One-year follow up of patients with chronic tinnitus treated with left temporoparietal rTMS

Background and purpose:  Although there are a number of positive reports on the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) for treatment of tinnitus, there are few details about the duration of treatment effects or the relative efficiency of different rTMS protocols.
Methods:  Sixty six patients with chronic tinnitus were divided into four groups, receiving sham rTMS, 1, 10 and 25 Hz rTMS applied each day for 10 days over left temporoparietal cortex. They were followed up at 4 months and 1 year using the tinnitus questionnaire [Tinnitus Handicap Inventory(THI)] and self ratings of annoyance as well as measures of residual inhibition.
Results:  A two factor anova revealed a significant 'rTMS' × 'time' interaction indicating that real and sham rTMS had different effects on the THI scale and annoyance of tinnitus ( P  = 0.026 and 0.046 respectively). After 1 year, the tinnitus was absent in one or both ears of 10 patients who had received real rTMS: one of these was in the 1 Hz group, four patients were in the 10 Hz group and five patients were in the 25 Hz group.
Conclusion:  Some patients show a lasting benefit at 1 year after 10 days of rTMS treatment. It appears that treatment at 10 or 25 Hz may be more beneficial than at 1 Hz, although more work is necessary to validate this conclusion.     

Efficacy of different protocols of transcranial magnetic stimulation for the treatment of tinnitus: Pooled analysis of two randomized controlled studies

Objectives. Tinnitus is related to alterations in neuronal activity of auditory and nonauditory brain areas. Targeted modulation of these areas by repetitive transcranial magnetic stimulation (rTMS) has been proposed as a new therapeutic approach for chronic tinnitus. Methods. Two randomized, double-blind, parallel-group, controlled clinical trials were performed subsequently and pooled for analysis. A total of 192 tinnitus patients were randomly allocated to receive 10 stimulation sessions of either sham rTMS, PET-based neuronavigated 1 Hz rTMS, 1Hz r TMS over the left auditory cortex, or combined 20 Hz rTMS over the left frontal cortex, followed by 1 Hz rTMS over the left auditory cortex. Results. rTMS treatment was well tolerated and no severe side effects were observed. All active rTMS treatments resulted in significant reduction of the TQ as compared to baseline. The comparison between treatment groups failed to reach significant differences. The number of treatment responders was higher for temporal rTMS(38%) and combined frontal and temporal rTMS (43%), as compared to sham (6%). Conclusions. This large study demonstrates the safety and tolerability of rTMS treatment in patients with chronic tinnitus. While the overall effect did not prove superior to placebo, secondary outcome parameters argue in favour of the active stimulation groups, and specifically the combined frontal and temporal rTMS protocol.     

Transient tinnitus suppression induced by repetitive transcranial magnetic stimulation and transcranial direct current stimulation

Modulation of activity in the left temporoparietal area (LTA) by 10 Hz repetitive transcranial magnetic stimulation (rTMS) results in a transient reduction of tinnitus. We aimed to replicate these results and test whether transcranial direct current stimulation (tDCS) of LTA could yield similar effect. Patients with tinnitus underwent six different types of stimulation in a random order: 10-Hz rTMS of LTA, 10-Hz rTMS of mesial parietal cortex, sham rTMS, anodal tDCS of LTA, cathodal tDCS of LTA and sham tDCS. A non-parametric analysis of variance showed a significant main effect of type of stimulation ( P  = 0.002) and post hoc tests showed that 10-Hz rTMS and anodal tDCS of LTA resulted in a significant reduction of tinnitus. These effects were short lasting. These results replicate the findings of the previous study and, in addition, show preliminary evidence that anodal tDCS of LTA induces a similar transient tinnitus reduction as high-frequency rTMS.     

Dose-dependent attenuation of auditory phantom perception (tinnitus) by PET-guided repetitive transcranial magnetic stimulation

Recent data suggest that chronic tinnitus is a "phantom auditory perception" caused by maladaptive neuroplasticity and subsequent hyperactivity in an extended neuronal network including the primary auditory cortex, higher-order association areas, and parts of the limbic system. It was suggested that attenuation of this tinnitus-associated hyperactivity may offer a rational option for lasting tinnitus reduction. Here, we tested the hypothesis that tinnitus loudness can be attenuated by low-frequency repetitive transcranial magnetic stimulation (rTMS) individually navigated to cortical areas with excessive tinnitus-related activity as assessed by [(15)O]H(2)O positron-emission tomography (PET). Nine patients with chronic tinnitus underwent this combined functional imaging and rTMS-study. Group analysis of the PET data showed tinnitus-related increases of regional cerebral blood flow in the left middle and inferior temporal as well as right temporoparietal cortex and posterior cingulum. Repetitive TMS was performed at 1 Hz and 120% of the motor threshold for 5, 15, and 30 min, navigated to the individual maximum of tinnitus-related cortical hyperactivity. A noncortical stimulation site with the same distance to the ear served as sham control. Tinnitus loudness was reduced after temporoparietal, PET-guided low-frequency rTMS. This reduction, lasting up to 30 min, was dependent on the number of stimuli applied, differed from sham stimulation, and was negatively correlated with the length of the medical history of tinnitus in our patients. These data show the feasibility and effectiveness of rTMS guided by individual functional imaging to induce a lasting, dose-dependent attenuation of tinnitus. Of note, these effects were related to stimulation of cortical association areas, not primary auditory cortex, emphasizing the crucial role of higher-order sensory processing in the pathophysiology of chronic tinnitus.     

Effect of daily repetitive transcranial magnetic stimulation for treatment of tinnitus: comparison of different stimulus frequencies

We compared the effect of different frequencies of repetitive transcranial magnetic stimulation (rTMS) (1 Hz, 10 Hz, 25 Hz and sham (occipital, 1 Hz)), given daily over the left temporoparietal cortex for 2 weeks, on 66 patients with chronic tinnitus randomly divided into four treatment groups. Patients were assessed using the Tinnitus Handicap Inventory, self-ratings of symptoms and audiometric measures of residual inhibition before, immediately after 2 weeks' treatment and monthly thereafter for 4 consecutive months. RESULTS: There were no significant differences in basal measures between the four groups of patients. A two-factor ANOVA revealed a significant "rTMS" x "time" interaction for all measures. This was because real rTMS produced greater improvement than sham. However, there was no significant difference between the responses to different frequencies of rTMS. The response to rTMS depended on the duration of tinnitus: patients who had tinnitus for the longest period of time were the least likely to respond to treatment. CONCLUSION: Daily sessions of rTMS over the temporoparietal cortex may be a useful potential treatment for tinnitus.     

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.     

Contralateral versus ipsilateral rTMS of temporoparietal cortex for the treatment of chronic unilateral tinnitus: comparative study

Background: Repetitive transcranial magnetic stimulation (rTMS) applied over left temporoparietal cortex has been reported to have a long‐term therapeutic effect on tinnitus. We compare the impact of 1 and 25 Hz rTMS delivered either contralateral or ipsilateral to symptoms in 62 patients with unilateral chronic tinnitus. Material and methods: Patients were randomly assigned to one of four treatment groups: with stimulation at 1 or 25 Hz applied either ipsilateral or contralateral to symptoms. Two thousand pulses per session were given daily for 2 weeks. Changes in tinnitus handicap inventory (THI), self‐rating scores of loudness, awareness, and annoyance were measured monthly for 10 months. Duration of residual inhibition (RI) and psychiatric morbidity were evaluated monthly for 3 months. Results: There was a significant main effect of time (P < 0.0001) and a significant time × side interaction (P = 0.032) between groups. This was because of the fact that contralateral stimulation had a greater effect on THI than ipsilateral stimulation; it was also superior to left side stimulation (P = 0.027). Ratings of loudness improved more after contralateral rTMS (P = 0.037). Twenty patients had no remaining tinnitus after 3 months; the remainder had a significant increase in RI. Patients with the shortest history of tinnitus tended to respond better to rTMS. There was a significant correlation between changes in THI score and changes in Hamilton anxiety and depression scores. Conclusion: Ten daily treatments of 1 and 25 Hz rTMS contralateral to the side of tinnitus have a greater beneficial effect on symptoms than either ipsilateral or left side stimulation.     

Auditory cortex hyperconnectivity before rTMS is correlated with tinnitus improvement

IntroductionRepetitive transcranial magnetic stimulation (rTMS) has been used as a potential treatment for tinnitus; however, its effectiveness is variable and unpredictable. We hypothesized that resting-state functional connectivity before rTMS may be correlated with rTMS treatment effectiveness.MethodsWe applied 1-Hz rTMS to the left primary auditory (A1) and dorsolateral prefrontal cortices (DLPFC) of 10 individuals with tinnitus and 10 age-matched controls. Resting-state functional magnetic resonance imaging (fMRI) studies were performed approximately one week before rTMS. Seed-based connectivity analyses were conducted for each individual, with seed regions as rTMS target areas.ResultsCompared to controls, the left superior temporal areas showed significantly increased positive connectivity with the left A1 and negative connectivity with the left DLPFC in the tinnitus group. The left frontoparietal and right cerebellar areas showed significantly increased negative connectivity with the left A1 and positive connectivity with the left DLPFC. Seed-based hyperconnectivity was correlated with tinnitus improvement (pre-rTMS vs. 2-week post-rTMS Tinnitus Handicap Inventory scores). Tinnitus improvement was significantly correlated with left A1 hyperconnectivity; however, no correlation was observed with left DLPFC connectivity. Positive rTMS outcomes were associated with significantly increased positive connectivity in bilateral superior temporal areas and significantly increased negative connectivity in bilateral frontal areas.ConclusionsOur results suggest that oversynchronisation of left A1 connectivity before rTMS of the left A1 and DLPFC is associated with treatment effectiveness.     

Short duration repetitive transcranial magnetic stimulation for tinnitus treatment: a prospective Asian study

Background

Tinnitus is a subjective auditory perception of sounds or noise not triggered by external auditory stimuli. To date, treatment in severe cases is generally unsatisfactory. Characteristic functional brain imaging changes associated with tinnitus include hyperactivity encompassing both the primary auditory cortex (AC) and the secondary or associative cortex. Brief repetitive transcranial magnetic stimulation (rTMS) trains applied to the scalp overlying the hyperactive left AC is known to produce moderate tinnitus attenuation.

Objective

Although Western studies have documented the value of rTMS in tinnitus treatment, we evaluate the efficacy of a short duration rTMS protocol for the first time in the Asian setting.

Method

Consecutive patients were recruited at our tinnitus clinic. Detailed history, examination, audiogram and baseline tinnitus scales were recorded. RTMS consisted of 1000 pulses/day at 1 Hz and 110% of the motor threshold, for five consecutive days over the left temporoparietal cortex. Tinnitus ratings were determined weekly for 4 weeks after rTMS.

Result

Fifteen patients completed the trial; none experienced significant side effects. Repeated measures ANOVA showed significant linear decrease in Tinnitus Handicap Inventory (THI) scores over the time period (F_(1,14) = 4.7, p = 0.04). However, none of the other parameters (severity, annoyance, effect on lifestyle and overall impression: visual analogue scale) showed beneficial outcomes.

Conclusions

Our findings point to a positive effect of short duration rTMS in tinnitus treatment using the THI. However, no significant benefits were demonstrated for other subjective patient ratings. Although well tolerated and convenient, short duration rTMS may prove inadequate for modulating maladaptive plastic changes at the cortical level, and our results suggest the need for delivery of more stimuli. Future studies will utilize at least 2000 pulses/day, in line with previous experience in Western settings.     

The Effect of rTMS on Auditory Processing in Adults with Chronic,Bilateral Tinnitus: A Placebo-Controlled Pilot Study

BackgroundOn the basis that tinnitus may result from neural hyperactivity in the auditory cortex, researchers have investigated the use of low frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) as a potential modulator of this hyperactivity. While these investigations show promise, investigations to date have neglected to consider the possible effect of 1 Hz rTMS on other functions of the auditory cortex of these individuals, such as auditory processing.Objective/hypothesisThis placebo-controlled pilot study aimed to determine whether 1 Hz rTMS applied to the primary auditory cortex (PAC), specifically Brodmann Area 41 (BA41), of adults with chronic, bilateral tinnitus would influence their auditory processing abilities.MethodsEight participants with bilateral, chronic tinnitus were randomized to receive a 10-day course of neuronavigationally guided active rTMS (n = 4) or placebo rTMS (n = 4) treatment applied to a focal region of the left PAC (BA41). Participants' auditory processing was measured using Time Compressed Reverberant Speech and three-pair Dichotic Digits (DD). Their tinnitus was measured using the Tinnitus Handicap Inventory (THI) and a psychoacoustic measure of tinnitus perception. All outcome measures were administered at baseline (1 week prior to rTMS), 1 week, 1, 2 and 3 months post-rTMS.ResultsAll four participants in the active rTMS (A) group, and none of the participants in the sham (placebo) rTMS (S) group, showed improved auditory processing scores at multiple assessment points post-stimulation, with the group differences in median normalized gain scores reaching significance at the 5% level from 1 week or 1 month post-stimulation onwards. Three of the four participants in the active rTMS (A) group, and none of the participants in the sham rTMS (S) group, showed improved tinnitus scores at multiple assessment points post-stimulation, with some of the group differences in median normalized gain scores reaching significance at the 5% level.ConclusionsThe results of this preliminary study suggest that 1 Hz rTMS applied to the PAC (BA41) has the capacity to improve both auditory processing and tinnitus perception in some adults with chronic, bilateral tinnitus.     

Neural correlates of tinnitus duration and Distress: A positron emission tomography study

Cerebral ¹⁸F‐deoxyglucose positron emission tomography (FDG‐PET) has shown altered auditory pathway activity in tinnitus. However, the corresponding studies involved only small samples and analyses were restricted to the auditory cortex in most studies. Evidence is growing that also limbic, frontal, and parietal areas are involved in the pathophysiology of chronic tinnitus. These regions are considered to mediate perceptual, attentional, and emotional processes. Thus, the aim of the present study was the systematic evaluation of metabolic brain activity in a large sample of tinnitus patients. Ninety one patients with chronic tinnitus underwent FDG‐PET. The effects of tinnitus severity (assessed by a tinnitus questionnaire score), duration and laterality were evaluated with statistical parametric mapping (SPM) in whole brain analyses. In addition, region of interest analyses were performed for primary auditory areas. Tinnitus duration correlated positively with brain metabolism in right inferior frontal, right ventro‐medial prefrontal, and right posterior cingulate cortex. Tinnitus distress correlated positively with activation of left and right posterior inferior temporal gyrus as well as left and right posterior parahippocampal–hippocampal interface. Region of interest analysis demonstrated an overactivation of left in contrast to right Heschl's gyrus independently from tinnitus laterality and anatomical hemispheric differences. Tinnitus duration and distress were associated with areas involved in attentional and emotional processing. This is in line with recent findings indicating the relevance of higher order areas in the pathophysiology of tinnitus. Earlier results of asymmetric activation of the auditory cortices in tinnitus were confirmed, i.e., left‐sided overactivation was found independently from tinnitus laterality. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Functional connectivity revealed by single-photon emission computed tomography (SPECT) during repetitive transcranial magnetic stimulation (rTMS) of the motor cortex.

OBJECTIVE: In the present study, we studied effects of 1 Hz repetitive transcranial magnetic stimulation (rTMS) over the left primary motor cortex (M1) on regional cerebral blood flow (rCBF) using single-photon emission computed tomography (SPECT). METHODS: SPECT measurements were carried out under two experimental conditions: real and sham stimulation. In sham stimulation, to exclude other components besides currents in the brain in rTMS, we applied sound and electrical stimulation to the skin of the head. 99mTc-ethyl cysteinate dimer was injected during the real or sham stimulation. Images were analyzed with the statistical parametric mapping software (SPM99). Relative differences in adjusted rCBF between two conditions were determined by a voxel-by-voxel paired t test. RESULTS: 1 Hz rTMS at an intensity of 1.1 x active motor threshold evoked increase of rCBF in the contralateral (right) cerebellar hemisphere. Reduction of rCBF was observed in the contralateral M1, superior parietal lobule (most probably corresponding to PE area in the monkey) (Rizzolatti G, Luppino G, Matelli M. Electroenceph clin Neurophysiol 1998;106:283-296), inferior parietal lobule (PF area in the monkey (Rizzolatti et al., 1998)), dorsal and ventral premotor areas (dPM, vPM) and supplementary motor area (SMA). CONCLUSIONS: Increase of rCBF in the contralateral cerebellum must reflect facilitatory connection between the motor cortex and contralateral cerebellum. Reduced rCBF in the contralateral M1 may be produced by transcallosal inhibitory effect of the left motor cortical activation. CBF decrease in the right PM, SMA and parietal cortex may reflect some secondary effects. Low frequency rTMS at an intensity of around threshold for active muscles can evoke rCBF changes. Significance: We demonstrated that rCBF changes could be elicited even by low frequency rTMS at such a low intensity as the threshold for an active muscle. Combination of rTMS and SPECT is one of powerful tools to study interareal connection within the human brain.     

Left prefrontal transcranial magnetic stimulation (TMS) treatment of depression in bipolar affective disorder: a pilot study of acute safety and efficacy

Objectives:  Repetitive transcranial magnetic stimulation (rTMS) has been shown to improve depressive symptoms. We designed and carried out the following left prefrontal rTMS study to determine the safety, feasibility, and potential efficacy of using TMS to treat the depressive symptoms of bipolar affective disorder (BPAD).
Methods:  We recruited and enrolled 23 depressed BPAD patients (12 BPI depressed state, nine BPII depressed state, two BPI mixed state). Patients were randomly assigned to receive either daily left prefrontal rTMS (5 Hz, 110% motor threshold, 8 sec on, 22 sec off, over 20 min) or placebo each weekday morning for 2 weeks. Motor threshold and subjective rating scales were obtained daily, and blinded Hamilton Rating Scale for Depression (HRSD) and Young Mania Rating Scales (YMRS) were obtained weekly.
Results:  Stimulation was well tolerated with no significant adverse events and with no induction of mania. We failed to find a statistically significant difference between the two groups in the number of antidepressant responders (>50% decline in HRSD or HRSD <10 – 4 active and 4 sham) or the mean HRSD change from baseline over the 2 weeks ( t =−0.22, p=0.83). Active rTMS, compared with sham rTMS, produced a trend but not statistically significant greater improvement in daily subjective mood ratings post-treatment ( t =1.58, p=0.13). The motor threshold did not significantly change after 2 weeks of active treatment ( t =1.11, p=0.28).
Conclusions:  Daily left prefrontal rTMS appears safe in depressed BPAD subjects, and the risk of inducing mania in BPAD subjects on medications is small. We failed to find statistically significant TMS clinical antidepressant effects greater than sham. Further studies are needed to fully investigate the potential role, if any, of TMS in BPAD depression.     

Long-term effect of repetitive transcranial magnetic stimulation on motor function recovery after acute ischemic stroke

Objective –  Although there is evidence for short term benefits of rTMS in stroke, longer term effects have not been reported. The aim of the study was to evaluate the effect of two different frequencies of rTMS on motor recovery and on cortical excitability up to 1 year post-treatment.
Methods –  Forty-eight patients with acute ischemic stroke were randomly classified into three groups. The first two groups received real rTMS over motor cortex (3 and 10 Hz respectively) of the affected hemisphere and the third group received sham stimulation of the same site, daily for five consecutive days. Disability was assessed before, after fifth sessions, and then after 1, 2, 3 and 12 months. Cortical excitability was assessed for both hemispheres before and after the second and fifth sessions.
Results –  A significant 'rTMS × time' interaction was obtained indicating that real and sham rTMS had different effects on rating scales. This was because real rTMS produced greater improvement than sham that was evident even at one year follow-up. These improvements were associated with changes in cortical excitability over the period of treatment.
Conclusion –  These results confirm that real rTMS over motor cortex can enhance and maintain recovery and may be a useful add on therapy in treatment of acute stroke patients.     

Equivalent brain SPECT perfusion changes underlying therapeutic efficiency in pharmacoresistant depression using either high-frequency left or low-frequency right prefrontal rTMS

Background

Functional neuroimaging studies have suggested similar mechanisms underlying antidepressant effects of distinct therapeutics.

Objective

This study aimed to determine and compare functional brain patterns underlying the antidepressant response of 2 distinct protocols of repetitive transcranial magnetic stimulation (rTMS).

Methods

99mTc-ECD SPECT was performed before and after rTMS of dorsolateral prefrontal cortex in 61 drug-resistant right-handed patients with major depression, using high frequency (10 Hz) left-side stimulation in 33 patients, and low frequency (1 Hz) right-side stimulation in 28 patients. Efficiency of rTMS response was defined as at least 50% reduction of the baseline Beck Depression Inventory score. We compared the whole-brain voxel-based brain SPECT changes in perfusion after rTMS, between responders and non-responders in the whole sample (p < 0.005, uncorrected), and separately in the subgroup of patients with left- and right-stimulation.

Results

Before rTMS, the left- and right-prefrontal stimulation groups did not differ from clinical data and brain SPECT perfusion. rTMS efficiency (evaluated on % of responders) was statistically equivalent in the two groups of patients. In the whole-group of responder patients, a perfusion decrease was found after rTMS, in comparison to non-responders, within the left perirhinal cortex (BA35, BA36). This result was secondarily confirmed separately in the two subgroups, i.e. after either left stimulation (p = 0.017) or right stimulation (p < 0.001), without significant perfusion differences between these two subgroups.

Conclusions

These data show that distinct successful rTMS protocols induce equivalent brain functional changes associated to antidepressive efficiency, consisting to a remote brain limbic activity decrease within the left perirhinal cortex. However, these results will have to be confirmed in a double-blind randomized trial using a sham control group.     

Comparison of monophasic versus biphasic stimulation in rTMS over premotor cortex: SEP and SPECT studies

OBJECTIVE: To optimize the clinical uses of repetitive transcranial magnetic stimulation (rTMS), we compared the effects of rTMS on somatosensory-evoked potentials (SEPs) and regional cerebral blood flow (rCBF) using different phases (monophasic vs. biphasic) or frequencies (0.2Hz vs. 0.8Hz) of stimulation. METHODS: In the first experiment, different phases were compared (0.2Hz monophasic vs. 0.2Hz biphasic). Biphasic 1Hz or sham condition served as controls. The second experiment was to explore the effect of frequencies (0.2Hz vs. 0.8Hz) using the monophasic stimulation. Substhreshold TMS was applied 250 times over the left premotor cortex. Single photon emission computed tomography (SPECT) was performed before and after monophasic 0.2Hz or biphasic 1Hz rTMS. RESULTS: Monophasic rTMS of both 0.2 and 0.8Hz significantly increased the ratio of N30 amplitudes as compared with sham rTMS, whereas biphasic stimulation showed no significant effects. SPECT showed increased rCBF in motor cortices after monophasic 0.2Hz rTMS, but not after biphasic 1Hz stimulation. CONCLUSIONS: Monophasic rTMS exerted more profound effects on SEPs and rCBF than biphasic rTMS over the premotor cortex. SIGNIFICANCE: Monophasic rTMS over the premotor cortex could be clinically more useful than biphasic rTMS.     

SPECT mapping of cerebral activity changes induced by repetitive transcranial magnetic stimulation in depressed patients. A pilot study

Repetitive transcranial magnetic stimulation (rTMS) is being investigated as an alternative treatment for depression. However, little is known about the clinical role and the neurophysiological mechanisms of the action of rTMS in these patients. In this study, 99mTc-HMPAO single photon emission computed tomography (SPECT) was used to map the effects of left dorsolateral prefrontal rTMS on prefrontal activity in seven patients who met DSM-IV criteria for major depression resistant to pharmacological treatment. rTMS consisted of 30 trains of 2-s duration stimuli (20 Hz, 90% of motor threshold), separated by 30-s pauses. Each patient underwent three SPECTs: at baseline; during the first rTMS; and 1 week after 10 daily sessions of rTMS. Regional cerebral blood flow (rCBF) of each cerebral region was normalized to the rCBF value in the cerebellum and relative changes in normalized rCBF were addressed using a region-of-interest analysis. The Hamilton Depression Rating Scale (HDRS) was used for clinical evaluation before and after rTMS. A significant rCBF increase after the 10 sessions of rTMS was found in the left prefrontal region (MANOVA F=5.29, d.f.=2,10, P=0.027), but no significant rCBF changes were found during the first rTMS session. The remaining cerebral regions showed no significant rCBF changes at any time. Only two patients showed a clinical improvement after rTMS, with 50% reduction of the initial HDRS score. The study was repeated under placebo conditions (identical design but addressing coil discharges to the air) in these two patients, who failed to show any rCBF increase during sham-rTMS. No relationship was found between the percentage of left prefrontal rCBF change and the clinical findings. In conclusion, rTMS of the left prefrontal cortex induces a significant rCBF increase in this region, despite the limited clinical effect in our sample of depressed patients. Cerebral perfusion SPECT is a useful tool to map cerebral activity changes induced by rTMS.     

The time course of idiom processing

Recent neuropsychological and neurophysiological studies have suggested that the neural correlates of idiom processing are predominantly located in the left Brodmann's area (BA) 22 and, to some extent, in the prefrontal cortex. The present study explores the temporal dynamics of left prefrontal and temporal cortex in idiom processing by using repetitive transcranial magnetic stimulation (rTMS) in normal subjects.

Forty-five opaque highly familiar idioms and 45 literal sentences were used. Forty-three subjects completed 5 blocks of 18 trials (9 idioms, 9 literal sentences) corresponding to 4 stimulation conditions (left prefrontal, left temporal, vertex, no-stimulation baseline). Each subject was assigned to one of three groups, which differed in the timing of stimulation delivery.

A selective impairment in accuracy for idioms was found when rTMS was applied to the prefrontal and temporal cortex 80 ms after picture presentation, confirming the role of these regions in this task. Moreover, rTMS to the prefrontal cortex, but not to the temporal cortex, continued to affect the performance with idiomatic sentences at the later time of 120 ms. The results seem to suggest that the prefrontal region is involved in both the retrieval of the figurative meaning from semantic memory and the monitoring of the response by inhibiting alternative interpretations when a picture-matching task is used.     

Repetitive transcranial magnetic stimulation as treatment of poststroke depression: a preliminary study.

BACKGROUND: Depression has a significant impact on poststroke recovery and mortality. There are a proportion of patients with poststroke depression (PSD) who do not respond to antidepressants. Repetitive Transcranial Magnetic Stimulation (rTMS) might be a safe and effective alternative in these refractory cases. METHODS: We conducted a randomized, parallel, double-blind study of active versus sham left prefrontal rTMS in patients with refractory PSD. After discontinuing antidepressants, patients were randomly assigned to receive 10 sessions of active (10 Hz, 110% of the motor threshold, 20 trains of 5 seconds duration) or sham left prefrontal rTMS. Efficacy measures included HAM-D scores, response and remission rates. Patients completed a neuropsychological battery at baseline and after completing the protocol. RESULTS: When compared with sham stimulation, 10 sessions of active rTMS of the left dorsolateral prefrontal cortex were associated with a significant reduction of depressive symptoms. This reduction was not influenced by patient's age, type or location of stroke, volume of left frontal leukoaraiosis or by the distance of the stimulating coil to the prefrontal cortex. However, there was a significant positive correlation between the percentage of reduction of Ham-D scores and frontal gray and white matter volumes. There were no significant changes in cognitive functioning between the active and the sham stimulation groups. In addition, there were few and mild adverse effects that were equally distributed among groups. CONCLUSIONS: Taken together, these preliminary findings suggest that rTMS may be an effective and safe treatment alternative for patients with refractory depression and stroke.