Associations between physical fitness and cerebellar gray matter volume in adolescents.

Despite the importance of the developing cerebellum on cognition, the associations between physical fitness and cerebellar volume in adolescents remain unclear. We explored the associations of physical fitness with gray matter (GM) volume of VI, VIIb and Crus I & II, which are cerebellar lobules related to cognition, in 40 (22 females; 17.9 ± 0.8 year-old) adolescents, and whether the associations were sex-specific. Peak oxygen uptake (V̇O2peak ) and power were assessed by maximal ramp test on a cycle ergometer, muscular strength with standing long jump (SLJ), speed-agility with the shuttle-run test (SRT), coordination with the Box and Block Test (BBT) and neuromuscular performance index (NPI) as the sum of SLJ, BBT and SRT z-scores. Body composition was measured using a dual-energy X-ray absorptiometry. Cerebellar volumes were assessed by magnetic resonance imaging. V̇O2peak relative to lean mass was inversely associated with the GM volume of the cerebellum (standardized regression coefficient (ß) = -0.038, 95% confidence interval (CI) -0.075 to 0.001, p = 0.044). Cumulative NPI was positively associated with the GM volume of Crus I (ß = 0.362, 95% CI 0.045 to 0.679, p = 0.027). In females, better performance in SRT was associated with a larger GM volume of Crus I (ß = -0.373, 95% CI -0.760 to -0.028, p = 0.036). In males, cumulative NPI was inversely associated with the GM volume of Crus II (ß = -0.793, 95% CI -1.579 to -0.008 p = 0.048). Other associations were nonsignificant. In conclusion, cardiorespiratory fitness, neuromuscular performance and speed-agility were associated with cerebellar GM volume, and the strength and direction of associations were sex-specific.

Cortical thickness is inversely associated with transcranial magnetic stimulation-evoked N45 potential among young adults whose heavy drinking began in adolescence.

BACKGROUND: Adolescence is a particularly vulnerable stage of development in terms of the deleterious effects of alcohol. Both lower gray matter (GM) volume and greater GABAergic activity have been associated with chronic alcohol consumption during adolescence. However, the association between these measures has not been investigated. METHODS: In this exploratory study, we compared 26 young adults with a 10year history of heavy alcohol consumption with 21 controls who used little or no alcohol. Simultaneous transcranial magnetic stimulation and electroencephalography were used to assess transcranial magnetic stimulation-evoked N45 potentials, reflecting a balance between GABAergic inhibition and N-methyl-D-aspartate (NMDA) receptor-mediated glutaminergic excitation in the brain. GM thickness was measured from magnetic resonance images and GM and N45 potentials were then correlated. RESULTS: Cortical thickness was significantly lower in several brain regions in the heavy-drinking group than the light-drinking group. The N45 amplitude was significantly larger frontally in the heavy-drinking group. Among heavy drinkers, there were several statistically significant correlations between thinner GM and larger frontal N45 amplitudes that were not detectable in the light-drinking group. The strongest correlations were detected in the frontal and parietal lobes, especially in the left superior frontal gyrus and the left supramarginal gyrus, and in both hemispheres in the superior parietal lobes. CONCLUSIONS: These findings show that a thinner cortex and greater inhibitory neurotransmission are correlated in certain brain regions among young, long-term heavy alcohol users. Studies are needed to explore the possible causal mechanisms underlying these effects.

TMS combined with EEG: Recommendations and open issues for data collection and analysis.

Transcranial magnetic stimulation (TMS) evokes neuronal activity in the targeted cortex and connected brain regions. The evoked brain response can be measured with electroencephalography (EEG). TMS combined with simultaneous EEG (TMS-EEG) is widely used for studying cortical reactivity and connectivity at high spatiotemporal resolution. Methodologically, the combination of TMS with EEG is challenging, and there are many open questions in the field. Different TMS-EEG equipment and approaches for data collection and analysis are used. The lack of standardization may affect reproducibility and limit the comparability of results produced in different research laboratories. In addition, there is controversy about the extent to which auditory and somatosensory inputs contribute to transcranially evoked EEG. This review provides a guide for researchers who wish to use TMS-EEG to study the reactivity of the human cortex. A worldwide panel of experts working on TMS-EEG covered all aspects that should be considered in TMS-EEG experiments, providing methodological recommendations (when possible) for effective TMS-EEG recordings and analysis. The panel identified and discussed the challenges of the technique, particularly regarding recording procedures, artifact correction, analysis, and interpretation of the transcranial evoked potentials (TEPs). Therefore, this work offers an extensive overview of TMS-EEG methodology and thus may promote standardization of experimental and computational procedures across groups.

The effect of shunt surgery on corticospinal excitability in idiopathic normal pressure hydrocephalus: a transcranial magnetic stimulation study.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a multifactorial disease presenting with a classical symptom triad of cognitive decline, gait disturbance and urinary incontinence. The symptoms can be alleviated with shunt surgery but the etiology of the symptoms remains unclear. Navigated transcranial magnetic stimulation (nTMS) was applied to characterize corticospinal excitability and cortical motor function before and after shunt surgery in order to elucidate the pathophysiology of iNPH. We also aimed to determine, whether nTMS could be applied as a predictive tool in the pre-surgical work-up of iNPH. METHODS: 24 patients with possible or probable iNPH were evaluated at baseline, after cerebrospinal fluid drainage test (TAP test) and three months after shunt surgery (follow-up). Symptom severity was evaluated on an iNPH scale and with clinical tests (walking test, Box & Block test, grooved pegboard). In the nTMS experiments, resting motor threshold (RMT), silent period (SP), input-output curve (IO-curve), repetition suppression (RS) and mapping of cortical representation areas of hand and foot muscles were assessed. RESULTS: After shunt surgery, all patients showed improved performance in gait and upper limb function. The nTMS parameters showed an increase in the RMTs (hand and foot) and the maximum value of the IO-curve increased in subject with a good surgical outcome. The improvement in gait correlated with an increase in the maximum value of the IO-curve. SP, RS and mapping remained unchanged. CONCLUSION: The excitability of the motor cortex and the corticospinal tract increased in iNPH patients after shunt surgery. A favorable clinical outcome of shunt surgery is associated with a higher ability to re-form and maintain neuronal connectivity.

Identifying novel biomarkers with TMS-EEG - Methodological possibilities and challenges.

Biomarkers are essential for understanding the underlying pathologies in brain disorders and for developing effective treatments. Combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) is an emerging neurophysiological tool that can be used for biomarker development. This method can identify biomarkers associated with the function and dynamics of the inhibitory and excitatory neurotransmitter systems and effective connectivity between brain areas. In this review, we outline the current state of the TMS-EEG biomarker field by summarizing the existing protocols and the possibilities and challenges associated with this methodology.

Fast acquisition of resting motor threshold with a stimulus-response curve - Possibility or hazard for transcranial magnetic stimulation applications?

OBJECTIVE: Previous research has suggested that transcranial magnetic stimulation (TMS) related cortical excitability measures could be estimated quickly using stimulus-response curves with short interstimulus intervals (ISIs). Here we evaluated the resting motor threshold (rMT) estimated with these curves. METHODS: Stimulus-response curves were measured with three ISIs: 1.2-2 s, 2-3 s, and 3-4 s. Each curve was formed with 108 stimuli using stimulation intensities ranging from 0.75 to 1.25 times the rMTguess, which was estimated based on motor evoked potential (MEP) amplitudes of three scout responses. RESULTS: The ISI did not affect the rMT estimated from the curves (F = 0.235, p = 0.683) or single-trial MEP amplitudes at the group level (F = 0.90, p = 0.405), but a significant subject by ISI interaction (F = 3.64; p < 0.001) was detected in MEP amplitudes. No trend was observed which ISI was most excitable, as it varied between subjects. CONCLUSIONS: At the group level, the stimulus-response curves are unaffected by the short ISI. At the individual level, these curves are highly affected by the ISI. SIGNIFICANCE: Estimating rMT using stimulus-response curves with short ISIs impacts the rMT estimate and should be avoided in clinical and research TMS applications.

TMS-EEG responses across the lifespan: Measurement, methods for characterisation and identified responses.

The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) allows probing of the neurophysiology of any neocortical brain area in vivo with millisecond accuracy. TMS-EEG is particularly unique compared with other available neurophysiological methods, as it can measure the state and dynamics of excitatory and inhibitory systems separately. Because of these capabilities, TMS-EEG responses are sensitive to the brain state, and the responses are influenced by brain maturation and ageing, making TMS-EEG a suitable method to study age-specific pathophysiology. In this review, we outline the TMS-EEG measurement procedure, the existing methods used for characterising TMS-EEG responses and the challenges associated with identifying the responses. We also summarise the findings thus far on how TMS-EEG responses change across the lifespan and the TMS-EEG features that separate typical and atypical brain maturation and ageing. Finally, we give an overview of the gaps in current knowledge to provide directions for future studies.

Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST-MST): protocol for identification of novel biomarkers via neurophysiology.

BACKGROUND: Electroconvulsive therapy (ECT) is the most effective treatment for treatment-resistant depression (TRD), especially for acute suicidal ideation, but the associated cognitive adverse effects and negative stigma limit its use. Another seizure therapy under development is magnetic seizure therapy (MST), which could potentially overcome the restrictions associated with ECT with similar efficacy. The neurophysiological targets and mechanisms of seizure therapy, however, remain poorly understood. METHODS/DESIGN: This neurophysiological study protocol is published as a companion to the overall Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST-MST) protocol that describes our two-site, double-blind, randomized, non-inferiority clinical trial to develop MST as an effective and safe treatment for TRD. Our aim for the neurophysiological component of the study is to evaluate two biomarkers, one to predict remission of suicidal ideation (primary outcome) and the other to predict cognitive impairment (secondary outcome). Suicidal ideation will be assessed through cortical inhibition, which according to our preliminary studies, correlates with remission of suicidal ideation. Cortical inhibition will be measured with simultaneous transcranial magnetic stimulation (TMS) and electroencephalography (EEG), TMS-EEG, which measures TMS-evoked EEG activity. Cognitive adverse effects associated with seizure therapy, on the contrary, will be evaluated via multiscale entropy analysis reflecting the complexity of ongoing resting-state EEG activity. DISCUSSION: ECT and MST are known to influence cortical inhibition associated with depression, suicidal ideation severity, and clinical outcome. Therefore, evaluating cortical inhibition and brain temporal dynamics will help understand the pathophysiology of depression and suicidal ideation and define new biological targets that could aid clinicians in diagnosing and selecting treatments. Resting-state EEG complexity was previously associated with the degree of cognitive side effects after a seizure therapy. This neurophysiological metric may help clinicians assess the risk for adverse effects caused by these useful and effective treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT03191058 . Registered on June 19, 2017.

Heavy drinking from adolescence to young adulthood is associated with an altered cerebellum.

Excessive alcohol use results in cerebellar damage in adults, but there has been less research on how alcohol use during adolescence affects the cerebellum. In this study, we observed that heavy drinking from adolescence to young adulthood was associated with altered volumes of cerebellar lobules. The study included two groups consisting of 33 heavy-drinking and 25 light-drinking participants. The heavy-drinking participants were highly functional young adults without alcohol use disorder, but with a history of regular heavy alcohol consumption. The participants were 13-18 years old at baseline and were followed for 10 years. At the age of 21-28 years, the participants underwent magnetic resonance imaging (MRI). From the MR images, the cerebellum was segmented into 12 lobules using the CERES pipeline. Heavy drinking did not influence the absolute cerebellar volume, but changes were observed in posterior cerebellar lobules associated with motor and cognitive functions. The absolute volume (p = 0.038) and gray matter volume (p = 0.034) of Crus II (hemispheres combined) were smaller in the heavy-drinking group. Furthermore, the relative volume of the right VIIIB lobule was larger in the HD group (p = 0.036). However, there were no differences in the absolute right VIIIB volumes (p = 0.198) between the groups. Our results suggest changes in the cerebellum in healthy young adults with a history of heavy drinking from adolescence. The exact implications and significance of these findings require further research.

Spatial extent of cortical motor hotspot in navigated transcranial magnetic stimulation.

BACKGROUND: Motor mapping with navigated transcranial magnetic stimulation (nTMS) requires defining a "hotspot", a stimulation site consistently producing the highest-amplitude motor-evoked potentials (MEPs). The exact location of the hotspot is difficult to determine, and the spatial extent of high-amplitude MEPs usually remains undefined due to MEP variability and the spread of the TMS-induced electric field (E-field). Therefore, here we aim to define the hotspot as a sub-region of a motor map. NEW METHOD: We analyzed MEP amplitude distributions in motor mappings of 30 healthy subjects in two orthogonal directions on the motor cortex. Based on the widths of these distributions, the hotspot extent was estimated as an elliptic area. In addition, E-field distributions induced by motor map edge stimulations were simulated for ten subjects, and the E-field attenuation was analyzed to obtain another estimate for hotspot extent. RESULTS: The median MEP-based hotspot area was 13 mm2 (95% confidence interval (CI) = [10, 18] mm2). The mean E-field-based hotspot area was 26 mm2 (95% CI = [13, 38] mm2). COMPARISON WITH EXISTING METHODS: In contrast to the conventional hotspot, the new definition considers its spatial extent, indicating the most easily excited area where subsequent nTMS stimuli should be targeted for maximal response. The E-field-based hotspot provides an estimate for the extent of cortical structures where the E-field is close to its maximum. CONCLUSIONS: The nTMS hotspot should be considered as an area rather than a single qualitatively defined spot due to MEP variability and E-field spread.

Transcranial Photobiomodulation (tPBM) With 1,064-nm Laser to Improve Cerebral Metabolism of the Human Brain In Vivo.

BACKGROUND AND OBJECTIVES: In our previous proof-of-principle study, transcranial photobiomodulation (tPBM) with 1,064-nm laser was reported to significantly increase concentration changes of oxygenated hemoglobin (∆[HbO]) and oxidized-state cytochrome c oxidase (∆[oxi-CCO]) in the human brain. This paper further investigated (i) its validity in two different subsets of young human subjects at two study sites over a period of 3 years and (ii) age-related effects of tPBM by comparing sham-controlled increases of ∆[HbO] and ∆[oxi-CCO] between young and older adults. STUDY DESIGN/MATERIALS AND METHODS: We measured sham-controlled ∆[HbO] and ∆[oxi-CCO] using broadband near-infrared spectroscopy (bb-NIRS) in 15 young (26.7 ± 2.7 years of age) and 5 older (68.2 ± 4.8 years of age) healthy normal subjects before, during, and after right-forehead tPBM/sham stimulation with 1,064-nm laser. Student t tests were used to test statistical differences in tPBM-induced ∆[HbO] and ∆[oxi-CCO] (i) between the 15 young subjects and those of 11 reported previously and (ii) between the two age groups measured in this study. RESULTS: Statistical analysis showed that no significant difference existed in ∆[HbO] and ∆[oxi-CCO] during and post tPBM between the two subsets of young subjects at two study sites over a period of 3 years. Furthermore, the two age groups showed statistically identical net increases in sham-controlled ∆[HbO] and ∆[oxi-CCO]. CONCLUSIONS: This study provided strong evidence to validate/confirm our previous findings that tPBM with 1,064-nm laser enables to increase cerebral ∆[HbO] and ∆[oxi-CCO] in the human brain, as measured by bb-NIRS. Overall, it demonstrated the robust reproducibility of tPBM being able to improve cerebral hemodynamics and metabolism of the human brain in vivo in both young and older adults. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals, Inc.

Corticospinal excitability in idiopathic normal pressure hydrocephalus: a transcranial magnetic stimulation study.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease with an unknown etiology. Disturbed corticospinal inhibition of the motor cortex has been reported in iNPH and can be evaluated in a noninvasive and painless manner using navigated transcranial magnetic stimulation (nTMS). This is the first study to characterize the immediate impact of cerebrospinal fluid (CSF) drainage on corticospinal excitability. METHODS: Twenty patients with possible or probable iNPH (16 women and 4 men, mean age 74.4 years, range 67-84 years), presenting the classical symptom triad and radiological findings, were evaluated with motor function tests (10-m walk test, Grooved Pegboard and Box & Block test) and nTMS (silent period, SP, resting motor threshold, RMT and input-output curve, IO-curve). Evaluations were performed at baseline and repeated immediately after CSF drainage via lumbar puncture. RESULTS: At baseline, iNPH patients presented shorter SPs (p < 0.001) and lower RMTs (p < 0.001) as compared to normative values. Positive correlation was detected between SP duration and Box & Block test (rho = 0.64, p = 0.002) in iNPH patients. CSF drainage led to an enhancement in gait velocity (p = 0.002) and a steeper IO-curve slope (p = 0.049). CONCLUSIONS: Shorter SPs and lower RMTs in iNPH suggest impaired corticospinal inhibition and corticospinal hyperexcitability. The steeper IO-slope in patients who improve their gait velocity after CSF drainage may indicate a higher recovery potential. Corticospinal excitability correlated with the motor function of the upper limbs implying that the disturbance in motor performance in iNPH extends beyond the classically reported gait impairment.

Transcranial photobiomodulation with 1064-nm laser modulates brain electroencephalogram rhythms.

Noninvasive transcranial photobiomodulation (tPBM) with a 1064-nm laser has been reported to improve human performance on cognitive tasks as well as locally upregulate cerebral oxygen metabolism and hemodynamics. However, it is unknown whether 1064-nm tPBM also modulates electrophysiology, and specifically neural oscillations, in the human brain. The hypothesis guiding our study is that applying 1064-nm tPBM of the right prefrontal cortex enhances neurophysiological rhythms at specific frequency bands in the human brain under resting conditions. To test this hypothesis, we recorded the 64-channel scalp electroencephalogram (EEG) before, during, and after the application of 11 min of 4-cm-diameter tPBM (CW 1064-nm laser with 162 mW / cm 2 and 107 J / cm 2 ) to the right forehead of human subjects ( n = 20 ) using a within-subject, sham-controlled design. Time-resolved scalp topographies of EEG power at five frequency bands were computed to examine the tPBM-induced EEG power changes across the scalp. The results show time-dependent, significant increases of EEG spectral powers at the alpha (8 to 13 Hz) and beta (13 to 30 Hz) bands at broad scalp regions, exhibiting a front-to-back pattern. The findings provide the first sham-controlled topographic mapping that tPBM increases the strength of electrophysiological oscillations (alpha and beta bands) while also shedding light on the mechanisms of tPBM in the human brain.

Functional and structural asymmetry in primary motor cortex in Asperger syndrome: a navigated TMS and imaging study.

Motor functions are frequently impaired in Asperger syndrome (AS). In this study, we examined the motor cortex structure and function using navigated transcranial magnetic stimulation (nTMS) and voxel-based morphometry (VBM) and correlated the results with the box and block test (BBT) of manual dexterity and physical activity in eight boys with AS, aged 8-11 years, and their matched controls. With nTMS, we found less focused cortical representation areas of distinct hand muscles in AS. There was hemispheric asymmetry in the motor maps, silent period duration and active MEP latency in the AS group, but not in controls. Exploratory VBM analysis revealed less gray matter in the left postcentral gyrus, especially in the face area, and less white matter in the precentral area in AS as compared to controls. On the contrary, in the right leg area, subjects with AS displayed an increased density of gray matter. The structural findings of the left hemisphere correlated negatively with BBT score in controls, whereas the structure of the right hemisphere in the AS group correlated positively with motor function as assessed by BBT. These preliminary functional (neurophysiological and behavioral) findings are indicative of asymmetry, and co-existing structural alterations may reflect the motor impairments causing the deteriorations in manual dexterity and other motor functions commonly encountered in children with AS.

Repeated Transcranial Magnetic Stimulation-Induced Motor Evoked Potentials Correlate With the Subject-Specific Serum Metabolic Profile of Creatine.

PURPOSE: Transcranial magnetic stimulation-induced motor responses have been considered to mainly reflect the electrophysiological characteristics of the central motor system. However, certain motor phenomena, such as the magnitude of repetition suppression measured with motor evoked potentials (MEPs), could also in part be influenced by metabolic processes in the peripheral muscles and in both the peripheral and central nervous system. Repetition suppression is an inhibitory phenomenon in which the amplitude of MEP decreases in comparison to that of the first MEP in a train of transcranial magnetic stimulation pulses. This study aimed to identify possible metabolic processes influencing repetition suppression. METHODS: The metabolic profiles from serum samples and repetition suppression from the right abductor pollicis brevis muscle were measured in 73 subjects (37 female subjects). Repetition suppression was measured using trains of transcranial magnetic stimulation stimuli consisting of 4 identical single pulses at 1-second intervals. The trains were repeated every 20 seconds, and 30 trains were given with a stimulation intensity of 120% of the resting motor threshold of the abductor pollicis brevis. Thus, a total of 120 stimuli were administered. RESULTS: The main finding was a significant negative relationship between serum creatine levels and the magnitude of repetition suppression (standardized ß coefficient (ß) = -0.43; P < 0.001). In other words, higher creatine levels corresponded to a smaller decrement in the MEP amplitude in response to repetition. When MEPs were not repeated, no relationship was observed (ß = 0.09; P = 0.454). Creatine is used to form phosphocreatine, which in turn is needed to resynthesize adenosine triphosphate from adenosine diphosphate in situations requiring high amounts of energy in muscles and neural cells. CONCLUSIONS: For the first time, this study demonstrated a connection between repeated MEPs and peripheral serum metabolites linked to muscle function. These findings could explain some of the intersubject variability commonly observed in MEPs when the pulses are repeated.

Maturation changes the excitability and effective connectivity of the frontal lobe: A developmental TMS-EEG study.

The combination of transcranial magnetic stimulation with simultaneous electroencephalography (TMS-EEG) offers direct neurophysiological insight into excitability and connectivity within neural circuits. However, there have been few developmental TMS-EEG studies to date, and they all have focused on primary motor cortex stimulation. In the present study, we used navigated high-density TMS-EEG to investigate the maturation of the superior frontal cortex (dorsal premotor cortex [PMd]), which is involved in a broad range of motor and cognitive functions known to develop with age. We demonstrated that reactivity to frontal cortex TMS decreases with development. We also showed that although frontal cortex TMS elicits an equally complex TEP waveform in all age groups, the statistically significant between-group differences in the topography of the TMS-evoked peaks and differences in current density maps suggest changes in effective connectivity of the right PMd with maturation. More generally, our results indicate that direct study of the brain's excitability and effective connectivity via TMS-EEG co-registration can also be applied to pediatric populations outside the primary motor cortex, and may provide useful information for developmental studies and studies on developmental neuropsychiatric disorders.

Cortical Inhibition of Face and Jaw Muscle Activity and Discomfort Induced by Repetitive and Paired-Pulse TMS During an Overt Object Naming Task.

Modulatory effects of transcranial magnetic stimulation (TMS) strongly depend on the stimulation parameters. Here, we compared the immediate, task-locked inhibitory effects on speech-related muscles and the tolerability of different TMS protocols during a language production task. Repetitive TMS (rTMS) and paired-pulse TMS (PP) were applied in 13 healthy subjects over the primary motor cortex (M1) during a finger-tapping/tongue-twisting tasks. The lowest subject-specific TMS intensity leading to movement disruptions was used for TMS over left-sided speech-related areas during picture naming. Here, time-locked PP and rTMS (10/30/50 Hz; randomized sequence) were applied. Cortical silent periods (cSPs) were analyzed from electromyography obtained from various face muscles. 30 Hz- and 50 Hz-rTMS reliably evoked tongue movement disruption (ICC = 0.65) at lower rTMS intensities compared to 10 Hz-rTMS or PP. CSPs were elicited from the left hemisphere by all TMS protocols, most reliably by PP (p < 0.001). Also, cSPs with longest durations were induced by PP. Exploratory analyses of PP suggest that the trials with strongest motor inhibitory effects (presence of cSP) were associated with more articulatory naming errors, hence hinting at the utility of TMS-elicited, facial cSP for mapping of language production areas. Higher-frequency rTMS and PP evoked stronger inhibitory effects as compared to 10 Hz-rTMS during a language task, thus enabling a probably more efficient and tolerable routine for language mapping. The spatial distribution of cranial muscle cSPs implies that TMS might affect not only M1, but also distant parts of the language network.

Magnetic Seizure Therapy: Towards Personalized Seizure Therapy for Major Depression.

Magnetic seizure therapy (MST) is a noninvasive neuromodulation therapy under investigation for the treatment of severe neuropsychiatric disorders. MST involves inducing a therapeutic seizure under anesthesia in a setting similar to electroconvulsive therapy (ECT). To date, randomized controlled trials suggest that MST has similar antidepressant efficacy as ECT, but without significant cognitive adverse effects. Large scale clinical trials are currently underway to confirm these preliminary findings. So far, there has only been one study evaluating the clinical predictors of response to MST and more research is needed. This study found that patients with fewer episodes of depression and a positive family history of depression had a better response to MST. Overall, the ability of MST to focus the delivery of the electric field and the resultant seizure makes targeting seizure therapy to specific brain regions possible, and further research will be helpful in identifying personalized targets to maximize clinical benefit. In this review, we describe MST methodology and how it could be individualized to each patient. We also summarize the clinical and cognitive effects of MST and provide indications of which patients may be most likely to benefit. Finally, we summarize the studied neurophysiological predictors of response.

A Critical Review and Synthesis of Clinical and Neurocognitive Effects of Noninvasive Neuromodulation Antidepressant Therapies.

There is a plethora of current and emerging antidepressant therapies in the psychiatric armamentarium for the treatment of major depressive disorder. Noninvasive neuromodulation therapies are one such therapeutic category; they typically involve the transcranial application of electrical or magnetic stimulation to modulate cortical and subcortical brain activity. Although electroconvulsive therapy (ECT) has been used since the 1930s, with the prevalence of major depressive disorder and treatment-resistant depression (TRD), the past three decades have seen a proliferation of noninvasive neuromodulation antidepressant therapeutic development. The purpose of this critical review was to synthesize information regarding the clinical effects, neurocognitive effects, and possible mechanisms of action of noninvasive neuromodulation therapies, including ECT, transcranial magnetic stimulation, magnetic seizure therapy, and transcranial direct current stimulation. Considerable research has provided substantial information regarding their antidepressant and neurocognitive effects, but their mechanisms of action remain unknown. Although the four therapies vary in how they modulate neurocircuitry and their resultant antidepressant and neurocognitive effects, they are nonetheless useful for patients with acute and chronic major depressive disorder and TRD. Continued research is warranted to inform dosimetry, algorithm for administration, and integration among the noninvasive neuromodulation therapies and with other antidepressant strategies to continue to maximize their safety and antidepressant benefit.