Brain Deficits Research Articles

Human stem cells harboring a suicide gene improve the\xa0safety and standardisation of neural transplants in Parkinsonian rats

Despite advancements in human pluripotent stem cells (hPSCs) differentiation protocols to generate appropriate neuronal progenitors suitable for transplantation in Parkinson’s disease, resultant grafts contain low proportions of dopamine neurons. Added to this is the tumorigenic risk associated with the potential presence of incompletely patterned, proliferative cells within grafts. Here, we utilised a hPSC line carrying a FailSafeTM suicide gene (thymidine kinase linked to cyclinD1) to selectively ablate proliferative cells in order to improve safety and purity of neural transplantation in a Parkinsonian model. The engineered FailSafeTM hPSCs demonstrated robust ventral midbrain specification in vitro, capable of forming neural grafts upon transplantation. Activation of the suicide gene within weeks after transplantation, by ganciclovir administration, resulted in significantly smaller grafts without affecting the total yield of dopamine neurons, their capacity to innervate the host brain or reverse motor deficits at six months in a rat Parkinsonian model. Within ganciclovir-treated grafts, other neuronal, glial and non-neural populations (including proliferative cells), were significantly reduced—cell types that may pose adverse or unknown influences on graft and host function. These findings demonstrate the capacity of a suicide gene-based system to improve both the standardisation and safety of hPSC-derived grafts in a rat model of Parkinsonism.

Large-scale network topology reveals brain functional abnormality in Chinese dyslexic children

It has been revealed that dyslexic children learning alphabetic languages are characterized by aberrant topological organization of brain networks. However, little is known about the functional organization and the reconfiguration pattern of brain networks in Chinese dyslexic children. Using graph theoretical analysis and functional magnetic resonance images (fMRI), we examined this issue specifically from the perspective of functional integration and segregation. We first compared large-scale topological organizations between dyslexic children and typically developing children during a Chinese phonological rhyming task, and found that dyslexic children showed increased local efficiency and clustering coefficient compared with typically developing children, which were negatively correlated with task performance. Furthermore, dyslexic children and typically developing children could be accurately distinguished at the individual-subject level based on the nodal local efficiency or clustering coefficient. Second, we studied the group difference of network reconfiguration and found that dyslexic children showed more difficulty when shifting from the resting state to the phonological task. Our results suggest an over-segregated brain functional organization and deficits in brain network reconfiguration in Chinese dyslexic children, which helps to advance our knowledge on the neural mechanisms underlying dyslexia.

Repetitive mild head trauma induces activity mediated lifelong brain deficits in a novel Drosophila model

Mild head trauma, including concussion, can lead to chronic brain dysfunction and degeneration but the underlying mechanisms remain poorly understood. Here, we developed a novel head impact system to investigate the long-term effects of mild head trauma on brain structure and function, as well as the underlying mechanisms in Drosophila melanogaster. We find that Drosophila subjected to repetitive head impacts develop long-term deficits, including impaired startle-induced climbing, progressive brain degeneration, and shortened lifespan, all of which are substantially exacerbated in female flies. Interestingly, head impacts elicit an elevation in neuronal activity and its acute suppression abrogates the detrimental effects in female flies. Together, our findings validate Drosophila as a suitable model system for investigating the long-term effects of mild head trauma, suggest an increased vulnerability to brain injury in female flies, and indicate that early altered neuronal excitability may be a key mechanism linking mild brain trauma to chronic degeneration.

Plasma lipidome profiling of newborns with antenatal exposure to Zika virus.

The 2015-2016 Zika virus (ZIKV) outbreak in Brazil was remarkably linked to the incidence of microcephaly and other deleterious clinical manifestations, including eye abnormalities, in newborns. It is known that ZIKV targets the placenta, triggering an inflammatory profile that may cause placental insufficiency. Transplacental lipid transport is delicately regulated during pregnancy and deficiency on the delivery of lipids such as arachidonic and docosahexaenoic acids may lead to deficits in both brain and retina during fetal development. Here, plasma lipidome profiles of ZIKV exposed microcephalic and normocephalic newborns were compared to non-infected controls. Our results reveal major alterations in circulating lipids from both ZIKV exposed newborns with and without microcephaly relative to controls. In newborns with microcephaly, the plasma concentrations of hydroxyoctadecadienoic acid (HODE), primarily as 13-HODE isomer, derived from linoleic acid were higher as compared to normocephalic ZIKV exposed newborns and controls. Total HODE concentrations were also positively associated with levels of other oxidized lipids and several circulating free fatty acids in newborns, indicating a possible plasma lipidome signature of microcephaly. Moreover, higher concentrations of lysophosphatidylcholine in ZIKV exposed normocephalic newborns relative to controls suggest a potential disruption of polyunsaturated fatty acids transport across the blood-brain barrier of fetuses. The latter data is particularly important given the neurocognitive and neurodevelopmental abnormalities observed in follow-up studies involving children with antenatal ZIKV exposure, but normocephalic at birth. Taken together, our data reveal that plasma lipidome alterations associated with antenatal exposure to ZIKV could contribute to identification and monitoring of the wide spectrum of clinical phenotypes at birth and further, during childhood.

Brain deficits in prediabetic adults: A systematic review.

Previous findings on the relationship between prediabetes (the precursor stage of type 2 diabetes) and brain health in humans are inconsistent. Thus, this systematic review of cross-sectional and longitudinal studies aimed to summarize what is currently known about brain deficits in prediabetic adults. Following the PRISMA reporting standards for systematic reviews, we conducted a comprehensive review of peer-reviewed journal articles published from 2009 to present, focusing on studies that assessed brain volume, structural connectivity, and cerebrovascular health in prediabetic adults and older adults (i.e., 18years or older). We systematically searched PsychINFO, Scopus, Web of Science, Ovid MEDLINE, CINAHL, and EMbase databases. Quality assessment was based on the NIH Quality Assessment Tool for Observational and Cross-sectional Studies. In total, 19 studies were included in our review. Results from these studies show that prediabetes may be associated with deficits in brain structure and pathology, however, several studies also refute these findings. Moreover, we identified clear inconsistencies in study methodologies, including diabetes measures and classification, across studies that may account for these conflicting findings.

Omega-3 fatty acids during adolescence prevent schizophrenia-related behavioural deficits: Neurophysiological evidences from the prenatal viral infection with PolyI:C

The likely involvement of inflammation and oxidative stress (IOS) in mental disease has led to advocate anti-oxidant and anti-inflammatory drugs as therapeutic strategies in the treatment of schizophrenia. Since omega-3 fatty acids (ω-3) show anti-inflammatory/neuroprotective properties, we aim to evaluate whether ω-3 treatment during adolescence in the maternal immune stimulation (MIS) animal model of schizophrenia could prevent the brain and behavioural deficits described in adulthood. At gestational day 15, PolyI:C (4 mg/kg) or saline (VH) were injected to pregnant Wistar rats. Male offspring received ω-3 (800 mg/kg) or saline (Sal) daily from postnatal day (PND) 35–49, defining 4 groups: MIS-ω-3; MIS-Sal; VH-ω-3 and VH-Sal. At PND70, rats were submitted to prepulse inhibition test (PPI). FDG-PET and T2-weighted MRI brain studies were performed in adulthood and analyzed by means of SPM12. IOS markers were measured in selected brain areas. MIS-offspring showed a PPI deficit compared with VH-offspring and ω-3 treatment prevented this deficit. Also, ω-3 reduced the brain metabolism in the deep mesencephalic area and prevented the volumetric abnormalities in the hippocampus but not in the ventricles in MIS-offspring. Besides, ω-3 reduced the expression of iNOS and Keap1 and increased the activity/concentration of HO1, NQO1 and GPX. Our study demonstrates that administration of ω-3 during adolescence prevents PPI behavioural deficits and hippocampal volumetric abnormalities, and partially counteracts IOS deficits via iNOS and Nrf2–ARE pathways in the MIS model. This study highlights the need for novel strategies based on anti-inflammatory/anti-oxidant compounds to alter the disease course in high-risk populations at early stages.

Pharmacological rescue in patient iPSC and mouse models with a rare DISC1 mutation

We previously identified a causal link between a rare patient mutation in DISC1 (disrupted-in-schizophrenia 1) and synaptic deficits in cortical neurons differentiated from isogenic patient-derived induced pluripotent stem cells (iPSCs). Here we find that transcripts related to phosphodiesterase 4 (PDE4) signaling are significantly elevated in human cortical neurons differentiated from iPSCs with the DISC1 mutation and that inhibition of PDE4 or activation of the cAMP signaling pathway functionally rescues synaptic deficits. We further generated a knock-in mouse line harboring the same patient mutation in the Disc1 gene. Heterozygous Disc1 mutant mice exhibit elevated levels of PDE4s and synaptic abnormalities in the brain, and social and cognitive behavioral deficits. Pharmacological inhibition of the PDE4 signaling pathway rescues these synaptic, social and cognitive behavioral abnormalities. Our study shows that patient-derived isogenic iPSC and humanized mouse disease models are integral and complementary for translational studies with a better understanding of underlying molecular mechanisms.

Cognitive complications of cancer and cancer-related treatments – Novel paradigms

As advances in diagnostics and therapeutic strategies in oncology have increased the number of cancer survivors, the investigation of the mechanisms associated with long-term cognitive complications of cancer treatment has become an important topic of interest. The neurotoxic effects of chemotherapeutic agents have been described in pre-clinical and clinical research. In vitro and rodent studies have identified some underlying mechanisms contributing to chemotherapy-induced neurotoxicity and cognitive impairment for various chemotherapy drugs and other cancer treatments. However, investigation of the direct biological effects of cancer and other potential contributing factors in the pathogenesis of cancer-related cognitive impairment (CRCI) has only recently come into focus. This review will highlight evidence from pre-clinical tumor-bearing rodent models suggesting that cancer influences the cognitive and behavioral changes reported in human cancer populations through direct or indirect pathways that alter the normal neuroinflammatory responses, induce structural brain deficits, and decrease neurogenesis. We reflect on human clinical cancer research indicating that cognitive and behavioral changes precede cancer treatment in some malignancies. We also highlight implications for future areas of CRCI research based on novel findings on the interplay between cancer, chemotherapy, inflammation, tau pathology, and dysregulation of the microbiota-gut-brain axis.

Consequences of NaCT/SLC13A5/mINDY deficiency: good versus evil, separated only by the blood-brain barrier.

NaCT/SLC13A5 is a Na+-coupled transporter for citrate in hepatocytes, neurons, and testes. It is also called mINDY (mammalian ortholog of ‘I'm Not Dead Yet’ in Drosophila). Deletion of Slc13a5 in mice leads to an advantageous phenotype, protecting against diet-induced obesity, and diabetes. In contrast, loss-of-function mutations in SLC13A5 in humans cause a severe disease, EIEE25/DEE25 (early infantile epileptic encephalopathy-25/developmental epileptic encephalopathy-25). The difference between mice and humans in the consequences of the transporter deficiency is intriguing but probably explainable by the species-specific differences in the functional features of the transporter. Mouse Slc13a5 is a low-capacity transporter, whereas human SLC13A5 is a high-capacity transporter, thus leading to quantitative differences in citrate entry into cells via the transporter. These findings raise doubts as to the utility of mouse models to evaluate NaCT biology in humans. NaCT-mediated citrate entry in the liver impacts fatty acid and cholesterol synthesis, fatty acid oxidation, glycolysis, and gluconeogenesis; in neurons, this process is essential for the synthesis of the neurotransmitters glutamate, GABA, and acetylcholine. Thus, SLC13A5 deficiency protects against obesity and diabetes based on what the transporter does in hepatocytes, but leads to severe brain deficits based on what the transporter does in neurons. These beneficial versus detrimental effects of SLC13A5 deficiency are separable only by the blood-brain barrier. Can we harness the beneficial effects of SLC13A5 deficiency without the detrimental effects? In theory, this should be feasible with selective inhibitors of NaCT, which work only in the liver and do not get across the blood-brain barrier.

PET Hypometabolism of the Prefrontal-Cingulate Cortices in Internet Gaming Disorder.

Recently, excessive and uncontrolled use of online games has been recognized as a public concern. Although previous neuroimaging studies have reported structural and functional brain deficits in Internet gaming disorder (IGD), very few studies have investigated the regional cerebral metabolic rate of glucose (rCMRglu). This study investigated the differences in rCMRglu between individuals with IGD and healthy controls using 18F-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET). A total of 23 adults with IGD and 23 controls underwent brain 18F-FDG PET scans and completed self-report questionnaires. A whole-brain voxel-wise analysis of rCMRglu was conducted and associations between rCMRglu and severity of IGD were assessed. The IGD group showed higher impulsivity (p = 0.04) and lower self-control (p = 0.002) than the control group. In addition, the IGD group had lower FDG uptake in the left medial orbitofrontal gyrus, left middle cingulate cortex, left superior frontal gyrus, and right anterior cingulate cortex (p < 0.001). A significant negative association was found between the rCMRglu in the right anterior cingulate cortex and the number of fulfilled diagnostic criteria for IGD (β = −0.50, p = 0.02). Our results suggest that IGD may be associated with deficits of glucose metabolism in the prefrontal-cingulate cortices.

Histological and Biochemical Alterations in the Superior Colliculus and Lateral Geniculate Nucleus of Juvenile Rats Following Prenatal Exposure to Marijuana Smoke.

Introduction:Prenatal exposure to Marijuana (MJN) has been associated with various brain deficits. The main activity in marijuana, Δ9-Tetrahydrocannabinol (THC), crosses the placenta and affects fetal brain development. Despite this, marijuana remains a commonly abused substance among pregnant women. The current study examined the histological and biochemical changes in the Superior Colliculus (SC) and Lateral Geniculate Nucleus (LGN) in rat brains prenatally exposed to marijuana.Methods:Four groups of pregnant rats (n=5 rats/group) were exposed to the smoke of 10 g/kg marijuana at various days during their gestational period, with a group (control), i.e., not exposed. After parturition, the litters from each group were sacrificed by cervical dislocation on postnatal days 7, 14, and 21; the superior colliculi and lateral geniculate nuclei were excised. Tissue sections were prepared for histological studies using Haematoxylin and Eosin stains. Biochemical studies were performed on alkaline phosphatase, acid phosphatase, lactate dehydrogenase, and glucose-6-phosphate dehydrogenase activity levels. The histological and biochemical analyses of tissues were performed.Results:Prenatal exposure to marijuana resulted in spontaneous abortion and affected neuronal morphology in the SC and LGN of the progeny. Furthermore, the levels of enzyme activities were altered following maternal exposure to MJN.Conclusion:These data suggested that histological changes in the SC and LGN were associated with oxidative damage.HighlightsPrenatal exposure to marijuana smoke in early gestation induced spontaneous abortion.Prenatal exposure to marijuana smoke-induced damage to the visual pathway in the progeny.Prenatal exposure to marijuana-induced histological changes in juvenile rats’ superior colliculus and lateral geniculate nucleus.Prenatal exposure to marijuana smoke resulted in biochemical alterations in juvenile rats’ superior colliculus and lateral geniculate nucleus.Plain Language SummaryMarijuana is the most widely used psychoactive substance in the western world, consumed for recreational, medicinal, and spiritual purposes. Although marijuana consumption by pregnant women has been linked with neurodevelopmental consequences, little is known of its effect on the visual pathway of the progeny. We examined juvenile rats using the rat model, the effect of prenatal exposure to marijuana smoke on the superior colliculus and lateral geniculate body (regions of the brain involved in visual information processing). Our result reveals that marijuana use in early gestation induces spontaneous abortion. Also, prenatal exposure to marijuana smoke produced histological changes in the brain mentioned above regions involved in visual information of the progeny. Our findings also include biochemical alterations in these regions. Hence, we highlight the damaging effects of marijuana smoke on the developing brain, specifically the superior colliculus and lateral geniculate nucleus, i.e., involved in visual information processing, of juvenile rats following prenatal exposure.

Comparison of regional brain deficit patterns in common psychiatric and neurological disorders as revealed by big data

Neurological and psychiatric illnesses are associated with regional brain deficit patterns that bear unique signatures and capture illness-specific characteristics. The Regional Vulnerability Index (RVI) was developed toquantify brain similarity by comparing individual white matter microstructure, cortical gray matter thickness and subcortical gray matter structural volume measures with neuroanatomical deficit patterns derived from large-scale meta-analytic studies. We tested the specificity of the RVI approach for major depressive disorder (MDD) and Alzheimer’s disease (AD) in a large epidemiological sample of UK Biobank (UKBB) participants (N = 19,393; 9138 M/10,255F; age = 64.8 ± 7.4 years). Compared to controls free of neuropsychiatric disorders, participants with MDD (N = 2,248; 805 M/1443F; age = 63.4 ± 7.4) had significantly higher RVI-MDD values (t = 5.6, p = 1·10−8), but showed no detectable difference in RVI-AD (t = 2.0, p = 0.10). Subjects with dementia (N = 7; 4 M/3F; age = 68.6 ± 8.6 years) showed significant elevation in RVI-AD (t = 4.2, p = 3·10−5) but not RVI-MDD (t = 2.1, p = 0.10) compared to controls. Even within affective illnesses, participants with bipolar disorder (N = 54) and anxiety disorder (N = 773) showed no significant elevation in whole-brain RVI-MDD. Participants with Parkinson’s disease (N = 37) showed elevation in RVI-AD (t = 2.4, p = 0.01) while subjects with stroke (N = 247) showed no such elevation (t = 1.1, p = 0.3). In summary, we demonstrated elevation in RVI-MDD and RVI-AD measures in the respective illnesses with strong replicability that is relatively specific to the respective diagnoses. These neuroanatomic deviation patterns offer a useful biomarker for population-wide assessments of similarity to neuropsychiatric illnesses.

Resistance exercise improves cognitive and brain health in overweight older adults

AbstractBackgroundApproximately 50% of Canadian older adults over the age of 60 are overweight or obese (based on body mass index; BMI). Individuals with high BMI (≥25) often experience cognitive and brain deficits (e.g., impaired memory, cortical atrophy, reduced neural activation), and are at high risk of dementia. One promising lifestyle intervention that may improve these deficits is exercise. For example, 6 months of aerobic training has been found to improve cognitive and brain function in overweight older adults, however studies examining whether resistance training (RT) can produce comparable results in this population is limited.MethodWe conducted a 6‐month, thrice‐weekly randomized controlled trial of RT in overweight older adults. Twenty‐four participants aged 60‐80 (sedentary; BMI ≥25) were randomized into one of two groups: 1) progressive resistance (weight) training, or 2) balance and tone (BAT; control; stretching exercises). At pre‐ and post‐intervention (0 and 6 months, respectively), we measured associative memory performance during functional MRI, and obtained high resolution T1 weighted structural images from a 3T scanner.ResultSix months of RT showed significant improvements in memory performance (6.38% reduced error rate) compared to BAT. Similarly, structural imaging showed increased hippocampal volume for RT (+0.04%) as well as increased percent signal change (neural activation) in memory‐related brain regions of interest, including the hippocampus, parahippocampal gyrus, lingual gyrus, and medial temporal gyrus, suggesting improved functional brain health overtime.ConclusionOverall, our findings offer a feasible, cost‐efficient lifestyle intervention strategy to improve cognitive and brain health in overweight older adults.

Chronic Methamphetamine Abuse and Brain Deficits Revealed by Neuroimaging

Chronic Methamphetamine Abuse and Brain Deficits Revealed by Neuroimaging

Extracellular complex of beta‐amyloid with glyceraldehyde‐3‐phosphate dehydrogenase contributes to neurodegeneration in Alzheimer’s disease

AbstractBackgroundThe discovery of migrating protein complexes armed with β‐amyloid (Aβ) and acting as the driving force of Alzheimer’s disease (AD) mechanism led us to suggest that besides the pathogenic peptide some other proteins may cooperate with the latter and enhance its cytotoxicity and intercellular propagation. One of such proteins was suggested to be glyceraldehyde‐3‐phosphatedehydrogenase (GAPDH), enzyme that in normal conditions maintains cellular glycolysis and under action of oxidative stress is converted to monomers and dimers and forms tight, insoluble complexes with aggregation‐prone polypeptides.MethodCSF samples were collected from patients of both genders. The cohort comprised four patient groups: (1) mild cognitive impairment (MCI) n = 21; (2) mild AD‐type dementia (‘Mild’), n = 58; (3) moderate AD‐type dementia (‘Moderate’) n = 57; and (4) severe AD‐type dementia (‘Severe’), n = 56. The diagnosis was established according to the NINCDS‐ARDRA criteria for AD and the Petersen criteria for MCI. Patients were assigned to severity subgroups based on their scores on the Mini‐Mental State Examination (MMSE). Two animal models of AD were used in this study: (1) “chemical” model in rats and (2) transgenic 5XFAD mice.ResultGAPDH is present in cerebrospinal fluid samples of AD patients as covalent complex with Aβ, and the heavier the stage of the disease, the higher is the level of such complexes. The increase of constitutional GAPDH level in AD animal models results in aggravation of cognitive and brain deficits linked to AD progression.ConclusionThe findings imply a potential role of GAPDH as biomarker and prerequisite of massive neuronal death on the late stages of Alzheimer’s disease Supported by RSF grant #19‐74‐30007.

Feasibility of a 26-Week Exercise Program to Improve Brain Health in Older Adults at Risk for Type 2 Diabetes: A Pilot Study

ObjectivesOlder adults at risk for type 2 diabetes (i.e. overweight individuals or those with prediabetes) experience accelerated cognitive and brain deficits. Aerobic training is known to improve these deficits, but the effects of resistance training are relatively unknown. Before conducting a large-scale, randomized, controlled trial to assess the effects of resistance training, we first conducted a pilot feasibility study to examine recruitment, attendance and retention rates in this population. MethodsProgram participants (aged 60 to 80 years, mean age 68.7±5.7 years, 50% females) at risk for type 2 diabetes (body mass index of ≥25 or fasting blood glucose of 6.1 to <7 mmol/L) underwent 26 weeks of thrice-weekly progressive resistance training (n=13) or balance-and-tone exercises (control group, n=11). Recruitment, attendance and retention rates were recorded, and study feedback from program participants and research assistants was collected via questionnaires. ResultsWe recruited 72 older adults (total number enrolled = 24) over 17 months. Program retention and attendance were 95.8% and 84.4%, respectively. Program participants and research assistants expressed a high level of study enjoyment, and suggestions on how to improve study procedures were provided. ConclusionsBased on our findings, a large-scale study in this at-risk group of older adults is feasible, and key strategies to improving future trials were identified.

Metabolic Dysregulation Contributes to the Progression of Alzheimer's Disease.

Alzheimer’s disease (AD) is an incurable neurodegenerative disease. Numerous studies have demonstrated a critical role for dysregulated glucose metabolism in its pathogenesis. In this review, we summarize metabolic alterations in aging brain and AD-related metabolic deficits associated with glucose metabolism dysregulation, glycolysis dysfunction, tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS) deficits, and pentose phosphate pathway impairment. Additionally, we discuss recent treatment strategies targeting metabolic defects in AD, including their limitations, in an effort to encourage the development of novel therapeutic strategies.

Complex Febrile Seizures Associated with Doose vs Dravet Syndrome Presentation of a Clinical Case

Complex Febrile Seizures Associated with Doose vs Dravet Syndrome Presentation of a Clinical Case

Self-limited focal epilepsy decreased regional brain activity in sensorimotor areas.

The fractional amplitude of low-frequency fluctuation (fALFF) method was used to identify the regional brain activity deficits of self-limited focal epilepsy with centrotemporal spikes (SLFECS) relative to normal controls (NCs). A total of 21 SLFECS (10 females, 11 males; mean age, 8.57±1.5years) and 21 status-matched (age, sex, and education) NCs (10 females, 11 males; mean age, 8.76±2.19years) were recruited. The fALFF method was applied to identify SLFECS-related regional brain alterations. Receiver operating characteristic (ROC) curve was applied to identify the ability of these regional brain areas in distinguishing the SLFECS group from the NCs group. The relationships between the regional brain activity deficits and clinical features were evaluated by Pearson's correlation analysis. Self-limited focal epilepsy with centrotemporal spikes was associated with widespread regional brain activity alterations, including left cuneus with higher fALFF values, and bilateral striatum, bilateral precentral gyrus, ventral and dorsal pathway of sensory area, left dorsolateral prefrontal cortex, and left Rolandic area with lower fALFF values. ROC curve revealed excellent AUC value (0.964) of these areas in distinguishing the SLFECS group from the NCs group with high degree of sensitivity (90.5%) and specificity (95.2%). Intelligence quotient score positively correlated with the fALFF value in the left striatum (r=0.453, p=0.039). The fALFF parameter could be served as a potential biomarker to identify the SLFECS-related regional brain deficits in the sensorimotor cortex and their pathways, which may be the etiology of paresthesia in SLFECS.

The Analysis of Semantic Field in Persian-Speaking Patients With Wernicke’s Aphasia

Objectives: Wernicke’s aphasia is one of the most prominent focal brain deficits affecting the comprehension abilities of patients while preserving their production abilities. Although a lot of studies in different languages have been conducted to analyze the nature of this deficit, still some controversies exist in this regard. While some research studies attribute this defect to a performance problem, some research highlight competence deficit and hypothesize qualitative problems. This research, considering the lack of sufficient literature in Persian, tries to reconcile this controversy by investigating the nature of the semantic field in Persian-speaking patients with Wernicke’s aphasia and to compare their semantic processing abilities with those of healthy controls. Methods: In doing so, a semantic judgment task was administered to 10 patients with Wernicke’s aphasia and their age- and education-matched controls to recognize different semantic relations between a group of words whose meanings were related to each other in some way or another. Results: The results showed dissociation in the subjects’ performance. While patients with Wernicke’s aphasia had severe deficits in semantic judgment tasks, healthy control performed very well. This selective performance was also observed in different semantic pairs. Also, patients with Wernicke’s aphasia performed poorly in almost all classes of semantic pairs, but the severity of their problems was more prominent in certain semantic categories. Discussion: The findings, in line with a competence deficit hypothesis, suggest that linguistic items are processed in the mental lexicon as a semantic unit. Hence, linguistic items are categorized in a brain network correlating with each other based on different semantic relationships.