Mapping the visual brain areas susceptible to phosphene induction through brain stimulation.

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique whose effects on neural activity can be uncertain. Within the visual cortex, phosphenes are a useful marker of TMS: They indicate the induction of neural activation that propagates and creates a conscious percept. However, we currently do not know how susceptible different areas of the visual cortex are to TMS-induced phosphenes. In this study, we systematically map out locations in the visual cortex where stimulation triggered phosphenes. We relate this to the retinotopic organization and the location of object- and motion-selective areas, identified by functional magnetic resonance imaging (fMRI) measurements. Our results show that TMS can reliably induce phosphenes in early (V1, V2d, and V2v) and dorsal (V3d and V3a) visual areas close to the interhemispheric cleft. However, phosphenes are less likely in more lateral locations (hMT+/V5 and LOC). This suggests that early and dorsal visual areas are particularly amenable to TMS and that TMS can be used to probe the functional role of these areas.This study was funded by the European Community’s Seventh Framework Programme (FP7/2007-2013) under agreement PITN-GA-2011-290011 and the Welcome Trust (095183/Z/10/Z).This is the final version of the article. It first appeared from Springer via https://doi.org/10.1007/s00221-016-4784-

Modeling transcranial magnetic stimulation from the induced electric fields to the membrane potentials along tractography-based white matter fiber tracts

Objective. Transcranial magnetic stimulation (TMS) is a promising non-invasive tool for modulating the brain activity. Despite the widespread therapeutic and diagnostic use of TMS in neurology and psychiatry, its observed response remains hard to predict, limiting its further development and applications. Although the stimulation intensity is always maximum at the cortical surface near the coil, experiments reveal that TMS can affect deeper brain regions as well. Approach. The explanation of this spread might be found in the white matter fiber tracts, connecting cortical and subcortical structures. When applying an electric field on neurons, their membrane potential is altered. If this change is significant, more likely near the TMS coil, action potentials might be initiated and propagated along the fiber tracts towards deeper regions. In order to understand and apply TMS more effectively, it is important to capture and account for this interaction as accurately as possible. Therefore, we compute, next to the induced electric fields in the brain, the spatial distribution of the membrane potentials along the fiber tracts and its temporal dynamics. Main results. This paper introduces a computational TMS model in which electromagnetism and neurophysiology are combined. Realistic geometry and tissue anisotropy are included using magnetic resonance imaging and targeted white matter fiber tracts are traced using tractography based on diffusion tensor imaging. The position and orientation of the coil can directly be retrieved from the neuronavigation system. Incorporating these features warrants both patient- and case-specific results. Significance. The presented model gives insight in the activity propagation through the brain and can therefore explain the observed clinical responses to TMS and their inter- and/or intra-subject variability. We aspire to advance towards an accurate, flexible and personalized TMS model that helps to understand stimulation in the connected brain and to target more focused and deeper brain regions

Cortical mapping of the neuronal circuits modulating the muscle tone. Introduction to the electrophysiological treatment of the spastic hand

L'objectiu d'aquest estudi es investigar l'organització cortical junt amb la connectivitat còrtico-subcortical en subjectes sans, com a estudi preliminar. Els mapes corticals s'han fet per TMS navegada, i els punts motors obtinguts s'han exportant per estudi tractogràfic i anàlisi de las seves connexions. El coneixement precís de la localització de l'àrea cortical motora primària i les seves connexions es la base per ser utilitzada en estudis posteriors de la reorganització cortical i sub-cortical en pacients amb infart cerebral. Aquesta reorganització es deguda a la neuroplasticitat i pot ser influenciada per els efectes neuromoduladors de la estimulació cerebral no invasiva.The purpose of this study is to investigate the motor cortex organisation together with the cortico-subcortical connectivity in healthy subjects, as a preliminary study. Cortical maps have been performed by navigated TMS and the motor points have been exported to DTI to study their subcortical connectivity. The precise knowledge of localization of the primary motor cortex area and its connectivity is the base to be used in later studies of cortical and subcortical re-organisation in stroke patients. This re-organisation is due to the neuroplascity and can be influenced by the neuromodulation effects of the non-invasive cerebral stimulation therapy by TMS

The neural processes generating visual phenomenal consciousness: ERP and neuronavigated brain stimulation studies

One of the greatest conundrums to the contemporary science is the relation between consciousness and brain activity, and one of the specifi c questions is how neural activity can generate vivid subjective experiences. Studies focusing on visual consciousness have become essential in solving the empirical questions of consciousness. Th e main aim of this thesis is to clarify the relation between visual consciousness and the neural and electrophysiological processes of the brain. By applying electroencephalography and functional magnetic resonance image-guided transcranial magnetic stimulation (TMS), we investigated the links between conscious perception and attention, the temporal evolution of visual consciousness during stimulus processing, the causal roles of primary visual cortex (V1), visual area 2 (V2) and lateral occipital cortex (LO) in the generation of visual consciousness and also the methodological issues concerning the accuracy of targeting TMS to V1. Th e results showed that the fi rst eff ects of visual consciousness on electrophysiological responses (about 140 ms aft er the stimulus-onset) appeared earlier than the eff ects of selective attention, and also in the unattended condition, suggesting that visual consciousness and selective attention are two independent phenomena which have distinct underlying neural mechanisms. In addition, while it is well known that V1 is necessary for visual awareness, the results of the present thesis suggest that also the abutting visual area V2 is a prerequisite for conscious perception. In our studies, the activation in V2 was necessary for the conscious perception of change in contrast for a shorter period of time than in the case of more detailed conscious perception. We also found that TMS in LO suppressed the conscious perception of object shape when TMS was delivered in two distinct time windows, the latter corresponding with the timing of the ERPs related to the conscious perception of coherent object shape. Th e result supports the view that LO is crucial in conscious perception of object coherency and is likely to be directly involved in the generation of visual consciousness. Furthermore, we found that visual sensations, or phosphenes, elicited by the TMS of V1 were brighter than identically induced phosphenes arising from V2. Th ese fi ndings demonstrate that V1 contributes more to the generation of the sensation of brightness than does V2. Th e results also suggest that top-down activation from V2 to V1 is probably associated with phosphene generation. The results of the methodological study imply that when a commonly used landmark (2 cm above the inion) is used in targeting TMS to V1, the TMS-induced electric fi eld is likely to be highest in dorsal V2. When V1 was targeted according to the individual retinotopic data, the electric fi eld was highest in V1 only in half of the participants. Th is result suggests that if the objective is to study the role of V1 with TMS methodology, at least functional maps of V1 and V2 should be applied with computational model of the TMS-induced electric fi eld in V1 and V2. Finally, the results of this thesis imply that diff erent features of attention contribute diff erently to visual consciousness, and thus, the theoretical model which is built up of the relationship between visual consciousness and attention should acknowledge these diff erences. Future studies should also explore the possibility that visual consciousness consists of several processing stages, each of which have their distinct underlying neural mechanisms.Tajunnallisuus ja sen suhde aivojen neuraalisiin tapahtumiin on yksi tieteen suurimmista ratkaisemattomista kysymyksistä. Tyypillisesti tajunnallisuudella viitataan fenomenaaliseen tajuntaan eli yksilön elämykselliseen ja välittömään kokemukseen tietystä sisällöstä. Tajunnallinen näkeminen eli visuaalinen tajunta on noussut keskiöön tajunnan neuraalisten korrelaattien tutkimuksessa. Tarkastelen tässä tutkimuksessa aivokuoren aktivaation ja visuaalisen tajunnan välistä korrelaatio- ja kausaalisuhdetta elektroenkefalografi an (EEG), toiminnallisten magneettikuvien avulla ohjatun transkraniaalisen magneettistimulaation (TMS) sekä TMS:n indusoiman sähkökentän mallinnuksen avulla. Erityisesti tavoitteena on tarkentaa näönvaraisen tajunnan ja tarkkaavaisuuden välistä suhdetta, tajunnan ajallista kehittymistä, ensimmäisen näköaivokuoren alueen (alue V1), alueen V2 ja lateraalisen näköaivokuoren (LO-alue) roolia visuaalisessa tajunnassa. Väitöskirja koostuu viidestä osatutkimuksesta. Tulokset osoittivat, että varhaisimmat visuaalisen tajunnan vaikutukset tapahtumasidonnaisiin herätevasteisiin (ERP) tulivat esiin noin 140 ms ärsykkeen esittämisen jälkeen ja selvästi ennen valikoivan tarkkaavaisuuden vaikutusta sekä riippumatta valikoivan tarkkaavaisuuden vaikutuksesta. Tulos viittaa siihen, että visuaalisen tajunnan ja valikoivan tarkkaavaisuuden taustalla on erilliset neuraaliset prosessit. Alueen V1 tiedetään olevan välttämätön normaalille näönvaraiselle tajunnalliselle kokemukselle, mutta kolmannen osatutkimuksen tulokset tukevat oletusta, että myös viereinen alue V2 on välttämätön normaalille visuaaliselle tajunnalle. Lisäksi havaittiin, että aktivaatio alueella V2 oli välttämätöntä visuaalisen ärsykkeen yksityiskohtien prosessoinnille pidempään kuin tajunnallisuudelle ärsykkeen läsnäolosta. LO-alueen stimulointi TMS:lla taas ehkäisi tajunnallisen kokemuksen tutusta objektista kahdessa erillisessä aikaikkunassa, joista jälkimmäisen ajoitus korreloi tajuntaan liittyvän tyypillisen ERP-vasteen ajoituksen kanssa. Tutkimustulos tuo tukea näkemykselle jonka mukaan LO-alueen aktivaatio liittyy suoraan niihin prosesseihin, jotka generoivat tajunnallisen havainnon objektista. Okkipitaalilohkon TMS- ja sähköstimuloinnin tiedetään aiheuttavan subjektiivisia valoaistimuksia eli fosfeeneja. Tutkimuksessa havaittiin, että alueen V1 ja alueen V2 stimuloinnin avulla tuotetut fosfeenit ovat keskenään hyvin samankaltaisia muodon, värin sekä koon osalta, mutta alueen V1 stimuloinnissa tuotetut fosfeenit olivat kaikilla tutkittavilla kirkkaampia kuin alueen V2 stimuloinnilla tuotetut fosfeenit. Menetelmällisessä tutkimuksessa havaittiin, että vaikka TMS-pulssi oli suunnattu alueelle V1 toiminnallisten magneettikuvien tai kallon muodon mukaan, oli todennäköisempää, että indusoitu sähkökenttä oli ollut voimakkaampi alueen V2 päällä. Toisaalta toisen osatutkimuksen tulokset osoittivat, että joillekin tutkittaville alueen V1 TMS-stimulaatio oli mahdollista, kun erityistä huomiota kiinnitettiin retinotooppisten edustusalueiden valitsemiseen ja hyödynnettiin sähkökentänmallinnusmenetelmää. Kokonaisuudessaan tämän tutkimuksen tulokset viittaavat siihen, että eri tarkkaavaisuuden muodot vaikuttavat eri tavoin näönvaraiseen tajuntaan, ja näin ollen, teoreettisen mallin visuaalisen tajunnan ja tarkkaavaisuuden välisestä suhteesta tulisi ottaa huomioon nämä erot. Tulevissa tutkimuksissa tulisi myös selvittää mahdollisuutta, jonka mukaan näönvarainen tajunta koostuu useista prosessointi tasosta, joista jokaisella on erilliset hermostolliset perustansa.Siirretty Doriast

Reconstruction of the Corticospinal Tract in Patients with Motor-Eloquent High-Grade Gliomas Using Multilevel Fiber Tractography Combined with Functional Motor Cortex Mapping

BACKGROUND AND PURPOSE: Tractography of the corticospinal tract is paramount to presurgical planning and guidance of intraoperative resection in patients with motor-eloquent gliomas. It is well-known that DTI-based tractography as the most frequently used technique has relevant shortcomings, particularly for resolving complex fiber architecture. The purpose of this study was to evaluate multilevel fiber tractography combined with functional motor cortex mapping in comparison with conventional deterministic tractography algorithms. MATERIALS AND METHODS: Thirty-one patients (mean age, 61.5 [SD, 12.2] years) with motor-eloquent high-grade gliomas underwent MR imaging with DWI (TR/TE ¼ 5000/78 ms, voxel size ¼ 2 × 2 × 2 mm3, 1 volume at b ¼ 0 s/mm2, 32 volumes at b ¼ 1000 s/mm2). DTI, constrained spherical deconvolution, and multilevel fiber tractography–based reconstruction of the corticospinal tract within the tumor-affected hemispheres were performed. The functional motor cortex was enclosed by navigated transcranial magnetic stimulation motor mapping before tumor resection and used for seeding. A range of angular deviation and fractional anisotropy thresholds (for DTI) was tested. RESULTS: For all investigated thresholds, multilevel fiber tractography achieved the highest mean coverage of the motor maps (eg, angular threshold = 60°; multilevel/constrained spherical deconvolution/DTI, 25% anisotropy threshold ¼ 71.8%, 22.6%, and 11.7%) and the most extensive corticospinal tract reconstructions (eg, angular threshold ¼ 60°; multilevel/constrained spherical deconvolution/DTI, 25% anisotropy threshold ¼ 26,485 mm3, 6308 mm3, and 4270 mm3). CONCLUSIONS: Multilevel fiber tractography may improve the coverage of the motor cortex by corticospinal tract fibers compared with conventional deterministic algorithms. Thus, it could provide a more detailed and complete visualization of corticospinal tract architecture, particularly by visualizing fiber trajectories with acute angles that might be of high relevance in patients with gliomas and distorted anatomy.</p

The antidepressant effect of intermittent theta burst stimulation (iTBS): study protocol for a randomized double-blind sham-controlled trial

Background Intermittent theta burst stimulation (iTBS) when applied over the left dorsolateral prefrontal cortex (DLPFC) has been shown to be equally effective and safe to treat depression compared to traditional repetitive transcranial magnetic stimulation (rTMS) paradigms. This protocol describes a funded single-centre, double-blind, randomized placebo-controlled, clinical trial to investigate the antidepressive effects of iTBS and factors associated with an antidepressive response. Methods In this trial, outpatients (N=96, aged 22–65 years) meeting the diagnostic criteria for at least moderate depression (Montgomery and Aasberg Depression Rating Scale score≥20) will be enrolled prospectively and receive ten, once-a-day sessions of either active iTBS or sham iTBS to the left DLPFC, localized via a neuronavigation system. Participants may have any degree of treatment resistance. Prior to stimulation, participants will undergo a thorough safety screening and a brief diagnostic assessment, genetic analysis of brain-derived neurotropic factor, 5-HTTLPR and 5-HT1A, and cerebral MRI assessments. A selection of neuropsychological tests and questionnaires will be administered prior to stimulation and after ten stimulations. An additional follow-up will be conducted 4 weeks after the last stimulation. The frst participant was enrolled on June 4, 2022. Study completion will be in December 2027. The project is approved by the Regional Ethical Committee of Medicine and Health Sciences, Northern Norway, project number 228765. The trial will be conducted according to Good Clinical Practice and published safety guidelines on rTMS treatment. Discussion The aims of the present trial are to investigate the antidepressive effect of a 10-session iTBS protocol on moderately depressed outpatients and to explore the factors that can explain the reduction in depressive symptoms after iTBS but also a poorer response to the treatment. In separate, but related work packages, the trial will assess how clinical, cognitive, brain imaging and genetic measures at baseline relate to the variability in the antidepressive effects of iTBS

Contributions of the PPC to online control of visually guided reaching movements assessed with fMRI-Guided TMS

The posterior parietal cortex (PPC) plays an important role in controlling voluntary movements by continuously integrating sensory information about body state and the environment. We tested which subregions of the PPC contribute to the processing of target- and body-related visual information while reaching for an object, using a reaching paradigm with 2 types of visual perturbation: displacement of the visual target and displacement of the visual feedback about the hand position. Initially, functional magnetic resonance imaging (fMRI) was used to localize putative target areas involved in online corrections of movements in response to perturbations. The causal contribution of these areas to online correction was tested in subsequent neuronavigated transcranial magnetic stimulation (TMS) experiments. Robust TMS effects occurred at distinct anatomical sites along the anterior intraparietal sulcus (aIPS) and the anterior part of the supramarginal gyrus for both perturbations. TMS over neighboring sites did not affect online control. Our results support the hypothesis that the aIPS is more generally involved in visually guided control of movements, independent of body effectors and nature of the visual information. Furthermore, they suggest that the human network of PPC subregions controlling goal-directed visuomotor processes extends more inferiorly than previously thought. Our results also point toward a good spatial specificity of the TMS effects. © 2010 The Author

Contributions of the PPC to online control of visually guided reaching movements assessed with fMRI-Guided TMS

The posterior parietal cortex (PPC) plays an important role in controlling voluntary movements by continuously integrating sensory information about body state and the environment. We tested which subregions of the PPC contribute to the processing of target- and body-related visual information while reaching for an object, using a reaching paradigm with 2 types of visual perturbation: displacement of the visual target and displacement of the visual feedback about the hand position. Initially, functional magnetic resonance imaging (fMRI) was used to localize putative target areas involved in online corrections of movements in response to perturbations. The causal contribution of these areas to online correction was tested in subsequent neuronavigated transcranial magnetic stimulation (TMS) experiments. Robust TMS effects occurred at distinct anatomical sites along the anterior intraparietal sulcus (aIPS) and the anterior part of the supramarginal gyrus for both perturbations. TMS over neighboring sites did not affect online control. Our results support the hypothesis that the aIPS is more generally involved in visually guided control of movements, independent of body effectors and nature of the visual information. Furthermore, they suggest that the human network of PPC subregions controlling goal-directed visuomotor processes extends more inferiorly than previously thought. Our results also point toward a good spatial specificity of the TMS effects. © 2010 The Author

Modern Developments in Transcranial Magnetic Stimulation (TMS) – Applications and Perspectives in Clinical Neuroscience

Transcranial magnetic stimulation (TMS) is being increasingly used in neuroscience and clinics. Modern advances include but are not limited to the combination of TMS with precise neuronavigation as well as the integration of TMS into a multimodal environment, e.g., by guiding the TMS application using complementary techniques such as functional magnetic resonance imaging (fMRI), electroencephalography (EEG), diffusion tensor imaging (DTI), or magnetoencephalography (MEG). Furthermore, the impact of stimulation can be identified and characterized by such multimodal approaches, helping to shed light on the basic neurophysiology and TMS effects in the human brain. Against this background, the aim of this Special Issue was to explore advancements in the field of TMS considering both investigations in healthy subjects as well as patients