Cognitive outcomes in Susac syndrome: A 2-year neuropsychological follow-up study.

BACKGROUND AND PURPOSE: Susac syndrome (SuS) is a rare, autoimmune, neurological disease characterized by a clinical triad of branch retinal artery occlusion, sensorineural hearing loss and encephalopathy. Neuropsychological functioning in SuS is little researched and the prevalence, nature, and evolution over time of cognitive deficits in SuS remain unclear. This study aimed to better understand the long-term neuropsychological outcomes of patients with SuS. METHODS: Thirteen patients with SuS (mean [SD] age 39.5 [11.1] years) were enrolled at the Ghent University Hospital by their treating neurologist. The cognitive functioning and emotional well-being of each patient was evaluated by means of a thorough neuropsychological test battery at baseline and after 2 years. Follow-up testing after 2 years was performed in 11 patients (mean [SD] age 42.2 [11.5] years). RESULTS: Patients showed normal neuropsychological test results at a group level, both at baseline and follow-up testing. Significant improvements over time were found for information processing speed, verbal recognition, and semantic and phonological fluency. Individual test results showed interindividual variability at baseline, with most impairments being in attention, executive functioning and language, which improved after a 2-year period. In addition, patients reported significantly lower mental and physical well-being, both at baseline and follow-up testing. CONCLUSIONS: Our results suggest that neuropsychological dysfunction in SuS is limited at a group level and improves over time. Nonetheless, individual test results reveal interindividual variability, making cognitive screening essential. Furthermore, a high psycho-emotional burden of the disease was reported, for which screening and follow-up are necessary.

Associations of habitual sedentary time with executive functioning and short-term memory in 7th and 8th grade adolescents.

BACKGROUND: While there is increasing evidence for negative physical health consequences of high volumes of sedentary time and prolonged sedentary time in adolescents, the association with cognition is less clear. This study investigated the association of volumes of habitual sedentary time and prolonged sedentary time with executive functions and short-term memory in adolescents. METHODS: This study has a cross-sectional observational study design. Volumes of sedentary time and prolonged sedentary time (accumulated sedentary time spent in bouts of  ≥ 30 min) were measured using the Axivity AX3 accelerometer. Six cognitive functions (spatial and verbal short-term memory; and working memory, visuospatial working memory, response inhibition and planning as executive functions) were measured using six validated cognitive assessments. Data were analysed using generalised linear models. RESULTS: Data of 119 adolescents were analysed (49% boys, 13.4 ± 0.6 year). No evidence for an association of volumes of sedentary time and prolonged sedentary time with spatial and verbal short-term memory, working memory, and visuospatial working memory was found. Volumes of sedentary time and prolonged sedentary time were significantly related to planning. One hour more sedentary time or prolonged sedentary time per day was associated with respectively on average 17.7% (95% C.I.: 3.5-29.7%) and 12.1% (95% C.I.: 3.9-19.6%) lower scores on the planning task. CONCLUSIONS: No evidence was found for an association of volumes of habitual sedentary time and prolonged sedentary time with short-term memory and executive functions, except for planning. Furthermore, the context of sedentary activities could be an important confounder in the association of sedentary time and prolonged sedentary time with cognition among adolescents. Future research should therefore collect data on the context of sedentary activities. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov in January 2020 (NCT04327414; released on March 11, 2020).

Aging and sex effects on phoneme perception: An exploratory mismatch negativity and P300 investigation.

BACKGROUND & AIMS: The mismatch negativity (MMN) and P300 event-related potentials (ERPs) have been studied in relation to phoneme discrimination and categorization, respectively. Although the effects of aging and sex on pure-tone perception have been widely investigated using these ERPs, evidence relating to phoneme perception is scarce. The current study aimed to provide insight into the effects of aging and sex on phoneme discrimination and categorization, as measured through the MMN and P300. METHOD: An inattentive and attentive oddball paradigm containing a phonemic articulation place contrast were administered during EEG registration in sixty healthy individuals (thirty males and females), of which an equal number of young (20-39 years), middle-aged (40-59 years) and elderly (60+ years) subjects were included. The amplitude, onset latency and topographical distribution of the MMN and P300 effect, as well as the amplitude of the P1-N1-P2 complex, were analyzed for age group and sex differences. RESULTS: With respect to aging, elderly subjects demonstrated a reduced MMN and P300 amplitude compared to the young group, whereas the scalp distribution of both components was unaffected. No aging effects on the P1-N1-P2 complex were found. In elderly individuals, the P300 was found to be delayed compared to the young group, while no such effect on MMN latency could be observed. No differences in MMN and P300 measures could be identified between males and females. CONCLUSION: Differential effects of aging were found on the MMN and P300, specifically in terms of latency, in relation to phoneme perception. In contrast, sex was found to scarcely affect both processes.

Atypical clinical and novel radiological findings in Susac syndrome: Experience from a large monocentric cohort.

Susac syndrome (SuS) is a rare immune-mediated endotheliopathy that affects the brain, retina and inner ear and is characterised by the variable clinical triad of encephalopathy, visual and vestibulocochlear dysfunction. Here, we present clinical and paraclinical data of 19 SuS patients followed at Ghent University Hospital and highlight some atypical clinical and novel radiological findings. Our findings suggest that spinal involvement expands the clinical phenotype of SuS. We further introduce dark blood sequences as a more sensitive technique to detect radiological disease activity in SuS. Our data add to the current understanding of the diagnosis, monitoring and treatment of SuS.

Continuous theta burst stimulation for drug-resistant epilepsy.

Introduction: Repetitive transcranial magnetic stimulation (rTMS) may have anti-epileptic effects, especially in patients with neocortical lesions. Initial clinical trials demonstrated that the duration of the seizure reducing effect is relatively short-lived. In the context of a chronic condition like epilepsy, theta burst stimulation (TBS) may represent a potential solution in optimizing treatment practicality and durability as it was demonstrated to be associated with longer-lasting after-effects. TBS has been studied extensively in diverse neuropsychiatric conditions, but a therapeutic TBS protocol has not previously been applied in epilepsy patients. Materials and methods: We performed a prospective open-label pilot study of 4-day accelerated continuous TBS (cTBS) treatment in patients with neocortical drug-resistant epilepsy (DRE). A treatment session consisted of 5 cTBS trains, each comprising 600 pulses presented in 50 Hz triplet bursts every 200 ms, delivered at 10-min intertrain-intervals, targeted over the epileptic focus (EF) using a neuronavigation-guided figure-of-8 coil. Safety and feasibility, and seizure frequency were assessed as primary and secondary endpoints, respectively, over a 4-week baseline period, a 1-week treatment period and a 7-week follow-up period, using adverse event logging, electro-encephalography, cognitive, and psychological questionnaires and a seizure diary kept by the patients and/or caregivers. Results: Seven subjects (4M:3F; median age 48, interquartile ranges 25) underwent the treatment protocol. Adverse events were reported in all subjects but were mild and transient. No clinical or electrographic seizures were evoked during or immediately following stimulation. No deterioration was found in cognition nor in psycho-emotional well-being following treatment. Treatment burden was acceptable, but seems to depend on clinical effect, duration of ongoing effect and stimulation site. Median weekly seizure frequency and ratio of seizure-free weeks did not change significantly in this small patient cohort. Conclusion: We report the results of the first ever trial of cTBS as a treatment for neocortical DRE. A 4-day accelerated cTBS protocol over the EF appears safe and feasible. Although the design and sample size of this open-label pilot study is unfit to reliably identify a therapeutic effect, results encourage further exploration of cTBS as an anti-epileptic treatment and potential optimization compared to conventional rTMS in a dedicated randomized controlled trial. (clinicaltrials.gov: NCT02635633).

The Dutch Oxford Cognitive Screen (OCS-NL): psychometric properties in Flemish stroke survivors.

BACKGROUND AND PURPOSE: The Oxford Cognitive Screen is a stroke-specific screen to evaluate attention, executive functions, memory, praxis, language, and numeric cognition. It was originally validated in England for acute stroke patients. In this study, we examined the psychometric properties of the Dutch OCS (OCS-NL). METHODS: A total of 193 (99 acute stroke unit, 94 rehabilitation unit) patients were included in our study. A subset of patients (n = 128) completed a retest with the parallel version of the OCS-NL. RESULTS: First, we did not find evidence for a difference in prevalence of impairment between patients in the acute stroke versus rehabilitation unit on all but one of the subtests. For praxis, we observed a 14% lower prevalence of impairment in the rehabilitation than the acute stroke unit. Second, the parallel-form reliability ranged from weak to excellent across subtests. Third, in stroke patients below age 60, the OCS-NL had a 92% sensitivity relative to the MoCA, while the MoCA had a 55% sensitivity relative to the OCS-NL. Last, although left-hemispheric stroke patients performed worse on almost all MoCA subdomains, they performed similarly to right-hemispheric stroke patients on non-language domains on the OCS-NL. CONCLUSIONS: Our results suggest that the OCS-NL is a reliable cognitive screen that can be used in acute stroke and rehabilitation units. The OCS-NL may be more sensitive to detect cognitive impairment in young stroke patients and less likely to underestimate cognitive abilities in left-hemispheric stroke patients than the MoCA.

Therapy-Induced Electrophysiological Changes in Primary Progressive Aphasia: A Preliminary Study.

Aims: This preliminary study aimed to investigate therapy-induced electrophysiological changes in persons with primary progressive aphasia (PPA). The investigated event-related potential (ERP) components associated with language processing were the mismatch negativity, P300, N400, and P600. Methods: A linguistic ERP test battery and standardized language assessment were administered in four patients with PPA of which two received speech-language therapy (SLT) and two did not receive therapy. The battery was administered twice with approximately 6 months in between in each patient. The results of the follow-up assessments were compared to the results of the initial assessments. Results: Although the results of the behavioral language assessment remained relatively stable between the initial and follow-up assessments, changes in the mean amplitudes, onset latencies, and duration of the ERP components were found in the four patients. In the two patients that did not receive SLT, an increased delay in 50% and a decreased mean amplitude in 25% of the measured ERP components were found. The electrophysiological changes found in the patients that received SLT were variable. Interestingly, the mismatch negativity and the N400 effect elicited by the categorical priming paradigm were less delayed and had an increased mean amplitude at the follow-up assessment in the patient with the non-fluent variant who received SLT. In this patient, the P600 component was absent at the initial assessment but present at the follow-up assessment. Conclusion: Although no clear patterns in electrophysiological changes between patients who received SLT and patients who did not receive SLT were found by our preliminary study, it seems like the SLT induced improvements or compensation mechanisms in some specific language comprehension processes in the patient with the NFV. The results of this study are still preliminary because only four heterogeneous patients were included. Future studies should include larger patient groups of the three clinical variants because the therapy-induced electrophysiological changes might differ depending on the clinical variant and the underlying pathology.

The potential of invasive and non-invasive vagus nerve stimulation to improve verbal memory performance in epilepsy patients.

It has been demonstrated that acute vagus nerve stimulation (VNS) improves word recognition memory in epilepsy patients. Transcutaneous auricular vagus nerve stimulation (taVNS) has gained interest as a non-invasive alternative to improve cognition. In this prospective randomized cross-over study, we investigated the effect of both invasive VNS and taVNS on verbal memory performance in 15 patients with drug-resistant epilepsy. All patients conducted a word recognition memory paradigm in 3 conditions: VNS ON, VNS OFF and taVNS (3-period 3-treatment cross-over study design). For each condition, patients memorized 21 highlighted words from text paragraphs. Afterwards, the intervention was delivered for 30 s. Immediate recall and delayed recognition scores were obtained for each condition. This memory paradigm was repeated after 6 weeks of VNS therapy in 2 conditions: VNS ON and VNS OFF (2-period 2-treatment cross-over study design). Acute VNS and taVNS did not improve verbal memory performance. Immediate recall and delayed recognition scores were significantly improved after 6 weeks of VNS treatment irrespective of the acute intervention. We can conclude that the previously described positive effects of invasive VNS on verbal memory performance could not be replicated with invasive VNS and taVNS. An improved verbal memory performance was seen after 6 weeks of VNS treatment, suggesting that longer and more repetitive stimulation of the vagal pathway is required to modulate verbal memory performance.Clinical trial registration number: NCT05031208.

GAD65 Autoimmune Encephalitis: A Cause of Rapidly Evolving Frontotemporal Atrophy.

We describe a patient who presented with subacute onset of short-memory impairment, disorientation, and gait instability, with progressive deterioration. Workup demonstrated glutamic acid decarboxylase antibody-related encephalitis. Aggressive immunotherapy with high-dose intravenous corticoids, followed by slow oral taper, plasmapheresis, rituximab, and cyclophosphamide did not halt disease progression. During follow-up, she developed a frontotemporal dementia phenotype. Serial imaging showed the appearance of marked atrophy of the frontal and anterior temporal regions. We conclude that glutamic acid decarboxylase antibody-related encephalitis may rarely present with a treatment-refractory frontotemporal phenotype.

Visual and Verbal Working Memory and Processing Speed Across the Adult Lifespan: The Effect of Age, Sex, Educational Level, Awakeness, and Hearing Sensitivity.

Objective: To strengthen future methodological choices regarding the measurement of cognition within the field of audiology, the current study aimed to examine the effect of, among other things, hearing sensitivity on the backward corsi tapping task (i.e., visual working memory and processing speed) and the letter-number sequencing task (i.e., verbal working memory and processing speed). Design and Study Sample: The backward corsi tapping task and the letter-number sequencing task were administered to 184 participants, aged between 18 and 69 years. The effect of age, sex, educational level, awakeness, and hearing sensitivity on verbal and visual working memory and processing speed was assessed using stepwise multiple regression analyses. Results: For all outcome variables, a decrease in performance was observed with increasing age. For visual and verbal working memory, males outperformed females, whereas no clear sex effect was observed for visual and verbal processing speed. Hearing sensitivity had only a significant impact on visual processing speed. Conclusion: The importance to evaluate cognitive construct validity within audiological research was highlighted. Further research should focus on investigating the associations between speech understanding on the one hand and the backward corsi tapping task and letter-number sequencing task on the other hand.

A case series of verbal semantic processing in primary progressive aphasia: Evidence from the N400 effect.

BACKGROUND: The semantic variant of primary progressive aphasia (PPA) is typically associated with a loss of semantic knowledge. Research on the semantic processing in the other clinical variants of PPA is, however, rather sparse and limited to off-line behavioural studies. AIMS: This study aimed to investigate verbal semantic processing in patients with the three variants of PPA by the event-related potential technique. The presence, latency, amplitude and/or topographic distribution of the N400 effect may be helpful in the diagnosis of PPA and its clinical variants and it provides temporal information about semantic processing (disturbances) in the three variants of PPA. METHODS & PROCEDURES: The N400 effect was studied by a categorical word-priming paradigm and a semantic-anomaly paradigm at sentence level in eight persons with PPA(-plus) and 30 age-matched healthy controls. The mean amplitudes and onset latencies of the N400 effect were compared between each patient and the control group by two methods that are applicable in clinical practice, namely visual inspection and Z-scores. OUTCOMES & RESULTS: The N400 effect elicited by the categorical-priming paradigm was only present in the two patients with the non-fluent variant of PPA. This effect was absent in the two patients with the semantic variant(-plus), two patients with the logopenic variant(-plus), one patient with the non-fluent variant-plus, and the patient with PPA not otherwise specified. The results of the N400 effect elicited by the semantic-anomaly task at the sentence level were variable, but differences in the presence, mean amplitudes, onset latencies and/or topographic distributions of the effect were found in all patients with PPA(-plus) in comparison with the control group. CONCLUSIONS & IMPLICATIONS: The results of our study showed that the evaluation of the N400 effect might have an added value in the diagnostic process of PPA in general and in the differentiation of patients with the non-fluent variant from patients with the logopenic and semantic variants. Furthermore, our results indicate the presence of difficulties with retrieving stored semantic knowledge or semantic integration of a word in the preceding context in patients with the three variants of PPA. These findings might help the speech-language pathologist in determining individualized therapy goals and indicate that it might be helpful to focus on verbal semantic processing in language therapy in patients with the three variants of PPA and not only in patients with the semantic variant. WHAT THIS PAPER ADDS: What is already known on the subject The semantic variant of PPA is characterized by an impaired object knowledge and single-word comprehension and these functions are relatively spared in the non-fluent and logopenic variants following the guidelines of Gorno-Tempini et al. (2011). Research on the semantic processing in patients with the non-fluent and logopenic variant is, however, rather sparse and limited to off-line behavioural studies. Only four group studies investigated verbal semantic processing by the N400 effect, and these studies indicate disturbances in the three variants of PPA. What this paper adds to existing knowledge Our results indicate the presence of difficulties with retrieving stored semantic knowledge or semantic integration of a word in the preceding context during a semantic-priming paradigm in patients with the semantic and logopenic variants of PPA and during a semantic-anomaly task at the sentence level in patients with the three variants of PPA. What are the potential or actual clinical implications of this work? The results of our study showed that the evaluation of the N400 effect might have an added value in the diagnostic process of PPA in general and in the differentiation of patients with the non-fluent variant from patients with the logopenic and semantic variants. The evaluation of the N400 effect might also help the speech-language pathologist in determining individualized therapy goals and indicate that it might be helpful to focus on verbal semantic processing in language therapy in patients with the three variants of PPA and not only in patients with the semantic variant.

The Electrophysiological Correlates of Phoneme Perception in Primary Progressive Aphasia: A Preliminary Case Series.

Aims: This study aimed to investigate phoneme perception in patients with primary progressive aphasia (PPA) by using the event-related potential (ERP) technique. These ERP components might contribute to the diagnostic process of PPA and its clinical variants (NFV: nonfluent variant, SV: semantic variant, LV: logopenic variant) and reveal insights about phoneme perception processes in these patients. Method: Phoneme discrimination and categorization processes were investigated by the mismatch negativity (MMN) and P300 in eight persons with early- and late-stage PPA (3 NFV, 2 LV, 2 SV, and 1 PPA-NOS; not otherwise specified) and 30 age-matched healthy adults. The mean amplitude, the onset latency, and the topographic distribution of both components in each patient were compared to the results of the control group. Results: The MMN was absent or the onset latency of the MMN was delayed in the patients with the NFV, LV, and PPA-NOS in comparison to the control group. In contrast, no differences in mean amplitudes and onset latencies of the MMN were found between the patients with the SV and the control group. Concerning the P300, variable results were found in the patients with the NFV, SV, and PPA-NOS, but the P300 of both patients with the LV was delayed and prolonged with increased mean amplitude in comparison to the control group. Conclusion: In this preliminary study, phoneme discrimination deficits were found in the patients with the NFV and LV, and variable deficits in phoneme categorization processes were found in all patients with PPA. In clinical practice, the MMN might be valuable to differentiate the SV from the NFV and the LV and the P300 to differentiate the LV from the NFV and the SV. Further research in larger and independent patient groups is required to investigate the applicability of these components in the diagnostic process and to determine the nature of these speech perception deficits in the clinical variants of PPA.

An Auditory Stroop Test to Implement in Cognitive Hearing Sciences: Development and Normative Data.

OBJECTIVE: This study developed and gained insight in an auditory Stroop test, implementable in cognitive hearing sciences. METHODS: An auditory Stroop test was developed and performed in 178 participants, aged between 18 and 69 years. This Auditory Stroop test consisted of two tests: Stroop-tones and Stroop-words whereby the pitch of pure-tones and spoken words (i.e., the words high and low) had to be identified by high or low, respectively. An interference score was calculated as a measure of verbal executive functioning. Regression models were conducted to examine the effect of age, sex, education, awakeness, hearing, as well as visual and verbal working memory, and processing speed on the auditory Stroop scores. Normative data were obtained per age decade. RESULTS: Compared to the visual counterparts, the auditory Stroop outcomes were better predicted by verbal working memory and processing speed. A trend was observed showing a decrease in performances with increasing age. No other participant-related variables had a significant relationship with the auditory Stroop test. CONCLUSION: This auditory Stroop test was considered a good test for measuring executive functioning using auditory stimuli. Implementing this auditory Stroop test within cognitive hearing sciences will contribute to unravel the auditory-cognitive perspective of speech understanding.

OBJETIVO: Este estudio desarrolló y alcanzó un claro entendimiento en una prueba auditiva de Stroop, implementable en las ciencias auditivas cognitivas. MÉTODOS: Se desarrolló un test auditivo de Stroop y se aplicó en 178 participantes entre los 18 y los 69 años de edad. Este test auditivo de Stroop constaba dos pruebas, a saber: Stroop-tonos y Stroop-palabras. El tono de los tonos puros y de las palabras habladas (es decir, las palabras alto y bajo) tenían que ser identificadas por alto o bajo, respectivamente. Se calculó una puntuación de interferencia como medida del funcionamiento ejecutivo verbal. Se realizaron modelos de regresión para examinar el efecto de la edad, el sexo, la educación, la vigilia, la audición, así como la memoria de trabajo visual y verbal y la velocidad de procesamiento en todas las puntuaciones auditivas de Stroop. Se obtuvieron datos normativos por década. RESULTADOS: Los resultados del Stroop auditivo podrían predecirse mejor por la memoria de trabajo verbal y la velocidad de procesamiento en comparación con las contrapartes visuales. Se observó una tendencia que mostraba una disminución de los resultados con el aumento de la edad. Ninguna otra variable relacionada con los participantes parecía tener una relación significativa con la prueba auditiva de Stroop. CONCLUSIÓN: Este test auditivo de Stroop se consideró una buena prueba para medir el funcionamiento ejecutivo utilizando estímulos auditivos. La aplicación de esta prueba auditiva de Stroop dentro de las ciencias auditivas cognitivas contribuirá a desentrañar la perspectiva auditivo-cognitiva de la comprensión del habla.

Language and Speech Markers of Primary Progressive Aphasia: A Systematic Review.

Purpose This systematic review aimed to establish language and speech markers to support the clinical diagnosis of primary progressive aphasia (PPA) and its clinical phenotypes. Our first objective was to identify behavioral language and speech markers of early-stage PPA. Our second objective was to identify the electrophysiological correlates of the language and speech characteristics in PPA. Method The databases MEDLINE, Web of Science, and Embase were searched for relevant articles. To identify behavioral markers, the initial subjective complaints and the language and speech deficits detected during the initial diagnostic evaluation were summarized for PPA in general and each clinical variant according to the 2011 consensus diagnostic criteria (nonfluent variant [NFV], semantic variant, and logopenic variant [LV]). To identify electrophysiological markers, the studies in which event-related potentials (ERPs) were elicited by a language or speech paradigm in patients with PPA were included. Results In total, 114 relevant studies were identified, including 110 behavioral studies and only four electrophysiological studies. This review suggests that patients with the semantic variant could be accurately differentiated from the NFV and LV in the initial stages based on the consensus criteria. Nonetheless, the early differentiation between the NFV and LV is not straightforward. In the four electrophysiological studies, differences in the latency, amplitude, and topographical distribution of the semantic N400 component were found between patients with PPA and healthy controls. Conclusions To accurately differentiate the NFV from the LV, it could be important to assess the language and speech degeneration by more specific assessments and by more objective diagnostic methods that offer insights into the language-related processes. Electrophysiological markers of PPA were not identified in this review due to the low number of studies that investigated language-related ERPs. More controlled ERP studies in larger patient cohorts are needed to investigate the diagnostic applicability of language-related ERPs in PPA. Supplemental Material https://doi.org/10.23641/asha.12798080.

Transcutaneous Vagus Nerve Stimulation Does Not Affect Verbal Memory Performance in Healthy Volunteers.

INTRODUCTION: Invasive vagus nerve stimulation (VNS) improves word recognition memory in patients with epilepsy. Recent studies with transcutaneous VNS (tVNS) have also shown positive effects on various subdomains of cognitive functioning in healthy volunteers. In this randomized, controlled, crossover study, we investigated the effect of tVNS on a word recognition memory paradigm in healthy volunteers to further investigate the potential of tVNS in the treatment of cognitive disorders. METHODS: We included 41 healthy participants aged between 18 and 30 years (young age group) and 24 healthy participants aged between 45 and 80 years (older age group). Each participant completed a word recognition memory paradigm during three different conditions: true tVNS, sham, and control. During true tVNS, stimulation was delivered at the cymba conchae. Sham stimulation was delivered by stimulating the earlobe. In the control condition, no stimulation was given. In each condition, participants were asked to remember highlighted words from three test paragraphs. Accuracy scores were calculated for immediate recall after each test paragraph and for delayed recognition at the end of the paradigm. We hypothesized that highlighted words from paragraphs in the true tVNS condition would be more accurately recalled and/or recognized compared to highlighted words from paragraphs in the sham or control condition. RESULTS: In this randomized study, tVNS did not affect the accuracy scores for immediate recall or delayed recognition in both age groups. The younger group showed significantly higher accuracy scores than the older group. The accuracy scores improved over time, and the most recently learned words were better recognized. Participants rated true tVNS as significantly more painful; however, pain was not found to affect accuracy scores. CONCLUSION: In this study, tVNS did not affect verbal memory performance in healthy volunteers. Our results could not replicate the positive effects of invasive VNS on word recognition memory in epilepsy patients. Future research with the aim of improving cognitive function should focus on the rational identification of optimized and individualized stimulation settings primarily in patients with cognitive deficits.

The moral brain and moral behaviour in patients with Parkinson's disease: a review of the literature.

Morality is a complex and versatile concept that necessitates the integrated activity of multiple interacting networks in the brain. Numerous cortical and subcortical areas, many of which are implicated in either emotional and cognitive control or Theory of Mind, are involved in the processing of moral behaviour. Different methods have been used to investigate various aspects of morality, which has lead to confusing and sometimes opposing results. Emotional, cognitive and personality changes have long been recognized in Parkinson's disease (PD) patients, suggesting a potential impact on moral aspects of behaviour in daily living situations. Alterations in social cognition have been described in all stages of PD but these are rather directly related to PD pathology and not to dopaminergic or DBS treatment. There are no convincing data supporting the hypothesis that dopaminergic treatment or deep brain stimulation of the STN per se interfere with morality in PD patients, although subgroups of patients may display socially unacceptable behaviour. Research in social cognition in PD patients is a fascinating topic that needs further attention in view of the impact on quality of life for PD patients and their caregivers.

Extended FTLD pedigree segregating a Belgian GRN-null mutation: neuropathological heterogeneity in one family.

BACKGROUND: In this paper, we describe the clinical and neuropathological findings of nine members of the Belgian progranulin gene (GRN) founder family. In this family, the loss-of-function mutation IVS1 + 5G > C was identified in 2006. In 2007, a clinical description of the mutation carriers was published that revealed the clinical heterogeneity among IVS1 + 5G > C carriers. We report our comparison of our data with the published clinical and neuropathological characteristics of other GRN mutations as well as other frontotemporal lobar degeneration (FTLD) syndromes, and we present a review of the literature. METHODS: For each case, standardized sampling and staining were performed to identify proteinopathies, cerebrovascular disease, and hippocampal sclerosis. RESULTS: The neuropathological substrate in the studied family was compatible in all cases with transactive response DNA-binding protein (TDP) proteinopathy type A, as expected. Additionally, most of the cases presented also with primary age-related tauopathy (PART) or mild Alzheimer's disease (AD) neuropathological changes, and one case had extensive Lewy body pathology. An additional finding was the presence of cerebral small vessel changes in every patient in this family. CONCLUSIONS: Our data show not only that the IVS1 + 5G > C mutation has an exclusive association with FTLD-TDP type A proteinopathy but also that other proteinopathies can occur and should be looked for. Because the penetrance rate of the clinical phenotype of carriers of GRN mutations is age-dependent, further research is required to investigate the role of co-occurring age-related pathologies such as AD, PART, and cerebral small vessel disease.

Current standards of neuropsychological assessment in epilepsy surgery centers across Europe.

We explored the current practice with respect to the neuropsychological assessment of surgical epilepsy patients in European epilepsy centers, with the aim of harmonizing and establishing common standards. Twenty-six epilepsy centers and members of "E-PILEPSY" (a European pilot network of reference centers in refractory epilepsy and epilepsy surgery), were asked to report the status of neuropsychological assessment in adults and children via two different surveys. There was a consensus among these centers regarding the role of neuropsychology in the presurgical workup. Strong agreement was found on indications (localization, epileptic dysfunctions, adverse drugs effects, and postoperative monitoring) and the domains to be evaluated (memory, attention, executive functions, language, visuospatial skills, intelligence, depression, anxiety, and quality of life). Although 186 different tests are in use throughout these European centers, a core group of tests reflecting a moderate level of agreement could be discerned. Variability exists with regard to indications, protocols, and paradigms for the assessment of hemispheric language dominance. For the tests in use, little published evidence of clinical validity in epilepsy was provided. Participants in the survey reported a need for improvement concerning the validity of the tests, tools for the assessment of everyday functioning and accelerated forgetting, national norms, and test co-normalization. Based on the present survey, we documented a consensus regarding the indications and principles of neuropsychological testing. Despite the variety of tests in use, the survey indicated that there may be a core set of tests chosen based on experience, as well as on published evidence. By combining these findings with the results of an ongoing systematic literature review, we aim for a battery that can be recommended for the use across epilepsy surgical centers in Europe.

Neurocognitive development and behaviour in school-aged children after surgery for univentricular or biventricular congenital heart disease.

OBJECTIVES: To assess the long-term neuropsychological and behavioural profile of school-aged children who were treated for univentricular heart (UVH) conditions or biventricular heart defect (BiVH) in infancy in a cross-sectional study design. METHODS: Sixty-three patients, 17 UVH (13 males, 4 females) and 46 BiVH (19 males, 27 females), were assessed at a mean age of 9.1 years (2.2 years) with an intelligence and neuropsychological test battery. Results were compared between subgroups (UVH, BiVH and a healthy control group). Associations between cognitive outcome, medical and socio-demographic factors were explored. Parents completed the Child Behavior Checklist (CBCL). RESULTS: Mean intelligence and neuropsychological scores were found within normal ranges for all diagnostic groups. Significant differences between UVH patients and controls emerged on auditory sustained and alternating attention, fine motor skills, visuospatial information processing, and to a lesser extent, memory performance. Parents of UVH patients reported more externalizing problems and school problems. Patient groups did not differ on neuropsychological outcome measures, nor on behavioural problems as rated by parents. CONCLUSIONS: After Fontan completion, patients at school age display intelligence scores within normal population-based ranges. However, they were found at risk for subtle shortcomings in attention, fine motor skills, visuospatial information processing and externalizing behaviour problems. Considerations pertaining to neurobehavioural outcome in school-aged children are discussed.

Quality of life in patients with PD and their caregiving spouses: A view from both sides.

OBJECTIVE: In contrast to the wealth of studies on quality of life (QoL) in patients with Parkinson's disease, the number of reports on QoL in caregivers, especially partners as primary caregivers, is fairly limited. In this report we wanted to investigate if patients and caregiving partners are able to reliably estimate each other's present and former QoL. METHODS: We used a visual analogue scale in order to obtain the patients' and their partners' scores of present and former QoL. Moreover we studied correlations of these mutual estimates with demographic variables and measures of patient dependency. RESULTS: As expected both patients and partners considered their QoL as decreased when compared to former QoL. Interestingly both patients and partners were able to reliably estimate each other's QoL. Patients judged their own former QoL and that of their partner as lower as did their partners. All QoL measures were significantly correlated to measures of mental state and patient dependency. There was a negative correlation with increasing age but not with disease duration. CONCLUSION: These results indicate the validity of using proxy information by a caregiving partner in estimations of QoL.