In this theme our main goal is to develop and implement combined brain imaging methods for the multi-parametric and multi-scale mapping of human brain functions. Such combined imaging approach enables us both to identify brain mechanism relevant for mental processing, as well as reliably targeting of specific processes for brain-computer interface procedures.

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Our main effort is on combined fMRI and EEG to enable a better temporal depiction of mental processing, revolutionizing this approach in Israel. Using simultaneous EEG/fMRI we have addressed long-standing basic research debates. For example we demonstrated that information transfer occurs faster from the right-to-left hemisphere than vice versa at the cortical level (ERP/fMRI) as well as at an earlier processing stages in the brainstem (fMRI)

 (Okon-Singer..Hendler 2010) (see pic1). This finding may have great implications for the diagnosis and treatment of attention and learning disturbances. In another project we showed that alpha EEG rhythm modulation is correlated with BOLD activation in distributed cortical and subcortical regions (fMRI), pointing to its role in resting state spontaneous activity (Ben Simon... Hendler, 2008). More recently the involvement of gamma oscillations was indicated in goal-directed mnemonic retrieval (Lichter Shapira... Hendler, 2016) and the dynamics in BOLD activation that is correlated to EEG theta/alpha ratio modulation, was depicted during entering to deep relaxation state

(Kinreich ... Hendler, 2014) (see pic 2).  

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To improve the clinical use of EEG/fMRI, especially for epilepsy, we have invented a unique platform that significantly reduces noise and artifacts in the combined acquisition (Klovach-Podlipsky and Gazit, Hendler and Medvedovsky 2016, Patent under review). This ground-breaking development of EEG cup (termed Dual Array EEG-fMRI) enables an improved resolution of EEG acquisition during fMRI.  This allows for a reliable non-invasive mapping of epileptic foci with highest spatial resolution (see pic 3).

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More recently, we have developed fMRI infused EEG to enable scalp recordings of deeply located brain regions (e.g. the amygdala, insula and ventral striatum) with EEG alone. For that advanced computational methods were applied to predict the fMRI BOLD activity modulation in a designated region from scalp EEG signal activation patterns termed; Electrical Finger Print (EFP) (Meir-Hasson... Hendler and Intrator 2014), (Meir-Hasson... Hendler and Intrator, 2016, Patnet under review), (see pic 4). To date, we have successfully acquired EFP of activity in regions known to involve traumatic stress; the Amygdala, and cognitive control; right Inferior Frontal Gyrus. This computational development has been validated in a recent fMRI/EEG project using the Amygdala-EFP to improve emotion regulation (Keynan... Hendler, 2016) (see pic 5).

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Altogether our innovation with EEG/fMRI procedures may allow for accessible and low cost translations of insights from neuroscience into true clinical solutions in neurology and psychiatry. The most promising potential for these new methods is their  integration into bed-side therapeutics and use as an on-line tool for empowering one's mental abilities via volitional neuro-modulation known as  neurofeedback.

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In addition we have been using intracranial EEG (iEEG) recordings from grids and depth electrodes implanted in epilepsy patients to  achieve superior spatial and temporal resolution to characterize emotion processing in humans. In specific we addressed a long standing debate with regard to brain mechanism that underlie intentionality of emotions by using short neutral movie clips alone or combined with emotional music excerpts (see paradigm description in(Eldar... Hendler, 2007) (see pic 6). Combined with fMRI testing prior to recording, ic recordings revealed detailed temporal profiles of activation sources in deep brain areas such as the amygdala, normally poorly detected by scalp-EEG recordings. We showed that intentionality of emotions as depicted by fMRI in the amygdala and lateral PFC, are in fact ignited by local amygdala high-gamma synchronization and followed by PFC sustained low-frequency desynchronization (Singer... Hendler, 2014),(see pics 7, 8, 9). In another study we took advantage of the superior spatial resolution of iEEG and examined the functional interplay between medial and lateral PFC activation during internally-generated action planning (Rozenberg, 2012).

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We are currently undertaking intracranial recording using higher temporal and spatial resolution with depth electrodes situated in the medial temporal and prefrontal cortices, investigating emotions all the way to the level of single unit activity (in reparation).