Success rates of intensive aphasia therapy: real-world data from 448 patients between 2003 and 2020.

BACKGROUND: Aphasia is a devastating consequence after stroke, affecting millions of patients each year. Studies have shown that intensive speech and language therapy (SLT) is effective in the chronic phase of aphasia. Leveraging a large single-center cohort of persons with aphasia (PWA) including patients also in the subacute phase, we assessed treatment effects of intensive aphasia therapy in a real-world setting. METHODS: Data were collected at the Aachen aphasia ward in Germany between 2003 and 2020. Immediate treatment responses across different language domains were assessed with the Aachen Aphasia Test (AAT) using single-case psychometrics, conducted before and after 6-7 weeks of intensive SLT (10 h per week, median (IQR) dosage = 68 (61-76)). We adjusted for spontaneous recovery in subacute patients. Differential treatment effects between subgroups of chronicity and predictors of therapy response were investigated. RESULTS: A total of 448 PWA were included (29% female, median (IQR) age = 54 (46-62) years, median (IQR) time post-onset = 11 (6-20) months) with 12% in the early subacute, 15% in the late subacute and 74% in the chronic phase of aphasia. The immediate responder rate was 59%. Significant improvements in all AAT subtests und subscales were observed hinting at broad effectiveness across language domains. The degree of therapy-induced improvement did not differ between the chronicity groups. Time post-onset, dosage of therapy and aphasia severity at the beginning of treatment were predictors of immediate treatment response. DISCUSSION: Intensive therapy protocols for aphasia after stroke are yielding substantial responder rates in a routine clinical setting including a wide range of patients.

Trainability of affordance judgments in right and left hemisphere stroke patients.

Whenever we are confronted with action opportunities in everyday life, e.g., when passing an opening, we rely on our ability to precisely estimate our own bodily capabilities in relation to the environmental conditions. So-called affordance judgments can be affected after brain damage. Previous studies with healthy adults showed that such judgments appeared to be trainable within one session. In the current study, we examined whether stroke patients with either right brain damage (n = 30) or left brain damage (n = 30) may similarly profit from training in an aperture task. Further, the role of neuropsychological deficits in trainability was investigated. In the administered task, stroke patients decided whether their hand would fit into a presented opening with varying horizontal width (Aperture Task). During one training session, patients were asked to try to fit their hand into the opening and received feedback on their decisions. We analyzed accuracy and the detection theory parameters perceptual sensitivity and judgment tendency. Both patients with right brain damage and patients with left brain damage showed improved performance during training as well as post training. High variability with differential profiles of trainability was revealed in these patients. Patients with impaired performance in a visuo-spatial or motor-cognitive task appeared to profit considerably from the target-driven action phase with feedback, but the performance increase in judgments did not last when the action was withdrawn. Future studies applying lesion analysis with a larger sample may shed further light on the dissociation in the trainability of affordance judgments observed in patients with versus without visuo-spatial or motor-cognitive deficits.

Don't SNARC me now! Intraindividual variability of cognitive phenomena - Insights from the Ironman paradigm.

Two implicit generalizations are often made from group-level studies in cognitive experimental psychology and their common statistical analysis in the general linear model: (1) Group-level phenomena are assumed to be present in every participant with variations between participants being often treated as random error in data analyses; (2) phenomena are assumed to be stable over time. In this preregistered study, we investigated the validity of these generalizations in the commonly used parity judgment task. In the proposed Ironman paradigm, the intraindividual presence and stability of three popular numerical cognition effects were tested in 10 participants on 30 days: the SNARC (Spatial-Numerical Association of Response Codes, i.e., faster left-/right-sided responses to small/large magnitude numbers, respectively; Dehaene, Bossini, & Giraux, 1993), MARC (Linguistic Markedness of Response Codes; i.e., faster left-/right-sided responses to odd/even numbers, respectively; Nuerk, Iversen, & Willmes, 2004), and Odd (i.e., faster responses to even numbers; Hines, 1990) effects. We replicated the group-level effects; however, they were reliably present in only four to five (SNARC), six (MARC) or five (Odd) of 10 participants. Fluctuations seemed unsystematic, although the SNARC effect decreased over time along with reaction times. No correlation between the SNARC and MARC effects and sleep duration, tiredness, daytime, and consumption of stimulants were detected in most participants. These results challenge the frequent generalizations from group-level phenomena to individual participants and from single sessions to typical behavior. The innovative Ironman paradigm combined with bootstrap analyses permits unique insights into the intraindividual presence and stability of cognitive phenomena.

Fat tails and the need to disclose distribution parameters of qEEG databases.

Neurometry (a.k.a. quantitative EEG or qEEG) is a popular method to assess clinically relevant abnormalities in the electroencephalogram. Neurometry is based on norm values for the distribution of specific EEG parameters and believed to show good psychometric properties such as test-retest reliability. Many psychometric properties only hold under the Gaussian distribution and become problematic when distributions are fat-tailed. EEG signals are typically fat-tailed and do not show fast convergence to a Gaussian distribution. To circumvent this property of EEG, log-transformations have frequently, but not always been employed. In Monte Carlo simulations, we investigated the impact of fat-tails (i.e. deviations from Gaussian) on the cut-off criteria and changeability of what in neurometry is termed "abnormal EEG". Even slight deviations from the Gaussian distribution as measured by skewness and kurtosis lead to large inflation in the number of false positive qEEG findings. The more stringent the cutoff value adopted, the larger the inflation. Moreover, "abnormal EEG" seems to recover spontaneously at rates not compatible with the alleged test-retest reliability of qEEG. Alternative methods should be employed to determine cut-off values for diagnostics purposes, since a large number of false positive results emerge even when slight deviations from the Gaussian distribution are present. We argue that distribution properties of qEEG databases should be disclosed in much more detail by commercial providers to avoid questionable research practices and promote diagnostic transparency. We provide recommendations for the improvement of psychometric properties of existing qEEG databases.

Occupational exposure to polychlorinated biphenyls: Development of neuropsychological functions over time.

Occupational exposure to polychlorinated biphenyls (PCBs) continues to affect the health of exposed individuals until today. This study aims to expand previous findings by examining the development of neuropsychological functions of occupationally exposed participants over time. Especially verbal fluency and sensorimotor processing, found to be impaired in a previous study, were thus of particular interest. A total of 116 participants, who were part of the HELPcB cohort, underwent a neuropsychological test battery covering a multitude of cognitive functions. Plasma PCB levels were determined for each participant and classified as elevated or normal based on comparative values drawn from the German general population. Two structural equation models were then used to examine the effects of elevated PCB levels on neuropsychological functions. Results suggest that participants who displayed increased PCB plasma levels continued to show impairments in verbal fluency but not in sensorimotor processing after a second examination one year after the first measurement. Specifically, low chlorinated PCBs are associated with impaired verbal fluency, as compared to high-chlorinated and dioxin-like congeners. Alteration of dopamine concentration in response to PCB exposure might be a potential explanation of this result.

Influences of cognitive control on number processing: New evidence from switching between two numerical tasks.

A growing body of research suggests that basic numerical abilities such as number magnitude and number parity processing are influenced by cognitive control. So far, however, evidence for number processing being influenced by cognitive control came primarily from observed adaptations to stimulus set characteristics (e.g., ratio or order of specific stimulus types) and switches between a numerical and non-numerical task. Complementing this previous research, the present study employed a task switching paradigm exclusively involving numerical tasks (i.e., magnitude comparisons and parity judgements) to examine how cognitive control processes influence number processing. Participants were presented with a single-digit number and had to either judge its parity or compare its magnitude with a standard of 5, depending on a preceding cue. Based on previous results, we expected the numerical distance effect and the spatial-numerical association of response codes (SNARC) effect to be modulated in switch trials requiring the exertion of cognitive control. Partly in line with our expectations, the numerical distance effect was reduced in switch trials. However, no modulation of the SNARC effect was observed. The results pattern suggests that number processing is influenced by cognitive control, depending on task requirements and the type of numerical information (i.e., numerical magnitude vs spatial association of numbers) that is processed. To reconcile the present and previous results, we propose an information prioritisation account, suggesting that cognitive control primarily influences the processing of the information type that requires the most explicit processing.

The prevalence of apraxia of speech in chronic aphasia after stroke: A bayesian hierarchical analysis.

Apraxia of speech is a motor speech disorder that occurs after lesions to the left cerebral hemisphere, most often concomitant with aphasia. It requires specific approaches in the study of its physiological and neuroanatomical basis and special expertise in clinical care. Knowing its prevalence in patients with aphasia after stroke is therefore relevant for planning specific resources in clinical research and in health care provision. Systematic studies of the frequency of this condition are lacking. We examined the frequency of apraxia of speech in a representative sample of 156 patients with chronic post-stroke aphasia. Three experts classified the patients' speech by best-practice auditory-perceptual methods. Bayesian hierarchical models were fitted to obtain probability distributions for prevalence estimates. A prior distribution was calculated in two steps, including Bayesian models for published frequency data (step 1) and prevalence estimates from experienced clinicians (step 2). Separate models were fitted for different severity ranges. Overall, a prevalence rate of .44 [.30, .58] was obtained. When only moderate and severe cases were taken into account, the rate was .35 [.23, .49]. After a further restriction to only severe impairment, prevalence dropped to .22 [.12, .34]. Patients identified with apraxia of speech had suffered more severe strokes according to clinical criteria and had more severe aphasias. The presence of apraxia of speech was predicted by the articulation/prosody and syntax rating scales of the Aachen Aphasia Test. Lower prevalence estimates published earlier are probably biased by low sensitivity of assessment instruments for mild speech impairment.

Deficits in or preservation of basic number processing in Parkinson's disease? A registered report.

Neurodegenerative diseases such as Parkinson's disease (PD) have a huge impact on patients, caregivers, and the health-care system. To date, the diagnosis of mild cognitive impairments in PD has been established based on domain-general functions such as executive functions, attention, or working memory. However, specific numerical deficits observed in clinical practice have not yet been systematically investigated. PD-immanent deterioration of domain-general functions and domain-specific numerical areas suggests the mechanisms of both primary and secondary dyscalculia. The current study will systematically investigate basic number processing performance in PD patients for the first time, targeting domain-specific cognitive representations of numerosity and the influence of domain-general factors. The overall sample consists of patients with a diagnosis of PD, according to consensus guidelines, and healthy controls. PD patients will be stratified into patients with normal cognition or mild cognitive impairment (level I-PD-MCI based on cognitive screening). Basic number processing will be assessed using transcoding, number line estimation, and (non)symbolic number magnitude comparison tasks. Discriminant analysis will be employed to assess whether basic number processing tasks can differentiate between a healthy control group and both PD groups. All participants will be subjected to a comprehensive numerical and a neuropsychological test battery, as well as sociodemographic and clinical measures. Study results will give the first broad insight into the extent of basic numerical deficits in different PD patient groups and will help us to understand the underlying mechanisms of the numerical deficits faced by PD patients in daily life.

Interplay of morphological configuration and language switching in numerical processing and word processing.

The aim of the present study was to examine the interplay of morphological configuration switching and language switching. The morphological configuration is present in word-formation whenever a word contains more than one free morpheme. The morphological configuration is variable both within and between languages for example in two-digit number names (is the decade named first as in twenty-one or the unit named first as in seventeen) and in compound words (is the modifier or the head named first). In the present experiments, participants had to switch between morphological configurations and between languages (German, English, and Spanish). Language-switch cost was measured as the performance difference between language-switch trials and language-repetition trials. In Experiments 1 and 2, participants performed language-comprehension tasks on two-digit numbers and a language-production task on compound words in Experiment 3. All three experiments revealed an under-additive switch cost pattern in which a larger language-switch cost occurred in morphological configuration-repetition trials than in morphological configuration-switch trials. Thus, the present data indicate integration of the morphological configuration and language into one language-related schema-irrespective of the language task (comprehension vs. production) and the type of stimuli (number words vs. compound nouns). (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Prelexical phonetic and early lexical development in German-acquiring infants: canonical babbling and first spoken words.

Prelexical phonetic capacities have widely been described to be a precursor for later speech and language development. However, studies so far varied greatly in the measurements used for the detection of canonical babbling onset or the description of infants' phonetic capacities at one or more set time points. The comparability of results is, therefore, questionable. Thus, the aims of this study were to investigate the associations between (1) different measurements of CBO, (2) different aspects of phonetic capacity at the age of 9 months and (3) age of CBO and phonetic capacities at 9 months. A further aim (4) was to explore whether one of the measures would be suitable to predict the age of word onset (WO) in 20 healthy German-acquiring individuals. The data were derived from monthly recorded spontaneous speech samples between 0 and 18 months. It was found that the different applied prelexical measures equally well serve as valid estimators for the detection of CBO or of infants' phonetic capacities. Further, age of CBO and phonetic capacities at 9 months were significantly associated even though the age of CBO did not reliably predict phonetic capacities. Prelexical measures and WO were not related. Reasons for no indication of a significant association are discussed.

The novel cognitive flexibility in aphasia therapy (CFAT): A combined treatment of aphasia and executive functions to improve communicative success.

PURPOSE: Over and above language deficits, persons with aphasia can present with impairments in executive functions, including deficits in cognitive flexibility. Cognitive flexibility constitutes the ability to update behaviour quickly and flexibly in a changing environment. Its deficits can restrict communicative ability, e. g. the ability to change a topic. To date, these deficits have been neglected in aphasia therapy, even though their consideration regarding language treatment may be beneficial for the persons affected. The present study aimed to evaluate whether aphasia therapy including cognitive flexibility leads to more improvement than conventional aphasia therapy. METHOD: A pilot group study with ten patients was conducted. The patients received both the novel Cognitive Flexibility in Aphasia Therapy (CFAT) and conventional aphasia therapy in a cross-over design. Each therapy method was delivered for 20 sessions within two weeks. An assessment battery was applied five times, including language skills, communicative ability and verbal/nonverbal cognitive flexibility. RESULT: Patients profited from CFAT regarding language skills, communicative ability and verbal cognitive flexibility. Furthermore, compared to conventional therapy, CFAT was more effective for verbal cognitive flexibility. CONCLUSION: This pilot study indicates that CFAT offers a novel opportunity to directly train cognitive flexibility in communicative settings and complements conventional therapy for optimal patient outcome.

Professional mathematicians do not differ from others in the symbolic numerical distance and size effects.

The numerical distance effect (it is easier to compare numbers that are further apart) and size effect (for a constant distance, it is easier to compare smaller numbers) characterize symbolic number processing. However, evidence for a relationship between these two basic phenomena and more complex mathematical skills is mixed. Previously this relationship has only been studied in participants with normal or poor mathematical skills, not in mathematicians. Furthermore, the prevalence of these effects at the individual level is not known. Here we compared professional mathematicians, engineers, social scientists, and a reference group using the symbolic magnitude classification task with single-digit Arabic numbers. The groups did not differ with respect to symbolic numerical distance and size effects in either frequentist or Bayesian analyses. Moreover, we looked at their prevalence at the individual level using the bootstrapping method: while a reliable numerical distance effect was present in almost all participants, the prevalence of a reliable numerical size effect was much lower. Again, prevalence did not differ between groups. In summary, the phenomena were neither more pronounced nor more prevalent in mathematicians, suggesting that extremely high mathematical skills neither rely on nor have special consequences for analogue processing of symbolic numerical magnitudes.

Multilingual two-digit number naming: The influence of composition rules on language switching.

The aim of this study was to examine language switching in a two-digit number naming task. In contrast to single digits, two-digit numbers have a composition rule (i.e., morphological configuration) that may differ between languages. For example, the Arabic number 21 is read with an inverted composition rule in German (unit before decade) and a non-inverted composition rule in English (decade before unit). In the present experiment, one group of German native speakers and one group of Spanish native speakers had to name two-digit numbers in German, English, or Spanish. The results demonstrate a language-switch cost, revealing better performance in language repetition than in language-switch trials. This switch cost was further modulated by repeating or switching the composition rule, since the language repetition benefit (i.e., the switch cost) was reduced in trials with composition-rule switches compared with trials with composition-rule repetitions. This finding indicates that the language in which the number word has to be produced and its composition rule are not switched independently but rather may be integrated into one language schema.

Metaphor processing is supramodal semantic processing: The role of the bilateral lateral temporal regions in multimodal communication.

This paper presents an fMRI study on healthy adult understanding of metaphors in multimodal communication. We investigated metaphors expressed either only in coverbal gestures ("monomodal metaphors") or in speech with accompanying gestures ("multimodal metaphors"). Monomodal metaphoric gestures convey metaphoric information not expressed in the accompanying speech (e.g. saying the non-metaphoric utterance, "She felt bad" while dropping down the hand with palm facing up; here, the gesture alone indicates metaphoricity), whereas coverbal gestures in multimodal metaphors indicate metaphoricity redundant to the speech (e.g. saying the metaphoric utterance, "Her spirits fell" while dropping the hand with palm facing up). In other words, in monomodal metaphors, gestures add information not spoken, whereas the gestures in multimodal metaphors can be redundant to the spoken content. Understanding and integrating the information in each modality, here spoken and visual, is important in multimodal communication, but most prior studies have only considered multimodal metaphors where the gesture is redundant to what is spoken. Our participants watched audiovisual clips of an actor speaking while gesturing. We found that abstract metaphor comprehension recruited the lateral superior/middle temporal cortices, regardless of the modality in which the conceptual metaphor is expressed. These results suggest that abstract metaphors, regardless of modality, involve resources implicated in general semantic processing and are consistent with the role of these areas in supramodal semantic processing as well as the theory of embodied cognition.

Segmental Bioelectrical Impedance Spectroscopy to Monitor Fluid Status in Heart Failure.

Bioelectrical impedance spectroscopy (BIS) measures body composition, including fluid status. Acute decompensated heart failure (ADHF) is associated with fluid overload in different body compartments. This investigation aimed to evaluate the feasibility of measuring and monitoring fluid accumulation in patients with ADHF using BIS. The extracellular impedance as a surrogate marker for fluid accumulation was measured in 67 participants (25 healthy reference volunteers and 42 patients admitted with ADHF) using BIS in the "transthoracic", "foot-to-foot", "whole-body" and "hand-to-hand" segments. At baseline, BIS showed significantly lower extracellular resistance values for the "whole-body" (P < 0.001), "foot-to-foot" (P = 0.03), "hand-to-hand" (P < 0.001) and "transthoracic" (P = 0.014) segments in patients with ADHF than the reference cohort, revealing a specific pattern for peripheral, central and general fluid accumulation. The "foot-to-foot" (AUC = 0.8, P < 0.001) and "hand-to-hand" (AUC = 0.74, P = 0.04) segments indicated compartments of fluid accumulation with good prediction. During cardiac recompensation, BIS values changed significantly and were in line with routine parameters for monitoring ADHF. Mean bodyweight change per day correlated moderately to good with BIS values in the "whole-body" (r = -0.4), "foot-to-foot" (r = -0.8) and "transthoracic" (r = -0.4) segments. Based on our analysis, we conclude that measuring and monitoring fluid accumulation in ADHF using segmental BIS is feasible and correlates with clinical parameters during recompensation.

Hemispheric Dominance for Language and Side Effects in Mapping the Inferior Frontal Junction Area with Transcranial Magnetic Stimulation.

BACKGROUND AND STUDY AIMS: Language mapping by navigated transcranial magnetic stimulation (TMS) is commonly applied over the left language-dominant hemisphere to indicate the language-related cortex. Detailed language mapping of Broca's region including stimulation targets in the immediate vicinity to the premotor cortex may raise concern about confounding unspecific motor effects. We performed interhemispheric comparisons to delineate such possible unspecific effects from true TMS-induced language inhibition. MATERIAL AND METHODS: Fifteen healthy German speakers named object pictures during navigated TMS over a left- and right-hemispheric target array covering the left inferior frontal junction area. Six mapping repetitions were conducted per hemisphere. Order of stimulation side was randomized between participants. Self-rating of discomfort was assessed after each stimulation; language errors and motor side effects were evaluated offline. RESULTS: Naming errors were observed significantly more frequently during left- than right-hemispheric stimulation. The same pattern was found for the most frequent error category of performance errors. Hierarchical cluster analyses of normalized ratings of error severity revealed a clear focus of TMS susceptibility for language inhibition in object naming at the dorsoposterior target sites only in the left hemisphere. We found no statistical difference in discomfort ratings between both hemispheres and also no interhemispheric difference in motor side effects, but we observed significantly stronger muscle contractions of the eyes as compared with the mouth. CONCLUSION: Our results of (1) unspecific pre-/motor effects similarly induced in both hemispheres, and (2) a specific focus of TMS susceptibility in the language-dominant hemisphere render any substantial contribution of nonlanguage-specific effects in TMS language mapping of the inferior frontal junction area highly unlikely.

Sucking patterns are not predictive of further feeding development in healthy preterm infants.

Preterm infants are at risk of experiencing difficulties in their feeding development. For a possible early identification of these, we examined the association between sucking patterns, assisted spoon feeding, and chewing skills in 40 healthy preterm infants, and the role of experience in the acquisition of these skills in a prospective longitudinal study. Sucking patterns were evaluated at 34, 37, and 44 weeks postmenstrual age (PMA), assisted spoon feeding was evaluated at 6, 9, and 12 months PMA, and chewing was evaluated at 9, 12, and 24 months PMA. Sucking patterns were rated using the Neonatal Oral Motor Assessment Scale, assisted spoon feeding was rated using the Observation List Spoon Feeding, and chewing was evaluated using the Mastication Observation and Evaluation Instrument. All infants showed progression in their oral motor skills during the study period, but not all demonstrated a stable progression of skills. Quality of sucking patterns was not associated with skill level achievement of assisted spoon feeding or with chewing. Length of experience in sucking was significantly associated with duration of supplemental tube feeding but not with the quality of the sucking pattern. Length of chewing experience was significantly associated with chewing abilities at 9 and 12 months PMA. No clinical characteristics were sufficiently predictive of oral motor skill development. Results show that sucking patterns are not predictive of subsequent feeding development in healthy preterm infants. The food consistency offered and the length of feeding experience influenced the acquisition and quality of oral motor skills differently.

Cardiac stress after electroconvulsive therapy and spontaneous generalized convulsive seizures: A prospective echocardiographic and blood biomarker study.

AIM: Knowledge about cardiac stress related to seizures in electroconvulsive therapy (ECT) and spontaneously occurring generalized convulsive seizures (GCS) is limited. The aim of the present study was to analyze cardiac function and circulating markers of cardiac stress in the early postictal period after ECT and GCS. METHODS: Patients undergoing ECT in the Department of Psychiatry, Psychotherapy and Psychosomatics and patients undergoing diagnostic video-EEG monitoring (VEM) in the Department of Neurology were prospectively enrolled between November 2017 and November 2018. Cardiac function was examined twice using transthoracic echocardiography within 60 min and >4 h after ECT or GCS. Established blood markers (troponin T high-sensitive, N-terminal pro brain natriuretic peptide) of cardiac stress or injury were collected within 30 min, 4 to 6 h, and 24 h after ECT or GCS. In the ECT group, the troponin T values were also correlated with periprocedural heart rate and blood pressure values. Because of organizational or technical reasons, the measurement was not performed in all patients. RESULTS: Twenty patients undergoing ECT and 6 patients with epilepsy with a GCS during VEM were included. Postictal echocardiography showed no wall motion disorders and no change in left ventricular and right ventricular functions. Four of 17 patients displayed a transient increase in high-sensitive cardiac troponin T 4-6 h after the seizure (3 patients with ECT-induced seizure). None of these 4 patients had signs of an acute cardiac event, and periprocedural blood pressure or heart rate peaks during ECT did not significantly differ in patients with and without troponin T elevation. CONCLUSIONS: Signs of mild cardiac stress can occur in some patients following ECT or GCS without clinical complications, probably related to excessive catecholamine release during the seizure.

Phonological picture-word interference in language mapping with transcranial magnetic stimulation: an objective approach for functional parcellation of Broca's region.

Functional imaging data suggest different regions for semantic, syntactic, and phonological processing in an anterior-to-posterior direction along the inferior frontal gyrus. Language mapping by use of neuro-navigated transcranial magnetic stimulation (TMS) is frequently applied in clinical research to identify language-related cortical regions. Recently, we proposed a high spatial resolution approach for more detailed language mapping of cortical sub-areas such as Broca's region. Here, we employed a phonological picture-word interference paradigm in healthy subjects to reveal functional specialization in Broca's region for phonological processing. The behavioral phonological priming effect is characterized by accelerated naming responses to target pictures accompanied by phonologically related auditory distractor words. We hypothesized that the inhibitory effects of TMS on language processing would reduce phonological priming only at stimulation sites involved in phonological processing. In active as compared to sham TMS, we found reduced phonological facilitation specifically at sites overlapping with the probabilistic cytoarchitectonic area 44. Our findings complemented functional imaging data by revealing structure-function relationship in Broca's region. The introduction of a reaction time based interference paradigm into TMS language mapping increases the objectivity of the method and allows to explore functional specificity with high temporal resolution. Findings may help to interpret results in clinical applications.

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.