The German version of the Oxford Cognitive Screen (D-OCS): Normative data and validation in acute stroke and a mixed neurological sample.

Given the frequency of stroke worldwide, tools for neuropsychological assessment of patients with acute stroke are needed to identify cognitive impairments, guide rehabilitation efforts and allow for a prognosis of outcome. However, requirements for assessment tools for acute cognitive deficits differ substantially from tests for chronic neuropsychological impairments and screening tools for suspected dementia. The Oxford Cognitive Screen (OCS) has been developed as a quick to administer neurocognitive screening for acute neurological patients providing information on various cognitive domains. It is available in different languages. The present study reports cut-off scores, parallel-test reliability and concurrent validity of the German version (D-OCS). Following standardized language adaptation and translation, the D-OCS was administered to 100 healthy individuals to generate cut-off scores (5th percentile). Subsequently, 88 neurological patients were assessed with both versions of the D-OCS as well as other tests to evaluate reliability and validity of the D-OCS subscales. In a further study, the D-OCS was compared to the MoCA test in 65 acute stroke patients revealing comparable sensitivity but also differences between both tools. The cut-off scores were comparable to other international versions of the OCS. Intraclass correlations were highly significant and document reliability of the D-OCS subtests. Scores on subtests correlated significantly with independent tests securing validity. Comparison with the MoCA revealed comparable sensitivity and specificity. The D-OCS is a reliable and valid assessment tool well suited for patients with acute stroke. Differences to the MoCA test are discussed.

Cognitive Deficits in Parkinson's Disease Are Associated with Neuronal Dysfunction and Not White Matter Lesions.

Background: Cognitive deficits considerably contribute to the patient's burden in Parkinson's disease (PD). While cognitive decline is linked to neuronal dysfunction, the additional role of white matter lesions (WML) is discussed controversially. Objective: To investigate the influence of WML, in comparison to neuronal dysfunction, on cognitive deficits in PD. Methods: We prospectively recruited patients with PD who underwent neuropsychological assessment using the Mattis Dementia Rating Scale 2 (DRS-2) or Parkinson Neuropsychometric Dementia Assessment (PANDA) and both MRI and PET with [18F]fluorodeoxyglucose (FDG). WML-load and PD cognition-related covariance pattern (PDCP) as a measure of neuronal dysfunction were read out. Relationship between cognitive performance and rank-transformed WML was analyzed with linear regression, controlling for the patients' age. PDCP subject scores were investigated likewise and in a second step adjusting for age and WML load. Results: Inclusion criteria were met by 76 patients with a mean (± SD) age of 63.5 ± 9.0 years and disease duration of 10.7 ± 5.4 years. Neuropsychological testing revealed front executive and parietal deficits and a median DRS-2 score of 137 (range 119-144)/144 and PANDA score of 22 (range 3-30)/30. No association between WML and cognition was observed, whereas PDCP subject scores showed a trend-level negative correlation with the DRS-2 (P = 0.060) as well as a negative correlation with PANDA (P = 0.049) which persisted also after additional correction for WML (P = 0.039). Conclusion: The present study indicates that microangiopathic WML do not have a relevant impact on neurocognitive performance in PD whereas neuronal dysfunction does.

More extensive hypometabolism and higher mortality risk in patients with right- than left-predominant neurodegeneration of the anterior temporal lobe.

BACKGROUND: Left-predominant neurodegeneration of the anterior temporal lobe (ATL) and the associated syndrome termed semantic variant primary progressive aphasia (svPPA) are well characterized. Less is known about right-predominant neurodegeneration of the ATL, which has been associated with the clinical syndrome named right temporal variant of frontotemporal dementia (rtvFTD). Here, we assessed glucose metabolism across the brain, cognitive performance, and mortality in patients with right-predominant neurodegeneration of the ATL. METHODS: Patients with predominant hypometabolism of the ATL on FDG PET (as a measure of neurodegeneration) were retrospectively identified and categorized into those with asymmetrical right, left, or symmetric bilateral involvement (N = 10, 17, and 8). We compared whole-brain, normalized regional glucose metabolism using SPM12, cognitive performance on the CERAD Neuropsychological Assessment Battery, and mortality risk (age- and sex-adjusted Cox proportional hazard model) between groups. RESULTS: Hypometabolism was most pronounced and extensive in patients with right-predominant neurodegeneration of the ATL. Beyond the right temporal lobe, right frontal and left temporal lobes were affected in these patients. Cognitive performance was similarly impaired in all three groups, with predominant naming and hippocampal-dependent memory deficits. Mortality risk was 6.1 times higher in patients with right- than left-predominant ATL neurodegeneration (p < 0.05). Median survival duration after PET was shortest in patients with right- and longest in patients with left-predominant ATL neurodegeneration (5.7 vs 8.3 years after examination). DISCUSSION: More extensive neurodegeneration and shorter survival duration in patients with right- than left-predominant neurodegeneration of the ATL might indicate that the former consult memory clinics at a later disease stage, when symptoms like naming and episodic memory deficits have already emerged. At the time of diagnosis, the shorter survival duration of patients with right- than left-predominant ATL neurodegeneration should be kept in mind when counseling patients and caregivers.

Widespread white matter oedema in subacute COVID-19 patients with neurological symptoms.

While neuropathological examinations in patients who died from COVID-19 revealed inflammatory changes in cerebral white matter, cerebral MRI frequently fails to detect abnormalities even in the presence of neurological symptoms. Application of multi-compartment diffusion microstructure imaging (DMI), that detects even small volume shifts between the compartments (intra-axonal, extra-axonal and free water/CSF) of a white matter model, is a promising approach to overcome this discrepancy. In this monocentric prospective study, a cohort of 20 COVID-19 inpatients (57.3 ± 17.1 years) with neurological symptoms (e.g. delirium, cranial nerve palsies) and cognitive impairments measured by the Montreal Cognitive Assessment (MoCA test; 22.4 ± 4.9; 70% below the cut-off value <26/30 points) underwent DMI in the subacute stage of the disease (29.3 ± 14.8 days after positive PCR). A comparison of whole-brain white matter DMI parameters with a matched healthy control group (n = 35) revealed a volume shift from the intra- and extra-axonal space into the free water fraction (V-CSF). This widespread COVID-related V-CSF increase affected the entire supratentorial white matter with maxima in frontal and parietal regions. Streamline-wise comparisons between COVID-19 patients and controls further revealed a network of most affected white matter fibres connecting widespread cortical regions in all cerebral lobes. The magnitude of these white matter changes (V-CSF) was associated with cognitive impairment measured by the MoCA test (r = -0.64, P = 0.006) but not with olfactory performance (r = 0.29, P = 0.12). Furthermore, a non-significant trend for an association between V-CSF and interleukin-6 emerged (r = 0.48, P = 0.068), a prominent marker of the COVID-19 related inflammatory response. In 14/20 patients who also received cerebral 18F-FDG PET, V-CSF increase was associated with the expression of the previously defined COVID-19-related metabolic spatial covariance pattern (r = 0.57; P = 0.039). In addition, the frontoparietal-dominant pattern of neocortical glucose hypometabolism matched well to the frontal and parietal focus of V-CSF increase. In summary, DMI in subacute COVID-19 patients revealed widespread volume shifts compatible with vasogenic oedema, affecting various supratentorial white matter tracts. These changes were associated with cognitive impairment and COVID-19 related changes in 18F-FDG PET imaging.

Neuropsychologic Profiles and Cerebral Glucose Metabolism in Neurocognitive Long COVID Syndrome.

During the coronavirus disease 2019 (COVID-19) pandemic, Long COVID syndrome, which impairs patients through cognitive deficits, fatigue, and exhaustion, has become increasingly relevant. Its underlying pathophysiology, however, is unknown. In this study, we assessed cognitive profiles and regional cerebral glucose metabolism as a biomarker of neuronal function in outpatients with long-term neurocognitive symptoms after COVID-19. Methods: Outpatients seeking neurologic counseling with neurocognitive symptoms persisting for more than 3 mo after polymerase chain reaction (PCR)-confirmed COVID-19 were included prospectively between June 16, 2020, and January 29, 2021. Patients (n = 31; age, 53.6 ± 2.0 y) in the long-term phase after COVID-19 (202 ± 58 d after positive PCR) were assessed with a neuropsychologic test battery. Cerebral 18F-FDG PET imaging was performed in 14 of 31 patients. Results: Patients self-reported impaired attention, memory, and multitasking abilities (31/31), word-finding difficulties (27/31), and fatigue (24/31). Twelve of 31 patients could not return to the previous level of independence/employment. For all cognitive domains, average group results of the neuropsychologic test battery showed no impairment, but deficits (z score < -1.5) were present on a single-patient level mainly in the domain of visual memory (in 7/31; other domains ≤ 2/31). Mean Montreal Cognitive Assessment performance (27/30 points) was above the cutoff value for detection of cognitive impairment (<26 points), although 9 of 31 patients performed slightly below this level (23-25 points). In the subgroup of patients who underwent 18F-FDG PET, we found no significant changes of regional cerebral glucose metabolism. Conclusion: Long COVID patients self-report uniform symptoms hampering their ability to work in a relevant fraction. However, cognitive testing showed minor impairments only on a single-patient level approximately 6 mo after the infection, whereas functional imaging revealed no distinct pathologic changes. This clearly deviates from previous findings in subacute COVID-19 patients, suggesting that underlying neuronal causes are different and possibly related to the high prevalence of fatigue.

Slow but Evident Recovery from Neocortical Dysfunction and Cognitive Impairment in a Series of Chronic COVID-19 Patients.

Cognitive impairment is a frequent complaint in coronavirus disease 2019 (COVID-19) and can be related to cortical hypometabolism on 18F-FDG PET at the subacute stage. However, it is unclear if these changes are reversible. Methods: We prospectively assessed the Montreal Cognitive Assessment scores and 18F-FDG PET scans of 8 COVID-19 patients at the subacute stage (once no longer infectious) and the chronic stage (˜6 mo after symptom onset). The expression of the previously established COVID-19-related covariance pattern was analyzed at both stages to examine the time course of post-COVID-19 cognitive impairment. For further validation, we also conducted a conventional group analysis. Results: Follow-up 18F-FDG PET revealed that there was a significant reduction in the initial frontoparietal and, to a lesser extent, temporal hypometabolism and that this reduction was accompanied by a significant improvement in cognition. The expression of the previously established COVID-19-related pattern was significantly lower at follow-up and correlated inversely with Montreal Cognitive Assessment performance. However, both 18F-FDG PET and cognitive assessment suggest a residual impairment. Conclusion: Although a significant recovery of regional neuronal function and cognition can be clearly stated, residuals are still measurable in some patients 6 mo after manifestation of COVID-19. Given the current pandemic situation and tremendous uncertainty concerning the long-term effects of COVID-19, the present study provides novel insights of the highest medical and socioeconomic relevance.

Cognitive impairment and altered cerebral glucose metabolism in the subacute stage of COVID-19.

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, neurological symptoms increasingly moved into the focus of interest. In this prospective cohort study, we assessed neurological and cognitive symptoms in hospitalized coronavirus disease-19 (COVID-19) patients and aimed to determine their neuronal correlates. Patients with reverse transcription-PCR-confirmed COVID-19 infection who required inpatient treatment primarily because of non-neurological complications were screened between 20 April 2020 and 12 May 2020. Patients (age > 18 years) were included in our cohort when presenting with at least one new neurological symptom (defined as impaired gustation and/or olfaction, performance < 26 points on a Montreal Cognitive Assessment and/or pathological findings on clinical neurological examination). Patients with ≥2 new symptoms were eligible for further diagnostics using comprehensive neuropsychological tests, cerebral MRI and 18fluorodeoxyglucose (FDG) PET as soon as infectivity was no longer present. Exclusion criteria were: premorbid diagnosis of cognitive impairment, neurodegenerative diseases or intensive care unit treatment. Of 41 COVID-19 inpatients screened, 29 patients (65.2 ± 14.4 years; 38% female) in the subacute stage of disease were included in the register. Most frequently, gustation and olfaction were disturbed in 29/29 and 25/29 patients, respectively. Montreal Cognitive Assessment performance was impaired in 18/26 patients (mean score 21.8/30) with emphasis on frontoparietal cognitive functions. This was confirmed by detailed neuropsychological testing in 15 patients. 18FDG PET revealed pathological results in 10/15 patients with predominant frontoparietal hypometabolism. This pattern was confirmed by comparison with a control sample using voxel-wise principal components analysis, which showed a high correlation (R2 = 0.62) with the Montreal Cognitive Assessment performance. Post-mortem examination of one patient revealed white matter microglia activation but no signs of neuroinflammation. Neocortical dysfunction accompanied by cognitive decline was detected in a relevant fraction of patients with subacute COVID-19 initially requiring inpatient treatment. This is of major rehabilitative and socioeconomic relevance.

[Neuropsychological disorders of memory]. / Neuropsychologische Störungen des Gedächtnisses.

This article provides an introduction to the neuropsychology of human memory. The terms short-term memory, working memory, episodic memory, semantic and procedural memory are defined and the anatomical correlates of these various memory systems are presented. Additionally, a brief introduction to the methods for neuropsychological research on human memory is given together with advice on the neuropsychological diagnostics and therapy.

Learning of novel compound nouns - A variant of lexical learning that requires intact verbal short-term memory.

Verbal short-term memory (vSTM) plays a crucial role in word learning, and patients with impaired vSTM have been demonstrated to fail on learning novel word forms. Word learning has exclusively been investigated with previously unknown or pseudowords. Several languages, however, make use of composition, i.e., combining morphemes into compounds. On the one hand, this is comparable to pseudoword learning because known elements are combined into novel representations, on the other hand compounds differ from pseudowords learning because they consist of previously known (lexical) elements. This may help to identify the role of vSTM in word learning. The present paper documents impaired word learning in a participant with impaired vSTM but also assessed, for the first time, the acquisition of novel noun-noun compounds. In two independent experiments, the participant was impaired in learning nonsense compounds ("ball door") and the names of previously unknown tools ("nail puller"; "drill bit"). Control experiments revealed her impairment of word learning and novel compound noun learning to be selective: IS could acquire information about the novel tools' function and purpose and was unimpaired in several experiments on paired associate learning including different stimuli. The results suggest that vSTM is involved in variants of lexical learning such as compound noun acquisition. Implications for the modeling of the relationship between vSTM and word learning are discussed.

Neural correlates of acute apraxia: Evidence from lesion data and functional MRI in stroke patients.

Behavioral deficits after stroke like apraxia can be related to structural lesions and to a functional state of the underlying network - three factors, reciprocally influencing each other. Combining lesion data, behavioral performance and passive functional activation of the network-of-interest, this study aims to disentangle those mutual influences and to identify 1) activation patterns associated with the presence or absence of acute apraxia in tool-associated actions and 2) the specific impact of lesion location on those activation patterns. Brain activity of 48 patients (63.31 ± 13.68 years, 35 male) was assessed in a fMRI paradigm with observation of tool-related actions during the acute phase after first-ever left-hemispheric stroke (4.83 ± 2.04 days). Behavioral assessment of apraxia in tool-related tasks was obtained independently. Brain activation was compared between patients versus healthy controls and between patient with versus without apraxia. Interaction effects of lesion location (frontal vs parietal) and behavioral performance (apraxia vs no apraxia) were assessed in a 2 × 2 factorial design. Action observation activated the ventro-dorsal parts of the network for cognitive motor function; activation was globally downregulated after stroke. Apraxic compared to non-apraxic patients showed relatively increased activity in bilateral posterior middle temporal gyrus and middle frontal gyrus/superior frontal sulcus. Altered activation occurred in regions for tool-related cognition, corroborating known functions of the ventro-dorsal and ventral streams for praxis, and comprised domain-general areas, functionally related to cognitive control. The interaction analyses revealed different levels of activation in the left anterior middle temporal gyrus in the ventral stream in apraxic patients with frontal compared to parietal lesions, suggesting a modulation of network activation in relation to behavioral performance and lesion location as separate factors. By detecting apraxia-specific activation patterns modulated by lesion location, this study underlines the necessity to combine structural lesion information, behavioral parameters and functional activation to comprehensively examine cognitive functions in acute stroke patients.

Dissociating frontal and temporal correlates of phonological and semantic fluency in a large sample of left hemisphere stroke patients.

Previous lesion studies suggest that semantic and phonological fluency are differentially subserved by distinct brain regions in the left temporal and the left frontal cortex, respectively. However, as of yet, this often implied double dissociation has not been explicitly investigated due to mainly two reasons: (i) the lack of sufficiently large samples of brain-lesioned patients that underwent assessment of the two fluency variants and (ii) the lack of tools to assess interactions in factorial analyses of non-normally distributed behavioral data. In addition, previous studies did not control for task resource artifacts potentially introduced by the generally higher task difficulty of phonological compared to semantic fluency. We addressed these issues by task-difficulty adjusted assessment of semantic and phonological fluency in 85 chronic patients with ischemic stroke of the left middle cerebral artery. For classical region-based lesion-behavior mapping patients were grouped with respect to their primary lesion location. Building on the extension of the non-parametric Brunner-Munzel rank-order test to multi-factorial designs, ANOVA-type analyses revealed a significant two-way interaction for cue type (semantic vs. phonological) by lesion location (left temporal vs. left frontal vs. other as stroke control group). Subsequent contrast analyses further confirmed the proposed double dissociation by demonstrating that (i) compared to stroke controls, left temporal lesions led to significant impairments in semantic but not in phonological fluency, whereas left frontal lesions led to significant impairments in phonological but not in semantic fluency, and that (ii) patients with frontal lesions showed significantly poorer performance in phonological than in semantic fluency, whereas patients with temporal lesions showed significantly poorer performance in semantic than in phonological fluency. The anatomical specificity of these findings was further assessed in voxel-based lesion-behavior mapping analyses using the multi-factorial extension of the Brunner-Munzel test. Voxel-wise ANOVA-type analyses identified circumscribed parts of left inferior frontal gyrus and left superior and middle temporal gyrus that significantly double-dissociated with respect to their differential contribution to phonological and semantic fluency, respectively. Furthermore, a main effect of lesion with significant impairments in both fluency types was found in left inferior frontal regions adjacent to but not overlapping with those showing the differential effect for phonological fluency. The present study hence not only provides first explicit evidence for the anatomical double dissociation in verbal fluency at the group level but also clearly underlines that its formulation constitutes an oversimplification as parts of left frontal cortex appear to contribute to both semantic and phonological fluency.

Dissociation among preserved resistance to proactive interference and impaired behavioral inhibition in a patient with bilateral lesions in the inferior frontal gyrus: A single-case study.

Inhibition is not a unitary construct, as different inhibition-related functions have been disentangled. The present single-case study compares performance of a patient with bilateral lesions in the inferior frontal gyrus (IFG) and anterior insula to healthy age-matched controls in different inhibition-related tasks. Particular focus was on the resolution of proactive interference that is supposed to rely on bilateral IFG and anterior insula. Two working memory tasks previously proven sensitive to deficits in proactive interference (recent-probes, n-back) and two tasks measuring behavioral inhibition (verb generation task, Stroop task) were administered. Against expectations, the patient did not show any deficits in measures of proactive interference. However, compared to controls, she demonstrated considerably reduced performance in both measures of behavioral inhibition, thus resulting in a classical dissociation between proactive interference and behavioral inhibition. Although performance improved during the chronic phase post stroke, the overall pattern of a classical dissociation between proactive interference and behavioral inhibition remained stable across time. Taken together, the present data support the role of the IFG in inhibition-related functions, but a direct relationship between lesions in the IFG and difficulties in resolution of proactive interference could not be corroborated.

Amyloid imaging for differential diagnosis of dementia: incremental value compared to clinical diagnosis and [18F]FDG PET.

PURPOSE: Cerebral beta-amyloid and regional glucose metabolism assessed by positron emission tomography (PET) are used as diagnostic biomarkers for Alzheimer's disease (AD). The present study validates the incremental diagnostic value of amyloid PET in addition to clinical diagnosis and [18F]FDG PET in a real-life memory clinic population. METHODS: Of 138 consecutive patients with cognitive impairment who received combined [18F]FDG and [11C]PIB PET, 84 were diagnosed with major neurocognitive disorder (DSM-5) and included. Baseline clinical and [18F]FDG PET diagnoses were independently established with and without access to amyloid PET results and were dichotomized into AD or non-AD disorders. The incremental value of amyloid PET was evaluated in terms of: (1) the change in clinical and [18F]FDG PET diagnoses, (2) the change in agreement between clinical and [18F]FDG PET diagnoses, and (3) diagnostic accuracy using an interdisciplinary consensus diagnosis after an extended follow-up (2.4 ± 1.3 years after PET) as the reference. RESULTS: After disclosure of the amyloid PET results, clinical and [18F]FDG PET diagnoses changed in 23% and 18% of patients, respectively, and agreement between both ratings increased from 62% to 86% (p < 0.001). The accuracy of clinical and [18F]FDG PET diagnoses improved from 71% to 89% (p < 0.01) and from 76% to 94% (p < 0.001), respectively. The additional value of amyloid PET was rather uniform in relation to age at onset and consistency with appropriate use criteria. CONCLUSION: Amyloid PET provides significant incremental diagnostic value beyond clinical and [18F]FDG PET diagnoses of AD. Given the high diagnostic accuracy of combined clinical and amyloid PET assessment, further studies are needed to clarify the role of an additional [18F]FDG PET scan in these patients.

Do all visual deficits cause pure alexia? Dissociations between visual processing and reading suggest "no".

Pure alexia is a deficit of reading affecting the ability to process a word's letters in parallel. Instead, a slow, effortful letter-by-letter reading strategy is employed. It has been claimed that a visual impairment caused the reading impairment. The present study compares visual processing and word reading of a patient with severe visuospatial deficits due to probable posterior cortical atrophy (PCA) to two patients with pure alexia. A double dissociation emerged between visual processing and word reading: The participant with PCA was severely impaired in all visual tasks but read fluently while the patients with pure alexia read slowly but exhibited better preserved visual processing. It is concluded that a visual impairment does not inevitably lead to pure alexia, and that this syndrome is more plausibly conceived of as an orthographic deficit. In addition, the PCA patient's hypometabolism was assessed, and the interaction of the dorsal and ventral visual stream in word reading is discussed.

Amyloid load but not regional glucose metabolism predicts conversion to Alzheimer's dementia in a memory clinic population.

PURPOSE: The value of imaging regional glucose metabolism with [18F]FDG PET for the prediction of progression from mild cognitive impairment (MCI) to Alzheimer's dementia (AD) is controversial. The predictive value of imaging with [18F]FDG PET was therefore tested and compared with that of imaging beta-amyloid load with [11C]PIB PET in the same memory clinic population of MCI patients. METHODS: Thirty-nine patients with MCI who had undergone [18F]FDG as well as [11C]PIB PET were identified from a single-centre clinical registry. [18F]FDG and [11C]PIB PET images were rated as positive or negative for the presence of regional hypometabolism typical of AD and beta-amyloid deposition, respectively. Raters were blinded to the clinical information. Patients were followed clinically for 2.7 ± 1.2 years after PET. Cox proportional hazards models, adjusted for age and sex, were used to test the predictive value of [18F]FDG PET, [11C]PIB PET, and both in combination. RESULTS: [18F]FDG PET did not significantly predict conversion to AD (p > 0.1). By contrast, models including [11C]PIB PET only (p < 0.05) or both [18F]FDG and [11C]PIB PET (p < 0.05) significantly predicted conversion to AD. The hazard ratio for AD in patients with a positive [11C]PIB scan was 10.2 (95% confidence interval 1.3-78.1). The results were confirmed by analysis of semiquantitative measures using normalized [18F]FDG uptake and [11C]PIB standardized uptake value ratios in AD-typical regions as continuous predictors. CONCLUSION: In contrast to [11C]PIB PET, [18F]FDG PET did not predict conversion from MCI to AD in this clinical patient sample. Therefore, amyloid PET should be preferred for individual prediction and patient counselling in clinical practice.

Neurocognition and Cerebral Lesion Burden in High-Risk Patients Before Undergoing Transcatheter Aortic Valve Replacement: Insights From the SENTINEL Trial.

OBJECTIVES: The authors sought to determine baseline neurocognition before transcatheter aortic valve replacement (TAVR) and its correlations with pre-TAVR brain imaging. BACKGROUND: TAVR studies have not shown a correlation between diffusion-weighted image changes and neurocognition. The authors wanted to determine the extent to which there was already impairment at baseline that correlated with cerebrovascular disease. METHODS: SENTINEL (Cerebral Protection in Transcatheter Aortic Valve Replacement) trial patients had cognitive assessments of attention, processing speed, executive function, and verbal and visual memory. Z-scores were based on normative means and SDs, combined into a primary composite z-score. Brain magnetic resonance images were obtained pre-TAVR on 3-T scanners with a T2 fluid-attenuated inversion recovery (FLAIR) sequence. Scores ≤-1.5 SD below the normative mean (7th percentile) were considered impairment. Paired t tests compared within-subject scores, and chi-square goodness-of-fit compared the percentage of subjects below -1.5 SD. Correlation and regression analyses assessed the relationship between neurocognitive z-scores and T2 lesion volume. RESULTS: Among 234 patients tested, the mean composite z-score was -0.65 SD below the normative mean. Domain scores ranged from -0.15 SD for attention to -1.32 SD for executive function. On the basis of the ≥1.5 SD normative reference, there were significantly greater percentages of impaired scores in the composite z-score (13.2%; p = 0.019), executive function (41.9%; p < 0.001), verbal memory (p < 0.001), and visual memory (p < 0.001). The regression model between FLAIR lesion volume and baseline cognition showed statistically significant negative correlations. CONCLUSIONS: There was a significant proportion of aortic stenosis patients with impaired cognition before TAVR, with a relationship between baseline cognitive function and lesion burden likely attributable to longstanding cerebrovascular disease. These findings underscore the importance of pre-interventional testing and magnetic resonance imaging in any research investigating post-surgical cognitive outcomes in patients with cardiovascular disease.

Distinct Contributions of Dorsal and Ventral Streams to Imitation of Tool-Use and Communicative Gestures.

Imitation of tool-use gestures (transitive; e.g., hammering) and communicative emblems (intransitive; e.g., waving goodbye) is frequently impaired after left-hemispheric lesions. We aimed 1) to identify lesions related to deficient transitive or intransitive gestures, 2) to delineate regions associated with distinct error types (e.g., hand configuration, kinematics), and 3) to compare imitation to previous data on pantomimed and actual tool use. Of note, 156 patients (64.3 ± 14.6 years; 56 female) with first-ever left-hemispheric ischemic stroke were prospectively examined 4.8 ± 2.0 days after symptom onset. Lesions were delineated on magnetic resonance imaging scans for voxel-based lesion-symptom mapping. First, while inferior-parietal lesions affected both gesture types, specific associations emerged between intransitive gesture deficits and anterior temporal damage and between transitive gesture deficits and premotor and occipito-parietal lesions. Second, impaired hand configurations were related to anterior intraparietal damage, hand/wrist-orientation errors to premotor lesions, and kinematic errors to inferior-parietal/occipito-temporal lesions. Third, premotor lesions impacted more on transitive imitation compared with actual tool use, pantomimed and actual tool use were more susceptible to lesioned insular cortex and subjacent white matter. In summary, transitive and intransitive gestures differentially rely on ventro-dorsal and ventral streams due to higher demands on temporo-spatial processing (transitive) or stronger reliance on semantic information (intransitive), respectively.

A formal analysis of alexia in persistent aura and a comparison to acquired pure alexia.

A patient is reported with reversible pure alexia in the context of migraine with aura. Following previous, anecdotal reports, the present study is the first to formally assess word reading, writing, and other linguistic and visual processing and to compare these to a patient with stroke-related pure alexia. The reading impairment, suggestive of letter-by-letter reading, was observed across 7 days but had remitted at a 3-month follow-up. The deficit also affected recognition of letters, suggesting a functional impairment at the level of letter recognition, not just word reading. It went along with reversible abnormalities in diffusion-weighted and fluid-attenuated inversion recovery imaging in areas known to be involved in word reading.

Frequency and Chunking in Derived Words: A Parametric fMRI Study.

In usage-based linguistic theories, the assumption that high-frequency language strings are mentally represented as unitary chunks has been invoked to account for a wide range of phenomena. However, neurocognitive evidence in support of this assumption is still lacking. In line with Gestalt psychological assumptions, we propose that a language string qualifies as a chunk if the following two conditions are simultaneously satisfied: The perception of the whole string does not involve strong activation of its individual component parts, but the component parts in isolation strongly evoke the whole. Against this background, we explore the relationship between different frequency metrics and the chunk status of derived words (e.g., "government," "worthless") in a masked visual priming experiment with two conditions of interest. One condition investigates "whole-to-part" priming (worthless-WORTH), whereas the other one analyzes "part-to-whole" priming (tear-TEARLESS). Both conditions combine mixed-effects regression analyses of lexical decision RTs with a parametric fMRI design. Relative frequency (the frequency of the whole word relative to that of its onset-embedded part) emerges as the only frequency metric to correlate with chunk status in behavioral terms. The fMRI results show that relative frequency modulates activity in regions that have been related to morphological (de)composition or general task performance difficulty (notably left inferior frontal areas) and in regions associated with competition between whole, undecomposed words (right inferior frontal areas). We conclude that relative frequency affects early stages of processing, thereby supporting the usage-based concept of frequency-induced chunks.