A novel variant in the COL6A1 gene causing Ullrich congenital muscular dystrophy in a consanguineous family: a case report.

BACKGROUND: Collagen VI-related dystrophies are a subtype of congenital muscular dystrophy caused by pathogenic variants in COL6A1, COL6A2 or COL6A3 genes affecting skeletal muscles and connective tissue. The clinical phenotype ranges from the milder Bethlem myopathy to the severe Ullrich congenital muscular dystrophy (UCMD). Herein, we report the first consanguineous Sri Lankan family with two children affected with UCMD due to a novel variant in the COL6A1 gene. CASE PRESENTATION: Two sisters, aged 10-years and 7-years, presented with progressive, bilateral proximal muscle weakness. Both probands had delayed motor milestones and demonstrated difficulty in standing from a squatting position, climbing stairs and raising arms above the shoulders. Cognitive, language and social development were age appropriate. Examination showed proximal muscle weakness of the upper and lower extremities and hyperlaxity of the wrist and fingers in both with some variability in clinical severity noted between the two siblings. Serum creatine kinase levels were elevated, and electromyography showed low polyphasic motor unit potentials in the 10-year-old and myopathic features with short duration motor unit potentials with no polyphasia in the 7-year-old. Whole exome sequencing (WES) was performed and a novel, homozygous missense, likely pathogenic variant in exon 25 of COL6A1 gene [NM_001848: c.1667G > T;NP_001839.2:p.Gly556Val] was identified in both probands. This variant was validated by Sanger sequencing in proband 1 as well as proband 2, and the parents and an unaffected sibling were found to be heterozygote carriers for the same variant. CONCLUSIONS: The findings in this family add to the expanding number of COL6A1 variants identified and provides a better understanding of the genotype-phenotype correlations associated with UCMD.

Case Report: Idiopathic Sclerosing Orbital Inflammation.

SIGNIFICANCE: Idiopathic sclerosing orbital inflammation (ISOI) is characterized by insidious, chronic, progressive inflammation and fibrosis that damage ocular structures and produce a mass effect. This case highlights the challenges in diagnosis and management of ISOI, as well as the associated ocular morbidities, including potential vision loss. PURPOSE: The purpose of this study was to provide education regarding a rare condition that exhibits variable presentation and has an unpredictable success rate with regard to treatment paradigm. Improved therapeutic options are promising. Ultimately, early detection and management are key and may allow for better visual outcome. CASE REPORT: A 46-year-old woman presented with complaints of chronic right-sided facial headaches and eye pain and gradual right globe prominence over the previous 6 months. Worsening vision and decreased right peripheral visual field were also noted. Upon examination, an afferent pupillary defect and florid disc edema were evident. Imaging studies revealed an orbital and extraorbital infiltrative mass involving the right orbital apex, inferior orbital fissure, pterygopalatine fossa, and cavernous sinus. Right anterior orbitotomy with biopsy revealed fragments of fibroconnective and adipose tissue with sclerosis and chronic focal inflammation, consistent with ISOI. Treatment included intravenous methylprednisone, followed by oral prednisone, beginning at 60 mg/d with a slow taper thereafter. Signs and symptoms improved dramatically and eventually resolved. Vision significantly improved, and the afferent pupillary defect resolved. The patient remained asymptomatic at 3-month follow-up. CONCLUSIONS: Idiopathic sclerosing orbital inflammation is difficult to diagnose and manage. No large studies exist because of the rare nature of the disease. Slowly progressive, nonspecific signs and symptoms may delay recognition and treatment. Orbital imaging and histopathologic analysis are critical for definitive diagnosis. Conventional treatment with corticosteroids is not uniformly successful, but newer combined therapy options can improve outcomes. Early identification and treatment are key to management and ultimate preservation of function and vision.

Automated detection of hippocampal sclerosis using clinically empirical and radiomics features.

OBJECTIVE: Temporal lobe epilepsy is a common form of epilepsy that might be amenable to surgery. However, magnetic resonance imaging (MRI)-negative hippocampal sclerosis (HS) can hamper early diagnosis and surgical intervention for patients in clinical practice, resulting in disease progression. Our aim was to automatically detect and evaluate the structural alterations of HS. METHODS: Eighty patients with pharmacoresistant epilepsy and histologically proven HS and 80 healthy controls were included in the study. Two automated classifiers relying on clinically empirical and radiomics features were developed to detect HS. Cross-validation was implemented on all participants, and specificity was assessed in the 80 controls. The performance, robustness, and clinical utility of the model were also evaluated. Structural analysis was performed to investigate the morphological abnormalities of HS. RESULTS: The computational model based on clinical empirical features showed excellent performance, with an area under the curve (AUC) of 0.981 in the primary cohort and 0.993 in the validation cohort. One of the features, gray-white matter boundary blurring in the temporal pole, exhibited the highest weight in model performance. Another model based on radiomics features also showed satisfactory performance, with AUC of 0.997 in the primary cohort and 0.978 in the validation cohort. In particular, the model improved the detection rate of MRI-negative HS to 96.0%. The novel feature of cortical folding complexity of the temporal pole not only played a crucial role in the classifier but also had significant correlation with disease duration. SIGNIFICANCE: Machine learning with quantitative clinical and radiomics features is shown to improve HS detection. HS-related structural alterations were similar in the MRI-positive and MRI-negative HS patient groups, indicating that misdiagnosis originates mainly from empirical interpretation. The cortical folding complexity of the temporal pole is a potentially valuable feature for exploring the nature of HS.

Interference of High Dose Biotin Supplementation with Thyroid Parameters in Immunoassays Utilizing the Interaction between Streptavidin and Biotin: a Case Report and Review of Current Literature.

BACKGROUND: Automated immunoassays utilizing the interaction between streptavidin and biotin are widely used. Nonetheless, biotin remains an often overlooked confounder. METHODS: We report the case of a 54-year-old female patient with progressive multiple sclerosis and Hashimoto's thyroiditis who presented herself for a follow-up. Measurements on Roche's cobas® 8000 modular analyzer series suggested severe hyperthyroidism. Initially, no relevant confounders could be identified. RESULTS: All requested thyroid parameters were measured with alternative methods, yielding plausible results. CONCLUSIONS: Biotin is a significant confounder in many immunoassays. Alternative measurement methods or methods of biotin neutralization need to be implemented for certain situations.

Hippocampal sclerosis induced in mice by a Taenia crassiceps metacestode factor.

An experimental Taenia crassiceps mouse model was used to assess the role of Taenia solium metacestode factor (Fac) in human neurocysticercosis. Intraperitoneal infection with T. crassiceps metacestodes or subcutaneous inoculation with a T. crassiceps metacestode factor (Fac) produced significant impairment of performance (learning) in the Barnes maze and induced bilateral hippocampal sclerosis in mice. Several staining techniques revealed important cell dispersion, extensive apoptosis and cell loss in the dentate gyrus, hilus and CA1-CA3 regions of both hippocampi, as well as intense deterioration of the adjacent cortex. An outstanding disruption of its histoarchitecture in the surrounding tissue of all these regions and apoptosis of the endothelial cells were also observed.

Idiothetic signal processing and spatial orientation in patients with unilateral hippocampal sclerosis.

The role of the hippocampus in spatial navigation and the presence of vestibular-responsive neurons in limbic areas are well-established from animal experiments. However, hippocampal spatial processing in humans is not fully understood. Here, we employed real whole body and head-on-trunk rotations to investigate how vestibular signals, either alone or in combination with neck-proprioceptive stimulation, shape the spatial frame of reference in patients with unilateral hippocampal sclerosis (HS). Patients were asked to point in darkness with a light spot, moved on a cylindrical screen by means of a joystick, into their visual straight-ahead direction (VSA), to remember this direction in space, and to revert back to this point after the rotations. Estimates in patients with HS were compared with those of healthy controls and of patients with epilepsy without hippocampal involvement. All groups produced similar errors after low-frequency vestibular stimuli. These errors were eliminated when rotations involved concurrent neck stimulation. Significantly increased variability was observed, however, in both the VSA and reposition estimates after the rotations in patients with HS compared with controls. These results suggest that cognitive processing of idiothetic signals for self-motion perception is inaccurate in patients with HS. Importantly, however, the responses of patients with HS showed no spatial lateralization with regard to right or left HS, suggesting that the underlying neuronal loss attenuates the precision of head-direction signal decoding in a nondirectional manner. Hence, patients are unable to use these signals as efficiently as normal subjects in the construction of a stable head-centric spatial frame of reference. NEW & NOTEWORTHY Spatial perception relies on combined processing of various idiothetic (vestibular and proprioceptive) and allothetic (visual and auditory) sensory signals. Despite the established knowledge of rodent vestibular-hippocampal interactions, human data are lacking. We investigated idiothetic orientational processing in subjects with unilateral hippocampal sclerosis using various combinations of vestibular and proprioceptive stimuli. Hippocampal impairment leads to less accurate, noisy decoding of the signal related to idiothetic orientation. However, patients did not show any lateralized deficits of visual straight-ahead perception or of target/self-displacement perception after idiothetic stimulation.

Kienböck Disease in the Skeletally Immature Patient.

Kienböck disease is uncommon in skeletally immature patients. Although there is no gold standard treatment for Kienböck disease in the skeletally immature patient, surgical and nonsurgical treatment options have been shown to be effective. Initial immobilization with a cast, protection with an orthosis, and avoidance of repetitive forceful activities have been shown to be effective in some cases. Surgery may be offered to the skeletally immature patient when nonsurgical treatment is ineffective. Among several surgical techniques used for treatment in the skeletally immature patient with Kienböck disease, distal radial osteotomies have been the most frequently performed surgery; however, radial overgrowth is a concern. There is a great potential for revascularization and remodeling of the lunate in the skeletally immature patients with Kienböck disease. Good and excellent clinical and radiological outcomes can be achieved with both nonsurgical and surgical treatments.

Impaired cerebral blood flow networks in temporal lobe epilepsy with hippocampal sclerosis: A graph theoretical approach.

Graph theory is an emerging method to investigate brain networks. Altered cerebral blood flow (CBF) has frequently been reported in temporal lobe epilepsy (TLE), but graph theoretical findings of CBF are poorly understood. Here, we explored graph theoretical networks of CBF in TLE using arterial spin labeling imaging. We recruited patients with TLE and unilateral hippocampal sclerosis (HS) (19 patients with left TLE, and 21 with right TLE) and 20 gender- and age-matched healthy control subjects. We obtained all participants' CBF maps using pseudo-continuous arterial spin labeling and analyzed them using the Graph Analysis Toolbox (GAT) software program. As a result, compared to the controls, the patients with left TLE showed a significantly low clustering coefficient (p=0.024), local efficiency (p=0.001), global efficiency (p=0.010), and high transitivity (p=0.015), whereas the patients with right TLE showed significantly high assortativity (p=0.046) and transitivity (p=0.011). The group with right TLE also had high characteristic path length values (p=0.085), low global efficiency (p=0.078), and low resilience to targeted attack (p=0.101) at a trend level. Lower normalized clustering coefficient (p=0.081) in the left TLE and higher normalized characteristic path length (p=0.089) in the right TLE were found also at a trend level. Both the patients with left and right TLE showed significantly decreased clustering in similar areas, i.e., the cingulate gyri, precuneus, and occipital lobe. Our findings revealed differing left-right network metrics in which an inefficient CBF network in left TLE and vulnerability to irritation in right TLE are suggested. The left-right common finding of regional decreased clustering might reflect impaired default-mode networks in TLE.

The emerging role of endothelin-1 in the pathogenesis of subchondral bone disturbance and osteoarthritis.

Mounting evidence suggests reconceptualizing osteoarthritis (OA) as an inflammatory disorder. Trauma and obesity, the common risk factors of OA, could trigger the local or systemic inflammatory cytokines cascade. Inflammatory bone loss has been well documented; yet it remains largely unknown about the link between the inflammation and hypertrophic changes of subchondral bone seen in OA, such as osteophytosis and sclerosis. Amid a cohort of inflammatory cytokines, endothelin-1 (ET-1) could stimulate the osteoblast-mediated bone formation in both physiological (postnatal growth of trabecular bone) and pathological conditions (bone metastasis of prostate or breast cancer). Also, ET-1 is known as a mitogen and contributes to fibrosis in various organs, e.g., skin, liver, lung, kidney heart and etc., as a result of inflammatory or metabolic disorders. Subchondral bone sclerosis shared the similarity with fibrosis in terms of the overproduction of collagen type I. We postulated that ET-1 might have a hand in the subchondral bone sclerosis of OA. Meanwhile, ET-1 was also able to stimulate the production of matrix metalloproteinase (MMP)-1 and 13 by articular chondrocytes and synoviocytes, by which it might trigger the enzymatic degradation of articular cartilage. Taken together, ET-1 signaling may play a role in destruction of bone-cartilage unit in the pathogenesis of OA; it warrants further investigations to potentiate ET-1 as a novel diagnostic biomarker and therapeutic target for rescue of OA.

Asymmetry of cerebral blood flow measured with three-dimensional pseudocontinuous arterial spin-labeling mr imaging in temporal lobe epilepsy with and without mesial temporal sclerosis.

BACKGROUND: To investigate the asymmetry of quantitative cerebral blood flow (CBF) values in interictal temporal lobe epilepsy (TLE) patients with (TLE-MTS) and without (TLE-no) mesial temporal sclerosis. METHODS: Twenty-six TLE patients (14 TLE-MTS/12 TLE-no) and 22 controls were studied with a three-dimensional whole-brain pseudocontinuous arterial spin-labeling technique at 3.0 Tesla. Regions of interest were placed at the bilateral hippocampal heads, amygdalas and temporal lobes to get the average regional cerebral blood flow (rCBF) and calculate asymmetry indices (AIs). Statistical parametric mapping detected the whole-brain CBF changes of the two subgroups (right-sided). RESULTS: AIs of the hippocampus and amygdala in TLE-MTS and AIs of hippocampus in TLE-no were significantly different versus controls (P < 0.001, P = 0.001, and P = 0.013). The lateralizing sensitivity increased to 96.154% by combining structural MRI and AIs of rCBF with optimal cutoff values. Hypoperfusion regions in the right TLE-MTS mainly clustered in the bilateral temporal lobes, frontal lobes, insular lobes, and left caudate nucleus. The right TLE-no showed hypoperfusion in the bilateral temporal lobes, frontal lobes, right insular lobe, parietal lobe, occipital lobe, and caudate nucleus. CONCLUSION: Asymmetry of CBF in the TLE-MTS and TLE-no is different and improves MRI performance in lateralizing the TLE.

Progression of renal injury toward interstitial inflammation and glomerular sclerosis is dependent on abnormal protein filtration.

Chronic proteinuric renal diseases, independent from the type of the initial insult, have in common a loss of selectivity of the glomerular barrier to protein filtration. Glomerular sclerosis is the progressive lesion affecting the glomerular capillary wall, the primary site at which the protein filtration is abnormally enhanced by disease. Dysfunction of podocytes, that serve to maintain the intact barrier, is a central event in lesion development. However, glomerular injury is signalled to tubular and interstitial structures largely in advance of nephron destruction. Glomerular ultrafiltration of excessive amounts of plasma-derived proteins and associated factors incites tubulointerstitial damage and might amplify an inherent susceptibility of the kidney to become dysfunctional in several disease conditions. Thus, noxious substances in the proteinuric ultrafiltrate promote apoptotic responses and multiple changes in the phenotype of tubule cells with generation of inflammatory and fibrogenic mediators. The severity of tubular interstitial damage has long been recognized to be highly correlated to the degree of deterioration of renal failure even better than glomerular lesions. This review focuses on pathways of tubular injury and apoptosis that in turn promote nephron-by-nephron degeneration and interstitial fibrosis during proteinuria contributing to multifaceted processes of kidney scarring and function loss.

Early and late age of seizure onset have a differential impact on brain resting-state organization in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is associated with abnormalities which extend into the entire brain. While the age of seizure onset (SO) has a large impact on brain plasticity, its effect on brain connectivity at rest remains unclear, especially, in interaction with factors such as the presence of mesial temporal sclerosis (MTS). In this context, we investigated whole-brain and regional functional connectivity (FC) organization in 50 TLE patients who underwent a resting-state fMRI scan, in comparison to healthy controls, using graph-theory measures. We first classified TLE patients according to the presence of MTS or not. Then, we categorized the patients based on their age of SO into two subgroups (early or late age of SO). Results revealed whole-brain differences with both reduced functional segregation and increased integration in the patients, regardless of the age of SO and MTS, relative to the controls. At a local level, we revealed that the connectivity of the ictal hippocampus remains the most impaired for an early SO, even in the absence of MTS. Importantly, we showed that the impact of age of SO on whole-brain and regional resting-state FC depends on the presence of MTS. Overall, our results highlight the importance of investigating the effect of age of SO when examining resting-state activity in TLE, as this factor leads different perturbations of network modularity and connectivity at the global and local level, with different implications for regional plasticity and adaptive organization.

[SCLEROSIS: LOCAL AND GENERAL PATTERNS OF DEVELOPMENT].

Sclerosis is a final substrate and outcome of structural lesions of different organs and tissues in various pathological conditions, such as hypertensive disease, coronaty heart disease, chronic obstructive pulmonary disease, systemic lupus erythematosus, rheumatoid arthritis, systemic scleroderma, etc. Not infrequently it as a determinant of severity and unfavourable outcome of the disease. Elucidation of general patterns of the development of sclerosis requires an integrated approach to the systemic analysis of clinical, genetic, biochemical, and morphological characteristics whereas a local analysis reveals peculiarities of formation of sclerosis in individual patients. Such combination permits to use methods of predictive-preventive personified medicine for planning the treatment of sclerosis.

Muscle proteomics reveals novel insights into the pathophysiological mechanisms of collagen VI myopathies.

Mutations in the collagen VI genes cause the Ullrich congenital muscular dystrophy (UCMD), with severe phenotype, and Bethlem myopathy (BM) with mild to moderate phenotype. Both, UCMD and BM patients show dystrophic features with degeneration/regeneration and replacement of muscle with fat and fibrous connective tissue. At molecular level, UCMD patients show autophagic impairment and increased PTP opening; these features are less severe in BM. To elucidate the biochemical mechanisms adopted by the muscle to adapt to collagen VI deficiency in BM and UCMD patients, a proteome analysis was carried out on human muscle biopsies. Qualitative and quantitative differences were assessed by 2D-DIGE coupled to MALDI-ToF/ToF MS. Proteomics results, coupled with immunoblotting, indicate changes in UPR, hexosamine pathway, and amino acid and fatty acid metabolism, suggesting an association of ER stress, metabolic dysregulation, autophagic impairment, and alteration in mechanotransduction signaling. Overall, these results indicate that despite the common downregulation of hexosamine pathway in UCMD and BM, in BM the protein quality control system is sustained by a metabolic adaptation supporting energy requirements for the maintenance of autophagy, counteracting ER misfolded protein overload. In UCMD, this multilayered system may be disrupted and worsened by the metabolic rewiring, which leads to lipotoxicity.

Aortic valve sclerosis in mice deficient in endothelial nitric oxide synthase.

Risk factors for fibrocalcific aortic valve disease (FCAVD) are associated with systemic decreases in bioavailability of endothelium-derived nitric oxide (EDNO). In patients with bicuspid aortic valve (BAV), vascular expression of endothelial nitric oxide synthase (eNOS) is decreased, and eNOS(-/-) mice have increased prevalence of BAV. The goal of this study was to test the hypotheses that EDNO attenuates profibrotic actions of valve interstitial cells (VICs) in vitro and that EDNO deficiency accelerates development of FCAVD in vivo. As a result of the study, coculture of VICs with aortic valve endothelial cells (vlvECs) significantly decreased VIC activation, a critical early phase of FCAVD. Inhibition of VIC activation by vlvECs was attenuated by N(G)-nitro-l-arginine methyl ester or indomethacin. Coculture with vlvECs attenuated VIC expression of matrix metalloproteinase-9, which depended on stiffness of the culture matrix. Coculture with vlvECs preferentially inhibited collagen-3, compared with collagen-1, gene expression. BAV occurred in 30% of eNOS(-/-) mice. At age 6 mo, collagen was increased in both bicuspid and trileaflet eNOS(-/-) aortic valves, compared with wild-type valves. At 18 mo, total collagen was similar in eNOS(-/-) and wild-type mice, but collagen-3 was preferentially increased in eNOS(-/-) mice. Calcification and apoptosis were significantly increased in BAV of eNOS(-/-) mice at ages 6 and 18 mo. Remarkably, these histological changes were not accompanied by physiologically significant valve stenosis or regurgitation. In conclusion, coculture with vlvECs inhibits specific profibrotic VIC processes. In vivo, eNOS deficiency produces fibrosis in both trileaflet and BAVs but produces calcification only in BAVs.

Auditory event-related potentials (P300) and mesial temporal sclerosis in temporal lobe epilepsy patients.

AIMS: To investigate the role of centrally recorded P300 in patients suffering from mesial temporal sclerosis-temporal lobe epilepsy (MTS-TLE). METHODS: Sixteen patients (3 men and 13 women; median age: 32.5 years old) suffering from TLE with MTS and 43 healthy controls (12 men and 31 women; median age: 35 years old) participated in the study. P300 was elicited using an auditory two-stimulus oddball paradigm. In order to address the aim of the study, we adopted two statistical approaches; hierarchical linear regression analyses and ROC curves. RESULTS: After adjusting for age, MTS patients had a mean reduction of P300 amplitude by 6.93 µV and a mean increase of P300 latency by 38.78 ms, compared to controls. Age and MTS-TLE status accounted for 32 and 16% of the variance of latency and amplitude, respectively. Diagnostic analyses to detect MTS-TLE status revealed a sensitivity and specificity of 88 and 65% for amplitude and 81 and 70% for latency, respectively. No association between duration of disease and P300 characteristics were found. CONCLUSIONS: This study, along with other studies, contributes to our understanding and clinical significance of centrally recorded P300s in MTS-TLE patients. Future studies should focus on the association of these P300s with cognition in such patients.

Network reconfiguration and working memory impairment in mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy (mTLE) is the most prevalent form of focal epilepsy, and hippocampal sclerosis (HS) is considered the most frequent associated pathological finding. Recent connectivity studies have shown that abnormalities, either structural or functional, are not confined to the affected hippocampus, but can be found in other connected structures within the same hemisphere, or even in the contralesional hemisphere. Despite the role of hippocampus in memory functions, most of these studies have explored network properties at resting state, and in some cases compared connectivity values with neuropsychological memory scores. Here, we measured magnetoencephalographic responses during verbal working memory (WM) encoding in left mTLE patients and controls, and compared their effective connectivity within a frontotemporal network using dynamic causal modelling. Bayesian model comparison indicated that the best model included bilateral, forward and backward connections, linking inferior temporal cortex (ITC), inferior frontal cortex (IFC), and the medial temporal lobe (MTL). Test for differences in effective connectivity revealed that patients exhibited decreased ipsilesional MTL-ITC backward connectivity, and increased bidirectional IFC-MTL connectivity in the contralesional hemisphere. Critically, a negative correlation was observed between these changes in patients, with decreases in ipsilesional coupling among temporal sources associated with increases contralesional frontotemporal interactions. Furthermore, contralesional frontotemporal interactions were inversely related to task performance and level of education. The results demonstrate that unilateral sclerosis induced local and remote changes in the dynamic organization of a distributed network supporting verbal WM. Crucially, pre-(peri) morbid factors (educational level) were reflected in both cognitive performance and (putative) compensatory changes in physiological coupling.

Brain plasticity for verbal and visual memories in patients with mesial temporal lobe epilepsy and hippocampal sclerosis: an fMRI study.

We aimed to identify the brain areas involved in verbal and visual memory processing in normal controls and patients with unilateral mesial temporal lobe epilepsy (MTLE) associated with unilateral hippocampal sclerosis (HS) by means of functional magnetic resonance imaging (fMRI). The sample comprised nine normal controls, eight patients with right MTLE, and nine patients with left MTLE. All subjects underwent fMRI with verbal and visual memory paradigms, consisting of encoding and immediate recall of 17 abstract words and 17 abstract drawings. A complex network including parietal, temporal, and frontal cortices seems to be involved in verbal memory encoding and retrieval in normal controls. Although similar areas of activation were identified in both patient groups, the extension of such activations was larger in the left-HS group. Patients with left HS also tended to exhibit more bilateral or right lateralized encoding related activations. This finding suggests a functional reorganization of verbal memory processing areas in these patients due to the failure of left MTL system. As regards visual memory encoding and retrieval, our findings support the hypothesis of a more diffuse and bilateral representation of this cognitive function in the brain. Compared to normal controls, encoding in the left-HS group recruited more widespread cortical areas, which were even more widespread in the right-HS group probably to compensate for their right mesial temporal dysfunction. In contrast, the right-HS group exhibited fewer activated areas during immediate recall than the other two groups, probably related to their greater difficulty in dealing with visual memory content.