Dr. Michael A. Nitsche "Physiology, and functional effects of tDCS and related techniques"
Neuroplasticity, and functional connectivity are important physiological derivates of cognition, and behaviour. Recently introduced non-invasive brain stimulation techniques are suited to induce, and modulate respective physiological alterations. One of these techniques is transcranial direct current stimulation (tDCS). Its primary mechanism of action is a polarity-dependent subthreshold shift of resting membrane potentials, the after-effects of stimulation depend on the glutamatergic system. Beyond these regional effects, tDCS has been shown recently to alter cortical, as well as cortico-subcortical functional network connectivity. This talk will give an overview about the physiological effects, and will cover functional effects of tDCS on cognitive, emotional and behavioural processes in healthy humans and patients suffering from neuropsychiatric dieases. Finally, it will be shown how alterations of functional oscillatory connectivity via transcranial alternating current stimulation can modify cognitive performance.
Peter T. Fox, M.D. “TMS/PET Studies of TMS Aiming, Network Modeling and Parametric Modulation”
TMS can be delivered during the acquisition of whole-brain, H215O PET images of cerebral blood flow with no inter-device interference. In our laboratory, we have used TMS/PET to address several basic issues regarding TMS, including: the brain locations of the TMS-induced neural activation, both at the site of stimulation and remotely; the effects of stimulus intensity and frequency on the TMS-induced neural activation, both locally and remotely; and, the network properties of TMS-induced responses. Although it is often assumed that TMS-induced effects are wide-spread and poorly localized, PET/TMS clearly shows that this is not the case. TMS-induced responses are highly focal, e.g., activating a similar volume of primary motor cortex (M1) as volitional finger movement. Although it has been repeatedly posited that TMS activates cortical regions nearest to the stimulating coil (i.e., on gyral crowns), TMS/PET clearly demonstrates that the primary site of TMS-induced activation is sulcal (i.e., no scalp-normal surfaces), where the E-field is maximally column alligned. This has been demonstrated both in M1 and in supplementary motor area (SMA). TMS/PET-drived SEM models of M1 and SMA show high concordance with those obtained by meta-analytic connectivity mapping and outstanding model fit statistics. The M1-derived network exhibits strong driving-frequency preferences, with 5 Hz being the most effective stimulation frequency.
Dr. Peter Bandettini, “Functional MRI of the Individual: From biomarkers to neurofeedback to neuromodulation guidance”
In contrast to the preponderance of group studies in fMRI over the past 20+ years, for the first few years after fMRI was discovered, results mostly from individuals were reported. However, while these first studies clearly demonstrated primary motor and sensory activation as well as higher order cognition, nothing could be said with certainty about the subjects themselves. While activation was clearly observed in each individual, group studies were necessary to draw general conclusions about large groups of normal controls or those with a specific disorder. While there is certainly still a role for group studies in deriving general differences between groups, the time is ripe to make a concerted effort towards moving fMRI back to individual studies. The primary reasons are that 1. fMRI acquisition is more stable, higher resolution, and generally has higher signal to noise, 2. fMRI processing has reached a level of sophistication - going well beyond univariate “blobology" to multivariate information mapping and classification, and 3. There is a substantial and pressing need to enhance the clinical traction of fMRI. The only way to bring fMRI into the clinic is to scan, and derive meaningful and clinically relevant information, from individuals. In this talk, I outline the ways in which fMRI has been and perhaps may be used for individual assessment. These individual assessment avenues include the growing development of group-study derived biomarkers that might then be applied to diagnose or predict outcome of individuals, the use of fMRI as means for therapy through neurofeedback, and the use of fMRI in concert with MRI and DTI as a means for guiding the application of external neuromodulation. Biomarkers would be subtle patterns of activation or resting state connectivity that have been determined to indicate some specific trait of a subject. Against these templates the pattern of activation and/or connectivity of an individual could be compared, thus allowing a diagnosis or a guidance on clinical decisions to be made. Neurofeedback involves the use of a specific fMRI activation pattern or magnitude that is compared with the subject’s activation pattern and fed back to the subject who is asked to “figure out” a way to make the templates match more. Usually the relevant data is “collapsed” into an easily digestible visual and/or auditory feedback to the subject. The result, once the subject is able to perform this difficult task, is a corresponding mental strategy that results in alleviated pain or reduced depression symptoms, or other types of improvements. Lastly, there is a growing realization that a number of invasive and non-invasive external modulations have an effect on neuronal function. These include deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACDS), focussed ultrasound, and near infrared laser or diode stimulation, among others. All of these suffer from an uncertainty of where to direct the modulation. Functional MRI, and DTI, revealing the unique functional activation maps and connectivity structure in individuals, is proving fundamentally critical to the effective application of these modulations. Overall, it’s clear that while group studies have filled out the bulk of fMRI over the past 20 years, the future clearly belongs to fMRI of the individual.
Dr. Giulio Ruffini, “Transcranial Current Stimulation: Going Multifocal”
Transcranial current stimulation (tCS, including tDCS, tACS and tRNS) is a noninvasive neuromodulatory technique using weak electrical currents to alter cortical excitability. Currently, studies worldwide are exploring distinct stimulation parameters to optimize tDCS effects. Most of the research carried out so far has relied on the use of bipolar montages using large electrodes. In this talk I will argue the is a source of error and variability in study results, which as a result become harder to replicate. With this motivation, I will describe a new class of devices using multi electrode montages and small, EEG-compatible electrodes, complemented by advanced biophysical models. This technology provides the means for a) more focal stimulation on a given target, b) cortically distributed stimulation. While the former is of clear interest, I will argue that the latter can provide the means for stimulation of brain networks, and provide some examples of what can be done. The importance of measuring EEG, the potential for closed loop applications will also be discussed.
Dr. Katie Witkiewitz, “Integration of Brain Stimulation and Imaging in Clinical Research and Treatment of Addiction”
Addiction has often been described as chronic relapsing condition, characterized by debilitating neuroadaptations that facilitate continued use and exacerbate likelihood of relapse following attempts at cessation. For example, more than 60% of those who receive treatment for nicotine dependence resume smoking within 30 days of quitting, and up to 90% resume within the first year. Given these high relapse rates, continued development of innovative and efficacious interventions that specifically target neurobiological risk factors for relapse to smoking is thus clearly warranted. Transcranial direct current stimulation (tDCS), which modulates brain activity to alter behavior, enhance learning, and influence decision making processes holds incredible promise for use in behavioral intervention protocols for addiction, including nicotine dependence. For example, in two separate studies tDCS was shown to predict significantly lower smoking cue induced nicotine craving among non-treatment seeking smokers, as compared to non-active (i.e., “sham”) stimulation (Boggio et al., 2009; Fregni et al., 2008). However these prior studies have used tDCS without a behavioral intervention that has demonstrated efficacy in the treatment of nicotine dependence. Our recent pilot research has sought to enhance learning of mindfulness taught in a mindfulness-based intervention for smokers by applying tDCS during mindfulness training. Weekly group sessions that included 30 minutes of mindfulness+tDCS, followed by 60 minutes of mindfulness and smoking cessation intervention content were conducted over four weeks with electroencephalography (EEG) assessments at baseline and end of treatment. Results from a small sample of individuals (n=9; 57.1% female, average age 38.9, SD=9.8) indicated acceptability and feasibility of the 4-week group-based mindfulness+tDCS intervention and a large effect size reduction in cigarettes per smoking day at the end-of-treatment (d=0.95). The challenges and opportunities of combining tDCS with EEG in treatment research with a clinical population will be discussed.
Dr. Marom Bikson, “Targeting transcranial Electrical Stimulation using EEG: The scalp space approach”
Novel methodology to guide targeted noninvasive electrical brain stimulation using EEG is presented. First approaches for targeted transcranial electrical stimulation (tES) are reviewed, including transcranial Direct Current Simulation (tDCS) and High-Definition tDCS (HD-tDCS). Next, how to optimize tES based on either evoked or spontaneous EEG recording is discussed including a novel “scalp space” approach which requires no source localization and no computational modeling. The scalp space approach is thus a highly reproducible and deployable approach that can be used to deign indication specific or subject specific targeted tES interventions. Finally, cellular data on how weak stimulation can modulate evoked and ongoing activity is presented to provide a mechanistic substrate for interventions.
Keynote Speaker Abstracts