Modulation of visual cortical excitability in migraine with aura: effects of 1 Hz repetitive transcranial magnetic stimulation

Recent studies showed hyperexcitability of the occipital cortex in subjects affected by migraine with aura. It has been shown that 1 Hz repetitive transcranial magnetic stimulation (rTMS) reduces excitability of visual cortex in normal subjects. The aim of the study was to investigate the effects of low frequency (1 Hz) rTMS on visual cortical excitability by measuring changes in phosphene threshold (PT) in subjects with migraine with aura. Thirteen patients with migraine with aura and 15 healthy controls were examined. Using a standardized transcranial magnetic stimulation protocol of the occipital cortex, we assessed the PT (the lowest magnetic stimulation intensity at which subjects just perceived phosphenes) before and after a 1-Hz rTMS train delivered at PT intensity for 15 min. The difference in the proportion of subjects reporting phosphenes in migrainer and control groups was significant (migrainers: 100% vs controls 47%; P<0.05), and 1 Hz rTMS over the occipital cortex led to a significantly increased visual cortex excitability expressed as a decrease in PT in subjects affected by migraine with aura. Conversely, after a 1-Hz TMS train normal subjects showed increased PT values, which suggests a decreased visual cortex excitability. Our findings confirm that the visual cortex is hyperexcitable in migrainers and suggest a failure of inhibitory circuits, which are unable to be upregulated by low frequency rTMS.     

Posture-cognitive dual-tasking: A relevant marker of depression-related psychomotor retardation. An illustration of the positive impact of repetitive transcranial magnetic stimulation in patients with major depressive disorder

This study examined whether postural control variables, particularly the center-of-pressure (COP) velocity-based parameters, could be a relevant hallmark of depression-related psychomotor retardation (PMR). We first aimed at investigating the interplay between the PMR scores and the COP performance in patients with major depressive disorder (MDD), as compared to age-matched healthy controls; secondly, we focused on the impact of a repetitive transcranial magnetic stimulation (rTMS) treatment on depression, PMR scores and postural performance. 16 MDD patients, and a control group of 16 healthy adults, were asked to maintain quiet standing balance during two trials with or without vision, and while backward counting (dual task). All the position and velocity-based COP variables were computed. Before and after the rTMS session (n eligible MDD = 10), we assessed the depression level with the Montgomery–Asberg Depression Rating Scale (MADRS), the PMR scores with the French Retardation Rating Scale for Depression (ERD), and postural performance. Before the treatment, significant positive partial correlations were found between the pre-ERD scores and the velocity-based COP variables, especially in the dual-task conditions (p < 0.05). In contrast, there was no significant correlation between the post-ERD scores and any postural parameter after the treatment. The MADRS and ERD scores showed a significant decrease between before and after the rTMS intervention. For the first time, the findings clearly validated the view that the assessment of postural performance - easy to envisage in clinical settings-constitutes a reliable and objective marker of PMR in MDD patients.     

A Double-blind,Randomized Trial of Deep Repetitive Transcranial Magnetic Stimulation (rTMS) for Autism Spectrum Disorder

BackgroundBiomedical treatment options for autism spectrum disorder (ASD) are extremely limited. Repetitive transcranial magnetic stimulation (rTMS) is a safe and efficacious technique when targeting specific areas of cortical dysfunction in major depressive disorder, and a similar approach could yield therapeutic benefits in ASD, if applied to relevant cortical regions.ObjectiveThe aim of this study was to examine whether deep rTMS to bilateral dorsomedial prefrontal cortex improves social relating in ASD.Methods28 adults diagnosed with either autistic disorder (high-functioning) or Asperger's disorder completed a prospective, double-blind, randomized, placebo-controlled design with 2 weeks of daily weekday treatment. This involved deep rTMS to bilateral dorsomedial prefrontal cortex (5 Hz, 10-s train duration, 20-s inter-train interval) for 15 min (1500 pulses per session) using a HAUT-Coil. The sham rTMS coil was encased in the same helmet of the active deep rTMS coil, but no effective field was delivered into the brain. Assessments were conducted before, after, and one month following treatment.ResultsParticipants in the active condition showed a near significant reduction in self-reported social relating symptoms from pre-treatment to one month follow-up, and a significant reduction in social relating symptoms (relative to sham participants) for both post-treatment assessments. Those in the active condition also showed a reduction in self-oriented anxiety during difficult and emotional social situations from pre-treatment to one month follow-up. There were no changes for those in the sham condition.ConclusionDeep rTMS to bilateral dorsomedial prefrontal cortex yielded a reduction in social relating impairment and socially-related anxiety. Further research in this area should employ extended rTMS protocols that approximate those used in depression in an attempt to replicate and amplify the clinical response.     

Abnormal Anterior Cingulate N-Acetylaspartate and Executive Functioning in Treatment-Resistant Depression After rTMS Therapy

Background:

Cognitive impairment is a key feature of treatment-resistant depression (TRD) and can be related to the anterior cingulate cortex (ACC) function. Repetitive transcranial magnetic stimulation (rTMS) as an antidepressant intervention has increasingly been investigated in the last two decades. However, no studies to date have investigated the association between neurobiochemical changes within the anterior cingulate and executive dysfunction measured in TRD being treated with rTMS.

Methods:

Thirty-two young depressed patients with treatment-resistant unipolar depression were enrolled in a double-blind, randomized study [active (n=18) vs. sham (n=14)]. ACC metabolism was investigated before and after high-frequency (15Hz) rTMS using 3-tesla proton magnetic resonance spectroscopy (1H-MRS). The results were compared with 28 age- and gender-matched healthy controls. Executive functioning was measured with the Wisconsin Card Sorting Test (WCST) among 34 subjects with TRD and 28 healthy subjects.

Results:

Significant reductions in N-acetylaspartate (NAA) and choline-containingCompound levels in the left ACC were found in subjects with TRD pre-rTMS when compared with healthy controls. After successful treatment, NAA levels increased significantly in the left ACC of subjects and were not different from those of age-matched controls. In the WCST, more perseverative errors and fewer correct numbers were observed in TRD subjects at baseline. Improvements in both perseverative errors and correct numbers occurred after active rTMS. In addition, improvement of perseverative errors was positively correlated with enhancement of NAA levels in the left ACC in the active rTMS group.

Conclusions:

Our results suggest that the NAA concentration in the left ACC is associated with an improvement in cognitive functioning among subjects with TRD response to active rTMS.     

Effects of Repetitive Transcranial Magnetic Stimulation on Behavioral Recovery during Early Stage of Traumatic Brain Injury in Rats

Repetitive transcranial magnetic stimulation (rTMS) is a promising technique that modulates neural networks. However, there were few studies evaluating the effects of rTMS in traumatic brain injury (TBI). Herein, we assessed the effectiveness of rTMS on behavioral recovery and metabolic changes using brain magnetic resonance spectroscopy (MRS) in a rat model of TBI. We also evaluated the safety of rTMS by measuring brain swelling with brain magnetic resonance imaging (MRI). Twenty male Sprague-Dawley rats underwent lateral fluid percussion and were randomly assigned to the sham (n=10) or the rTMS (n=10) group. rTMS was applied on the fourth day after TBI and consisted of 10 daily sessions for 2 weeks with 10 Hz frequency (total pulses=3,000). Although the rTMS group showed an anti-apoptotic effect around the peri-lesional area, functional improvements were not significantly different between the two groups. Additionally, rTMS did not modulate brain metabolites in MRS, nor was there any change of brain lesion or edema after magnetic stimulation. These data suggest that rTMS did not have beneficial effects on motor recovery during early stages of TBI, although an anti-apoptosis was observed in the peri-lesional area.     

Repetitive transcranial magnetic stimulation (rTMS) versus transcranial direct current stimulation (tDCS) in the management of patients with fibromyalgia: A randomized controlled trial

ObjectivesThe aim of this study was to compare the effects of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) on pain and quality of life in patients with fibromyalgia.MethodsThirty participants were randomized into two groups of 15 patients, to receive 3 sessions of either high-frequency (10 Hz) rTMS or 2 mA, 20 min anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex (DLPFC) over 1 week. Pain was assessed using a Visual Analog Scale (VAS) before treatment, immediately after treatment, 6 and 12 weeks later. Quality of life was evaluated using the Revised Fibromyalgia Impact Questionnaire (FIQR) and psychiatric symptoms were measured using the Depression Anxiety Stress Scale-21 Item (DASS-21) before treatment, and 6 and 12 weeks after treatment.ResultsFor the VAS there was a significant time-group interaction, showing that the behavior of two groups differed regarding changes of VAS in favor of the RTMS group (df = 1.73, F = 4.80, p = <0.016). Time-group interaction effect on DASS-21 and FIQR was not significant. 66.6% of patients in rTMS group and 26.6% of patients in tDCS group experienced at least a 30% reduction of VAS from baseline to last follow-up (p = 0.028).DiscussionWith the methodology used in this study, both rTMS and tDCS were safe modalities and three sessions of rTMS over DLPFC had greater and longer lasting analgesic effects compared to tDCS in patients with FM. However, considering the limitations of this study, further studies are needed to explore the most effective modality.     

Effect of repetitive transcranial magnetic stimulation on the cognitive impairment induced by sleep deprivation: a randomized trial

ObjectiveCurrently, an efficient method for improving cognitive impairment due to sleep deprivation (SD) is lacking. The aim of this study is to evaluate the effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) during SD on reversing the adverse effects of SD.MethodsA total of 66 healthy people were randomized into the rTMS group and sham group. Both groups were deprived of sleep for 24 h. During SD, participants were asked to complete several cognitive tasks and underwent mood assessments. Saliva cortisol levels, plasma concentrations of brain-derived neurotrophic factor (BDNF), precursor BDNF (proBDNF), and tissue-type plasminogen activator (tPA), and frontal blood activation were detected before and after SD. The rTMS group received real rTMS stimulation for 2 sessions of 10 Hz rTMS (40 trains of 50 pulses with a 20-second intertrain interval) to the left dorsolateral prefrontal cortex and the sham group received sham stimulation during SD.ResultsTwenty-four hours of SD induced a reduced accuracy in the n-back task, increases in both anxiety and depression, increased cortisol levels, decreased frontal blood activation and decreased BDNF levels in healthy people. Notably, rTMS improved the hyperactivity of the hypothalamic-pituitary-adrenal axis and decreased frontal blood activation induced by SD, and reduced the consumption of plasma proBDNF.ConclusionsTwenty-four hours of SD induced a cognitive impairment. The administration of high-frequency rTMS during sleep deprivation exerted positive effects on HPA axis and frontal activation and might help alleviate cognitive impairment in the long term.     

Offset-related brain activity in the left ventrolateral prefrontal cortex promotes long-term memory formation of verbal events

BackgroundRecent evidence suggests that brain activity following the offset of a stimulus during encoding contributes to long-term memory formation, however the exact mechanisms underlying offset-related encoding are still unclear.ObjectivesHere, in three repetitive transcranial magnetic stimulation studies (rTMS) we investigated offset-related activity in the left ventrolateral prefrontal cortex (VLPFC). rTMS was administered at different points in time around stimulus offset while participants encoded visually-presented words or pairs of words. The analyses focused on the effects of the stimulation on subsequent memory performance.ResultsrTMS administered at the offset of the stimuli, but not during online encoding, disrupted subsequent memory performance. In Experiment 1 we found that rTMS specifically disrupted encoding mechanisms initiated by the offset of the stimuli rather than general, post-stimulus processes. Experiment 2 showed that this effect was not dependent upon rTMS-induced somatosensory effects. In a third rTMS experiment we further demonstrated a robust decline in associative memory performance when the stimulation was delivered at the offset of the word pairs, suggesting that offset-related encoding may contribute to the binding of information into an episodic memory trace.ConclusionsThe offset of the stimulus may represent an event boundary that promotes the reinstatement of the previously experienced event and episodic binding.