Impact Of Transcranial Magnetic Stimulation Research Articles

Psychological Stress Analysis to Evaluate the Effects of Transcranial Magnetic Stimulation on Mood Regulation and Quality of Life in Patients with Bipolar Disorder.

To explore the impact of transcranial magnetic stimulation on emotion regulation and quality of life in patients with bipolar disorder (BD) and to evaluate the effectiveness of the mental stress analyzer. Patients with BD admitted to our hospital from August 2022 to August 2023 were retrospectively selected. For the present study, 60 patients who received drug therapy served as the control group, and the other 60 patients who received repeated transcranial stimulation on this basis served as the observation group. The heart rate variability (HRV) of the two groups of patients was detected by a mental stress analyzer/HRV analysis system. Hamilton Depression Rating Scale (HAMD), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) were used to evaluate the mental state of the two groups of patients. The quality of life of the two groups was assessed using the Comprehensive Quality of Life Questionnaire 74 (GQOLI-74). Clinical effectiveness global rating scale-illness severity (CGI-SI) was used to evaluate the clinical symptoms of the two groups of patients, and the incidence of adverse reactions was calculated. In comparison to the control group, the high-frequency power (HF) of the patients demonstrated an elevation in the observation group, and the low-frequency power (LF) and LF/HF were significantly reduced (p < 0.05). The standard deviation of NN intervals (SDNN), standard deviation of all five-minute NN intervals (SDANN), root mean square of successive differences (rMSSD), and percent RR intervals with a difference in duration higher than 50 ms (PNN50) of patients in the observation group showed a notable increase compared to the control group (p < 0.05). Compared with the control group, the HAMD, SAS, and SDS scores of the patients in the observation group demonstrated a substantial decline relative to the control group (p < 0.05). In contrast to the control group, there was a significant increase in the overall clinical effectiveness rate among patients in the observation group, and the incidence of adverse reactions was significantly reduced (p < 0.05). Repetitive transcranial magnetic stimulation (rTMS) has significant clinical effects in treating BD and can effectively improve patients' anxiety, suppress emotions, and regulate patients' emotions. At the same time, rTMS has high safety and little impact on the balance of patients' autonomic nervous function, reduces the incidence of adverse reactions, accelerates the patient's recovery process, and is suitable for clinical promotion.

Fatigue Potentially Reduces the Effect of Transcranial Magnetic Stimulation on Depression Following COVID-19 and Its Vaccination.

COVID-19's long-term effects, known as Long-COVID, present psychiatric and physical challenges in recovered patients. Similarly, rare long-term post-vaccination side effects, resembling Long-COVID, are emerging (called Post-Vaccine). However, effective treatments for both conditions are scarce. Our clinical experience suggests that transcranial magnetic stimulation (TMS) often aids recovery in Long-COVID and Post-Vaccine patients. However, its effectiveness is reduced in patients with severe fatigue. Therefore, we retrospectively analysed Tokyo TMS Clinic's outpatient records (60 in total; mean age, 38 years) to compare Long-COVID and post-vaccine patients' characteristics and symptoms, assess the impact of TMS on their symptoms, and investigate the role of fatigue in depression recovery with TMS. The primary outcome was the regression coefficient of the initial fatigue score on depression score improvement using TMS. Secondary outcomes included psychiatric/physical scores before and after TMS and their improvement rates. We found no differences in the initial symptoms and background factors between Long-COVID and Post-Vaccine patients. After ten TMS sessions, all psychiatric and physical symptom scores improved significantly. TMS improves depression, insomnia, anxiety, and related neuropsychiatric symptoms, which were the primary complaints in this study. Thus, we conclude that TMS improves depression and anxiety. The effectiveness of TMS in treating depression in Long-COVID and Post-Vaccine patients decreased as fatigue severity increased. In conclusion, TMS relieved depressive symptoms following COVID-19 and vaccination; however, fatigue may hinder its effectiveness.

Impact of transcranial magnetic stimulation on motor function in children with acquired brain injury: a scoping review protocol

BackgroundChildren with severe acquired brain injury (ABI) require early and effective neurorehabilitation provision to promote a good long-term functional outcome. Transcranial magnetic stimulation (TMS) has been used to improve motor...

Transcranial Stimulation for the Treatment of Stimulant Use Disorder

The increasing prevalence of stimulant use disorder (StUD) involving methamphetamine and cocaine has been a growing healthcare concern in the United States. Cocaine usage is associated with atherosclerosis, systolic and diastolic dysfunction, and arrhythmias. Furthermore, approximately one of every four MIs is cocaine-induced among patients aged 18 to 45. Methamphetamine use has been associated with nerve terminal damage in the dopaminergic system resulting in impaired motor function, cognitive decline, and co-morbid psychiatric disorders. Current treatment options for StUD are extremely limited, and there are currently no FDA-approved pharmacotherapies. Behavioral interventions are considered first-line treatment; however, in a recent meta-analysis comparing behavioral treatment options for cocaine, contingency management programs provided the only significant reduction in use. Current evidence points to the potential of various neuromodulation techniques as the next best modality in treating StUD. The most promising evidence thus far has been transcranial magnetic stimulation which several studies have shown to reduce risk factors associated with relapse. Another more invasive neuromodulation technique being studied is deep-brain stimulation, which has shown promising results in its ability to modulate reward circuits to treat addiction. Results showing the impact of transcranial magnetic stimulation (TMS) in the treatment of StUD are limited by the lack of studies conducted and the limited understanding of the neurological involvement driving addiction-based diseases such as StUD. Future studies should seek to provide data on consumption-reducing effects rather than craving evaluations.

Cortical-subcortical structural connections support transcranial magnetic stimulation engagement of the amygdala.

The amygdala processes valenced stimuli, influences emotion, and exhibits aberrant activity across anxiety disorders, depression, and PTSD. Interventions modulating amygdala activity hold promise as transdiagnostic psychiatric treatments. In 45 healthy participants, we investigated whether transcranial magnetic stimulation (TMS) elicits indirect changes in amygdala activity when applied to ventrolateral prefrontal cortex (vlPFC), a region important for emotion regulation. Harnessing in-scanner interleaved TMS/functional MRI (fMRI), we reveal that vlPFC neurostimulation evoked acute and focal modulations of amygdala fMRI BOLD signal. Larger TMS-evoked changes in the amygdala were associated with higher fiber density in a vlPFC–amygdala white matter pathway when stimulating vlPFC but not an anatomical control, suggesting this pathway facilitated stimulation-induced communication between cortex and subcortex. This work provides evidence of amygdala engagement by TMS, highlighting stimulation of vlPFC–amygdala circuits as a candidate treatment for transdiagnostic psychopathology. More broadly, it indicates that targeting cortical-subcortical structural connections may enhance the impact of TMS on subcortical neural activity and, by extension, subcortex-subserved behaviors.

The impact of Transcranial Magnetic Stimulation (TMS) on seizure course in people with and without epilepsy

ObjectiveTo elucidate the effects of single and paired-pulse TMS on seizure activity at electrographic and clinical levels in people with and without epilepsy. MethodsA cohort of 35 people with epilepsy, two people with alternating hemiplegia of childhood (AHC) with no epilepsy, and 16 healthy individuals underwent single or paired-pulse TMS combined with EEG. Clinical records and subject interviews were used to examine seizure frequency four weeks before and after TMS. ResultsThere were no significant differences in seizure frequency in any subject after TMS exposure. There was no occurrence of seizures in healthy individuals, and no worsening of hemiplegic attacks in people with AHC. ConclusionsNo significant changes in seizure activity were found before or after TMS. SignificanceThis study adds evidence on the safety of TMS in people with and without epilepsy with follow-up of four weeks after TMS.

State-dependent TMS effects in the visual cortex after visual adaptation: A combined TMS–EEG study

ObjectiveThe impact of transcranial magnetic stimulation (TMS) has been shown to depend on the initial brain state of the stimulated cortical region. This observation has led to the development of paradigms that aim to enhance the specificity of TMS effects by using visual/luminance adaptation to modulate brain state prior to the application of TMS. However, the neural basis of interactions between TMS and adaptation is unknown. Here, we examined these interactions by using electroencephalography (EEG) to measure the impact of TMS over the visual cortex after luminance adaptation. MethodsSingle-pulses of neuronavigated TMS (nTMS) were applied at two different intensities over the left visual cortex after adaptation to either high or low luminance. We then analyzed the effects of adaptation on the global and local cortical excitability. ResultsThe analysis revealed a significant interaction between the TMS-evoked responses and the adaptation condition. In particular, when nTMS was applied with high intensity, the evoked responses were larger after adaptation to high than low luminance. ConclusionThis result provides the first neural evidence on the interaction between TMS with visual adaptation. SignificanceTMS can activate neurons differentially as a function of their adaptation state.

Mapping causal circuit dynamics in stroke using simultaneous electroencephalography and transcranial magnetic stimulation

BackgroundMotor impairment after stroke is due not only to direct tissue loss but also to disrupted connectivity within the motor network. Mixed results from studies attempting to enhance motor recovery with Transcranial Magnetic Stimulation (TMS) highlight the need for a better understanding of both connectivity after stroke and the impact of TMS on this connectivity. This study used TMS-EEG to map the causal information flow in the motor network of healthy adult subjects and define how stroke alters these circuits.MethodsFourteen stroke patients and 12 controls received TMS to two sites (bilateral primary motor cortices) during two motor tasks (paretic/dominant hand movement vs. rest) while EEG measured the cortical response to TMS pulses. TMS-EEG based connectivity measurements were derived for each hemisphere and the change in connectivity (ΔC) between the two motor tasks was calculated. We analyzed if ΔC for each hemisphere differed between the stroke and control groups or across TMS sites, and whether ΔC correlated with arm function in stroke patients.ResultsRight hand movement increased connectivity in the left compared to the right hemisphere in controls, while hand movement did not significantly change connectivity in either hemisphere in stroke. Stroke patients with the largest increase in healthy hemisphere connectivity during paretic hand movement had the best arm function.ConclusionsTMS-EEG measurements are sensitive to movement-induced changes in brain connectivity. These measurements may characterize clinically meaningful changes in circuit dynamics after stroke, thus providing specific targets for trials of TMS in post-stroke rehabilitation.

The immediate impact of transcranial magnetic stimulation on brain structure: Short-term neuroplasticity following one session of cTBS

Recent evidence demonstrates that activation-dependent neuroplasticity on a structural level can occur in a short time (2 hour or less) in the human brain. However, the exact time scale of structural plasticity in the human brain remains unclear. Using voxel-based morphometry (VBM), we investigated changes in grey matter (GM) after one session of continuous theta-burst stimulation (cTBS) delivered to the anterior temporal lobe (ATL). Twenty-five participants received cTBS over the left ATL or the occipital pole as a control site outside of the scanner, followed by structural and functional imaging. During functional imaging, participants performed a semantic association task and a number judgment task as a control task. VBM results revealed decreased GM in the left ATL and right cerebellum after the ATL stimulation compared to the control stimulation. In addition, cTBS over the left ATL induced slower semantic reaction times, reduced regional activity at the target site, and altered functional connectivity between the left and right ATL during semantic processing. Furthermore, the decreased ATL GM density was associated with the interhemispheric ATL-connectivity changes after the ATL stimulation. These results demonstrate that structural alterations caused by one session of cTBS are mirrored in the functional reorganizations in the semantic representation system, showing the rapid dynamics of cortical plasticity. Our findings support fast adapting neuronal plasticity such as synaptic morphology changes. Our results suggest that TBS is able to produce powerful changes in regional synaptic activity in the adult human brain.

Statistical Analysis of Graph-Theoretic Indices to Study EEG-TMS Connectivity in Patients With Depression.

AimThe objective of this work was to demonstrate the usefulness of a novel statistical method to study the impact of transcranial magnetic stimulation (TMS) on brain connectivity in patients with depression using different stimulation protocols, i.e., 1 Hz repetitive TMS over the right dorsolateral prefrontal cortex (DLPFC) (protocol G1), 10 Hz repetitive TMS over the left DLPFC (G2), and intermittent theta burst stimulation (iTBS) consisting of three 50 Hz burst bundle repeated at 5 Hz frequency (G3).MethodsElectroencephalography (EEG) connectivity analysis was performed using Directed Transfer Function (DTF) and a set of 21 indices based on graph theory. The statistical analysis of graph-theoretic indices consisted of a combination of the k-NN rule, the leave-one-out method, and a statistical test using a 2 × 2 contingency table.ResultsOur new statistical approach allowed for selection of the best set of graph-based indices derived from DTF, and for differentiation between conditions (i.e., before and after TMS) and between TMS protocols. The effects of TMS was found to differ based on frequency band.ConclusionA set of four brain asymmetry measures were particularly useful to study protocol- and frequency-dependent effects of TMS on brain connectivity.SignificanceThe new approach would allow for better evaluation of the therapeutic effects of TMS and choice of the most appropriate stimulation protocol.

Effect of repetitive transcranial magnetic stimulation on fronto-posterior and hemispheric asymmetry in depression

AimThe objective of this work was to study the impact of Transcranial Magnetic Stimulation (TMS) on brain asymmetry in patients with depression using different stimulation protocols, i.e. 1 Hz repetitive TMS over the right dorsolateral prefrontal cortex (DLPFC) (protocol G1), 10 Hz repetitive TMS over the left DLPFC (G2), and intermittent theta burst stimulation (iTBS) consisting of three 50 Hz burst bundle repeated at 5 Hz frequency (G3). MethodsEEG analysis was performed using Directed Transfer Function (DTF) and four brain asymmetry measures. The Spearman correlations between the asymmetry measures and the scores of four psychiatric tests were calculated. ResultsThe left hemisphere activity decreased in lower frequency bands (i.e., theta and alpha) for G1 and also in higher frequency bands (i.e., beta and gamma) for G3. Moreover, frontal lobe activity decreased in theta, alpha, beta and gamma bands for G1, but increased in delta, theta, and alpha bands for G2. The highest correlations were found between the frontal-posterior asymmetry measure and the HAM-D test independently on the frequency band when the iTBS protocol was applied, whereas the application of 1 Hz rTMS protocol caused the changes in the hemispheric asymmetry in theta and alpha bands. ConclusionsFour brain asymmetry measures derived from DTF allowed for differentiation between conditions (i.e., before and after TMS) as well as between TMS protocols. SignificanceThe asymmetry measures allow for evaluation of the therapeutic effect of TMS and for the choice of the most appropriate stimulation protocol.

Changes in sleep with transcranial magnetic stimulation in adults with treatment resistant depression: Preliminary results from a naturalistic study

IntroductionSleep disturbance specifically insomnia, non-restorative sleep, and hypersomnia are common symptoms of major depressive disorder (MDD). As it alleviates major depressive disorder, transcranial magnetic stimulation (TMS) may improve associated sleep disturbances, and may also have inherent sedating or activating properties.ObjectivesTo examine the impact of TMS on sleep disturbances in adults with treatment resistant depression in a clinical setting, we retrospectively reviewed de-identified data from naturalistically-treated MDD patients undergoing an initial acute course of TMS therapy at St.Louis Park MinCEP Clinic.MethodsAdults with treatment-resistant depression received daily TMS treatments. 9-item Patient Health Questionnaire (PHQ-9) total scores were used to calculate % change at endpoint (relative to pretreatment baseline); response on both measures was defined as 50% reduction in scores, with remission defined as a final total score 4 on the PHQ-9. Insomnia was measured with a 3-item subscale of the Inventory of Depressive Symptomatology Self Report (IDS-SR). Hypersomnia was measured with a single IDS-SR item. Pairwise comparisons were performed using Student’s T-test. Categorical variables were compared using Fisher’s Exact test. Continuous outcome measures were tested with an analysis of covariance, using baseline PHQ-9 score as a fixed effect covariate.ResultsTMS appears to have differential modulatory effects on insomnia and hypersomnia in adults with treatment resistant depression.ConclusionsThese results may provide the basis for further investigation into therapeutic applications of TMS in addressing sleep disturbances in treatment-resistant depression. Measures that separate hypersomnia and insomnia should be implemented in future work addressing effects of TMS in treatment-resistant depression.DisclosureNo significant relationships.

The impact of transcranial magnetic stimulation (TMS) on irritability occurring with acute major depressive disorder (MDD).

To examine the impact (if any) of a course of transcranial magnetic stimulation (TMS) on irritability occurring in association with acute major depressive disorder (MDD). In a naturalistic study, patients with MDD according to DSM-5 criteria were given 20 daily TMS treatments. A visual analogue scale for irritability (VAS-I) was developed. Objective tools included the six-item Hamilton Depression Rating Scale (HAMDS6) and the Clinical Global Impression - Severity (CGI-S). Fifty patients received 53 courses. Forty-seven courses achieved remission on both HAMD6 and CGI-S and six courses did not achieve remission with either. Irritability significantly reduced when MDD remission was achieved but was unchanged when remission was not achieved. TMS reduces irritability occurring in association with MDD when this treatment affects MDD remission, but not when remission is not affected.

The impact of TMS and PNS frequencies on MEP potentiation in PAS with high-frequency peripheral component.

Paired associative stimulation (PAS) combines transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS) to induce plastic changes in the corticospinal tract. PAS employing single 0.2-Hz TMS pulses synchronized with the first pulse of 50–100 Hz PNS trains potentiates motor-evoked potentials (MEPs) in a stable manner in healthy participants and enhances voluntary motor output in spinal cord injury (SCI) patients. We further investigated the impact of settings of this PAS variant on MEP potentiation in healthy subjects. In experiment 1, we compared 0.2-Hz vs 0.4-Hz PAS. In experiment 2, PNS frequencies of 100 Hz, 200 Hz, and 400 Hz were compared. In experiment 3, we added a second TMS pulse. When compared with 0.4-Hz PAS, 0.2-Hz PAS was significantly more effective after 30 minutes (p = 0.05) and 60 minutes (p = 0.014). MEP potentiation by PAS with 100-Hz and 200-Hz PNS did not differ. PAS with 400-Hz PNS was less effective than 100-Hz (p = 0.023) and 200-Hz (p = 0.013) PNS. Adding an extra TMS pulse rendered PAS strongly inhibitory. These negative findings demonstrate that the 0.2-Hz PAS with 100-Hz PNS previously used in clinical studies is optimal and the modifications employed here do not enhance its efficacy.

Noninvasive Transcranial Magnetic Stimulation (TMS) in Chronic Refractory Pain: A Systematic Review.

Efficacy and tolerance of pharmacological medications in chronic pain are limited. Therefore, repetitive transcranial magnetic stimulation (rTMS) is regarded as a secure therapeutic option for pain relief, and it was proven to produce an analgesic effect. A wide variety of stimulation parameters can influence its long-lasting antalgic effect. Defining the best stimulation protocol can afford greater uniformity and consistency for considering rTMS as a promising effective tool. We aimed to systematically review and evaluate the current literature on transcranial magnetic stimulation for patients suffering from chronic pain, assess its efficacy, and estimate the best stimulation protocol. The Screened and tested electronic databases comprised PubMed, Ovid Medline, Cochrane database library, and Google scholar from the year 2000 till 2018. The keywords utilizing search terms “Transcranial magnetic stimulation”, “chronic pain”, “neuropathic pain” were used to study all possible randomized clinical trials about the impact of transcranial magnetic stimulation on long-lasting pain. All articles were judged for the possibility of prejudice using the Cochrane risk of bias tool for data extraction. Search engines produced seventy applicable results. Twelve randomized controlled clinical trials were included involving 350 patients with focal and generalized chronic pain. An existing proof showed a null response of low-frequency rTMS stimulation, rTMS delivered to the dorsolateral prefrontal cortex in chronic pain patients. However, a witnessed pain-killing response was documented when applying active high- frequency TMS on the motor cortex M1 area compared to sham. Pain relief was detected for a short time following the application of active high-frequency motor cortex stimulation in nine clinical trials, and the long-lasting analgesic effect was proved. No side effects were mentioned for the technique. Repetitive TMS can produce clinically meaningful relief from chronic pain, despite positive results, heterogeneity among all studies preclude firm conclusions regarding the optimal target stimulation site and parameters. Further studies are required to minimize bias, enhance performance, and define the best brain stimulation conditions and qualifications to maximize its potency.

Impact of transcranial magnetic stimulation on the symptom profile of major depressive episode.

This study aimed to explore the effects of a four-week course of transcranial magnetic stimulation (TMS) on the following symptoms of major depressive episode (MDE): mood, work activities, health concerns, guilt, anxiety and retardation. Patients underwent 20 daily sessions of 10 Hz TMS (two sets of 10 daily treatments separated by two days of rest). The six-item Hamilton Depression Rating Scale (HAMD-6) was administered before and after treatment. Remission was operationalised as a HAMD-6 score of <4. Descriptive statistics and t-tests were used to compare pre/post scores on HAMD-6 subscales, and logistic regression was used to understand symptoms that predicted remission/non-remission. There were 104 participants (79 female; 76%), with a mean age of 44.6 years (SD=15.7 years). There was a significant improvement in the whole sample and in remitters (n=70) on all subscales. However, those who failed to remit did not achieve significant reductions in 'health concerns' and 'retardation'. There were no difference in age and sex between remitters and non-remitters. Also, there were no significant differences between the remitters and non-remitters on the pretreatment depression symptom profiles. No predictors of response were identified, as expected. TMS has the ability to reduce all listed MDE symptoms. No pretreatment MDE symptom profile was identified which might carry prognostic value.

The impact of transcranial magnetic stimulation on diagnostic confidence in patients with Alzheimer disease

BackgroundCholinergic dysfunction is a key abnormality in Alzheimer disease (AD) that can be detected in vivo with transcranial magnetic stimulation (TMS) protocols. Although TMS has clearly demonstrated analytical validity, its clinical utility is still debated. In the present study, we evaluated the incremental diagnostic value, expressed in terms of diagnostic confidence of Alzheimer disease (DCAD; range 0–100), of TMS measures in addition to the routine clinical diagnostic assessment in patients evaluated for cognitive impairment as compared with validated biomarkers of amyloidosis.MethodsOne hundred twenty patients with dementia were included and scored in terms of DCAD in a three-step assessment based on (1) demographic, clinical, and neuropsychological evaluations (clinical work-up); (2) clinical work-up plus amyloid markers (cerebrospinal fluid or amyloid positron emission tomographic imaging); and (3) clinical work-up plus TMS intracortical connectivity measures. Two blinded neurologists were asked to review the diagnosis and diagnostic confidence at each step.ResultsTMS measures increased the discrimination of DCAD in two clusters (AD-like vs FTD-like) when added to the clinical and neuropsychological evaluations with levels comparable to established biomarkers of brain amyloidosis (cluster distance of 55.1 for clinical work-up alone, 76.0 for clinical work-up plus amyloid markers, 80.0 for clinical work-up plus TMS). Classification accuracy for the “gold standard” diagnosis (dichotomous - AD vs FTD - variable) evaluated in the three-step assessment, expressed as AUC, increased from 0.82 (clinical work-up alone) to 0.98 (clinical work-up plus TMS) and to 0.99 (clinical work-up plus amyloidosis markers).ConclusionsTMS in addition to routine assessment in patients with dementia has a significant effect on diagnosis and diagnostic confidence that is comparable to well-established amyloidosis biomarkers.

On the Mechanisms of Transcranial Magnetic Stimulation (TMS): How Brain State and Baseline Performance Level Determine Behavioral Effects of TMS.

The behavioral effects of Transcranial Magnetic Stimulation (TMS) can change qualitatively when stimulation is preceded by initial state manipulations such as priming or adaptation. In addition, baseline performance level of the participant has been shown to play a role in modulating the impact of TMS. Here we examined the link between these two factors. This was done using data from a previous study using a TMS-priming paradigm, in which, at group level, TMS selectively facilitated targets incongruent with the prime while having no statistically significant effects on other prime-target congruencies. Correlation and linear mixed-effects analyses indicated that, for all prime-target congruencies, a significant linear relationship between baseline performance and the magnitude of the induced TMS effect was present: low levels of baseline performance were associated with TMS-induced facilitations and high baseline performance with impairments. Thus as performance level increased, TMS effects turned from facilitation to impairment. The key finding was that priming shifted the transition from facilitatory to disruptive effects for targets incongruent with the prime, such that TMS-induced facilitations were obtained until a higher level of performance than for other prime-target congruencies. Given that brain state manipulations such as priming operate via modulations of neural excitability, this result is consistent with the view that neural excitability, coupled with non-linear neural effects, underlie behavioral effects of TMS.

Using neurostimulation to understand the impact of pre-morbid individual differences on post-lesion outcomes

Neuropsychological data have proven invaluable in advancing our understanding of higher cognition. The interpretation of such data is, however, complicated by the fact that post-lesion behavioral abnormalities could reflect pre-morbid individual differences in the cognitive domain of interest. Here we exploited the virtual lesion methodology offered by transcranial magnetic stimulation (TMS) to explore the impact of pre-morbid individual differences on post-lesion performance. We applied this approach to the domain of reading, a crucial ability in which there are known to be considerable individual differences in the normal population. As predicted by neuropsychological studies of surface dyslexia in semantic dementia and the connectionist triangle model of reading, previous empirical work has shown that healthy participants vary in their reliance on meaning for reading words with atypical correspondences between spelling and sound. We therefore selected participants who varied along this dimension and applied a virtual lesion to the left anterior temporal lobe. As expected, we observed a significant three-way interaction between "pre-morbid" reading status, stimulation, and word type, such that TMS increased the disadvantage for spelling-sound atypical words more for the individuals with stronger semantic reliance. This successful test-case study provides an approach to understanding the impact of pre-morbid individual variation on post-lesion outcomes that could be fruitfully applied to a variety of cognitive domains.

Common framework for “virtual lesion” and state-dependent TMS: The facilitatory/suppressive range model of online TMS effects on behavior

The behavioral effects of Transcranial Magnetic Stimulation (TMS) are often nonlinear; factors such as stimulation intensity and brain state can modulate the impact of TMS on observable behavior in qualitatively different manner. Here we propose a theoretical framework to account for these effects. In this model, there are distinct intensity ranges for facilitatory and suppressive effects of TMS – low intensities facilitate neural activity and behavior whereas high intensities induce suppression. The key feature of the model is that these ranges are shifted by changes in neural excitability: consequently, a TMS intensity, which normally induces suppression, can have a facilitatory effect if the stimulated neurons are being inhibited by ongoing task-related processes or preconditioning. For example, adaptation reduces excitability of adapted neurons; the outcome is that TMS intensities which inhibit non-adapted neurons induce a facilitation on adapted neural representations, leading to reversal of adaptation effects. In conventional “virtual lesion” paradigms, similar effects occur because neurons not involved in task-related processes are inhibited by the ongoing task. The resulting reduction in excitability can turn high intensity “inhibitory” TMS to low intensity “facilitatory” TMS for these neurons, and as task-related neuronal representations are in the inhibitory range, the outcome is a reduction in signal-to-noise ratio and behavioral impairment.