V5/MT Stimulation on Reading and Reading-related Measures in Developmental Dyslexia

Study Overview
=================
Brief Summary
-----------------
The present study grounds on the absence of evidence-based treatment in individuals with developmental dyslexia (DD). At this topic, the present study will explore the potential effect of transcranial direct current stimulation (tDCS) over left hemispheric direct Lateral Geniculate Nucleus (LGN)-V5/MT pathway, cerebral areas usually disrupted in individuals with DD. The investigators hypothesized that active tDCS over V5/MT will boost reading skills in children and adolescents with DD. On the contrary, sham (placebo condition) tDCS over V5/MT or active (control condition) tDCS over V1 will not have significant effect in improving reading skills. Further, both active and sham tDCS will be safe and well tolerated.

Detailed Description
-----------------
Over the last few decades, a huge number of studies has revealed that Developmental Dyslexia (DD), a brain-based neurodevelopmental disorder characterized by a severe and persistent impairment in the acquisition of reading skills may depend on multiple neurocognitive impairments, ranging from language-specific to cognitive-general deficits. Besides the most influential hypothesis of a phonological core deficit, there is also evidence for difficulties in low-level visual-temporal information processing, as the magnocellular deficit theory supports, as well as for visual-spatial attentional deficits, visual-perceptual impairments, and rapid automatized naming (RAN)-speed deficits. Replicated structural/functional neuroimaging studies have demonstrated a DD hypoactivation relative to typical readers in the left temporo-occipital regions-critical for the automatic visual processing of word strings or print-and in the left temporo-parietal regions-important for grapheme-to-phoneme mapping. Moreover, findings from animal models and post mortem studies in humans suggest that DD might also be associated with structural alterations in subcortical sensory pathways, particularly in visual and auditory thalamic nuclei and in their connections with high-order sensory cortices (i.e., the left hemispheric direct Lateral Geniculate Nucleus (LGN)-V5/MT pathway and the left hemispheric direct Medial Geniculate Body (MGB)-mPT pathway). In addition, in adults with DD, left V5/MT-LGN connectivity strength correlated with RAN abilities - a key deficit in DD. A number of studies have demonstrated the positive effect of transcranial direct current stimulation (tDCS), a non-invasive brain stimulation used for transiently modifying neural activity of target areas, on reading and, particularly, in DD. However, the few non-invasive brain stimulation studies on improving reading in DD yielded heterogeneous results and this variability might be partly due to the lack of neurobiological understanding of the underlying DD mechanism or to the use of traditional tDCS rather than a more focal technique such as the high-definition tDCS (HD-tDCS). Starting from this, the aim of the current study is testing the effectiveness of a cutting-edge stimulation technique (i.e., HD-tDCS) in a within-subject experiment involving children and adolescents with DD. Especially, we will work to test i) the specific effect of HD-tDCS over high-order sensory cortices (i.e., V5/MT vs V1) on reading in children with DD; ii) the preconditions and neurobiological mechanisms that lead to high treatment outcomes. If the stimulation over V5/MT is effective and specifically related to reading improvement, our results could help to i) understand the contribution and neurobiological mechanism of V5/MT in reading of children and adolescents with DD; ii) select criteria for potential responders to non-invasive brain stimulation; iii) develop evidence-based interventions in DD.

Official Title
-----------------
Probing the Efficacy of V5/MT Stimulation on Reading and Reading-related Measures in Children and Adolescents With Developmental Dyslexia

Conditions
-----------------
Developmental Dyslexia

Intervention / Treatment
-----------------
* Device: Active HD-tDCS over V5/MT
* Device: Active HD-tDCS over V1
* Device: Sham HD-tDCS over V5/MT or V1


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Italian speakers right-handed children and adolescents with dyslexia (DSM-5, APA 2013); Word/nonword/text reading accuracy and/or speed at least 2 Standard Deviations below the mean for school-age; nv IQ ≥ 85; normal hearing and normal or corrected-to-normal vision. Exclusion Criteria: Having a comorbidity with other primary psychiatric/neurological diagnosis (e.g., depression, anxiety, autism, ADHD); Having a personal history of neurological/medical/genetic diseases; Having ongoing drug treatment influencing brain function; Having epilepsy o family history of epilepsy.

Ages Eligible for Study
-----------------
Minimum Age: 8 Years
Maximum Age: 13 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HD-tDCS V5/MT, HD-tDCS V1, Sham<br>Active HD-tDCS over V5/MT Active HD-tDCS over V1 Sham HD-tDCS over V5/MT or V1 | Device: Active HD-tDCS over V5/MT<br>* For HD-tDCS a 4 × 1 montage (Kessler et al., 2013), small circular electrodes (diameter 1 cm) will be used with the anode placed centrally with a current intensity of 1 mA for a total of 20 minutes (30 s ramp up/down). Hereby, the anodal electrode modulates the excitability of the targeted area left V5/MT, whereas the other 4 electrodes return electrical currents that flow away from that area. V5/MT will be localised via published procedures and electrode's placement will be done according to the 10-20 International EEG 10-20 System for electrode placement.<br>Device: Active HD-tDCS over V1<br>* For HD-tDCS a 4 × 1 montage (Kessler et al., 2013), small circular electrodes (diameter 1 cm) will be used with the anode placed centrally with a current intensity of 1 mA for a total of 20 minutes (30 s ramp up/down). Hereby, the anodal electrode modulates the excitability of the targeted area left V1, whereas the other 4 electrodes return electrical currents that flow away from that area. V1 will be localised via published procedures and electrode's placement will be done according to the 10-20 International EEG 10-20 System for electrode placement.<br>Device: Sham HD-tDCS over V5/MT or V1<br>* Sham HD-tDCS will be delivered over left V5/MT or left V1. The same electrodes placement as well as the stimulation set-up will be used as in the active stimulation conditions, but the current will be applied for 30 s and will be ramped down (0 mA) during the rest of the session without the participants awareness. .<br>|
| Experimental: HD-tDCS V5/MT, Sham, HD-tDCS V1<br>Active HD-tDCS over V5/MT Sham HD-tDCS over V5/MT or V1 Active HD-tDCS over V1 | Device: Active HD-tDCS over V5/MT<br>* For HD-tDCS a 4 × 1 montage (Kessler et al., 2013), small circular electrodes (diameter 1 cm) will be used with the anode placed centrally with a current intensity of 1 mA for a total of 20 minutes (30 s ramp up/down). Hereby, the anodal electrode modulates the excitability of the targeted area left V5/MT, whereas the other 4 electrodes return electrical currents that flow away from that area. V5/MT will be localised via published procedures and electrode's placement will be done according to the 10-20 International EEG 10-20 System for electrode placement.<br>Device: Active HD-tDCS over V1<br>* For HD-tDCS a 4 × 1 montage (Kessler et al., 2013), small circular electrodes (diameter 1 cm) will be used with the anode placed centrally with a current intensity of 1 mA for a total of 20 minutes (30 s ramp up/down). Hereby, the anodal electrode modulates the excitability of the targeted area left V1, whereas the other 4 electrodes return electrical currents that flow away from that area. V1 will be localised via published procedures and electrode's placement will be done according to the 10-20 International EEG 10-20 System for electrode placement.<br>Device: Sham HD-tDCS over V5/MT or V1<br>* Sham HD-tDCS will be delivered over left V5/MT or left V1. The same electrodes placement as well as the stimulation set-up will be used as in the active stimulation conditions, but the current will be applied for 30 s and will be ramped down (0 mA) during the rest of the session without the participants awareness. .<br>|
| Experimental: HD-tDCS V1, HD-tDCS V5/MT, Sham<br>Active HD-tDCS over V1 Active HD-tDCS over V5/MT Sham HD-tDCS over V5/MT or V1 | Device: Active HD-tDCS over V5/MT<br>* For HD-tDCS a 4 × 1 montage (Kessler et al., 2013), small circular electrodes (diameter 1 cm) will be used with the anode placed centrally with a current intensity of 1 mA for a total of 20 minutes (30 s ramp up/down). Hereby, the anodal electrode modulates the excitability of the targeted area left V5/MT, whereas the other 4 electrodes return electrical currents that flow away from that area. V5/MT will be localised via published procedures and electrode's placement will be done according to the 10-20 International EEG 10-20 System for electrode placement.<br>Device: Active HD-tDCS over V1<br>* For HD-tDCS a 4 × 1 montage (Kessler et al., 2013), small circular electrodes (diameter 1 cm) will be used with the anode placed centrally with a current intensity of 1 mA for a total of 20 minutes (30 s ramp up/down). Hereby, the anodal electrode modulates the excitability of the targeted area left V1, whereas the other 4 electrodes return electrical currents that flow away from that area. V1 will be localised via published procedures and electrode's placement will be done according to the 10-20 International EEG 10-20 System for electrode placement.<br>Device: Sham HD-tDCS over V5/MT or V1<br>* Sham HD-tDCS will be delivered over left V5/MT or left V1. The same electrodes placement as well as the stimulation set-up will be used as in the active stimulation conditions, but the current will be applied for 30 s and will be ramped down (0 mA) during the rest of the session without the participants awareness. .<br>|
| Experimental: HD-tDCS V1, Sham, HD-tDCS V5/MT<br>Active HD-tDCS over V1 Sham HD-tDCS over V5/MT or V1 Active HD-tDCS over V5/MT | Device: Active HD-tDCS over V5/MT<br>* For HD-tDCS a 4 × 1 montage (Kessler et al., 2013), small circular electrodes (diameter 1 cm) will be used with the anode placed centrally with a current intensity of 1 mA for a total of 20 minutes (30 s ramp up/down). Hereby, the anodal electrode modulates the excitability of the targeted area left V5/MT, whereas the other 4 electrodes return electrical currents that flow away from that area. V5/MT will be localised via published procedures and electrode's placement will be done according to the 10-20 International EEG 10-20 System for electrode placement.<br>Device: Active HD-tDCS over V1<br>* For HD-tDCS a 4 × 1 montage (Kessler et al., 2013), small circular electrodes (diameter 1 cm) will be used with the anode placed centrally with a current intensity of 1 mA for a total of 20 minutes (30 s ramp up/down). Hereby, the anodal electrode modulates the excitability of the targeted area left V1, whereas the other 4 electrodes return electrical currents that flow away from that area. V1 will be localised via published procedures and electrode's placement will be done according to the 10-20 International EEG 10-20 System for electrode placement.<br>Device: Sham HD-tDCS over V5/MT or V1<br>* Sham HD-tDCS will be delivered over left V5/MT or left V1. The same electrodes placement as well as the stimulation set-up will be used as in the active stimulation conditions, but the current will be applied for 30 s and will be ramped down (0 mA) during the rest of the session without the participants awareness. .<br>|
| Experimental: Sham, HD-tDCS V5/MT, HD-tDCS V1<br>Sham HD-tDCS over V5/MT or V1 Active HD-tDCS over V5/MT Active HD-tDCS over V1 | Device: Active HD-tDCS over V5/MT<br>* For HD-tDCS a 4 × 1 montage (Kessler et al., 2013), small circular electrodes (diameter 1 cm) will be used with the anode placed centrally with a current intensity of 1 mA for a total of 20 minutes (30 s ramp up/down). Hereby, the anodal electrode modulates the excitability of the targeted area left V5/MT, whereas the other 4 electrodes return electrical currents that flow away from that area. V5/MT will be localised via published procedures and electrode's placement will be done according to the 10-20 International EEG 10-20 System for electrode placement.<br>Device: Active HD-tDCS over V1<br>* For HD-tDCS a 4 × 1 montage (Kessler et al., 2013), small circular electrodes (diameter 1 cm) will be used with the anode placed centrally with a current intensity of 1 mA for a total of 20 minutes (30 s ramp up/down). Hereby, the anodal electrode modulates the excitability of the targeted area left V1, whereas the other 4 electrodes return electrical currents that flow away from that area. V1 will be localised via published procedures and electrode's placement will be done according to the 10-20 International EEG 10-20 System for electrode placement.<br>Device: Sham HD-tDCS over V5/MT or V1<br>* Sham HD-tDCS will be delivered over left V5/MT or left V1. The same electrodes placement as well as the stimulation set-up will be used as in the active stimulation conditions, but the current will be applied for 30 s and will be ramped down (0 mA) during the rest of the session without the participants awareness. .<br>|
| Experimental: Sham, HD-tDCS V1, HD-tDCS V5/MT<br>Sham HD-tDCS over V5/MT or V1 Active HD-tDCS over V1 Active HD-tDCS over V5/MT | Device: Active HD-tDCS over V5/MT<br>* For HD-tDCS a 4 × 1 montage (Kessler et al., 2013), small circular electrodes (diameter 1 cm) will be used with the anode placed centrally with a current intensity of 1 mA for a total of 20 minutes (30 s ramp up/down). Hereby, the anodal electrode modulates the excitability of the targeted area left V5/MT, whereas the other 4 electrodes return electrical currents that flow away from that area. V5/MT will be localised via published procedures and electrode's placement will be done according to the 10-20 International EEG 10-20 System for electrode placement.<br>Device: Active HD-tDCS over V1<br>* For HD-tDCS a 4 × 1 montage (Kessler et al., 2013), small circular electrodes (diameter 1 cm) will be used with the anode placed centrally with a current intensity of 1 mA for a total of 20 minutes (30 s ramp up/down). Hereby, the anodal electrode modulates the excitability of the targeted area left V1, whereas the other 4 electrodes return electrical currents that flow away from that area. V1 will be localised via published procedures and electrode's placement will be done according to the 10-20 International EEG 10-20 System for electrode placement.<br>Device: Sham HD-tDCS over V5/MT or V1<br>* Sham HD-tDCS will be delivered over left V5/MT or left V1. The same electrodes placement as well as the stimulation set-up will be used as in the active stimulation conditions, but the current will be applied for 30 s and will be ramped down (0 mA) during the rest of the session without the participants awareness. .<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Text reading accuracy (Experimental reading task) | Change in text reading accuracy from baseline compared after to Active HD-tDCS over V5/MT sessions than after Active HD-tDCS over V1 and Sham sessions. Text reading accuracy is considered as the percentage (%) of accuracy and computed as the ratio between the number of correctly read stimuli and the total number of stimuli presented multiplied by 100. The time points will be pre- (baseline) vs post-stimulation session. | during procedure | 
| Text reading speed (Experimental reading task) | Change in text reading speed from baseline compared to after Active HD-tDCS over V5/MT sessions than after Active HD-tDCS over V1 and Sham sessions. Text reading speed is considered as the syllables/seconds ratio and calculated dividing the total number of syllables pronounced by the total time spent to complete the reading (in seconds). The time points will be pre- (baseline) vs post-stimulation session. | during procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Word reading accuracy (Experimental reading task) | Change in word reading accuracy from baseline compared to after Active HD-tDCS over V5/MT sessions than after Active HD-tDCS over V1 and Sham sessions. Word reading accuracy is considered as the percentage (%) of accuracy and computed as the ratio between the number of correctly read stimuli and the total number of stimuli presented multiplied by 100. The time points will be pre- (baseline) vs post-stimulation session. | during procedure | 
| Word reading speed (Experimental reading task) | Change in word reading speed from baseline compared to after Active HD-tDCS over V5/MT sessions than during Active HD-tDCS over V1 and Sham sessions. Word reading speed is considered as the syllables/seconds ratio and calculated dividing the total number of syllables pronounced by the total time spent to complete the reading (in seconds). The time points will be pre- (baseline) vs post-stimulation session. | during procedure | 
| Non-word reading accuracy (Experimental reading task) | Change in non-word reading accuracy from baseline compared to after Active HD-tDCS over V5/MT sessions than after Active HD-tDCS over V1 and Sham sessions. Non-word reading accuracy is considered as the percentage (%) of accuracy and computed as the ratio between the number of correctly read stimuli and the total number of stimuli presented multiplied by 100. The time points will be pre- (baseline) vs post-stimulation session. | during procedure | 
| Non-word reading speed (Experimental reading task) | Change in non-word reading speed from baseline compared to after Active HD-tDCS over V5/MT sessions than after Active HD-tDCS over V1 and Sham sessions. Non-word reading speed is considered as the syllables/seconds ratio and calculated dividing the total number of syllables pronounced by the total time spent to complete the reading (in seconds). The time points will be pre- (baseline) vs post-stimulation session. | during procedure | 
| Right visual hemisphere-motion perception (Experimental reading task) | Change in right visual hemisphere-motion perception from baseline compared to after Active HD-tDCS over V5/MT sessions than after Active HD-tDCS over V1 and Sham sessions. Right visual hemisphere-motion perception is considered as the number of correct saccades. The time points will be pre- (baseline) vs post-stimulation session. | during procedure | 
| Rapid automatized naming letter and number (Experimental reading task) | Change in rapid automatized naming letter and number from baseline compared to after Active HD-tDCS over V5/MT sessions than after Active HD-tDCS over V1 and Sham sessions. Rapid automatized naming letter and number is considered as the total time spent (in seconds) to complete the task. The time points will be pre- (baseline) vs post-stimulation session. | during procedure | 
| Phoneme blending (Experimental reading task) | Change in phoneme blending from baseline compared to after Active HD-tDCS over V5/MT sessions than after Active HD-tDCS over V1 and Sham sessions. Phoneme blending is considered as the number of correctly blended phonemes. The time points will be pre- (baseline) vs post-stimulation session. | during procedure | 
| Eye-movements during reading (Experimental reading task) | Change in eye-movements from baseline compared to after reading during Active HD-tDCS over V5/MT sessions than after Active HD-tDCS over V1 and Sham sessions. Eye-movements during reading is considered as the number of saccades and the number of dwells. The time points will be pre- (baseline) vs post-stimulation session. | during procedure | 
| Spontaneous EEG (Experimental reading task) | Change in spontaneous EEG from baseline compared to after Active HD-tDCS over V5/MT sessions than after Active HD-tDCS over V1 and Sham sessions. Spontaneous EEG is considered as the individual alpha-peak frequency and the beta and theta/gamma oscillations. The time points will be pre- (baseline) vs post-stimulation session. | during procedure | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Children, Adolescents, tDCS, transcranial direct current stimulation, neurodevelopmental disorders, non-invasive brain stimulation, transcranial electrical stimulation, EEG, reading abilities