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How can we determine which language task is relevant for examining functional hemispheric asymmetry? A problem in measuring brain asymmetry using functional magnetic resonance imaging lies in the uncertain reliability of the computed index regarding the “true” asymmetry degree. Strictly speaking, the results from the Wada test or direct cortical stimulation cannot be an exact “ground truth”, specifically for the degree of asymmetry. Therefore, we developed a method to evaluate task performance using reproducibility independent of the phenomenon of functional lateralization. Kendall’s coefficient of concordance (W) was used as the statistical measure. The underlying idea was that although various algorithms to compute the lateralization index show considerably different index values for the same data, a superior language task would reproduce similar individual ranking sequences across the algorithms; the high reproducibility of rankings across various index types would indicate a reliable task to investigate functional asymmetry regardless of index computation algorithms. Consequently, we found specificity for brain locations; a verb-generation task demonstrated the highest concordance across index types along with sufficiently high index values in the inferior frontal gyrus, whereas a narration–listening task demonstrated the highest concordance in the posterior temporo-parietal junction area.

The neural face perception network is distributed across both hemispheres. However, the dominant role in humans is virtually unanimously attributed to the right hemisphere. Interestingly, there are, to our knowledge, no imaging studies that systematically describe the distribution of hemispheric lateralization in the core system of face perception across subjects in large cohorts so far. To address this, we determined the hemispheric lateralization of all core system regions (i.e., occipital face area - OFA, fusiform face area - FFA, posterior superior temporal sulcus - pSTS) in 108 healthy subjects using functional magnetic resonance imaging (fMRI). We were particularly interested in the variability of hemispheric lateralization across subjects and explored how many subjects can be classified as right-dominant based on the fMRI activation pattern. We further assessed lateralization differences between different regions of the core system and analyzed the influence of handedness and sex on the lateralization with a generalized mixed effects regression model. As expected, brain activity was on average stronger in right-hemispheric brain regions than in their left-hemispheric homologues. This asymmetry was, however, only weakly pronounced in comparison to other lateralized brain functions (such as language and spatial attention) and strongly varied between individuals. Only half of the subjects in the present study could be classified as right-hemispheric dominant. Additionally, we did not detect significant lateralization differences between core system regions. Our data did also not support a general leftward shift of hemispheric lateralization in left-handers. Only the interaction of handedness and sex in the FFA revealed that specifically left-handed men were significantly more left-lateralized compared to right-handed males. In essence, our fMRI data did not support a clear right-hemispheric dominance of the face perception network. Our findings thus ultimately question the dogma that the face perception network – as measured with fMRI – can be characterized as “typically right lateralized”.

ObjectiveThe aim of this study was to evaluate the rate of adrenal venous sampling (AVS) performance in patients with primary aldosteronism (PA), the main reasons for its non-performance, and the success and complications rate of this procedure in Spain. Moreover, the concordance between CT/MRI and AVS for PA subtyping was evaluated.MethodsA retrospective multicenter study of PA patient follow-up in 20 Spanish tertiary hospitals between 2018–2021 was performed (SPAIN-ALDO Register).ResultsOf the 440 patients with PA included in the study, 153 underwent AVS (34.8%). The main reasons for not performing AVS were: patient rejection to the procedure, low catheterization rate in the center and unilateral disease based on CT/MRI. The overall success rate was 44.4% (the left adrenal vein was properly canulated in 77.8% and the right adrenal vein in 48.4%). Only 3 patients experienced minor complications. In the 45 patients with unilateral disease according to AVS, CT/MRI indicated bilateral disease or normal adrenal glands in 17. In the 23 patients with bilateral disease, CT/MRI indicated unilateral disease in 14. However, no significant differences were observed in biochemical response (P = 0.051) and hypertension resolution (P = 0.150) between patients who underwent surgery based on CT/MRI results and those who underwent surgery based on AVS results.ConclusionIn our setting, AVS is still an underused technique in patients with PA. The low experience and success rate in AVS partially justify these results. More training for providers and patients needs to be done to include appropriate well performed AVS in the diagnosis algorithm of PA.

Abstract Context Clinical practice guidelines recommend the lateralization index (LI) as the standard for determining surgical eligibility in primary aldosteronism (PA). Objective Our goal was to identify the optimal LI cutoffs in adrenal venous sampling (AVS) for diagnosing PA that is amenable to surgical cure. Methods We conducted a retrospective international cohort study across 16 institutions in 11 countries, including 1550 patients with PA who underwent AVS, with and/or without adrenocorticotropin (ACTH) stimulation. The establishment of optimal cutoffs was informed by a survey of 82 patients with PA in Japan, aimed at determining the LI cutoff aligned with patient expectations for a surgical cure rate. Results The survey revealed that a median cure rate expectation of 80% would motivate patients with PA towards undergoing adrenalectomy. The optimal LI cutoffs achieving an adjusted positive predictive value (PPV) of 80% were identified as 3.8 for unstimulated AVS and 3.4 for ACTH-stimulated AVS. Furthermore, a contralateral ratio of less than 0.4 and the detection of an adrenal nodule on computed tomography imaging were identified as independent predictors of surgically curable PA. Incorporating these factors with the optimal LI cutoffs, the adjusted PPV increased to 96.6% for unstimulated AVS and 89.6% for ACTH-stimulated AVS. No clear differences in predictive ability between unstimulated and ACTH-stimulated LI were found. Conclusion The present study clarified the optimal LI cutoffs for without and with ACTH stimulation. The presence of contralateral suppression and adrenal nodule on CT imaging seems to provide additional available information besides LI for surgical indication.

In deaf children, huge emphasis was given to language; however, emotional cues decoding and production appear of pivotal importance for communication capabilities. Concerning neurophysiological correlates of emotional processing, the gamma band activity appears a useful tool adopted for emotion classification and related to the conscious elaboration of emotions. Starting from these considerations, the following items have been investigated: (i) whether emotional auditory stimuli processing differs between normal-hearing (NH) children and children using a cochlear implant (CI), given the non-physiological development of the auditory system in the latter group; (ii) whether the age at CI surgery influences emotion recognition capabilities; and (iii) in light of the right hemisphere hypothesis for emotional processing, whether the CI side influences the processing of emotional cues in unilateral CI (UCI) children. To answer these matters, 9 UCI (9.47 ± 2.33 years old) and 10 NH (10.95 ± 2.11 years old) children were asked to recognize nonverbal vocalizations belonging to three emotional states: positive (achievement, amusement, contentment, relief), negative (anger, disgust, fear, sadness), and neutral (neutral, surprise). Results showed better performances in NH than UCI children in emotional states recognition. The UCI group showed increased gamma activity lateralization index (LI) (relative higher right hemisphere activity) in comparison to the NH group in response to emotional auditory cues. Moreover, LI gamma values were negatively correlated with the percentage of correct responses in emotion recognition. Such observations could be explained by a deficit in UCI children in engaging the left hemisphere for more demanding emotional task, or alternatively by a higher conscious elaboration in UCI than NH children. Additionally, for the UCI group, there was no difference between the CI side and the contralateral side in gamma activity, but a higher gamma activity in the right in comparison to the left hemisphere was found. Therefore, the CI side did not appear to influence the physiologic hemispheric lateralization of emotional processing. Finally, a negative correlation was shown between the age at the CI surgery and the percentage of correct responses in emotion recognition and then suggesting the occurrence of a sensitive period for CI surgery for best emotion recognition skills development.

Background Current guidelines recommend discontinuing mineralocorticoid receptor antagonists (MRA) at least 4 weeks before adrenal venous sampling (AVS) in primary aldosteronism (PA) to avoid interference with the lateralization index (LI). However, discontinuing MRA can cause hypertension and hypokalemia. This study aimed to evaluate the impact of continuing MRA use prior to AVS. Methods A 5-year retrospective cohort study of patients aged ≥ 18 with PA who underwent successful AVS was conducted. Patients were divided into two groups: those who continued MRA during AVS and those who discontinued it for at least 4 weeks prior. Outcomes included differences in LI, plasma renin activity (PRA) levels before AVS, and post-adrenalectomy outcomes. Linear regression analysis clustered by subtypes of PA was used to adjust for confounders. Results A total of 66 patients were included, with 30 (45.5%) in the continued MRA group and 36 (54.5%) in the discontinued MRA group. After adjustment for confounders, PRA levels before AVS showed no significant difference between the groups (β-coefficient 0.5, 95% CI -2.0 to 3.0; p  = 0.239) and there was no significant difference in the LI between the continued and discontinued MRA groups (β-coefficient 7.9, 95% CI -27.8 to 43.7; p  = 0.216). Clinical and biochemical success after unilateral adrenalectomy were similar between the two groups ( p  = 0.141 and p  = 0.596, respectively). Conclusion Continuing MRA prior to AVS did not appear to affect the interpretation of lateralization and may be a reasonable option for patients at high risk of complications from MRA withdrawal. Further prospective studies are needed to confirm these observations.

Background and aims: Frequent failure of adrenal vein (AV) cannulation is a major obstacle to the universal use of adrenal vein sampling (AVS) for subtyping primary aldosteronism (PA). This study aimed to confirm and modify the value of a previously reported AVS parameter for PA subtyping in the case of cannulation failure on one side. Methods: Successfully catheterized AVS studies in 157 patients (121 patients as a derivation cohort and 36 patients as a validation cohort) from two tertiary hospitals were retrospectively reviewed. The AV/inferior vena cava (IVC) index was defined by dividing the aldosterone/cortisol ratio (ACR) of AV by the ACR of the IVC. Cutoff values for lateralized PA were obtained from two methods: scatterplots and the values corresponding to Youden’s index in receiver operating characteristic (ROC) curves, on the assumption of catheterization failure on one side. Results: Due to multiple samplings in a single AVS procedure, 252 left AV/IVC ratios (LIRs) and 272 right AV/IVC ratios (RIRs) were calculated. Scatterplot cutoffs of LIR >5.4 or <0.5 predicted unilateral PA with a sensitivity of 42.1% and a specificity of 98.6%. Scatterplot cutoffs of RIR <0.5 or >7.0 showed a sensitivity of 55.1% and a specificity of 98.6%. ROC curve cutoffs of LIR ⩽0.8 or >3.1 predicted unilateral PA with a sensitivity of 82.5% and a specificity of 69.6%. ROC curve cutoffs of RIR ⩽0.8 or >3.9 resulted in 87.4% sensitivity and 80.7% specificity. Conclusion: In the case of unilateral AVS failure, the AV/IVC index may help in diagnosing PA subtype.

Purpose: To evaluate the diagnostic accuracy of the 131I-6β-iodomethyl-19-norcholesterol (NP-59) adrenal scintigraphy for the subtyping diagnosis of primary aldosteronism (PA), considering as gold standard for the diagnosis of unilateral PA (UPA), either the results of the adrenal venous sampling (AVS) or the outcome after adrenalectomy. Methods: A retrospective multicenter study was performed on PA patients from 14 Spanish tertiary hospitals who underwent NP-59 scintigraphy with an available subtyping diagnosis. Patients were classified as UPA if biochemical cure was achieved after adrenalectomy or/and if an AVS lateralization index > 4 with ACTH stimulation or >2 without ACTH stimulation was observed. Patients were classified as having bilateral PA (BPA) if the AVS lateralization index was ≤4 with ACTH or ≤2 without ACTH stimulation or if there was evidence of bilateral adrenal nodules >1 cm in each adrenal gland detected by CT/MRI. Results: A total of 86 patients with PA were included (70.9% (n = 61) with UPA and 29.1% (n = 25) with BPA). Based on the NP-59 scintigraphy results, 16 patients showed normal suppressed adrenal gland uptake, and in the other 70 cases, PA was considered unilateral in 49 patients (70%) and bilateral in 21 (30%). Based on 59-scintigraphy results, 10.4% of the patients with unilateral uptake had BPA, and 27.3% of the cases with bilateral uptake had UPA. The AUC of the ROC curve of the NP-59 scintigraphy for PA subtyping was 0.812 [0.707–0.916]. Based on the results of the CT/MRI and NP-59 scintigraphy, only 6.7% of the patients with unilateral uptake had BPA, and 24% of the cases with bilateral uptake had UPA. The AUC of the ROC curve of the model combining CT/MRI and 59-scintigraphy results for subtyping PA was 0.869 [0.782–0.957]. Conclusion: The results of NP-59 scintigraphy in association with the information provided by the CT/MRI may be useful for PA subtyping. However, their diagnostic accuracy is only moderate. Therefore, it should be considered a second-line diagnostic tool when AVS is not an option.

Surgery is often the only effective treatment for intractable epilepsy, but its benefits must be balanced by potential disruption of eloquent cortical functions. Wada test is the standard technique to lateralize language before surgery; however, it is invasive and associated with complications. fMRI provides an attractive noninvasive alternative, which has been previously shown to correlate with Wada results. However this correlation is imperfect since standard fMRI laterality indices are dependent on a particular arbitrary statistical threshold used in the data processing. We report a novel automated, threshold-independent fMRI methodology to assess language lateralization, which we hypothesize provides a robust and unbiased pre-operative assessment. This hemispheric histogram analysis method can accurately interrogate language lateralization, as validated against the Wada test. Fifty-nine subjects with intractable epilepsy received preoperative evaluation for language lateralization using fMRI. fMRI data then were analyzed using a novel automated threshold-independent method for determining language lateralization. The methodology generated a lateralization score based on hemispheric activation of language areas and a quality index based on multiple factors, including patient motion and signal-to-noise characteristics. Lateralization scores were compared to Wada test results (51 patients), direct cortical stimulation (3 patients), and subdural grid stimulation (5 patients). Data sets were used to generate a probability score for language lateralization for each subject. The lateralization scores correlated well with the objective measures of language lateralization (r2=0.46). Cumulative historical data were utilized to prospectively determine probabilities of language lateralization for individual patients. In conclusion, hemispheric language lateralization can be accurately determined using a novel objective and automated methodology that calculates language lateralization in a threshold-independent manner and can be used to determine the probability of language dominance in individual patients. ►Most methods to compute language lateralization from fMRI use a threshold. ►Threshold dependant methods have been shown to be unreliable. ►We present an automatic method without a threshold, using hemispheric histograms. ►The method is applied to 63 patients with known lateralization from invasive means. ►A derived database helps predict lateralization from new patients.

The aim of this study is to determine the accuracy of adrenal vein sampling (AVS) with and without adrenocorticotropic hormone (ACTH) stimulation to distinguish between unilateral and bilateral primary hyperaldosteronism (PA). Retrospective analysis of a prospective database from a referral center between 1984 and 2009, 76 patients had simultaneous cannulation of bilateral adrenal veins and AVS with and without ACTH stimulation. All patients had adrenalectomies. The selectivity index (SI, cut-off value ≥2) was used for confirmation of successful cannulation of the adrenal vein. The lateralization index (LI, cut-off value >2 and >4) was used for distinguishing between unilateral and bilateral PA. The SI ratio was higher with ACTH stimulation compared to without for the right adrenal vein (p = 0.027). The LI > 2 ratio was higher with ACTH stimulation compared to without (p = 0.007). For the LI > 4 ratio, there was no difference between with and without ACTH stimulation (p = 0.239). However, for a LI > 4, 7 patients (9.2%) were not lateralized with ACTH stimulation, but they did lateralize without ACTH stimulation. AVS with ACTH stimulation is associated with a higher SI ratio compared to AVS without ACTH stimulation. However, when using LI > 4 for AVS, samples without ACTH stimulation should also be included to detect a subset of patients with unilateral disease that are not detected with ACTH stimulation.