Multimodal approaches supporting the diagnosis, prognosis and investigation of neural correlates of disorders of consciousness: A systematic review.

The limits of the standard, behaviour-based clinical assessment of patients with disorders of consciousness (DoC) prompted the employment of functional neuroimaging, neurometabolic, neurophysiological and neurostimulation techniques, to detect brain-based covert markers of awareness. However, uni-modal approaches, consisting in employing just one of those techniques, are usually not sufficient to provide an exhaustive exploration of the neural underpinnings of residual awareness. This systematic review aimed at collecting the evidence from studies employing a multimodal approach, that is, combining more instruments to complement DoC diagnosis, prognosis and better investigating their neural correlates. Following the PRISMA guidelines, records from PubMed, EMBASE and Scopus were screened to select peer-review original articles in which a multi-modal approach was used for the assessment of adult patients with a diagnosis of DoC. Ninety-two observational studies and 32 case reports or case series met the inclusion criteria. Results highlighted a diagnostic and prognostic advantage of multi-modal approaches that involve electroencephalography-based (EEG-based) measurements together with neuroimaging or neurometabolic data or with neurostimulation. Multimodal assessment deepened the knowledge on the neural networks underlying consciousness, by showing correlations between the integrity of the default mode network and the different clinical diagnosis of DoC. However, except for studies using transcranial magnetic stimulation combined with electroencephalography, the integration of more than one technique in most of the cases occurs without an a priori-designed multi-modal diagnostic approach. Our review supports the feasibility and underlines the advantages of a multimodal approach for the diagnosis, prognosis and for the investigation of neural correlates of DoCs.

State-dependent effectiveness of cathodal transcranial direct current stimulation on cortical excitability.

The extensive use of transcranial direct current stimulation (tDCS) in experimental and clinical settings does not correspond to an in-depth understanding of its underlying neurophysiological mechanisms. In previous studies, we employed an integrated system of Transcranial Magnetic Stimulation and Electroencephalography (TMS-EEG) to track the effect of tDCS on cortical excitability. At rest, anodal tDCS (a-tDCS) over the right Posterior Parietal Cortex (rPPC) elicits a widespread increase in cortical excitability. In contrast, cathodal tDCS (c-tDCS) fails to modulate cortical excitability, being indistinguishable from sham stimulation. Here we investigated whether an endogenous task-induced activation during stimulation might change this pattern, improving c-tDCS effectiveness in modulating cortical excitability. In Experiment 1, we tested whether performance in a Visuospatial Working Memory Task (VWMT) and a modified Posner Cueing Task (mPCT), involving rPPC, could be modulated by c-tDCS. Thirty-eight participants were involved in a two-session experiment receiving either c-tDCS or sham during tasks execution. In Experiment 2, we recruited sixteen novel participants who performed the same paradigm but underwent TMS-EEG recordings pre- and 10 min post- sham stimulation and c-tDCS. Behavioral results showed that c-tDCS significantly modulated mPCT performance compared to sham. At a neurophysiological level, c-tDCS significantly reduced cortical excitability in a frontoparietal network likely involved in task execution. Taken together, our results provide evidence of the state dependence of c-tDCS in modulating cortical excitability effectively. The conceptual and applicative implications are discussed.

Mind the stimulation site: Enhancing and diminishing sentence comprehension with anodal tDCS.

In a previous sham-controlled study, we showed the feasibility of increasing language comprehension in healthy participants by applying anodal transcranial direct current stimulation (atDCS) over the left inferior frontal gyrus (LIFG). In the present work, we present a follow-up experiment targeting with atDCS the left inferior parietal cortex (LIPC) while participants performed the same auditory comprehension task used in our previous experiment. Both neural sites (LIFG and LIPC) are crucial hubs of Baddeley's model of verbal short-term memory (vSTM). AtDCS over LIPC decreased accuracy as compared to sham and LIFG stimulation, suggesting the involvement of this area in sentence comprehension. Crucially, our results highlighted that applying tDCS over different hubs of the same neural network can lead to opposite behavioural results, with relevant implications from a clinical perspective.

Tracking the Effect of Cathodal Transcranial Direct Current Stimulation on Cortical Excitability and Connectivity by Means of TMS-EEG.

Transcranial direct current stimulation (tDCS) is increasingly used in both research and therapeutic settings, but its precise mechanisms remain largely unknown. At a neuronal level, tDCS modulates cortical excitability by shifting the resting membrane potential in a polarity-dependent way: anodal stimulation increases the spontaneous firing rate, while cathodal decreases it. However, the neurophysiological underpinnings of anodal/cathodal tDCS seem to be different, as well as their behavioral effect, in particular when high order areas are involved, compared to when motor or sensory brain areas are targeted. Previously, we investigated the effect of anodal tDCS on cortical excitability, by means of a combination of Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG). Results showed a diffuse rise of cortical excitability in a bilateral fronto-parietal network. In the present study, we tested, with the same paradigm, the effect of cathodal tDCS. Single pulse TMS was delivered over the left posterior parietal cortex (PPC), before, during, and after 10 min of cathodal or sham tDCS over the right PPC, while recording HD-EEG. Indexes of global and local cortical excitability were obtained both at sensors and cortical sources level. At sensors, global and local mean field power (GMFP and LMFP) were computed for three temporal windows (0-50, 50-100, and 100-150 ms), on all channels (GMFP), and in four different clusters of electrodes (LMFP, left and right, in frontal and parietal regions). After source reconstruction, Significant Current Density was computed at the global level, and for four Broadmann's areas (left/right BA 6 and 7). Both sensors and cortical sources results converge in showing no differences during and after cathodal tDCS compared to pre-stimulation sessions, both at global and local level. The same holds for sham tDCS. These data highlight an asymmetric impact of anodal and cathodal stimulation on cortical excitability, with a diffuse effect of anodal and no effect of cathodal tDCS over the parietal cortex. These results are consistent with the current literature: while anodal-excitatory and cathodal-inhibitory effects are well-established in the sensory and motor domains, both at physiological and behavioral levels, results for cathodal stimulation are more controversial for modulation of exitability of higher order areas.

Goal Achievement Failure Drives Corticospinal Modulation in Promotion and Prevention Contexts.

When making decisions, people are typically differently sensitive to gains and losses according to the motivational context in which the choice is performed. As hypothesized by Regulatory Focus Theory (RFT), indeed, goals are supposed to change in relation to the set of possible outcomes. In particular, in a promotion context, the goal is achieving the maximal gain, whereas in a prevention context it turns into avoiding the greatest loss. We explored the neurophysiological counterpart of this phenomenon, by applying Transcranial Magnetic Stimulation (TMS) and recording the motor evoked potentials (MEPs) in participants taking part in an economic game, in which they observed actions conveying different goal attainment levels, framed in different motivational contexts. More than the actual value of the economic exchange involved in the game, what affected motor cortex excitability was the goal attainment failure, corresponding to not achieving the maximal payoff in a promotion context and not avoiding the greatest snatch in a prevention context. Therefore, the results provide support for the key predictions of RFT, identifying a neural signature for the goal attainment failure.

Anodal transcranial direct current stimulation over left inferior frontal gyrus enhances sentence comprehension.

We tested the possibility of enhancing natural language comprehension through the application of anodal tDCS (a-tDCS) over the left inferior frontal gyrus, a key region for verbal short-term memory and language comprehension. We designed a between subjects sham- and task-controlled study. During tDCS stimulation, participants performed a sentence to picture matching task in which targets were sentences with different load on short-term memory. Regardless of load on short-term memory, the Anodal group performed significantly better than the Sham group, thus providing evidence that a-tDCS over LIFG enhances natural language comprehension. To our knowledge, we apply for the first time tDCS to boost sentence comprehension. This result is of special interest also from a clinical perspective: applying a-tDCS in patients manifesting problems at the sentence level due to brain damage could enhance the effects of behavioral rehabilitation procedures aimed to improve language comprehension.