Lateralization, functional specialization, and dysfunction of attentional networks.

The present review covers the latest findings on the lateralization of the dorsal and ventral attention systems, their functional specialization, and their clinical relevance for stroke-induced attentional dysfunction. First, the original assumption of a bilateral dorsal system for top-down attention and a right-lateralized ventral system for stimulus-driven attention is critically reviewed. The evidence for the involvement of the left parietal cortex in attentional functions is discussed and findings on putative pathways linking the dorsal and ventral network are presented. In the second part of the review, we focus on the different attentional subsystems and their lateralization, discussing the differences between spatial, feature- and object-based attention, and motor attention. We also review studies based on predictive coding frameworks of attentional functions. Finally, in the third section, we provide an overview of the consequences of specific disruption within the attention networks after stroke. The role of the interhemispheric (im)balance is discussed, and the results of new promising therapeutic approaches employing brain stimulation techniques such as transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) are presented.

Bilateral Contralaterally Controlled Functional Electrical Stimulation Reveals New Insights Into the Interhemispheric Competition Model in Chronic Stroke.

Background. Upper-limb chronic stroke hemiplegia was once thought to persist because of disproportionate amounts of inhibition imposed from the contralesional on the ipsilesional hemisphere. Thus, one rehabilitation strategy involves discouraging engagement of the contralesional hemisphere by only engaging the impaired upper limb with intensive unilateral activities. However, this premise has recently been debated and has been shown to be task specific and/or apply only to a subset of the stroke population. Bilateral rehabilitation, conversely, engages both hemispheres and has been shown to benefit motor recovery. To determine what neurophysiological strategies bilateral therapies may engage, we compared the effects of a bilateral and unilateral based therapy using transcranial magnetic stimulation. Methods. We adopted a peripheral electrical stimulation paradigm where participants received 1 session of bilateral contralaterally controlled functional electrical stimulation (CCFES) and 1 session of unilateral cyclic neuromuscular electrical stimulation (cNMES) in a repeated-measures design. In all, 15 chronic stroke participants with a wide range of motor impairments (upper extremity Fugl-Meyer score: 15 [severe] to 63 [mild]) underwent single 1-hour sessions of CCFES and cNMES. We measured whether CCFES and cNMES produced different effects on interhemispheric inhibition (IHI) to the ipsilesional hemisphere, ipsilesional corticospinal output, and ipsilateral corticospinal output originating from the contralesional hemisphere. Results. CCFES reduced IHI and maintained ipsilesional output when compared with cNMES. We found no effect on ipsilateral output for either condition. Finally, the less-impaired participants demonstrated a greater increase in ipsilesional output following CCFES. Conclusions. Our results suggest that bilateral therapies are capable of alleviating inhibition on the ipsilesional hemisphere and enhancing output to the paretic limb.

Modulating the interhemispheric balance in healthy participants with transcranial direct current stimulation: No significant effects on word or sentence processing.

Patient studies and brain stimulation evidence suggest that language processing can be enhanced by altering the interhemispheric balance: namely, preferentially enhancing left-hemisphere activity while suppressing right-hemisphere activity. To our knowledge, no study has yet compared the effects of such bilateral brain stimulation to both logically necessary control conditions (separate left- and right-hemisphere stimulation). This study did so in a between-group sham-controlled design, applying transcranial direct current stimulation over Broca's area and/or its homologue in 72 healthy participants. The effects were measured not only in a single-word-level task but also in a sentence-level task, rarely tested previously. We did not find either any significant overall effects of stimulation or greater stimulation effects in the bilateral compared to control groups. This null result, obtained in a large sample, contributes to the debate on whether tDCS can modulate language processing in healthy individuals.

Revisiting interhemispheric imbalance in chronic stroke: A tDCS study.

OBJECTIVE: Chronic stroke patients with moderate-severe motor impairment may have an increased reliance on contralesional vs ipsilesional motor areas to control the paretic arm. We hypothesised that increasing contralesional excitability with anodal transcranial direct current stimulation (a-tDCS) would benefit motor performance in patients with moderate-severe impairment. METHODS: Ten patients with motor impairment at the chronic stage after stroke received a-tDCS, cathodal (c-tDCS) and sham with the target electrode over contralesional motor cortex (M1). Motor performance was quantified from the circularity and size of planar movements made with the paretic arm. Contralateral and ipsilateral corticospinal excitability was inferred using transcranial magnetic stimulation. Corticospinal tract integrity and basal GABA concentration were assessed with magnetic resonance imaging and spectroscopy. RESULTS: Anodal tDCS increased contralesional corticomotor excitability evident from motor evoked potentials in both wrist extensors (both P<0.043). Cathodal tDCS did not affect corticomotor excitability (P>0.37). The effect of tDCS on motor performance with the paretic limb was negatively associated with ipsilesional GABA concentration after c-tDCS (P=0.001). CONCLUSIONS: Further investigation of noninvasive brain stimulation protocols that facilitate contralesional M1 is warranted. SIGNIFICANCE: The inter-hemispheric imbalance model of stroke recovery may not apply to patients with more severe impairment.

Dynamic interhemispheric competition and vestibulo-cortical control in humans; A theoretical proposition.

Neuroscientific research has made a concerted effort to determine cortical localization using various functional imaging techniques. This approach has undoubtedly yielded important novel anatomical knowledge, albeit at times contradictory, regarding the structural organization of the vestibular cortex. Unfortunately however, this knowledge has not translated to our understanding regarding how neural mechanisms control vestibular function. Based upon recent functional imaging, lesion and neuro-physiological data that have demonstrated (i) the close behavioral and neuro-anatomical relationship between cortical processing of vestibular and spatial attention signals, and (ii) that inducing interhemispheric competition can in-turn strongly modulate vestibular function akin to that observed in cortical lesion patients, I herewith propose the hypothesis that vestibular cortical processing is controlled, as per for spatial attention, via dynamic interhemispheric competition. In the first half of this review I discuss previous key findings in the field of vestibular neuroscience that can be reinterpreted to support the role of interhemispheric competition for the control of high-level vestibular functions. Contrastingly, in the second half of this review, I present previous findings that show how disrupting interhemispheric interactions can modulate the brainstem-mediated vestibular-ocular reflex (VOR). I conclude by speculating why interhemispheric competition induces correlated biases at the cortical and brainstem level respectively. Specifically, I propose that brainstem-mediated vestibulo-spatial and vestibulo-temporal transformations, in addition to coding for head displacement, underpin a generalized cortical magnitude estimation system which the CNS uses to construct dynamic spatio-temporal maps of the physical world, in-turn ensuring spatial orientation.

Bidirectional Modulation of Numerical Magnitude.

Numerical cognition is critical for modern life; however, the precise neural mechanisms underpinning numerical magnitude allocation in humans remain obscure. Based upon previous reports demonstrating the close behavioral and neuro-anatomical relationship between number allocation and spatial attention, we hypothesized that these systems would be subject to similar control mechanisms, namely dynamic interhemispheric competition. We employed a physiological paradigm, combining visual and vestibular stimulation, to induce interhemispheric conflict and subsequent unihemispheric inhibition, as confirmed by transcranial direct current stimulation (tDCS). This allowed us to demonstrate the first systematic bidirectional modulation of numerical magnitude toward either higher or lower numbers, independently of either eye movements or spatial attention mediated biases. We incorporated both our findings and those from the most widely accepted theoretical framework for numerical cognition to present a novel unifying computational model that describes how numerical magnitude allocation is subject to dynamic interhemispheric competition. That is, numerical allocation is continually updated in a contextual manner based upon relative magnitude, with the right hemisphere responsible for smaller magnitudes and the left hemisphere for larger magnitudes.

The impact of transcranial direct current stimulation (tDCS) combined with modified constraint-induced movement therapy (mCIMT) on upper limb function in chronic stroke: a double-blind randomized controlled trial.

PURPOSE: This pilot double-blind sham-controlled randomized trial aimed to determine if the addition of anodal tDCS on the affected hemisphere or cathodal tDCS on unaffected hemisphere to modified constraint-induced movement therapy (mCIMT) would be superior to constraints therapy alone in improving upper limb function in chronic stroke patients. METHODS: Twenty-one patients with chronic stroke were randomly assigned to receive 12 sessions of either (i) anodal, (ii) cathodal or (iii) sham tDCS combined with mCIMT. Fugl-Meyer assessment (FMA), motor activity log scale (MAL), and handgrip strength were analyzed before, immediately, and 1 month (follow-up) after the treatment. Minimal clinically important difference (mCID) was defined as an increase of ≥5.25 in the upper limb FMA. RESULTS: An increase in the FMA scores between the baseline and post-intervention and follow-up for active tDCS group was observed, whereas no difference was observed in the sham group. At post-intervention and follow-up, when compared with the sham group, only the anodal tDCS group achieved an improvement in the FMA scores. ANOVA showed that all groups demonstrated similar improvement over time for MAL and handgrip strength. In the active tDCS groups, 7/7 (anodal tDCS) 5/7 (cathodal tDCS) of patients experienced mCID against 3/7 in the sham group. CONCLUSION: The results support the merit of association of mCIMT with brain stimulation to augment clinical gains in rehabilitation after stroke. However, the anodal tDCS seems to have greater impact than the cathodal tDCS in increasing the mCIMT effects on motor function of chronic stroke patients. IMPLICATIONS FOR REHABILITATION: The association of mCIMT with brain stimulation improves clinical gains in rehabilitation after stroke. The improvement in motor recovery (assessed by Fugl-Meyer scale) was only observed after anodal tDCS. The modulation of damaged hemisphere demonstrated greater improvements than the modulation of unaffected hemispheres.

A toggle switch of visual awareness?

Major clues to the human brain mechanisms of spatial attention and visual awareness have come from the syndrome of neglect, where patients ignore one half of space. A longstanding puzzle, though, is that neglect almost always comes from right-hemisphere damage, which suggests that the two sides of the brain play distinct roles. But tests of attention in healthy people have revealed only slight differences between the hemispheres. Here we show that major differences emerge if we look at the timing of brain activity in a task optimized to identify attentional functions. Using EEG to map cortical activity on a millisecond timescale, we found transient (20-30 ms) periods of interhemispheric competition, followed by short phases of marked right-sided activity in the ventral attentional network. Our data are the first to show interhemispheric interactions that, much like a toggle switch, quickly allocate neural resources to one or the other hemisphere.

Transcranial direct current stimulation over posterior parietal cortex modulates visuospatial localization.

Visual localization is based on the complex interplay of bottom-up and top-down processing. Based on previous work, the posterior parietal cortex (PPC) is assumed to play an essential role in this interplay. In this study, we investigated the causal role of the PPC in visual localization. Specifically, our goal was to determine whether modulation of the PPC via transcranial direct current stimulation (tDCS) could induce visual mislocalization similar to that induced by an exogenous attentional cue (Wright, Morris, & Krekelberg, 2011). We placed one stimulation electrode over the right PPC and the other over the left PPC (dual tDCS) and varied the polarity of the stimulation. We found that this manipulation altered visual localization; this supports the causal involvement of the PPC in visual localization. Notably, mislocalization was more rightward when the cathode was placed over the right PPC than when the anode was placed over the right PPC. This mislocalization was found within a few minutes of stimulation onset, it dissipated during stimulation, but then resurfaced after stimulation offset and lasted for another 10-15 min. On the assumption that excitability is reduced beneath the cathode and increased beneath the anode, these findings support the view that each hemisphere biases processing to the contralateral hemifield and that the balance of activation between the hemispheres contributes to position perception (Kinsbourne, 1977; Szczepanski, Konen, & Kastner, 2010).