Table 2.

PRISMA-P Protocol for Systematic Review (103).

Rationale	To identify any neuroanatomical structures whose atypical function may be associated with the cognitive deficits exhibited by individuals with dyslexia and dyscalculia
Objectives	The review answered the following questions: • “What brain regions show atypical activity in dyslexia alone?” • “What brain regions are show atypical activity in dyscalculia alone?” • “What brain regions are atypical activity in comorbid dyslexia-dyscalculia?
Eligibility criteria	Studies published in academic research journals since January 1, 2004. This marks the beginning of the current definition of specific learning disability (104) •The studies involved 20+ participants, males and females ages 6 and older •The studies followed a quasi-experimental design with at least two groups: one group with a learning disability (dyslexia or dyscalculia) and a control group •The studies did not involve individuals with any medical condition (other than dyslexia or dyscalculia) or any other life circumstance that could have influenced their performance on the cognitive tasks (ADHD, neurodegenerative disease, lack of education, etc.) •The investigators applied one of the three following techniques:   a) Functional magnetic resonance imaging (fMRI) to examine physiological correlates of cognitive activity during phonological or numerical magnitude comparison tasks   b) Diffusion tensor imaging (DTI) to examine structural differences in white or gray matter composition between key neurological structures   c) Lesion-symptom mapping (caused by either a stroke or a brain tumor)
Information sources	•Google Scholar •American Psychological Association (PsycINFO) •Education Resources Information Center (ERIC) •NIH MEDLINE Database (PubMed) •Web of Science
Search strategy	Step 1: Preliminary Search A preliminary search was performed using Google Scholar to find the leading authors in learning disabilities research, identify their seminal publications on dyslexia, dyscalculia, and provide a working definition for each disorder Step 2: Existing Meta-Analyses A secondary search was performed to using PsycINFO and ERIC to identify studies that examined comorbid dyslexia-dyscalculia, and to identify any existing meta-analyses on the cognitive or neurological correlates of each learning disability Step 3: Detailed Search A detailed search of medical literature was performed using PubMed and Web of Science to identify empirical studies that used functional or structural MRI to examine individuals with (i) dyscalculia and (ii) dyslexia, and that report the neuroanatomical structures where atypical function, white matter composition, or functional connectivity is associated with each disorder   a) A combination of the following search terms were used to identify functional and structural neuroimaging studies on dyslexia: “neurobiological dyslexia” “neurobiological reading disability” “brain region dyslexia” “brain region reading disability” “neuroimaging dyslexia” “neuroimaging reading disability” “fMRI dyslexia” “fMRI reading disability” “MRI dyslexia” “MRI reading disability” “DTI dyslexia” “DTI reading disability”   b) A combination of the following search terms were used to identify functional and structural neuroimaging studies on dyscalculia: “neurobiological dyscalculia” “neurobiological math disability” “brain region dyscalculia” “brain region math disability” “neuroimaging dyscalculia” “neuroimaging math disability” “fMRI dyscalculia” “fMRI math disability” “MRI dyscalculia” “MRI math disability” “DTI dyscalculia” “DTI math disability” Step 4: Lesion-symptom Mapping Studies A second detailed search of medical literature was performed using PubMed and Web of Science to identify empirical studies that examined patients with alexia (acquired dyslexia) or acalculia (acquired dyscalculia), who had suffered damage to structures that mediate in math or reading ability, caused by an ischemic stroke or brain tumor   a) A combination of the following search terms were used to identify lesion-symptom case studies of patients with alexia: “neurobiology AND acquired dyslexia” “neurobiology AND alexia” “lesion AND acquired dyslexia” “lesion AND alexia” “stroke AND acquired dyslexia” “stroke AND alexia” “brain tumor AND acquired dyslexia” “brain tumor AND alexia”   b) A combination of the following search terms for acquired dyscalculia: “neurobiology AND acquired dyscalculia” “neurobiology AND acalculia” “lesion AND acquired dyscalculia” “lesion AND acalculia” “stroke AND acquired dyscalculia” “stroke AND acalculia” “brain tumor AND acquired dyscalculia” “brain tumor AND acalculia”
Study records	One independent reviewer selected the published studies that fit the eligibility criteria. The selected publications were legally stored and classified using Mendeley Desktop (Version 1.15.2) for Windows 10
Outcomes and prioritization	The desired outcome was a list of brain regions that are involved in dyslexia and dyscalculia. Priority was given to studies that included participants all four groups (participants with dyslexia, dyscalculia, comorbid dyslexia-dyscalculia, and controls)
Synthesis	The results of the systematic review are synthesized using a table as displayed below. Each brain region identified in the review is classified by learning disability (whether the region is associated with dyslexia, dyscalculia), as well as by the type of atypical functionality displayed (whether the brain region is generally more active or inactive in individuals with the learning disability). Of primary interest are the neuroanatomical structures whose atypical function is common to dyslexia and dyscalculia; these structures are underlined in the table