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.     

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.     

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.     

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.     

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.     

Left prefrontal-repetitive transcranial magnetic stimulation (rTMS) and regional cerebral glucose metabolism in normal volunteers

Repetitive transcranial magnetic stimulation (rTMS) holds promise as a probe into the pathophysiology and possible treatment of neuropsychiatric disorders. To explore its regional effects, we combined rTMS with positron emission tomography (PET). Fourteen healthy volunteers participated in a baseline 18-fluorodeoxyglucose (FDG) PET scan. During a second FDG infusion on the same day, seven subjects received 30 min of 1 Hz rTMS at 80% of motor threshold to left prefrontal cortex, and seven other subjects received sham rTMS under identical conditions. Global and normalized regional cerebral glucose metabolic rates (rCMRglu) from the active and sham conditions were compared to baseline and then to each other. Sham, but not active 1 Hz rTMS, was associated with significantly increased global CMRglu. Compared to baseline, active rTMS induced normalized decreases in rCMRglu in right prefrontal cortex, bilateral anterior cingulate, basal ganglia (L>R), hypothalamus, midbrain, and cerebellum. Increases in rCMRglu were seen in bilateral posterior temporal and occipital cortices. Sham rTMS compared to baseline resulted in isolated normalized decreases in rCMRglu in left dorsal anterior cingulate and left basal ganglia, and increases in posterior association and occiptal regions. Differences between the 1 Hz active versus sham changes from baseline revealed that active rTMS induced relative decrements in rCMRglu in the left superior frontal gyrus and increases in the cuneus (L>R). One Hertz rTMS at 80% motor threshold over the left prefrontal cortex in healthy subjects compared to sham rTMS in another group (each compared to baseline) induced an area of decreased normalized left prefrontal rCMRglu not directly under the stimulation site, as well as increases in occipital cortex. While these results are in the predicted direction, further studies using other designs and higher intensities and frequencies of rTMS are indicated to better describe the local and distant changes induced by rTMS.     

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.     

Non-invasive neuromodulation for tinnitus: A meta-analysis and modeling studies

BackgroundPatients with tinnitus often have poor quality of life, as well as severe anxiety and depression. New approaches to treat tinnitus are needed.ObjectiveEvaluate the effects of non-invasive neuromodulation on tinnitus through a metaanalysis and modeling study. The main hypothesis was that real as compared to sham neuromodulation that decreases tinnitus will modulate regions in line with the neurobiological models of tinnitus.Methods and resultsThe systematic review, conducted from Pubmed, Cochrane and PsycINFO databases, showed that active as compared to sham repetitive transcranial magnetic stimulation (rTMS) reduced tinnitus, but active and sham transcranial direct current stimulation did not significantly differ. Further, rTMS over the auditory cortex was the most effective protocol. The modeling results indicate that this rTMS protocol elicited the strongest electric fields in the insula. Also, rTMS was particularly beneficial in women. Finally, the placebo effects were highly variable, highlighting the importance of conducting sham-controlled trials.ConclusionIn sum, neuromodulation protocols that target the auditory cortex and the insula may hold clinical potential to treat tinnitus.     

The effects of repetitive transcranial magnetic stimulation on depressive symptoms and the P300 event-related potential

Changes in the Hamilton Depression Rating Scale and the P₃₀₀ auditory event-related potential were assessed in 10 patients with depression before and after a treatment course of five daily sessions of 10?Hz repetitive transcranial magnetic stimulation (rTMS) over the left prefrontal cortex. The patients were initially randomly allocated either to an active or a placebo rTMS treatment. All patients received both types of treatment separated by an interval of 4?weeks. The median Hamilton score decreased by 7 points following active rTMS and by 1?point after sham (p=0.075). Active rTMS was associated with a significant increase in the P₃₀₀ amplitude compared with sham (p=0.02). There was no correlation between changes in P₃₀₀ measurements and the Hamilton scores after active treatment. We conclude that five daily sessions of left prefrontal rTMS treatment is not of sufficient duration to make a significant improvement in depressive symptoms.     

Hearing Safety of Long-Term Treatment with Theta Burst Stimulation

BackgroundRepetitive transcranial magnetic stimulation (rTMS) for the experimental treatment of tinnitus or auditory hallucinations aims at a modulation of cortical activity in areas of auditory perception and processing. Continuous theta burst stimulation (cTBS) is a patterned rTMS paradigm with lower stimulation intensity and shorter stimulus duration that is increasingly used for the optimization of rTMS-treatment paradigms. Possible interference with physiological brain function and the noise emitted by the rTMS device might induce relevant unwanted impairment of hearing and speech perception.Objective/HypothesisHere, we investigate the audiological safety of long-term, bilateral cTBS for the treatment of auditory phantom perception.MethodsForty-eight patients with chronic tinnitus were treated for four weeks with bilateral continuous theta burst stimulation to the temporal (n = 16), temporoparietal (n = 16) or a non-cortical control (n = 16) site. Measurements in these patients were obtained before and four weeks after treatment. The rTMS-induced noise was measured at various frequency levels.ResultsNo evidence was found for auditory threshold shifts or alterations in the perception of speech in quiet or in background noise by bilateral, long-term theta burst stimulation to the temporal or temporoparietal cortex with a loudness of up to 84 dB SPL (A).ConclusionsTheta burst stimulation of the temporal and temporoparietal cortex appears to be safe with respect to hearing and speech perception. These data provide evidence for the audiological safety of rTMS in the experimental treatment of auditory phantom perception.     

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.     

Unilateral and bilateral MRI-targeted repetitive transcranial magnetic stimulation for treatment-resistant depression: a randomized controlled study

BackgroundSeveral factors may mitigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) over sham rTMS in patients with treatment-resistant depression (TRD). These factors include unilateral stimulation (i.e., treatment of only the left dorsolateral prefrontal cortex [DLPFC]), suboptimal methods of targeting the DLPFC and insufficient stimulation intensity (based on coil-to-cortex distance).MethodsWe recruited patients with TRD between the ages of 18 and 85 years from a university hospital, and participants were randomized to receive sequential bilateral rTMS (600 pulses at 1 Hz followed by 1500 pulses at 10 Hz), unilateral high-frequency left (HFL)-rTMS (2100 pulses at 10 Hz) or sham rTMS for 3 or 6 weeks depending on treatment response. Stimulation was targeted with MRI localization over the junction of the middle and anterior thirds of the middle frontal gyrus, using 120% of the coil-to-cortex adjusted motor threshold. Our primary outcome of interest was the remission rate.ResultsA total of 121 patients participated in this study. The remission rate was significantly higher in the bilateral group than the sham group. The remission rate in the HFL-rTMS group was intermediate and did not differ statistically from the rate in the 2 other groups. There were no significant differences in reduction of depression scores among the 3 groups.LimitationsThe number of pulses used per session in the unilateral group was somewhat lower in our trial than in more recent trials, and the sham condition did not involve active stimulation.ConclusionOur findings suggest that sequential bilateral rTMS is superior to sham rTMS; however, adjusting for coil-to-cortex distance did not yield enhanced efficacy rates.     

Metabolic Changes of Cerebrum by Repetitive Transcranial Magnetic Stimulation over Lateral Cerebellum: A Study with FDG PET

To better understand the functional role of cerebellum within the large-scale cerebellocerebral neural network, we investigated the changes of neuronal activity elicited by cerebellar repetitive transcranial magnetic stimulation (rTMS) using (18)F-fluorodeoxyglucose (FDG) and positron emission tomography (PET). Twelve right-handed healthy volunteers were studied with brain FDG PET under two conditions: active rTMS of 1?Hz frequency over the left lateral cerebellum and sham stimulation. Compared to the sham condition, active rTMS induced decreased glucose metabolism in the stimulated left lateral cerebellum, the areas known to be involved in voluntary motor movement (supplementary motor area and posterior parietal cortex) in the right cerebral hemisphere, and the areas known to be involved in cognition and emotion (orbitofrontal, medial frontal, and anterior cingulate gyri) in the left cerebral hemisphere. Increased metabolism was found in cognition- and language-related brain regions such as the left inferior frontal gyrus including Broca's area, bilateral superior temporal gyri including Wernicke's area, and bilateral middle temporal gyri. Left cerebellar rTMS also led to increased metabolism in the left cerebellar dentate nucleus and pons. These results demonstrate that rTMS over the left lateral cerebellum modulates not only the target region excitability but also excitability of remote, but interconnected, motor-, language-, cognition-, and emotion-related cerebral regions. They provide further evidence that the cerebellum is involved not only in motor-related functions but also in higher cognitive abilities and emotion through the large-scale cerebellocereberal neural network.     

Slow transcranial magnetic stimulation can rapidly reduce resistant auditory hallucinations in schizophrenia.

BACKGROUND: Almost a quarter of patients with schizophrenia present with resistant auditory verbal hallucinations (AVH), a phenomenon that may relate to activation of brain areas underlying speech perception. Repetitive transcranial magnetic stimulation (rTMS) at 1 Hz reduces cortical activation, and recent results have shown that 1-Hz left temporoparietal rTMS may reduce AVH. The aim of this study was to replicate recent data and investigate whether low-frequency rTMS with a high total stimulation number delivered in a shorter 5-day block produces similar benefit. METHODS: Ten right-handed schizophrenia patients with resistant AVH received 5 days of active rTMS and 5 days of sham rTMS (2,000 stimulations per day at 90% of motor threshold) over the left temporoparietal cortex in a double-blind crossover design. The two weeks of stimulation were separated by a 1-week washout period. RESULTS: AVH were robustly improved (56%) by 5 days active rTMS, whereas no variation was observed after sham. Seven patients were responders to active treatment, five of whom maintained improvement for at least 2 months. CONCLUSIONS: These data confirm the efficiency of low-frequency rTMS applied to the left temporoparietal cortex, compared with sham stimulation, in reducing resistant AVH. This improvement can be obtained in only 5 days without serious initial adverse events.     

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.     

Treating auditory hallucinations by transcranial magnetic stimulation: a randomized controlled cross-over trial

BACKGROUND: In a previous functional magnetic resonance imaging study, the authors succeeded in demonstrating the activation of Heschl's gyrus during auditory hallucinations (AH). OBJECTIVES: This study aims to treat AH specifically by repetitive transcranial magnetic stimulation (rTMS). METHODS: 16 patients with AH were included in a randomized, cross-over, sham-controlled trial. 1 Hz rTMS was administered over the left and right temporo-parietal cortex and sham position, respectively, on 5 consecutive days; 900 stimuli each, strength 100% of motor threshold. Using the Psychotic Symptom Rating Scales (PSYRATS), the hallucinations during the stimulation periods and 4-week follow-ups were quantified. Electroencephalograms (EEG) were acquired before and after each period. RESULTS: Treatment responses were observed after left hemisphere rTMS only. The 5 patients who showed a response did so already after 2 days. However, group mean hallucination scores did not differ across treatment conditions. No significant changes were found in EEG after rTMS. CONCLUSIONS: A subgroup of patients suffering from AH benefits soon after treatment start from rTMS over the left superior temporal gyrus as revealed by the decrease of AH scores compared to right-sided and sham procedures.     

Neuroimaging mechanisms of high-frequency repetitive transcranial magnetic stimulation for treatment of amnestic mild cognitive impairment: a double-blind randomized sham-controlled trial

Individuals with amnestic mild cognitive impairment(aMCI) have a high risk of developing Alzheimer's disease. Although repetitive transcranial magnetic stimulation(rTMS) is considered a potentially effective treatment for cognitive impairment in patients with aMCI, the neuroimaging mechanisms are poorly understood. Therefore, we performed a double-blind randomized sham-controlled trial in which rTMS was applied to the left dorsolateral prefrontal cortex of aMCI patients recruited from a community near the Third Hospital Affiliated to Sun Yat-sen University, China. Twenty-four patients with aMCI were randomly assigned to receive true rTMS(treatment group, n = 12, 6 men and 6 women; age 65.08 ± 4.89 years) or sham stimulation(sham group, n = 12, 5 men and 7 women; age 64.67 ± 4.77 years). rTMS parameters included a stimulation frequency of 10 Hz, stimulation duration of 2 seconds, stimulation interval of 8 seconds, 20 repetitions at 80% of the motor threshold, and 400 pulses per session. rTMS/sham stimulation was performed five times per week over a period of 4 consecutive weeks. Our results showed that compared with baseline, Montreal Cognitive Assessment scores were significantly increased and the value of the amplitude of low-frequency fluctuation(ALFF) was significantly increased at the end of treatment and 1 month after treatment. Compared with the sham group, the ALFF values in the right inferior frontal gyrus, triangular part of the inferior frontal gyrus, right precuneus, left angular gyrus, and right supramarginal gyrus were significantly increased, and the ALFF values in the right superior frontal gyrus were significantly decreased in the treatment group. These findings suggest that high-frequency rTMS can effectively improve cognitive function in aMCI patients and alter spontaneous brain activity in cognitive-related brain areas. This study was approved by the Ethics Committee of Shenzhen Baoan Hospital of Southern Medical University, China(approval No. BYL20190901) on September 3, 2019 and registered in the Chinese Clinical Trials Registry(registration No. ChiCTR1900028180) on December 14, 2019.