Age-related dissociation of N400 effect and lexical priming.

The use of contextual information is an important capability to facilitate language comprehension. This can be shown by studying behavioral and neurophysiological measures of accelerated word recognition when semantically or phonemically related information is provided in advance, resulting in accompanying attenuation of the respective event-related potential, i.e. the N400 effect. Against the background of age-dependent changes in a broad variety of lexical capacities, we aimed to study whether word priming is accomplished differently in elderly compared to young persons. 19 young (29.9 ± 5.6 years) and 15 older (69.0 ± 7.2 years) healthy adults participated in a primed lexical decision task that required the classification of target stimuli (words or pseudo-words) following related or unrelated prime words. We assessed reaction time, task accuracy and N400 responses. Acceleration of word recognition by semantic and phonemic priming was significant in both groups, but resulted in overall larger priming effects in the older participants. Compared with young adults, the older participants were slower and less accurate in responding to unrelated word-pairs. The expected N400 effect was smaller in older than young adults, particularly during phonemic word and pseudo-word priming, with a rather similar N400 amplitude reduction by semantic relatedness. The observed pattern of results is consistent with preserved or even enhanced lexical context sensitivity in older compared to young adults. This, however, appears to involve compensatory cognitive strategies with higher lexical processing costs during phonological processing in particular, suggested by a reduced N400 effect in the elderly.

Increased conceptual switching by dopaminergic treatment in patients with Parkinson's disease.

Cognitive changes including reduced word production in verbal fluency (VF) tasks are frequently observed in Parkinson's disease (PD) with ambiguous effects of dopaminergic medication on these symptoms. Here, we studied the impact of dopaminergic medication on specific cognitive components underlying VF task performance in 21 participants with PD on their regular medication and following dopamine withdrawal compared with healthy controls. We used temporal cluster analysis (TCA) to differentiate phases of VF output relating to fast automatic lexical activation ('clusters') and slower attention-demanding shifts ('switches'). Dopaminergic medication led to increased switching and, in non-alternating VF tasks, to the formation of smaller and shorter word clusters. The number of switches was correlated with higher cognitive scores and showed an inverse relationship with VF error rates. Increased switching operations during VF task performance can be interpreted in view of nigrostriatal dopaminergic roles for balancing system state versus change propensities. The additional effect on word clustering suggests a modulation of semantic spreading activation mechanisms underlying lexical search, presumably involving non-nigrostriatal, e.g., mesocortical dopaminergic networks.

Phenotypic Variability in Autosomal Dominant Familial Alzheimer Disease due to the S170F Mutation of Presenilin-1.

BACKGROUND: In rare cases, patients with Alzheimer disease (AD) present at an early age and with a family history suggestive of an autosomal dominant mode of inheritance. Mutations of the presenilin-1 (PSEN1) gene are the most common causes of dementia in these patients. Early-onset and particularly familial AD patients frequently present with variable non-amnestic cognitive symptoms such as visual, language or behavioural changes as well as non-cognitive, e.g. motor, symptoms. OBJECTIVE: To investigate the phenotypic variability in carriers of the PSEN1 S170F mutation. METHODS: We report a family with 4 patients carrying the S170F mutation of whom 2 underwent detailed clinical examinations. We discuss our current findings in the context of previously reported S170F cases. RESULTS: The clinical phenotype was consistent regarding initial memory impairment and early onset in the late twenties found in all S170F patients. There were frequent non-amnestic cognitive changes and, at early stages of the disease, indications of a more pronounced disturbance of visuospatial abilities as compared to face and object recognition. Non-cognitive symptoms most often included myoclonus and cerebellar ataxia. A review of the available case reports indicates some phenotypic variability associated with the S170F mutation including different constellations of symptoms such as parkinsonism and delusions. CONCLUSION: The variable clinical findings associated with the S170F mutation highlight the relevance of atypical phenotypes in the context of research and under a clinical perspective. CSF sampling and detection of Aß species may be essential to indicate AD pathology in unclear cases presenting with cognitive and motor symptoms at a younger age.

Subcortical roles in lexical task processing: Inferences from thalamic and subthalamic event-related potentials.

Subcortical functions for language capacities are poorly defined, but may be investigated in the context of deep brain stimulation. Here, we studied event-related potentials recorded from electrodes in the subthalamic nucleus (STN) and the thalamic ventral intermediate nucleus (VIM) together with surface-EEG. Participants completed a lexical decision task (LDT), which required the differentiation of acoustically presented words from pseudo-words by button press. Target stimuli were preceded by prime-words. In recordings from VIM, a slow potential shift apparent at the lower electrode contacts persisted during target stimulus presentation (equally for words and pseudo-words). In contrast, recordings from STN electrodes showed a short local activation on prime-words but not target-stimuli. In both depth-recording regions, further components related to contralateral motor responses to target words were evident. On scalp level, mid-central activations on (pseudo)lexical stimuli were obtained, in line with the expression of N400 potentials. The prolonged activity recorded from VIM, exclusively accompanying the relevant LDT phase, is in line with the idea of thalamic "selective engagement" for supporting the realization of the behavioral focus demanded by the task. In contrast, the phasic prime related activity rather indicates "procedural" STN functions, for example, for trial sequencing or readiness inhibition of prepared target reactions. Hum Brain Mapp 38:370-383, 2017. © 2016 Wiley Periodicals, Inc.

Thalamic deep brain stimulation decelerates automatic lexical activation.

BACKGROUND: Deep Brain Stimulation (DBS) of the thalamic ventral intermediate nucleus (VIM) is a therapeutic option for patients with essential tremor. Despite a generally low risk of side effects, declines in verbal fluency (VF) have previously been reported. OBJECTIVES: We aimed to specify effects of VIM-DBS on major cognitive operations needed for VF task performance, represented by clusters and switches. Clusters are word production spurts, thought to arise from automatic activation of associated information pertaining to a given lexical field. Switches are slow word-to-word transitions, presumed to indicate controlled operations for stepping from one lexical field to another. PATIENTS & METHODS: Thirteen essential tremor patients with VIM-DBS performed verbal fluency tasks in their VIM-DBS ON and OFF conditions. Clusters and switches were formally defined by mathematical criteria. All results were compared to those of fifteen healthy control subjects, and significant OFF-ON-change scores were correlated to stimulation parameters. RESULTS: Patients produced fewer words than healthy controls. DBS ON compared to DBS OFF aggravated this deficit by prolonging the intervals between words within clusters, whereas switches remained unaffected. This stimulation effect correlated with more anterior electrode positions. CONCLUSION: VIM-DBS seems to influence word output dynamics during verbal fluency tasks on the level of word clustering. This suggests a perturbation of automatic lexical co-activation by thalamic stimulation, particularly if delivered relatively anteriorly. The findings are discussed in the context of the hypothesized role of the thalamus in lexical processing.

The face-responsive M170 is modulated by sensor selection: An example of circularity in the analysis of MEG-data.

BACKGROUND: Magnetoencephalography (MEG) experiments create large data sets obtained from many sensors at different locations. Therefore, a process of sensor-selection prior to hypothesis-driven data analysis is common, e.g., when studying the face-selective M170 component occurring at temporal sites around 170ms post-stimulus. However, the strategies to identify sensors of interest vary across investigations, and frequently the contrast used for sensor-selection is not independent from the contrast between experimental conditions. NEW METHOD: We re-analyzed data from a previously published MEG-experiment where participants viewed faces of either a loved person or two friends. We included different strategies for identifying face-responsive sensors based on all or each one of the face-categories before comparing M170 amplitudes across conditions. RESULTS: When sensor-selection was based on signal strength elicited by one experimental condition alone, a comparison across face-categories revealed significantly increased M170 amplitudes for the respective face category. Conducting the same analysis following sensor-selection based on averaged activity across all face-categories did not yield different M170 amplitudes. COMPARISON WITH EXISTING METHOD: Whereas this pitfall of selective analysis has been studied and discussed in detail for fMRI methods there is no comparable re-analysis of real EEG/MEG-data. CONCLUSIONS: Our results demonstrate that selection-bias is as relevant for EEG/MEG analysis as for fMRI methods. Sensor-selection must be independent from the contrast analyzed with statistical comparisons, because otherwise a distorted or 'circular' analysis might result.

A different pattern of lateralised brain activity during processing of loved faces in men and women: a MEG study.

Viewing personally familiar and loved faces evokes a distinct pattern of brain activity as demonstrated by research employing imaging and electrophysiological methods. The aim of the current investigation was to study the perception of loved faces combined with recalling past emotional experiences using whole-head magnetoencephalograpy (MEG). Twenty-eight participants (fourteen female) viewed photographs of their romantic partner as well as of two long-term friends while imagining a positive emotional encounter with the respective person. Face-stimuli evoked a slow and sustained shift of magnetic activity from 300ms post-stimulus onwards which differentiated loved from friends' faces in female participants and left-sided sensors only. This late-latency evoked magnetic field resembled (as its magnetic counterpart) ERP-modulations by affective content and memory, most notably the late positive potential (LPP). We discuss our findings in the light of studies suggesting greater responsiveness to affective cues in women as well as sex differences in autobiographical and emotional memory.

Differential impact of thalamic versus subthalamic deep brain stimulation on lexical processing.

Roles of subcortical structures in language processing are vague, but, interestingly, basal ganglia and thalamic Deep Brain Stimulation can go along with reduced lexical capacities. To deepen the understanding of this impact, we assessed word processing as a function of thalamic versus subthalamic Deep Brain Stimulation. Ten essential tremor patients treated with thalamic and 14 Parkinson׳s disease patients with subthalamic Deep Brain Stimulation performed an acoustic Lexical Decision Task ON and OFF stimulation. Combined analysis of task performance and event-related potentials allowed the determination of processing speed, priming effects, and N400 as neurophysiological correlate of lexical stimulus processing. 12 age-matched healthy participants acted as control subjects. Thalamic Deep Brain Stimulation prolonged word decisions and reduced N400 potentials. No comparable ON-OFF effects were present in patients with subthalamic Deep Brain Stimulation. In the latter group of patients with Parkinson' disease, N400 amplitudes were, however, abnormally low, whether under active or inactive Deep Brain Stimulation. In conclusion, performance speed and N400 appear to be influenced by state functions, modulated by thalamic, but not subthalamic Deep Brain Stimulation, compatible with concepts of thalamo-cortical engagement in word processing. Clinically, these findings specify cognitive sequels of Deep Brain Stimulation in a target-specific way.

Sex-differences of face coding: evidence from larger right hemispheric M170 in men and dipole source modelling.

The processing of faces relies on a specialized neural system comprising bilateral cortical structures with a dominance of the right hemisphere. However, due to inconsistencies of earlier findings as well as more recent results such functional lateralization has become a topic of discussion. In particular, studies employing behavioural tasks and electrophysiological methods indicate a dominance of the right hemisphere during face perception only in men whereas women exhibit symmetric and bilateral face processing. The aim of this study was to further investigate such sex differences in hemispheric processing of personally familiar and opposite-sex faces using whole-head magnetoencephalography (MEG). We found a right-lateralized M170-component in occipito-temporal sensor clusters in men as opposed to a bilateral response in women. Furthermore, the same pattern was obtained in performing dipole localization and determining dipole strength in the M170-timewindow. These results suggest asymmetric involvement of face-responsive neural structures in men and allow to ascribe this asymmetry to the fusiform gyrus. This specifies findings from previous investigations employing event-related potentials (ERP) and LORETA reconstruction methods yielding rather extended bilateral activations showing left asymmetry in women and right lateralization in men. We discuss our finding of an asymmetric fusiform activation pattern in men in terms of holistic face processing during face evaluation and sex differences with regard to visual strategies in general and interest for opposite faces in special. Taken together the pattern of hemispheric specialization observed here yields new insights into sex differences in face perception and entails further questions about interactions between biological sex, psychological gender and influences that might be stimulus-driven or task dependent.