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Background: There has been a debate over how a word’s syntactic class is represented in the mind. One model claims that information is represented solely at the semantic level while another account...

Der vorliegende Beitrag gibt eine Einfuhrung in die Neuropsychologie des menschlichen Gedachtnisses. Die Begriffe Kurzzeit‑, Arbeits-, episodisches Gedachtnis sowie semantisches und prozedurales Gedachtnis werden beschrieben, die anatomischen Korrelate der verschiedenen Gedachtnissysteme werden dargestellt. Zudem wird eine kurze Einfuhrung in die Methodik der neuropsychologischen Gedachtnisforschung gegeben, zusammen mit Hinweisen zur neuropsychologischen Diagnostik und Therapie.

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 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.

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.

During the Corona Virus 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 suffering from long-term neurocognitive symptoms after COVID-19. Methods: Outpatients seeking neurological counseling with neurocognitive symptoms persisting for more than three months after polymerase chain reaction (PCR)-confirmed COVID-19 were included prospectively between June 16, 2020, and January 29, 2021. Patients (n = 31, 54±2.0 years) in the long-term phase after COVID-19 (202±58 days after positive PCR) were assessed with a neuropsychological test battery. Cerebral 18F-FDG PET imaging was performed in 14/31 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 neuropsychological test-battery showed no impairment, but deficits (z-score

Ziel/Aim Given the rapid spread of SARS-CoV-2 and emerging evidence of neurological symptoms particularly in hospitalized COVID-19 patients, we examined the impact of COVID-19 on the CNS in inpatients at the subacute stage by F-18-FDG PET. Methodik/Methods We assessed neurological and neuropsychological symptoms (MoCA) and F-18-FDG PET scans in 15 COVID-19 inpatients (once patients were no longer infectious). All scans were visually read using a 3-step rating scale (normal, mildly and severely abnormal). Principal components analysis (PCA;avoiding the need of a currently unknown reference region) was employed to explore whether a spatial covariance pattern exists in COVID-19 (compared to 45 control patients without somatic CNS disease). Exploratory, we assessed mean normalized F-18-FDG uptake (lean body weight- and plasma glucose-adjusted standardized uptake value, SUV) in 10 % voxels with highest covariance weights (positive and negative). Ergebnisse/Results Visual reads indicated pathological results in 10/15 patients (mainly frontotemporal hypometabolism). We detected a highly significant (p .39] in 10 % voxels with most negative and positive weights, respectively). Schlussfolgerungen/Conclusions Neocortical dysfunction accompanied by cognitive impairment was detected in two-thirds of inpatients with subacute COVID-19. A clear indication of regional hypermetabolism (suggesting inflammation) was not found. Follow-up studies are currently underway.

Cognitive impairment is a frequent complaint in coronavirus disease-19 (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 Montreal Cognitive Assessment (MoCA) and 18F-FDG PET scans in 8 COVID-19 patients at the subacute (as no longer infectious) and chronic stages (approximately six months 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 a significant reduction of initial frontoparietal and, to a lesser extent, temporal glucose hypometabolism that 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 MoCA performance. However, both 18F-FDG PET and cognitive assessment suggest a residual impairment. Conclusions: Although a significant recovery of regional neuronal function and cognition can be clearly stated, residuals are still measurable in some patients six months after the 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 highest medical and socioeconomic relevance.

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.

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.

We report on a pregnant patient who contracted tick-borne encephalitis (TBE) during her second trimester in an endemic region in Southern Germany. The patient presented with typical symptoms including fever and headache, and TBE infection was confirmed by positive blood and cerebrospinal fluid (CSF) testing. During acute infection there was no evidence of pregnancy complications, and the mother recovered well. We performed a clinical follow-up examination of both mother and child eight months after the diagnosis of TBE, which revealed no signs of sequelae. This case study presents rare evidence of TBE infection during pregnancy and may provide guidance for both physicians as well as mothers-to-be dealing with TBE.

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

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.

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. 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. [18F]FDG PET did not significantly predict conversion to AD (p > 0.1). By contrast, models including [11C]PIB PET only (p

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 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.

Zusammenfassung. Welche Relevanz besitzt eine einzelne widersprüchliche empirische Beobachtung für Modelle, deren Vorhersagen ansonsten von Dutzenden, wenn nicht Hunderten von empirischen Beobachtungen bestätigt worden sind? Reicht die Beobachtung eines Patienten aus, um ein kognitives Modell zu falsifizieren, dessen Vorhersagen in einer Studie mit 100 Datensätzen bestätigt wurden? Diese Diskussion wird derzeit mit großer Vehemenz in der kognitiven Neuropsychologie geführt, nachdem prominente Neuropsychologen den Einzelfallansatz neuerdings kritisch beurteilen und stattdessen Fallserien propagieren. Die unterschiedlichen methodischen Ansätze sind verknüpft mit konkurrierenden kognitiven Modellen der Sprachverarbeitung. Der vorliegende Beitrag stellt die Debatte, die für die Zukunft der kognitiven Neuropsychologie von großer Bedeutung ist, mit ihren Protagonisten, Modellen und zentralen empirischen Befunden dar.

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.

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. Keywords: Verbal fluency, Brain lesion, Frontal lobe, Temporal lobe, Double dissociation

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.

Studies on verbal learning in patients with impaired verbal short-term memory (vSTM) have revealed dissociations among types of verbal information. Patients with impaired vSTM are able to learn lists of known words but fail to acquire new word forms. This suggests that vSTM is involved in new word learning. The present study assessed both new word learning and the learning of digit sequences in two patients with impaired vSTM. In two experiments, participants were required to learn people's names, ages and professions, or their four digit 'phone numbers'. The STM patients were impaired on learning unknown family names and phone numbers, but managed to acquire other verbal information. In contrast, a patient with a severe verbal episodic memory impairment was impaired across information types. These results indicate verbal STM involvement in the learning of digit sequences.

The ability to recognize and respond to actions performed by others is fundamental for a wide range of activities involving social interactions. However, despite an enormous number of functional imaging studies, a precise delineation of the brain regions crucial for distinct aspects of action recognition has remained elusive. Moreover, the degree of overlap between regions involved in active action performance is controversial. To elucidate these issues, 98 acute stroke patients (68 male, age mean ± SD, 65 ± 13 years) were examined in the acute period after stroke (mean ± SD 4.4 ± 2 days after symptom onset). First, action recognition was assessed with a newly designed test which required patients to distinguish between correctly and incorrectly performed tool-associated actions depicted in short videos. Errors categories comprised conceptual (e.g., spreading jam on toast with a paint brush), and spatio-temporal errors (orientation of the tool, hand configuration, and movement kinematics). Second, actual use of tools was probed using an established test which, in analogy to the error categories for action recognition, included separate measures for the ability to match tools and recipients (e.g., hammer – nail; conceptual score), and for the quality of the executed action (e.g., hammering; spatio-temporal score). Lesions were delineated on diffusion-weighted scans for voxel-based lesion-symptom mapping. Impaired recognition of conceptual errors was associated mainly with lesions to the anterior middle temporal gyrus as well as to the caudal middle frontal gyrus. Conversely, the detection of spatio-temporal errors depended on the posterior superior temporal gyrus and sulcus, inferior parietal lobule (IPL) and ventral premotor cortex (vPMC). Analyses for distinct spatio-temporal error subcategories revealed that superior temporal lesions specifically affected the recognition of kinematic and tool orientation errors, while inferior parietal and premotor damage selectively impaired the discrimination of hand configurations. Lastly, compared to the recognition of conceptual and spatio-temporal errors, both active tool-recipient matching and action execution, respectively, were more dependent on the IPL and vPMC; conversely, action recognition deficits were more strongly associated with occipito-temporal and superior temporal lesions. The results demonstrate that action recognition is enabled by a network of dissociable regions that are specialized for the processing of distinct action features. While the decoding of conceptual action aspects relies mainly on anterior temporal regions, IPL and vPMC mediate the recognition of hand configurations, and the posterior superior temporal lobe is crucial for the processing of movement kinematics and tool orientation. Our findings show that, with the exception of the hand configuration, action recognition does not rely on the fronto-parietal regions that subserve the performance of actual tool use.

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.

The authors sought to determine baseline neurocognition before transcatheter aortic valve replacement (TAVR) and its correlations with pre-TAVR brain imaging.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.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.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.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.

Apraxia is a cognitive disorder of skilled movements that characteristically affects the ability to imitate meaningless gestures, or to pantomime the use of tools. Despite substantial research, the neural underpinnings of imitation and pantomime have remained debated. An influential model states that higher motor functions are supported by different processing streams. A dorso-dorsal stream may mediate movements based on physical object properties, like reaching or grasping, whereas skilled tool use or pantomime rely on action representations stored within a ventro-dorsal stream. However, given variable results of past studies, the role of the two streams for imitation of meaningless gestures has remained uncertain, and the importance of the ventro-dorsal stream for pantomime of tool use has been questioned. To clarify the involvement of ventral and dorsal streams in imitation and pantomime, we performed voxel-based lesion-symptom mapping in a sample of 96 consecutive left-hemisphere stroke patients (mean age ± SD, 63.4 ± 14.8 years, 56 male). Patients were examined in the acute phase after ischaemic stroke (after a mean of 5.3, maximum 10 days) to avoid interference of brain reorganization with a reliable lesion-symptom mapping as best as possible. Patients were asked to imitate 20 meaningless hand and finger postures, and to pantomime the use of 14 common tools depicted as line drawings. Following the distinction between movement engrams and action semantics, pantomime errors were characterized as either movement or content errors, respectively. Whereas movement errors referred to incorrect spatio-temporal features of overall recognizable movements, content errors reflected an inability to associate tools with their prototypical actions. Both imitation and pantomime deficits were associated with lesions within the lateral occipitotemporal cortex, posterior inferior parietal lobule, posterior intraparietal sulcus and superior parietal lobule. However, the areas specifically related to the dorso-dorsal stream, i.e. posterior intraparietal sulcus and superior parietal lobule, were more strongly associated with imitation. Conversely, in contrast to imitation, pantomime deficits were associated with ventro-dorsal regions such as the supramarginal gyrus, as well as brain structures counted to the ventral stream, such as the extreme capsule. Ventral stream involvement was especially clear for content errors which were related to anterior temporal damage. However, movement errors were not consistently associated with a specific lesion location. In summary, our results indicate that imitation mainly relies on the dorso-dorsal stream for visuo-motor conversion and on-line movement control. Conversely, pantomime additionally requires ventro-dorsal and ventral streams for access to stored action engrams and retrieval of tool-action relationships.

Background: The syndrome of conduction aphasia is an umbrella term to label clinically heterogeneous language disorders that all include a deficit of repetition due to impaired immediate memory or, in some patients, impaired speech production. The present article reviews the currently available literature on conduction aphasia. It covers aspects of the history of conduction aphasia as a fascicular disconnection syndrome and the objections to this view and discusses the proposed subtypes of this syndrome and the underlying cortical and white matter lesions.Aims: The primary objectives of this article are to critically review the influence of historical concepts on recent approaches to optimise existing theoretical synergies. In addition, the article seeks to advance our understanding of the first steps of verbal auditory processing in individuals with normal and impaired language skills.Main Contribution: We present first indications for an involvement of the left hemisphere in both short- and long-term in...

BACKGROUND Posterior cortical atrophy (PCA) is a rare neurodegenerative syndrome with visuospatial deficits. PET studies have identified hypometabolism of the occipital cortex in PCA. There is, however, a huge overlap in clinical presentation and involvement of the occipital cortex between PCA, dementia with Lewy bodies (DLB), and Alzheimer's disease (AD). Syndrome-specific patterns of metabolism have not yet been demonstrated that allow for a reliable differentiation with [F-18]-FDG-PET. METHODS A total of 33 dementia patients (PCA n = 6, DLB n = 12, AD n = 15) who underwent [F-18]-FDG-PET imaging and a neuropsychological examination were retrospectively analyzed. Group comparisons of regional cerebral glucose metabolism were calculated with statistical parametric mapping. Extracted clusters were used to evaluate discrimination accuracy by logistic regression. RESULTS PCA patients showed a syndrome-specific area of hypometabolism in the right lateral temporooccipital cortex. DLB patients showed specific hypometabolism predominantly in the left occipital cortex. Logistic regression based on these two regions correctly separated patients with a sensitivity/specificity of 83/93% for PCA, 75/86% for DLB and 67/78% for AD. Overall accuracy was 73%. CONCLUSION [F-18]-FDG-PET could reveal syndrome-specific patterns of glucose metabolism in PCA and DLB. Accurate group discrimination in the differential diagnosis of dementia with visuospatial impairment is feasible.

Pure alexia is a severe impairment of word reading in which individuals process letters serially with a pronounced length effect. Yet, there is considerable variation in the performance of alexic readers with generally very slow, but also occasionally fast responses, an observation addressed rarely in previous reports. It has been suggested that "fast" responses in pure alexia reflect residual parallel letter processing or that they may even be subserved by an independent reading system. Four experiments assessed fast and slow reading in a participant (DN) with pure alexia. Two behavioral experiments investigated frequency, neighborhood, and length effects in forced fast reading. Two further experiments measured eye movements when DN was forced to read quickly, or could respond faster because words were easier to process. Taken together, there was little support for the proposal that "qualitatively different" mechanisms or reading strategies underlie both types of responses in DN. Instead, fast responses are argued to be generated by the same serial-reading strategy.

We describe the case of a dysgraphic aphasic individual-S.G.W.-who, in writing to dictation, produced high rates of formally related errors consisting of both lexical substitutions and what we call morphological-compound errors involving legal or illegal combinations of morphemes. These errors were produced in the context of a minimal number of semantic errors. We could exclude problems with phonological discrimination and phonological short-term memory. We also excluded rapid decay of lexical information and/or weak activation of word forms and letter representations since S.G.W.'s spelling showed no effect of delay and no consistent length effects, but, instead, paradoxical complexity effects with segmental, lexical, and morphological errors that were more complex than the target. The case of S.G.W. strongly resembles that of another dysgraphic individual reported in the literature-D.W.-suggesting that this pattern of errors can be replicated across patients. In particular, both patients show unusual errors resulting in the production of neologistic compounds (e.g., "bed button" in response to "bed"). These patterns can be explained if we accept two claims: (a) Brain damage can produce both a reduction and an increase in lexical activation; and (b) there are direct connections between phonological and orthographic lexical representations (a third spelling route). We suggest that both patients are suffering from a difficulty of lexical selection resulting from excessive activation of formally related lexical representations. This hypothesis is strongly supported by S.G.W.'s worse performance in spelling to dictation than in written naming, which shows that a phonological input, activating a cohort of formally related lexical representations, increases selection difficulties. © 2014 Taylor & Francis.

We investigated disease-specific cognitive profiles and their neural correlates in Lewy-body diseases (LBD) and tauopathies by CERAD assessment and FDG-PET. Analyses revealed a significant interaction between reduced semantic fluency in tauopathies and impaired verbal learning in LBD. Semantic fluency discriminated between groups with high accuracy (83%). Compared to LBD, tauopathy patients showed bilateral hypometabolism of midbrain, thalamus, middle cingulate gyrus and supplementary motor/premotor cortex. In the reverse contrast, LBD patients exhibited bilateral hypometabolism in posterior parietal cortex, precuneus and inferior temporal gyrus extending into occipital and frontal cortices. In diagnosis-independent voxel-based analyses, verbal learning/memory correlated with left temporal and right parietal metabolism, while fluency was coupled to bilateral striatal and frontal metabolism. Naming correlated with left frontal metabolism and drawing with metabolism in bilateral temporal and left frontal regions. In line with disease-specific patterns of regional glucose metabolism, tauopathies and LBD show distinct cognitive profiles, which may assist clinical differentiation.

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.

The study aimed to elucidate areas involved in recognizing tool-associated actions, and to characterize the relationship between recognition and active performance of tool use.We performed voxel-based lesion-symptom mapping in a prospective cohort of 98 acute left-hemisphere ischemic stroke patients (68 male, age mean ± standard deviation, 65 ± 13 years; examination 4.4 ± 2 days post-stroke). In a video-based test, patients distinguished correct tool-related actions from actions with spatio-temporal (incorrect grip, kinematics, or tool orientation) or conceptual errors (incorrect tool-recipient matching, e.g., spreading jam on toast with a paintbrush). Moreover, spatio-temporal and conceptual errors were determined during actual tool use.Deficient spatio-temporal error discrimination followed lesions within a dorsal network in which the inferior parietal lobule (IPL) and the lateral temporal cortex (sLTC) were specifically relevant for assessing functional hand postures and kinematics, respectively. Conversely, impaired recognition of conceptual errors resulted from damage to ventral stream regions including anterior temporal lobe. Furthermore, LTC and IPL lesions impacted differently on action recognition and active tool use, respectively.In summary, recognition of tool-associated actions relies on a componential network. Our study particularly highlights the dissociable roles of LTC and IPL for the recognition of action kinematics and functional hand postures, respectively.

The exploration and retrieval of words during category fluency involves different strategies to improve or maintain performance. Deficits in that task, which are common in patients with amnestic mild cognitive impairment (aMCI), mirror either impaired semantic memory or dysfunctional executive control mechanisms. Relating category fluency to tasks that place greater demands on either semantic knowledge or executive functions might help to determine the underlying cognitive process. The aims of this study were to compare performance and strategy use of 20 patients with aMCI to 30 healthy elderly controls (HC) and to identify the dominant component (either executive or semantic) for better task performance in category fluency. Thus, the relationship between category fluency, design fluency and naming was examined. As fluency tasks have been associated with the superior frontal gyrus (SFG), the inferior frontal gyrus (IFG), and the temporal pole, we further explored the relationship between gray matter volume in these areas and both performance and strategy use. Patients with aMCI showed significantly lower performance and significantly less strategy use during fluency tasks compared to HC. However, both groups equally improved their performance when repeatedly confronted with the same task. In aMCI, performance during category fluency was significantly predicted by design fluency performance, while in HC, it was significantly predicted by naming performance. In HC, volume of the SFG significantly predicted both category and design fluency performance, and strategy use during design fluency. In aMCI, the SFG and the IFG predicted performance during both category and design fluency. The IFG significantly predicted strategy use during category fluency in both groups. The reduced category fluency performance in aMCI seems to be primarily due to dysfunctional executive control mechanisms rather than impaired semantic knowledge. This finding is directly relevant to patients in the different stages of Alzheimer's disease as it links the known semantic fluency deficit in this population to executive functions. Although patients with aMCI are impaired in both performance and strategy use compared to HC, they are able to increase performance over time. However, only HC were able to significantly improve the utilization of fluency strategies in both category and design fluency over time. HC seem to rely more heavily on the SFG during fluency tasks, while in patients with aMCI additional frontal brain areas are involved, possibly reflecting compensational processes.

3 prominent psycholinguistic models of oral language production are introduced by discussing their respective core assumptions (the models of Morton, Levelt and Dell), all of which have had a strong impact on research and diagnostics in aphasiology. As a multi-modal model of language processing, only the logogen model of Morton includes explicit assumptions about written language production and its relationship to oral language planning. Part of its architecture is an orthographic output lexicon that can be accessed independently of output phonology, an assumption strongly evidenced by dissociations found in patient studies. However, attempts to extend the autonomous basis of writing to the syntactic level are not supported by neuropsychological evidence. This leads to the question of how syntactic information that is modelled via the so-called lemma level in the theories of Levelt and Dell comes into play in more complex writing tasks (e. g., writing phrases or sentences). We suggest that capacities of oral language planning (and associated working memory) might form the prerequisites of complex writing tasks.

Patients with surface dysgraphia are assumed to have an impairment of a lexical–semantic writing routine. In line with the suggested functional deficit, words with irregular orthography, particularly such of low frequency, are affected. Typically, errors are phonologically plausible (e.g., laugh→laf) suggesting the use of a sublexical phonological writing route. In the present brief report, a patient (MO) with surface dysgraphia was required to write phrases to dictation. Frequently, he reproduced short phrases (“lass das”, ‘leave it’) as one word ( ) and tended to delete such segments that are deleted during syllabification in spoken production. For example, MO wrote “kannst du?” (‘can you?’), formally spoken as /kanst du:/ but usually spoken as /kanstu:/, as . It is suggested that the patient uses ‘phonological words’ (syllabified phonological representations; cf. Levelt, W. J. M., Roelofs, A., & Meyer, A. S. (1999). A theory of lexical access in speech production. Behavioral and Brain Sciences, 22, 1–75.) as input to his phoneme–grapheme conversion mechanism.

Background: Semantic word substitutions are frequent errors of aphasic speakers when naming a picture. The role of word frequency in the generation of these semantic errors provides an important testing ground for models of lexical access. The discrete two‐stage model of Levelt, Roelofs, and Meyer (1999) predicts that frequency should not play a role in semantic errors. In contrast, cascading and interactive models of lexical access allow for an influence of frequency on lexical selection. Aims: To assess the role of word frequency in the generation of semantic substitutions. Methods & Procedures: We re‐analysed a large corpus of aphasic semantic word substitutions in response to target words from carefully controlled semantic categories. Frequency of these errors was compared to randomly selected pseudo‐errors from the same semantic category. Outcomes & Results: Errors were more frequent than randomly selected competitors from the same semantic category. Conclusions: The results support interactive or ca...

Impaired tool use despite preserved basic motor functions occurs after stroke in the context of apraxia, a cognitive motor disorder. To elucidate the neuroanatomical underpinnings of different tool use deficits, prospective behavioral assessments of 136 acute left-hemisphere stroke patients were combined with lesion delineation on magnetic resonance imaging (MRI) images for voxel-based lesion-symptom mapping. Deficits affecting both the selection of the appropriate recipient for a given tool (ToolSelect, e.g., choosing the nail for the hammer), and the performance of the typical tool-associated action (ToolUse, e.g., hammering in the nail) were associated with ventro-dorsal stream lesions, particularly within inferior parietal lobule. However, ToolSelect compared with ToolUse deficits were specifically related to damage within ventral stream regions including anterior temporal lobe. Additional retrospective error dichotomization based on the videotaped performances of ToolUse revealed that spatio-temporal errors (movement errors) were mainly caused by inferior parietal damage adjacent to the intraparietal sulcus while content errors, that is, perplexity, unrecognizable, or semantically incorrect movements, resulted from lesions within supramarginal gyrus and superior temporal lobe. In summary, our results suggest that in the use of tools, conceptual and production-related aspects can be differentiated and are implemented in anatomically distinct streams.

Clinical Alzheimer's disease affects both cerebral hemispheres to a similar degree in clinically typical cases. However, in atypical variants like logopenic progressive aphasia, neurodegeneration often presents asymmetrically. Yet, no in vivo imaging study has investigated whether lateralized neurodegeneration corresponds to lateralized amyloid-β burden. Therefore, using combined (11)C-Pittsburgh compound B and (18)F-fluorodeoxyglucose positron emission tomography, we explored whether asymmetric amyloid-β deposition in Alzheimer's disease is associated with asymmetric hypometabolism and clinical symptoms. From our database of patients who underwent positron emission tomography with both (11)C-Pittsburgh compound B and (18)F-fluorodeoxyglucose (n = 132), we included all amyloid-positive patients with prodromal or mild-to-moderate Alzheimer's disease (n = 69). The relationship between (11)C-Pittsburgh compound B binding potential and (18)F-fluorodeoxyglucose uptake was assessed in atlas-based regions of interest covering the entire cerebral cortex. Lateralizations of amyloid-β and hypometabolism were tested for associations with each other and with type and severity of cognitive symptoms. Positive correlations between asymmetries of Pittsburgh compound B binding potential and hypometabolism were detected in 6 of 25 regions (angular gyrus, middle frontal gyrus, middle occipital gyrus, superior parietal gyrus, inferior and middle temporal gyrus), i.e. hypometabolism was more pronounced on the side of greater amyloid-β deposition (range: r = 0.41 to 0.53, all P < 0.001). Stronger leftward asymmetry of amyloid-β deposition was associated with more severe language impairment (P < 0.05), and stronger rightward asymmetry with more severe visuospatial impairment (at trend level, P = 0.073). Similarly, patients with predominance of language deficits showed more left-lateralized amyloid-β burden and hypometabolism than patients with predominant visuospatial impairment and vice versa in several cortical regions. Associations between amyloid-β deposition and hypometabolism or cognitive impairment were predominantly observed in brain regions with high amyloid-β load. The relationship between asymmetries of amyloid-β deposition and hypometabolism in cortical regions with high amyloid-β load is in line with the detrimental effect of amyloid-β burden on neuronal function. Asymmetries were also concordant with lateralized cognitive symptoms, indicating their clinical relevance.

Background/Aims: Inflammation is a major and critical component of the lung pathology in the hereditary disease cystic fibrosis. The molecular mechanisms of chronic inflammation in cystic fibrosis require definition. Methods: We used several genetic mouse models to test a role of iNKT cells and ceramide in pulmonary inflammation of cystic fibrosis mice. Inflammation was determined by the pulmonary cytokine profil and the abundance of inflammatory cells in the lung. Results: Here we provide a new concept how inflammation in the lung of individuals with cystic fibrosis is initiated. We show that in cystic fibrosis mice the mutation in the Cftr gene provokes a significant up-regulation of iNKT cells in the lung. Accumulation of iNKT cells serves to control autoimmune disease, which is triggered by a ceramide-mediated induction of cell death in CF organs. Autoimmunity becomes in particular overt in cystic fibrosis mice lacking iNKT cells and although suppression of the autoimmune response by iNKT cells is beneficial, IL-17+ iNKT cells attract macrophages and neutrophils to CF lungs resulting in chronic inflammation. Genetic deletion of iNKT cells in cystic fibrosis mice prevents inflammation in CF lungs. Conclusion: Our data demonstrate an important function of iNKT cells in the chronic inflammation affecting cystic fibrosis lungs. iNKT cells suppress the auto-immune response induced by ceramide-mediated death of epithelial cells in CF lungs, but also induce a chronic pulmonary inflammation.

Early diagnosis of different modalities in neglect after right hemisphere ischemic lesion and subsequent adequate therapy is crucial in regard to the clinical outcome (e.g. Buxbaum et al., 2004). Bed-side tests in the acute phase after stroke usually include only clinical examination and paper based cancellation tests (e.g. Ota search task, Bell‘s Cancellation). Additional testing such as recording of deficit in visual exploration by tracking of eye movements and standardized test for diagnosis of representational neglect have so far been only conducted in as non-bed-side tests in sub-acute or chronic stages (Isihai et al., 1989). The present study thus investigates the visual exploration during two different tasks in the acute phase of neglect, using a mobile eye-tracking device. Altogether, 31 acute stroke patients with right hemisphere lesion were included. Out of these, 28 could tolerate the eye-tracking device. The first task was a modified baking tray task in which the patients had to collect (first trial) and redistribute (second trial) 16 "cookies" equally on a tray (modified baking tray Task, Fig. 1a and b; Tham, 1996). For diagnosis of representational deficits a second task consisted of enlisting objects presented on a picture board (third trial, Fig. 2a) and to reproduce the named objects while focussing the white back of the board (fourth trial). The eye movements were tracked during all trials (Fig. 2b and c). Additionally, well-established clinical and paper-based evaluation was carried out. Behavioural results of the modified baking tray task confirm a neglect to the left during collection and redistribution of the cookies ( F =14.710, p F =10.458; p =.004). Enlisting of the objects on the picture board also confirmed a neglect to the left ( F =24.238; p F =48.438; p F =30.221; p Both bedside tests for diagnosis of neglect were proved to be applicable in the very acute phase after ischemic stroke: during collection of the cookies as well as naming and recalling of objects on the picture board, the left space was disregarded. We further demonstrate additional representational deficits in these patients that exceed the deficits in visual neglect. For redistribution of the cookies as well as naming the objects from memory – even though all cookies had been collected before and all objects named before - a stronger deficit to the left was found. Representation of the spatial setup thus seems to be even more biased during intrinsically motivated tasks. Tracking of the visual exploration additionally helped to objectify these results and showed to be, at least partly, applicably in acute bed-side tests. Since the diagnosis of the modality of representational deficits has so far not been investigated in the very acute stage of stroke, only little is known about its development and impact on rehabilitation. Further studies will be necessary on this topic.

Background Meaningful gestures are one of the key features of social interaction and comprise both object-associated transitive movements (e.g. hammering) as well as intransitive movements referring to a communicative content (e.g. waving goodbye). The ability to imitate meaningful gestures is frequently impaired in apraxia due to left-hemispheric stroke. However, the pathophysiology behind these deficits so far remained unresolved. A dual stream-model for a dichotomized organisation of higher cognitive functions such as language or praxis has been proposed, with a dorsal stream involved in sensorimotor processing and a ventral stream for content and imagery. Aim of the study was to elucidate the role of the dual stream-model in imitation of meaningful movements using voxel-based lesion-symptom mapping (VLSM). Methods We performed VLSM in a sample of 136 left-hemispheric stroke patients (mean age ± SD 65 years ± 15, 83 male). Neuropsychological testing and MR-imaging were carried out in the acute phase after ischemic stroke (5.1 ± 1.9 days after symptom onset) to avoid interference with brain reorganization. Imitation deficits were assessed with a block of ten object-related movements and a block of ten communicative gestures presented by the examiner, patients were instructed to imitate the movement. Lesions were mapped on the diffusion-weighted image (if not available on Flair- image), statistical analysis with Brunner–Munzel Test was performed using non-parametric statistics implemented in MRIcron. Results Deficits in both, imitation of transitive and intransitive movements were associated with lesions in areas of the dorsal stream involved in motor control and action representations, such as the inferior parietal lobule, and the supramarginal gyrus. In addition to these common areas, deficits in imitation of intransitive movements showed a specific association with the superior and middle temporal lobe, whereas deficient transitive movements were also related to lesions within the ventral premotor cortex without involvement of temporal structures. Conclusion Deficits affecting imitation of transitive and intransitive gestures result from different and characteristic neuroanatomical lesion patterns. Our data suggest that imitation of transitive gestures depicting common tool-associated actions mainly involves stored motor programs and, thus, is mainly based on the dorsal stream. Conversely, imitation of intransitive communicative gestures additionally relies on the ventral stream, probably due to the higher semantic content, given the often symbolic character of intransitive gestures.