung T , Landgrebe M , Hajak G , Langguth B .

Department of Psychiatry, University of Regensburg , Universitaetsstrasse 84, 93053 Regensburg , Germany .

Results of neurophysiological and neuroimaging studies suggest that some forms of chronic tinnitus can be regarded to be "hyperexcitability syndromes", caused by abnormal focal brain activity. Low frequency repetitive magnetic stimulation (rTMS) is an efficient method to selectively reduce the abnormally increased activity in distinct cortical areas. An increasing amount of clinical data suggest that low frequency rTMS might be an effective therapy that is directed at the cause of some forms of chronic tinnitus. To further explore the underlying neurobiological mechanisms we investigated the effect of rTMS on cortical excitability in healthy human subjects using the protocol, which has been successfully used for the treatment of tinnitus. We determined different parameters of motor cortex excitability (resting motor threshold, RMT; active motor threshold, AMT; short intracortical inhibition, ICI; short intracortical facilitation, ICF; and the duration of the cortical silent period, CSP) before and after 5 days of low frequency rTMS (2000 stimuli/day at 110% of RMT) over the left auditory cortex. Five sessions of low frequency rTMS resulted in a significant prolongation of the CSP. All other signs of cortical excitability that we studied remained unchanged. These findings suggest, that low frequency rTMS may evoke long-term depression (LTD)-like effects resulting in enhancement of subcortical inhibition.

PMID: 17956801 [PubMed - in process]



Otolaryngol Head Neck Surg. 2007 Oct;137(4):589-95.

Which tinnitus patients benefit from transcranial magnetic stimulation?

Kleinjung T , Steffens T , Sand P , Murthum T , Hajak G , Strutz J , Langguth B , Eichhammer P .

Department of Otorhinolaryngology, University of Regensburg , Germany . tobias.kleinjung@klinik.uni-regensburg.de

OBJECTIVES: Chronic tinnitus is associated with hyperactivity of the central auditory system. Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the temporal cortex has been proposed as a treatment for chronic tinnitus. This study determined the factors that predict a beneficial outcome with rTMS treatment. STUDY DESIGN: Forty-five patients with chronic tinnitus underwent 10 sessions of low-frequency rTMS to their left auditory cortex. The treatment outcome was assessed with a tinnitus questionnaire. Therapeutic success was related to the patients' clinical characteristics. RESULTS: A significant reduction in tinnitus complaints occurred after rTMS. In the questionnaire, 40% of the patients improved by five points or more. Treatment responders were characterized by shorter duration of tinnitus complaints and no hearing impairment. CONCLUSION: Tinnitus-related neuroplastic changes might be less pronounced in patients with normal hearing and a short history of complaints. This could explain why those patients benefitted more from rTMS treatment.



J Neurosurg. 2007 Sep;107(3):555-9.

Reduction of intractable deafferentation pain due to spinal cord or peripheral lesion by high-frequency repetitive transcranial magnetic stimulation of the primary motor cortex.

Saitoh Y , Hirayama A , Kishima H , Shimokawa T , Oshino S , Hirata M , Tani N , Kato A , Yoshimine T .

Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita-shi , Japan . neurosaitoh@mbk.nifty.com

OBJECT: The authors previously reported that navigation-guided repetitive transcranial magnetic stimulation (rTMS) of the precentral gyrus relieves deafferentation pain. Stimulation parameters were 10 trains of 10-second 5-Hz TMS pulses at 50-second intervals. In the present study, they used various stimulation frequencies and compared efficacies between two types of lesions. METHODS: Patients were divided into two groups: those with a cerebral lesion and those with a noncerebral lesion. The rTMS was applied to all the patients at frequencies of 1, 5, and 10 Hz and as a sham procedure in random order. The effect of rTMS on pain was rated by patients using a visual analog scale. RESULTS: The rTMS at frequencies of 5 and 10 Hz, compared with sham stimulation, significantly reduced pain, and the pain reduction continued for 180 minutes. A stimulation frequency of 10 Hz may be more effective than 5 Hz, and at 1 Hz was ineffective. The effect of rTMS at frequencies of 5 and 10 Hz was greater in patients with a noncerebral lesion than those with a cerebral lesion. CONCLUSIONS: High-frequency (5- or 10-Hz) rTMS of the precentral gyrus can reduce intractable deafferentation pain, but low-frequency stimulation (at 1 Hz) cannot. Patients with a noncerebral lesion are more suitable candidates for high-frequency rTMS of the precentral gyrus.



Int J Neuropsychopharmacol. 2007 Sep 20;:1-28

A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression.

Loo CK , McFarquhar TF , Mitchell PB .

Black Dog Institute, Sydney , Australia .

There is growing interest worldwide in rTMS as a clinical treatment for depression. Apart from efficacy, its safety as a clinical treatment must be considered before its widespread use can be advocated. All published, sham-controlled rTMS depression trials were reviewed for reported side-effects and outcomes of formal neuropsychological testing. In addition, all reports of seizures occurring with rTMS were reviewed. Other safety concerns (effects on hearing; headache, pain, induced currents in electrical circuits, histotoxicity, electromagnetic field exposure, psychiatric complications, safety in pregnancy) are discussed. Common side-effects were of a minor nature, e.g. headache. There was a low incidence of accidental seizures and induced hypomania, both of which were associated with identified risk factors for which subjects should be screened. Long-term effects of repeated rTMS sessions are as yet unknown. When given within recommended guidelines, the overall safety profile of rTMS is good, and supports its further development as a clinical treatment.



Arq Neuropsiquiatr. 2007 Sep;65(3A):697-9.

Relief of primary cervical dystonia symptoms by low frequency transcranial magnetic stimulation of the premotor cortex: case report.

Allam N , Brasil-Neto JP , Brandão P , Weiler F , Barros Filho J , Tomaz C .

Laboratório de Neurociências e Comportamento, Departamento de Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade de Brasília, 70919-970 Brasília, DF, Brazil.

OBJECTIVE: To evaluate the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) on the symptoms of a patient with primary segmental dystonia (PSD). METHOD: 1200 TMS pulses at a frequency of 1Hz, over the premotor cortex, with an intensity of 90% of the motor threshold (MT), using an eight-shaped coil; a total of 5 sessions were carried out. RESULTS: A reduction of 50 percent in the neck subset of the Burke, Fahn and Marsden torsion dystonia scale (BFM) was observed in our patient. CONCLUSION: The reduction in the BFM scale supports the concept that rTMS of the premotor cortex may reduce specific motor symptoms in PSD.