Alpha power increase after transcranial alternating current stimulation at alpha frequency (α-tacs) reflects plastic changes rather than entrainment

Background: Periodic stimulation of occipital areas using transcranial alternating current stimulation (tACS) at alpha (α) frequency (8–12 Hz) enhances electroencephalographic (EEG) α-oscillation long after tACS-offset. Two mechanisms have been suggested to underlie these changes in oscillatory EEG activity: tACS-induced entrainment of brain oscillations and/or tACS-induced changes in oscillatory circuits by spike-timing dependent plasticity.<p></p> Objective: We tested to what extent plasticity can account for tACS-aftereffects when controlling for entrainment “echoes.” To this end, we used a novel, intermittent tACS protocol and investigated the strength of the aftereffect as a function of phase continuity between successive tACS episodes, as well as the match between stimulation frequency and endogenous α-frequency.<p></p> Methods: 12 healthy participants were stimulated at around individual α-frequency for 15–20 min in four sessions using intermittent tACS or sham. Successive tACS events were either phase-continuous or phase-discontinuous, and either 3 or 8 s long. EEG α-phase and power changes were compared after and between episodes of α-tACS across conditions and against sham.<p></p> Results: α-aftereffects were successfully replicated after intermittent stimulation using 8-s but not 3-s trains. These aftereffects did not reveal any of the characteristics of entrainment echoes in that they were independent of tACS phase-continuity and showed neither prolonged phase alignment nor frequency synchronization to the exact stimulation frequency.<p></p> Conclusion: Our results indicate that plasticity mechanisms are sufficient to explain α-aftereffects in response to α-tACS, and inform models of tACS-induced plasticity in oscillatory circuits. Modifying brain oscillations with tACS holds promise for clinical applications in disorders involving abnormal neural synchrony

Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee

These guidelines provide an up-date of previous IFCN report on "Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application" (Rossini et al., 1994). A new Committee, composed of international experts, some of whom were in the panel of the 1994 "Report", was selected to produce a current state-of-the-art review of non-invasive stimulation both for clinical application and research in neuroscience. Since 1994, the international scientific community has seen a rapid increase in non-invasive brain stimulation in studying cognition, brain-behavior relationship and pathophysiology of various neurologic and psychiatric disorders. New paradigms of stimulation and new techniques have been developed. Furthermore, a large number of studies and clinical trials have demonstrated potential therapeutic applications of non-invasive brain stimulation, especially for TMS. Recent guidelines can be found in the literature covering specific aspects of non-invasive brain stimulation, such as safety (Rossi et al., 2009), methodology (Groppa et al., 2012) and therapeutic applications (Lefaucheur et al., 2014). This up-dated review covers theoretical, physiological and practical aspects of non-invasive stimulation of brain, spinal cord, nerve roots and peripheral nerves in the light of more updated knowledge, and include some recent extensions and developments

Repetitive Transcranial Magnetic Stimulation by Theta Burst

Transcranial magnetic stimulation (TMS) is a non-invasive diagnostic and therapeutic technique used to stimulate the brain in several neurological and psychiatric diseases, even though the main bases underlying its action are not fully understood. Theta Burst Stimulation (TBS), a patterned form of repetitive TMS, has been assuming particular importance due to its faster application. Research of TBS effects on some higher cortical functions such as cognition after stimulation of the prefrontal cortex (PFC), or its possible influence in some less studied cortical regions (as the temporal cortex) has been limited and revealed inconsistent results. One of the problems assessing the cognitive TBS after-effects relates to the use of multiple evaluation methods, with different sensitivities. In this matter, the use of neurophysiology studies such as the auditory P300, a cognitive evoked potential, may be of particular importance. To date, studies addressing the association between auditory P300 and TBS are scarce, and some contradictory results were found. The study of other higher cognitive domains such as creativity is even rarer, but it may be relevant given that part of the neural networks involved in creative processing are associated with the PFC. The effect of TMS over the PFC, studying the modulation of functions mediated by the autonomic nervous system has also been reported, but there is still a significant disagreement between the rare studies performed. So far, the extent of the modulatory effects associated with TBS at the sensory level is still poorly known, and research with TBS over the auditory cortex, despite showing some positive results, remains inconclusive, with some reports of sound hypersensitivity after sessions with higher intensity stimulation. It should also be noted that a significant part of the knowledge about the effects of TBS derives from studies in patients, with dysfunctional neuronal networks or hemispheric lesions, which add challenges to the search for scientific evidence in healthy individuals. Given the uncertainties that remain regarding the extent of the neuromodulatory effects of TBS, the primary objective of this thesis focused on increasing the scientific knowledge related to the use of TBS in the healthy brain. Therefore, we intended to study the neurophysiological responses (such as auditory P300), the functional responses (such as auditory thresholds), and the physiological responses (such as cerebral oximetry and blood pressure) associated with the application of TBS in the prefrontal and temporal cortices. All studies used a target population of healthy young adults, with an average age of approximately 23 years, and similar education. TBS was performed accordingly to the 600-pulse paradigm described by Huang et al. (continuous and intermittent). Sham-controlled, double-blind intervention protocols were used, with random distribution by the respective groups. The main objective of the study in chapter III was to evaluate the effect of TBS on the dorsolateral prefrontal cortex (DLPFC) of both cerebral hemispheres in cognitive processing. The objective was to assess if the auditory P300 would be influenced by the stimulation type. Results revealed that the mean P300 peak latency after TBS decreased only after leftward iTBS. A significant delay in P300 latency was originated from both right and left cTBS. Amplitude response did not change significantly. The results covered in chapter IV derived from the use of TBS on the left DLPFC, studying the possibility of a relationship between the post-TBS auditory P300 and the post-TBS neuropsychological tests: Trail Making Test (TMT) and the Stroop Test of Words and Colours. Results revealed that cTBS led to a delay of the P300, also significantly influencing the expected performance on Stroop C and Stroop Interference when compared to the groups submitted to iTBS and sham stimulation. No significant results were found in the TMT tests for any type of TBS stimulation. In Chapter V, we studied the cerebral oximetry using Near Infra-Red Spectroscopy, blood pressure, and heart rate, after applying TBS to the right and left DLPFC. We found a significant reduction in oximetry in the left frontal region after ipsilateral cTBS and a significant decrease in systolic blood pressure after cTBS to the right DLPFC. Chapter VI covered the evaluation of the effects of TBS over the left temporal cortex, specifically studying the auditory thresholds in the ear closest to the coil. Results showed no major side effects after iTBS, cTBS, or sham stimulation. It was also found that iTBS led to lower hearing thresholds, especially when comparing the iTBS and sham groups at 500Hz and between the iTBS and cTBS groups at 4000Hz. Chapter VII addresses a patent concerning the technique and possible use of iTBS as a method to influence creative processing. After iTBS over the right DLPFC, results of an adapted selection of the Torrance Tests of Creative Thinking suggest that divergent thinking, originality and fluency improved significantly compared to the sham group. An integrative analysis of the results shows that TBS seems to effectively influence the underlying cortical neurons and cortico-subcortical networks. The findings thus support the existence of a trans-synaptic effect advocated initially for the classic repetitive TMS, which after the publication of our research can continue to be extended with greater confidence to TBS protocols. Our results also support the most consensual theory about the modulatory effects of the two main forms of TBS – intermittent (excitatory) and continuous (inhibitory) – particularly on the prefrontal and temporal cortices. The effects of TBS seem to be intrinsically correlated with the hemispheric lateralization and this may be related to the specific functions or dominance of each hemisphere and the specific stimulated cortical regions. The combined results of this investigation also seem to suggest that the inhibition induced by cTBS seems more effective when compared to the excitatory effect of iTBS, which seemed stronger in the left hemisphere. After all our research with TBS in more than one cortical region, we can infer that this is a safe technique, with rare and incipient side effects. The encouraging results after using iTBS in the auditory cortex opens new perspectives regarding future implementations of the technique and should be replicated in patients, particularly with mild sensorineural hearing loss, in order to assess whether this stimulation protocol can be a valid therapeutic technique in these cases. We also conclude that the techniques used to study TBS-related effects, as the P300 or the NIRS, can be very useful in the future, as an attempt to identify the effectiveness of the therapeutic use of TBS protocols, possibly allowing to adapt and modify the idealized interventions, leading to a personalized patient intervention. Our findings provide relevant information, necessary to increase the technical and scientific credibility required for achieving a more comprehensive and reliable clinical use of TBS. This is crucial at a time when transcranial magnetic stimulation use as an off-label therapy for numerous neurological and psychiatric diseases grows unregulated, and the patient best interests must be defended.A estimulação magnética transcraniana (EMT) é uma técnica de diagnóstico e terapêutica não invasiva, que tem vindo a evoluir nos últimos 35 anos. A aplicação terapêutica da forma repetitiva da EMT (EMTr), tem vindo a demonstrar a sua utilidade científica e clínica, com aplicação em várias doenças neurológicas e psiquiátricas como a depressão major, a perturbação obsessivo-compulsiva, dor e reabilitação em doentes com acidentes vasculares cerebrais, ainda que as principais bases subjacentes à sua acção não sejam totalmente compreendidas. A EMT baseia-se no princípio da indução magnética e na sua capacidade de induzir correntes elétricas no tecido cortical. Esses campos magnéticos (pulsos) originados por uma bobina adjacente ao couro cabeludo originam um fluxo iónico intracraniano que irá provocar a despolarização da membrana neuronal, desencadeando assim um potencial de ação. Embora a EMT exerça os seus efeitos predominantemente na área cortical adjacente à bobina, os potenciais de ação induzidos espalham-se trans-sinapticamente, originando a propagação da ativação para regiões corticais e subcorticais vizinhas pertencentes à rede neuronal em questão. Parece ocorrer ainda a aparente capacidade de influenciar a função do hemisfério contralateral à estimulação possivelmente por mediação calossal. Os efeitos da EMTr ao nível da modulação da excitabilidade neuronal estão intrinsecamente dependentes das características da estimulação, nomeadamente ao nível da frequência e padronização dos estímulos. A aplicação de frequências inferiores ou iguais a 1 Hz (EMTr de baixa frequência) são associadas à indução de um efeito inibitório neuronal, enquanto que a aplicação de frequências acima de 1 Hz, normalmente acima dos 5 Hz (EMTr de alta frequência), podem induzir um efeito excitatório. Em 2005 surgiu uma forma padronizada de aplicação dos pulsos magnéticos, denominada Theta Burst Stimulation (TBS), na qual grupos de 3 pulsos com alta frequência (bursts de 50Hz) são enviados a cada 200 milissegundos (5 Hz – frequência teta), implicando normalmente a aplicação de 600 pulsos por cada sessão de estimulação. Este é um protocolo que assume particular importância pela sua rápida aplicação, levando menos de 3 minutos a executar, sendo significativamente mais célere do que os protocolos clássicos de EMTr (que podem exceder 30 minutos). Efeitos neuromodulatórios opostos podem ser igualmente induzidos com TBS, sendo que a aplicação ininterrupta da estimulação durante 40 segundos – TBS contínua (cTBS) – parece originar uma diminuição na excitabilidade cortical com uma duração de até 50 minutos pós-estimulação, enquanto que a aplicação de apenas 2 segundos de TBS intervalada por 8 segundos de pausa – TBS intermitente (iTBS) – durante 190 segundos, terá a capacidade de induzir aumento na excitabilidade cortical até cerca de 60 minutos pós-estimulação. Apesar do volume significativo de investigação acumulada na estimulação com EMTr e TBS, demonstrando a sua capacidade modulatória e a sua aplicabilidade na prática clínica, a investigação dos seus efeitos sobre algumas funções corticais superiores como a cognição ou os efeitos da aplicação em algumas regiões corticais menos estudadas como a região temporal tem sido mais limitada (principalmente com a TBS) e apresentado alguns resultados contraditórios. O córtex pré-frontal assume particular importância associado à aplicação da EMTr/TBS dada a extensa rede de conexões com outras regiões corticais (como o córtex motor, o córtex sensitivo, a amígdala, o tálamo e o hipocampo), importantes em doenças como a depressão (desequilíbrio inter-hemisférico pré-frontal verificado por neuroimagem), e ainda pela sua aparente capacidade de influenciar funções autonómicas e cardiovasculares. Meta-análises como a de Lowe et al. 2018, avaliando os efeitos da TBS sobre o córtex pré-frontal, revelam que parece existir um efeito negativo no desempenho das tarefas de função executiva após estimulação com cTBS e um efeito positivo mas em menor grau após estimulação com iTBS. No entanto, o efeito mais definido da estimulação sobre as várias dimensões cognitivas permanece envolto em alguma dúvida, dado que por um lado têm surgido alguns resultados negativos e por outro lado a maioria dos estudos tem usado populações relativamente pequenas, com infrequente recurso a grupos sham. Um dos principais problemas na avaliação dos possíveis efeitos da estimulação magnética repetitiva prende-se com o uso de diversos métodos de avaliação, com diferentes sensibilidades para o estudo das várias dimensões cognitivas, ou ainda com técnicas com menor resolução temporal (como os estudos de imagem cerebral funcional) comparativamente a técnicas neurofisiológicas. Neste ponto, a utilização de estudos no âmbito da neurofisiologia, como os potenciais de longa latência, pode assumir particular importância. O P300 auditivo, é um potencial evocado cognitivo, dependente da atenção e capacidade de discriminação do sujeito, traduzindo estadios mais superiores ou avançados de processamento associado a uma tarefa. As origens neuronais do P300 são múltiplas e bi-hemisféricas, associando-se a regiões como o hipocampo, o córtex pré-frontal ventrolateral e o córtex cingulado posterior. Até à data, são raros os estudos que abordaram a associação entre o P300 auditivo e a EMTr e ainda mais raros combinando a estimulação com TBS e o P300. A avaliação dos resultados prévios sugere que a estimulação magnética pode ser capaz de influenciar o processamento cognitivo e que as alterações podem ser monitorizadas pelo P300, mas são encontrados alguns resultados contraditórios, existindo significativas discrepâncias na metodologia usada. […

Motor imagery and motor illusion: from plasticity to a translational approach

Motor imagery e illusione motoria: dalla plasticit\ue0 ad un approccio traslazional