Theta Burst Transcranial Magnetic Stimulation Research Articles

Theta burst transcranial magnetic stimulation of the dorsomedial prefrontal cortex in schizophrenia and depression

Negative symptoms in schizophrenia and core depressive symptoms share phenomenology and repetitive transcranial magnetic stimulation (rTMS) is a treatment modality for both conditions. The most com ...

A useful electroencephalography (EEG) marker of brain plasticity: delta waves.

A useful electroencephalography (EEG) marker of brain plasticity: delta waves.

Bilateral prefrontal rTMS and theta burst TMS as an add-on treatment for depression: A randomized placebo controlled trial

Objectives. Repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral-prefrontal cortex (DLPFC) exerts antidepressant effects. In this randomised controlled clinical trial we aimed to test the safety and therapeutic efficacy of bilateral theta-burst stimulation (TBS) as an add-on therapy to standard treatment of major depression. Methods. Fifty-six patients diagnosed with a moderate to severe depressive episode received 15 daily treatments of either rTMS (110% motor-threshold; rightDLPFC, 1000 stimuli at 1 Hz + leftDLPFC, 1000 stimuli at 10 Hz), theta-burst stimulation (80% motor-threshold; rightDLPFC, continuous TBS, 1200 stimuli + leftDLPFC, intermittent TBS, 1200 stimuli), or sham TMS (N = 17, sham coil with the TBS protocol). Results. There was no significant effect in the primary outcome measures (change of the 21-item Hamilton Rating Scale for Depression). However, there was a tendency towards an increased responder rate at the end of the follow-up period for both active treatments as compared to sham, and this tendency was most pronounced for the TBS group. Conclusions. This pilot study did not reveal significant advantages of bilateral TBS or rTMS over sham treatment as an add-on treatment for major depression. A tendency towards a superior effect of bilateral TBS at the end of the follow-up period may warrant further studies.

Left middle temporal and inferior frontal regions contribute to speed of lexical decision: A TMS study

Activation of left anterior inferior frontal gyrus (aLIFG) and left middle temporal gyrus (LMTG) has been observed in some functional neuroimaging studies of lexical decision but not others. It is thus unclear whether these two regions are necessary for word recognition. By applying continuous theta-burst transcranial magnetic stimulation (TMS) which temporally suppresses local brain function, we examined whether aLIFG and LMTG play causal roles in word recognition in a visual lexical decision task (LDT). Furthermore, we manipulated stimulus onset asynchrony (SOA) between prime and target to test whether these regions contribute to word recognition differently. In the LDT task, target words were preceded by semantically related primes (Related Condition; RC) or semantically unrelated words (Unrelated Condition; UC), under both short (150ms) and long (600ms) SOA conditions. TMS of aLIFG and LMTG significantly affected the word recognition speed compared to TMS of Vertex. Our results provide evidence that both aLIFG and LMTG contribute to word recognition speed. Furthermore, at short SOA, TMS of aLIFG or LMTG prolonged reaction time (RT). In contrast, at long SOA, there was a significant region by SOA by TMS interaction such that TMS of aLIFG prolonged RT, whereas TMS of LMTG speeded RT. These results suggest that aLIFG and LMTG may play different roles in word recognition.

Antidepressant efficacy of theta-burst transcranial magnetic stimulation in treatment of first-episode depression: a randomized, double blind controlled trial

Objective To evaluate the antidepressant efficacy, cognitive effect and safety of theta-burst transcranial magnetic stimulation (TBS) in treatment of first-episode depression. Methods 43 hospitalized patients with first-episode depression meeting with Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) were randomly divided into theta-burst stimulation group(TBS group, n=21)and sham-stimulation group(sham group, n=22). All patients were treated at left dorsolateral prefrontal cortex (DLPFC) for 4 weeks, and were concomitantly taking venlafaxine (150-300)mg/d. Hamilton Depression Scale-24 was used to assess the severity of depression before treatment, at week 2 and week 4 in both groups. Wisconsin Card Sorting Test (WCST) and Continuous Performance Test (CPT) were used to estimate cognitive function of depression before and after treatment. Results There was no difference on HAMD score before treatment between two groups((38.2±7.1)vs.(37.5±6.8), t=0.314, P=0.754). The reduction of HAMD score in TBS group showed significantly faster than that in sham group at week 2 ((20.5±4.8)vs.(16.1±5.9), t=2.547, P=0.015) and week 4((30.3±5.2)vs.(26.0±6.3), t=2.318, P=0.026). After 2-week stimulation, the response rate was higher in TBS group than that in sham group (57.9%vs. 25%, χ2 =4.358, P=0.037). The response and remission rates were significantly higher in TBS group than those in sham group after 4-week stimulation period (94.7%vs.65%, χ2 =5.284, P=0.021; 78.9%vs.45%, χ2=4.744, P=0.029). The improvements on WCST and CPT after treatment in TBS group, such as categories completed, correct responses, error responses, perseverative responses errors, nonperseverative responses errors, CPT1, CPT2 and CPT3, were significant than those in sham group (P<0.05). Conclusions Theta-burst stimulation of the left dorsolateral prefrontal cortex is safe and well-tolerated, while offering the potential to enhance early effects and modulate cognition in first-episode depressive patients. Key words: Theta-burst stimulation; Transcranial magnetic stimulation; Depression

Global versus local: double dissociation between MT+ and V3A in motion processing revealed using continuous theta burst transcranial magnetic stimulation.

The functional properties of motion selective areas in human visual cortex, including V3A, MT+, and intraparietal sulcus (IPS) are not fully understood. To examine the functional specialization of these areas for global and local motion processing, we used off-line, neuronavigated, continuous theta burst (cTBS) transcranial magnetic stimulation to temporarily alter neural activity within unilateral V3A, MT+, and IPS. A within-subjects design was employed and stimulation sessions were separated by at least 24 h. In each session, subjects were asked to discriminate the global motion directions of successively presented random dot kinematograms (RDKs) before and after cTBS. RDKs were presented at either 100 or 40 % coherence in either the left or right visual field. We found that V3A stimulation selectively impaired discrimination of 100 % coherent motion, while MT+ stimulation selectively impaired discrimination of 40 % coherent motion. IPS stimulation impaired discrimination of both motion stimuli. All cTBS effects were specific to stimuli presented contralaterally to the stimulation site and vertex stimulation had no effect. The double dissociation between the cTBS effects on MT+ and V3A indicates distinct roles for these two regions in motion processing. Judging the direction of 100 % coherent motion can rely on local motion processing because every dot moves in the same direction. However, judging the global direction of 40 % coherent motion requires global processing. Thus, our results suggest separate, parallel processing of local and global motion in V3A and MT+, respectively, with the outputs of these two areas being combined within the IPS.

Intermittent theta-burst stimulation of the lateral cerebellum increases functional connectivity of the default network.

Cerebral cortical intrinsic connectivity networks share topographically arranged functional connectivity with the cerebellum. However, the contribution of cerebellar nodes to distributed network organization and function remains poorly understood. In humans, we applied theta-burst transcranial magnetic stimulation, guided by subject-specific connectivity, to regions of the cerebellum to evaluate the functional relevance of connections between cerebellar and cerebral cortical nodes in different networks. We demonstrate that changing activity in the human lateral cerebellar Crus I/II modulates the cerebral default mode network, whereas vermal lobule VII stimulation influences the cerebral dorsal attention system. These results provide novel insights into the distributed, but anatomically specific, modulatory impact of cerebellar effects on large-scale neural network function.

Combined TMS and fMRI Reveal Dissociable Cortical Pathways for Dynamic and Static Face Perception

Faces contain structural information, for identifying individuals, as well as changeable information, which can convey emotion and direct attention. Neuroimaging studies reveal brain regions that exhibit preferential responses to invariant [1, 2] or changeable [3-5] facial aspects but the functional connections between these regions are unknown. We addressed this issue by causally disrupting two face-selective regions with thetaburst transcranial magnetic stimulation (TBS) and measuring the effects of this disruption in local and remote face-selective regions with functional magnetic resonance imaging (fMRI). Participants were scanned, over two sessions, while viewing dynamic or static faces and objects. During these sessions, TBS was delivered over the right occipital face area (rOFA) or right posterior superior temporal sulcus (rpSTS). Disruption of the rOFA reduced the neural response to both static and dynamic faces in the downstream face-selective region in the fusiform gyrus. In contrast, the response to dynamic and static faces was doubly dissociated in the rpSTS. Namely, disruption of the rOFA reduced the response to static but not dynamic faces, while disruption of the rpSTS itself reduced the response to dynamic but not static faces. These results suggest that dynamic and static facial aspects are processed via dissociable cortical pathways that begin in early visual cortex, a conclusion inconsistent with current models of face perception [6-9].

Perfusion MRI indexes variability in the functional brain effects of theta-burst transcranial magnetic stimulation.

Transcranial Magnetic Stimulation (TMS) is an important tool for testing causal relationships in cognitive neuroscience research. However, the efficacy of TMS can be variable across individuals and difficult to measure. This variability is especially a challenge when TMS is applied to regions without well-characterized behavioral effects, such as in studies using TMS on multi-modal areas in intrinsic networks. Here, we examined whether perfusion fMRI recordings of Cerebral Blood Flow (CBF), a quantitative measure sensitive to slow functional changes, reliably index variability in the effects of stimulation. Twenty-seven participants each completed four combined TMS-fMRI sessions during which both resting state Blood Oxygen Level Dependent (BOLD) and perfusion Arterial Spin Labeling (ASL) scans were recorded. In each session after the first baseline day, continuous theta-burst TMS (TBS) was applied to one of three locations: left dorsolateral prefrontal cortex (L dlPFC), left anterior insula/frontal operculum (L aI/fO), or left primary somatosensory cortex (L S1). The two frontal targets are components of intrinsic networks and L S1 was used as an experimental control. CBF changes were measured both before and after TMS on each day from a series of interleaved resting state and perfusion scans. Although TBS led to weak selective increases under the coil in CBF measurements across the group, individual subjects showed wide variability in their responses. TBS-induced changes in rCBF were related to TBS-induced changes in functional connectivity of the relevant intrinsic networks measured during separate resting-state BOLD scans. This relationship was selective: CBF and functional connectivity of these networks were not related before TBS or after TBS to the experimental control region (S1). Furthermore, subject groups with different directions of CBF change after TBS showed distinct modulations in the functional interactions of targeted networks. These results suggest that CBF is a marker of individual differences in the effects of TBS.

P1081: Modulation of neocortical sensory processing by theta-burst transcranial magnetic stimulation in a rat model

P1081: Modulation of neocortical sensory processing by theta-burst transcranial magnetic stimulation in a rat model

P723: Therapeutic efficacy of continuous theta-burst magnetic stimulation (cTBS) in major depression: a double-blind sham-controlled study

In a previous open study (Chistyakov et al., 2010), we have demonstrated safety, tolerability and preliminary evidence of antidepressant properties of continuous theta-burst transcranial magnetic stimulation (cTBS) in patients with major depression (MD). The aim of the present study was to evaluate the therapeutic efficacy of cTBS in depressed patients using a double-blind sham-controlled design. A total of 29 patients with unipolar MD ( n =19) and bipolar depression ( n =10) were recruited for the study. Initially, patients were randomized to receive either active cTBS to the right dorsolateral prefrontal cortex ( n =15) or sham cTBS ( n =14) for 10 consecutive work days. After the 10th session, patients who received sham TMS were crossed over to the active cTBS treatment which consisted of 10 daily sessions. Patients who received active cTBS continued with the same treatment protocol for another 10 sessions. Each treatment session consisted of 3600 stimuli delivered in four consecutive trains of 900 stimuli each separated by a 15min interval at an intensity of 100% of the active motor threshold. Severity of depression was assessed weekly by the Hamilton Depression Rating Scale (HDRS) and Clinical Global Impression (CGI). Eight patients (27.6%) remained on their existing medication. In 18 patients (62.1%), medication status was changed before the trial. Three patients (10.3%) were medication free throughout the study. All but one patient from the sham-cTBS group completed the 2 week treatment protocol without any adverse effects. Two patients from the sham group dropped out 2 days after they crossed over to the active treatment. Following 2 and 4 weeks of treatment significant clinical improvement was observed in both active- and sham-TBS groups. Overall, there was no significant difference in the degree of clinical improvement between active and sham TBS groups after initial (2-week) as well as extended (4-week) phases of the trial. However, in patients whose medication status was not changed before the trial and in those who were medication free, active cTBS resulted in a significantly greater reduction of HDRS and CGI scores as compared to sham cTBS. The results of this study failed to demonstrate overall superiority of cTBS compared to sham treatment. However, cTBS might be beneficial in depressed patients who are nonresponsive to ongoing pharmacological treatment.

Theta-burst transcranial magnetic stimulation in depression: when less may be more.

This scientific commentary refers to ‘Efficacy of prefrontal theta-burst stimulation in refractory depression: a randomized sham-controlled study', by Li et al ., (doi:10.1093/brain/awu109). Major depressive disorder is associated with increased mortality, significant morbidity, and substantial impairments in functioning. It is estimated that by the year 2020, depression will be second only to heart disease in terms of disease burden as measured by disability-adjusted life years (Murray and Lopez, 1996). Treatment-resistant depression is conventionally defined as a failure to respond to at least two adequate medication trials or as a relapse during treatment; it represents a common dimension of this illness that translates into significant public healthcare costs. Only one-third of patients with major depressive disorder achieve full remission of their symptoms after a single trial of antidepressant medication and even with multiple medication trials, 30–40% of patients fail to respond fully (Keller et al. , 1992). Treatment-resistant depression is associated with significantly greater medical costs and productivity loss than treatment-responsive forms, highlighting the need for more effective non-pharmacological strategies. In this issue of Brain, Li et al. (2014). report data from a randomized sham-controlled study to show that a modified form of repetitive transcranial magnetic stimulation (TMS) produces therapeutic benefits in patients with treatment-resistant depression. High frequency (e.g. 10 Hz) repetitive TMS applied to the left dorsolateral prefrontal cortex is an FDA approved treatment for adults with resistant depression. A number of large multicentre studies and recent meta-analyses have indicated that high frequency repetitive TMS has reasonable therapeutic efficacy compared to sham stimulation. For example, O’Reardon et al. (2007) reported response rates of 24.5% with high frequency repetitive TMS compared to 13.7% with sham repetitive TMS following 6 weeks of treatment. In a recent meta-analysis, Berlim et al. (2014) reported response rates of 29.3% with high frequency repetitive …

Efficacy of prefrontal theta-burst stimulation in refractory depression: a randomized sham-controlled study.

Theta-burst transcranial magnetic stimulation could modulate cortical excitability and has the potential to treat refractory depression. However, there has been a lack of large randomized studies of the antidepressant efficacy of different forms of theta-burst stimulation, such as intermittent and continuous theta-burst stimulation. A randomized sham-controlled study was conducted to investigate antidepressant efficacy of theta-burst stimulation and to compare efficacy among left-prefrontal intermittent theta-burst stimulation, right-prefrontal continuous theta-burst stimulation and a combination of them in patients showing different levels of antidepressant refractoriness. A group of 60 treatment-refractory patients with recurrent major depressive disorder were recruited and randomized to four groups (Group A: continuous theta-burst stimulation; Group B: intermittent theta-burst stimulation; Group C: a combination of continuous and intermittent theta-burst stimulation; and Group D: sham theta-burst stimulation; 15 patients were included in each group). After 2 weeks of theta-burst stimulation treatment, depression improved in all groups. Groups B and C had better antidepressant responses (as reflected by % decreases in depression score) than Groups A and D (P = 0.001, post hoc analysis: B > A, B > D, C > A, and C > D), even after controlling for age and refractoriness scores. The mean antidepressant effect was highest in Group C and followed by that in Group B. Additionally, a significant placebo effect was found in patients with low refractoriness; this disappeared in patients with moderate-to-high refractoriness. A significant correlation existed between refractoriness scores and treatment responses. Treatment refractoriness was a significant factor negatively predicting efficacy of theta-burst stimulation (P = 0.039). This randomized sham-controlled study demonstrated that active theta-burst stimulation is a well-tolerated form of repetitive transcranial magnetic stimulation and has good antidepressant efficacy, particularly in depressed subjects within a certain range of treatment refractoriness.

In your eyes only: deficits in executive functioning after frontal TMS reflect in eye movements

This study investigated the roles of the right and left dorsolateral prefrontal (rDLPFC, lDLPFC) and the medial frontal cortex (MFC) in executive functioning using a theta burst transcranial magnetic stimulation (TMS) approach. Healthy subjects solved two visual search tasks: a number search task with low cognitive demands, and a number and letter search task with high cognitive demands. To observe how subjects solved the tasks, we assessed their behavior with and without TMS using eye movements when subjects were confronted with specific executive demands. To observe executive functions, we were particularly interested in TMS-induced changes in visual exploration strategies found to be associated with good or bad performance in a control condition without TMS stimulation. TMS left processing time unchanged in both tasks. Inhibition of the rDLPFC resulted in a decrease in anticipatory fixations in the number search task, i.e., a decrease in a good strategy in this low demand task. This was paired with a decrease in stimulus fixations. Together, these results point to a role of the rDLPFC in planning and response selection. Inhibition of the lDLPFC and the MFC resulted in an increase in anticipatory fixations in the number and letter search task, i.e., an increase in the application of a good strategy in this task. We interpret these results as a compensatory strategy to account for TMS-induced deficits in attentional switching when faced with high switching demands. After inhibition of the lDLPFC, an increase in regressive fixations was found in the number and letter search task. In the context of high working memory demands, this strategy appears to support TMS-induced working memory deficits. Combining an experimental TMS approach with the recording of eye movements proved sensitive to discrete decrements of executive functions and allows pinpointing the functional organization of the frontal lobes.

EPA-0228 - Non invasive brain stimulation in the treatment of schizophrenia

Auditory verbal hallucinations (AVH) are a characteristic symptom of schizophrenia. Previous studies have investigated 1-Hz repetitive transcranial magnetic stimulation (rTMS) to the left temporoparietal region as a non-invasive treatment option for treatment-resistant patients, with several studies with large sample sizes not demonstrating efficacy of rTMS compared to sham stimulation. A new stimulation protocol using continuous theta-burst rTMS could provide a more effective therapeutic option. In a double-blind study, forty-one patients with AVH were randomly allocated to either continuous theta-burst rTMS or sham treatment. The theta-burst TMS group received 10 treatments over left temporoparietal cortex distributed over five consecutive days. The placebo group received 10 treatments of sham stimulation following the same procedures as the theta-burst group. Severity of AVH was assessed using the psychotic symptom rating scales (PSYRATS), the auditory hallucinations rating scale (AHRS) and item P3 of the positive and negative syndrome scale (PANSS) before treatment, after five days of treatment, and during follow-up one month later. Data were analyzed using repeated measures ANOVA. Significant main effects of treatment were observed for the PSYRATS (p=0.017) and a trend was observed for the AHRS (p=0.053), indicating lower hallucination severity scores after treatment. No significant interaction effects were observed for any of the hallucination severity scales, indicating that AVH did not significantly improve after theta-burst stimulation compared to sham stimulation. These results suggest a placebo effect of continuous theta-burst rTMS on the left temporoparietal region.

Synaptic Plasticity and PDGF Signaling Defects Underlie Clinical Progression in Multiple Sclerosis

Neuroplasticity is essential to prevent clinical worsening despite continuing neuronal loss in several brain diseases, including multiple sclerosis (MS). The precise nature of the adaptation mechanisms taking place in MS brains, ensuring protection from disability appearance and accumulation, is however unknown. Here, we explored the hypothesis that long-term synaptic potentiation (LTP), potentially able to minimize the effects of neuronal loss by providing extra excitation of denervated neurons, is the most relevant form of adaptive plasticity in stable MS patients, and it is disrupted in progressing MS patients. We found that LTP, explored by means of transcranial magnetic theta burst stimulation over the primary motor cortex, was still possible, and even favored, in stable relapsing-remitting (RR-MS) patients, whereas it was absent in individuals with primary progressive MS (PP-MS). We also provided evidence that platelet-derived growth factor (PDGF) plays a substantial role in favoring both LTP and brain reserve in MS patients, as this molecule: (1) was reduced in the CSF of PP-MS patients, (2) enhanced LTP emergence in hippocampal mouse brain slices, (3) was associated with more pronounced LTP in RR-MS patients, and (4) was associated with the clinical compensation of new brain lesion formation in RR-MS. Our results show that brain plasticity reserve, in the form of LTP, is crucial to contrast clinical deterioration in MS. Enhancing PDGF signaling might represent a valuable treatment option to maintain brain reserve and to attenuate the clinical consequences of neuronal damage in the progressive phases of MS and in other neurodegenerative disorders.

P 39. Functional causality of the dorsal stream in sensorimotor integration of speech repetition

Acquisition of language skills is necessary for social interactions in humans, and speech repetition plays a fundamental role in its acquisition by mapping auditory speech input onto matching speech output. At the level of neuronal networks in the brain, speech repetition occurs within the auditory dorsal stream, which is constituted by a temporo-parieto-frontal network formed by the posterior part of superior temporal sulcus (pSTS), the posterior inferior frontal gyrus (pIFG), and the temporo-parietal junction (Tpj). However, it is less known which component of the dorsal stream plays an essential role in the modulation of speech repetition. To investigate the issue of causality of the dorsal stream in sensorimotor integration of speech repetition, we employed continuous theta-burst transcranial magnetic stimulation (cTBS) in order to disrupt neuronal activity in the stimulated areas. Nineteen right-handed German volunteers performed four behavioral speech tasks. (1) Word-picture matching test: subjects listened to a German noun and were asked to choose a picture which fit to the word heard from four different pictures; the target picture, pictures implying a phonemic or semantic error, and an unrelated picture. (2) Syllable repetition test: subjects listened to one of six different syllables and repeated the perceived syllable immediately. (3) Pseudo-word repetition test: subjects listened to meaningless pseudo-words and immediately repeated it. (4) Sentence repetition test: subjects listened to German sentences and immediately repeated it. In all the tests, error rates (ER) and reaction time (RT) were calculated. Inhibitory cTBS was applied over the individual activated regions of the left pIFG, Tpj, pSTS by using an fMRI-guided TMS neuronavigation system. Left middle occipital gyrus (MOG) was also stimulated as a control region to clarify the topographical specificity of cTBS effects because it is assumed that the MOG is concerned with visual processing. The behavioral speech tests were performed after cTBS over four sites mentioned above, and they were compared by repeated measures ANOVAs. (1) In word-picture matching test, cTBS of Tpj, pSTS and pIFG increased phonemic errors compared to cTBS of MOG. No other types of errors were affected by any sites of cTBS. (2) The syllable repetition ERs were significantly larger after cTBS of Tpj, pSTS and pIFG than after cTBS over MOG. (3) Pseudo-word repetition test demonstrated that ERs significantly increased after cTBS of Tpj and pSTS than after cTBS of MOG and pIFG. (4) In the sentence repetition test, no differences were observed in ERs between sites of cTBS. Throughout all the behavioral tests, RTs were not significantly different between sites of cTBS. Disruption of the dorsal stream led to increases of phonemic errors in word-picture matching test and to increases of errors of syllable and pseudo-word repetitions, demonstrating that the dorsal stream plays a crucial role in sensorimotor integration of phonological processing. The lack of cTBS effects on native sentences may be explained by the idea that the lexical/semantic material processing is done by the ventral auditory stream. The sensory phonological system performs critical modulation of subsequent articulation in the motor system via a sensorimotor interface, supporting evidence that the sensory system is situated hierarchically at higher level to modulate the motor articulation.

Continuous theta-burst stimulation modulates tactile synchronization

BackgroundTemporal order judgement (TOJ) is the ability to detect the order of occurrence of two sequentially delivered stimuli. Previous research has shown that TOJ in the presence of synchronized periodic conditioning stimuli impairs TOJ performance, and this phenomenon is suggested to be mediated by GABAergic interneurons that cause perceptual binding across the two skin sites. Application of continuous theta-burst repetitive TMS (cTBS) over primary somatosensory cortex (SI) alters temporal and spatial tactile perception. The purpose of this study was to examine TOJ perception in the presence and absence of synchronized periodic conditioning stimuli before and after cTBS applied over left-hemisphere SI. A TOJ task was administered on the right index and middle finger (D2 and D3) in two separate sessions in the presence and absence of conditioning stimuli (a background low amplitude sinusoidal vibration).ResultsCTBS reduced the impact of the conditioning stimuli on TOJ performance for up to 18 minutes following stimulation while sham cTBS did not affect TOJ performance. In contrast, the TOJ task performed in the absence of synchronized conditioning stimulation was unaltered following cTBS.ConclusionWe conclude that cTBS suppresses inhibitory networks in SI that mediate perceptual binding during TOJ synchronization. CTBS offers one method to suppress cortical excitability in the cortex and potentially benefit clinical populations with altered inhibitory cortical circuits. Additionally, TOJ measures with conditioning stimuli may provide an avenue to assess sensory processing in neurologically impaired patient populations.

Interleukin-1β Promotes Long-Term Potentiation in Patients with Multiple Sclerosis

The immune system shapes synaptic transmission and plasticity in experimental autoimmune encephalomyelitis (EAE), the mouse model of multiple sclerosis (MS). These synaptic adaptations are believed to drive recovery of function after brain lesions, and also learning and memory deficits and excitotoxic neurodegeneration; whether inflammation influences synaptic plasticity in MS patients is less clear. In a cohort of 59 patients with MS, we found that continuous theta-burst transcranial magnetic stimulation did not induce the expected long-term depression (LTD)-like synaptic phenomenon, but caused persisting enhancement of brain cortical excitability. The amplitude of this long-term potentiation (LTP)-like synaptic phenomenon correlated with the concentration of the pro-inflammatory cytokine interleukin-1β (IL-1β) in the cerebrospinal fluid. In MS and EAE, the brain and spinal cord are typically enriched of CD3(+) T lymphocyte infiltrates, which are, along with activated microglia and astroglia, a major cause of inflammation. Here, we found a correlation between the presence of infiltrating T lymphocytes in the hippocampus of EAE mice and synaptic plasticity alterations. We observed that T lymphocytes from EAE, but not from control mice, release IL-1β and promote LTP appearance over LTD, thereby mimicking the facilitated LTP induction observed in the cortex of MS patients. EAE-specific T lymphocytes were able to suppress GABAergic transmission in an IL-1β-dependent manner, providing a possible synaptic mechanism able to lower the threshold of LTP induction in MS brains. Moreover, in vivo blockade of IL-1β signaling resulted in inflammation and synaptopathy recovery in EAE hippocampus. These data provide novel insights into the pathophysiology of MS.

Continuous theta burst transcranial magnetic stimulation reduces resting state connectivity between visual areas

Continuous theta burst stimulation (cTBS) is a technique that allows for altering of brain activity. Research to date has focused on the effect of cTBS on the target area, but less is known about its effects on the resting state functional connectivity between different brain regions. We investigated this issue by applying cTBS to the occipital cortex and probing its influence in retinotopically defined regions in early visual cortex using functional MRI. We found that occipital cTBS reliably decreased the resting state functional connectivity (i.e., the correlation of spontaneous activity) between regions of the early visual cortex. In the context of a perceptual task, such an effect could mean that cTBS affects the strength of the perceptual signal, its variability, or both. We investigated this issue in a second experiment in which subjects performed a perceptual discrimination task and indicated their level of certainty on each trial. The results showed that occipital cTBS decreased both subjects' accuracy and confidence. Signal detection modeling suggested that these impairments resulted primarily from a decreased strength of the perceptual signal, with a nonsignificant trend of a decrease in signal variability. We discuss the implications of these experiments for understanding the mechanisms by which cTBS influences brain activity and perceptual processes.