Action language processing in Parkinson’s disease: Characterization of neuro-oscillatory dynamics and linguistic performance

Human language capacity is based on temporally coordinated neural activity across distributed brain regions. Although the left hemispheric perisylvian cortex constitutes the core region of language processing, a network of additional sites is further involved. For example, in the healthy brain, semantic access to action concepts has been associated with increased neural activity within frontal motor areas. These findings are complemented by studies demonstrating impaired action language processing in patients with Parkinson's disease, a condition leading to impaired motor control. Therefore, both lines of inquiry suggest an involvement of sensorimotor brain regions in the semantic access to action concepts. However, as the neural underpinnings of the putative action language deficit in Parkinson's disease are unknown, the contribution of motor areas to this phenomenon remains unresolved. This study therefore aimed at resolving this question by characterizing neurophysiological and behavioral correlates of action language processing in patients with Parkinson's disease. For this purpose, two experiments were carried out. The goal of Experiment 1 was to compile and validate a data set of action pictures for the German language. This part of the study aimed at identifying psycholinguistic variables affecting naming latency in a picture naming task, allowing the selection of matched sets of stimuli in prospective studies. Experiment 2 built upon these data and employed an action naming task and high-density electroencephalography to characterize oscillatory patterns during action language production in both healthy participants and patients with Parkinson's disease. Specifically, this part of the study examined whether action language processing is accompanied with aberrant oscillatory patterns in the mu and beta frequency range over motor cortical areas in the parkinsonian state. Furthermore, the influence of dopaminergic medication on these patterns was assessed. In Experiment 1, a total of 283 freely available action pictures could be assembled and characterized. The principal variables affecting naming latency describe the agreement in responses across subjects: Less homogeneous response distributions were associated with longer reaction times. Furthermore, word frequency as well as the motor content of the pictures and responses were significant predictors of naming latency. Experiment 2 could not replicate the behavioral action naming deficit in patients with Parkinson's disease when compared to healthy participants. However, differential neurophysiological correlates of action naming were observed. In contrast to healthy subjects, a transient episode of beta hypersynchronization was present over central to frontal electrodes in Parkinson's disease patients off medication within 300 to 700 ms after stimulus presentation. Cluster-based permutation tests confirmed this difference in oscillatory power and by reconstructing the sources of neural activity it could be localized to the left pre- and postcentral cortex and to the right anterior temporal lobe. Furthermore, subsequent mu power suppression (from 800 ms onwards) was stronger in patients with Parkinson's disease than in healthy controls. The associations between psycholinguistic variables and naming latency found in Experiment 1 were largely consistent with action naming normative studies carried out in other languages. The data set of 283 action pictures may therefore constitute a valuable resource for future psycholinguistic investigations of action language processing. In Experiment 2, behavioral results were not in keeping with a specific action language deficit in patients with Parkinson's disease, which stands in contrast to prior studies. However, patients included in this study attained a higher level of education as those examined in earlier reports, potentially compensating the hypothesized deficit. On the neurophysiological level though, exaggerated beta power in Parkinson's disease patients showed a spatiotemporal pattern which may reflect aberrant semantic access to action concepts grounded in the motor system: Differential neural activity was partly observed during a previously established time frame for semantic processing and located to brain regions that have been associated with access to action concepts, including the sensorimotor cortex. In conclusion, this study established a methodological basis for further psycholinguistic studies on action language processing by validating a normative action picture data set for the German language. By applying this data set in an action naming task and recording high density electroencephalography in Parkinson's disease patients and healthy controls, neurophysiological correlates of action language processing were examined. While behavioral results were not in keeping with a hypothesized action naming deficit, differential oscillatory activity in the beta frequency range suggests a contribution of the motor system to altered semantic processing of action concepts in patients with Parkinson's disease

Sensorimotor semantics on the spot: brain activity dissociates between conceptual categories within 150 ms

Although semantic processing has traditionally been associated with brain responses maximal at 350–400 ms, recent studies reported that words of different semantic types elicit topographically distinct brain responses substantially earlier, at 100–200 ms. These earlier responses have, however, been achieved using insufficiently precise source localisation techniques, therefore casting doubt on reported differences in brain generators. Here, we used high-density MEG-EEG recordings in combination with individual MRI images and state-of-the-art source reconstruction techniques to compare localised early activations elicited by words from different semantic categories in different cortical areas. Reliable neurophysiological word-category dissociations emerged bilaterally at ~ 150 ms, at which point action-related words most strongly activated frontocentral motor areas and visual object-words occipitotemporal cortex. These data now show that different cortical areas are activated rapidly by words with different meanings and that aspects of their category-specific semantics is reflected by dissociating neurophysiological sources in motor and visual brain systems

Online neurostimulation of Broca's area does not interfere with syntactic predictions: A combined TMS-EEG approach to basic linguistic combination

Categorical predictions have been proposed as the key mechanism supporting the fast pace of syntactic composition in human language. Accordingly, grammar-based expectations facilitate the analysis of incoming syntactic information—e.g., hearing the determiner “the” enhances the prediction of a noun—which is then checked against a single or few other word categories. Previous functional neuroimaging studies point towards Broca’s area in the left inferior frontal gyrus (IFG) as one fundamental cortical region involved in categorical prediction during on-line language processing. Causal evidence for this hypothesis is however still missing. In this study, we combined Electroencephalography (EEG) and Transcranial Magnetic Stimulation (TMS) to test whether Broca’s area is functionally relevant in predictive mechanisms for language. Specifically, we transiently perturbed Broca’s area during the categorical prediction phase in two-word constructions, while simultaneously measuring the Event-Related Potential (ERP) correlates of syntactic composition. We reasoned that if Broca’s area is involved in predictive mechanisms for syntax, disruptive TMS during the processing of the first word (determiner/pronoun) would mitigate the difference in ERP responses for predicted and unpredicted categories when composing basic phrases and sentences. Contrary to our hypothesis, perturbation of Broca’s area at the predictive stage did not affect the ERP correlates of basic composition. The correlation strength between the electrical field induced by TMS and the magnitude of the EEG response on the scalp further confirmed this pattern. We discuss the present results in light of an alternative account of the role of Broca’s area in syntactic composition, namely the bottom-up integration of words into constituents

Semantic radical consistency and character transparency effects in Chinese: an ERP study

BACKGROUND: This event-related potential (ERP) study aims to investigate the representation and temporal dynamics of Chinese orthography-to-semantics mappings by simultaneously manipulating character transparency and semantic radical consistency. Character components, referred to as radicals, make up the building blocks used dur...postprin

Modern Developments in Transcranial Magnetic Stimulation (TMS) – Applications and Perspectives in Clinical Neuroscience

Transcranial magnetic stimulation (TMS) is being increasingly used in neuroscience and clinics. Modern advances include but are not limited to the combination of TMS with precise neuronavigation as well as the integration of TMS into a multimodal environment, e.g., by guiding the TMS application using complementary techniques such as functional magnetic resonance imaging (fMRI), electroencephalography (EEG), diffusion tensor imaging (DTI), or magnetoencephalography (MEG). Furthermore, the impact of stimulation can be identified and characterized by such multimodal approaches, helping to shed light on the basic neurophysiology and TMS effects in the human brain. Against this background, the aim of this Special Issue was to explore advancements in the field of TMS considering both investigations in healthy subjects as well as patients

Neurophysiological aspects of speech perception and production in stuttering

Stuttering is a speech disorder in which the smooth succession of speech sounds is interrupted by frequent blocks, prolongations and/or repetitions of sounds or syllables. When stuttering manifests itself for the first time during childhood, it is called developmental stuttering. When stuttering is of non-developmental origin, it is referred to as acquired stuttering. Acquired stuttering mostly derives from damage to the central nervous system which is called neurogenic stuttering. Neurologically, stuttering is characterized by alterations in cortical and subcortical brain regions related to speech motor planning, initiation, execution and monitoring. Neurological research in stuttering contains a plethora of spatial neuroimaging studies (e.g. fMRI) but a dearth of neurophysiological studies, especially when it comes to speech motor control. However, fluent speech does not only require the appropriate amount of (de)activation of specific brain regions, it also needs a timely and precise coordination of these brain regions. Therefore, the present thesis aimed to identify neurophysiological characteristics of speech motor control in stuttering by the use of electro-encephalography. First, temporal coordination of motor related activity during a visual word recognition task was assessed. Time points of motor related activity during hand action and non-action verb processing were compared in a group of fluent speakers and a group of adults with developmental stuttering. Secondly, speech motor preparatory activity preceding single word production was measured in real time by evoking a contingent negative variation (CNV) during a picture naming task. The CNV is an event-related potential reflecting motor preparatory activity in the basal ganglia-thalamo-cortical – loop. Speech motor preparation was compared between fluent speakers, and both fluent and stuttered words of stuttering speakers. Thirdly, although developmental and neurogenic stuttering are suggested to share common neural substrates, both types of stuttering were compared to assess whether this also accounts for speech motor preparatory activity. To that purpose, the same CNV picture naming task was performed in a case of neurogenic stuttering. Timing of motor related activation was considerable altered in the stuttering group, even during a silent reading task without (speech) movement requirements. The time point of maximal motor difference between both verb types was delayed with 100 ms and showed a reversed activation pattern compared to that of fluent speakers. This reversal is hypothesized to encompass two different motor abnormalities: a general motor hyperactivation, presenting during non-action verb processing, and a specific hand motor deficit, causing decreased excitability of this region during hand action verb processing. These findings confirm that temporal alterations in neural motor activations in stuttering are not restricted to overt speech production. Secondly, speech motor preparatory activity generated by the basal ganglia-thalamo-cortical – loop was found to have a crucial role in stuttering. Not only has its amount of activation a determining role in the actual moment of a stutter, its activation seems also related to the underlying stuttering pathology. An important divergence between left and right hemisphere is seen in this respect. When motor preparatory activity in right basal ganglia-thalamo-cortical – loop is markedly increased, no stutter will occur. The more frequent and/or the more severe a person stutters, the higher this increase is or must be to enable fluent speech production. The lower the motor preparatory activity preceding a stutter in the left basal ganglia-thalamo-cortical – network, the more this person will stutter in general. As such, left basal ganglia-thalamo-cortical – loop is suggested to have a link with the stuttering pathology. These findings concur with a growing amount of studies stating that right hemisphere alterations are related to (successful) compensation strategies, while the left hemisphere would contain the primary cause of stuttering. Thirdly, important differences emerged when comparing the findings concerning speech motor preparatory activity of the developmental stuttering group and the case with neurogenic stuttering. Roughly speaking, an increase in stuttering frequency was associated with an increase in CNV slope in the developmental stuttering group and a decrease in CNV in the case of neurogenic stuttering. Although neurogenic and developmental stuttering are believed to share common neural characteristics, these may be restricted to neuroanatomical findings. Both types of stuttering may show considerable variation in neurophysiological functioning, probably related to a difference in lesion localisation. Finally, when findings of the present studies are placed within a broader framework, the importance of the motor loop of feedforward processing in stuttering is highlighted. All observed motor alterations presented without simultaneous deficits in feedback processing or without obvious inferences of language impairments. Overall, the present thesis evidences that neurophysiology is able to discover interesting and intriguing neural findings that may aid in unravelling the enigma of stuttering

Is beta in agreement with the relatives? Using relative clause sentences to investigate MEG beta power dynamics during sentence comprehension.

There remains some debate about whether beta power effects observed during sentence comprehension reflect ongoing syntactic unification operations (beta-syntax hypothesis), or instead reflect maintenance or updating of the sentence-level representation (beta-maintenance hypothesis). In this study, we used magnetoencephalography to investigate beta power neural dynamics while participants read relative clause sentences that were initially ambiguous between a subject- or an object-relative reading. An additional condition included a grammatical violation at the disambiguation point in the relative clause sentences. The beta-maintenance hypothesis predicts a decrease in beta power at the disambiguation point for unexpected (and less preferred) object-relative clause sentences and grammatical violations, as both signal a need to update the sentence-level representation. While the beta-syntax hypothesis also predicts a beta power decrease for grammatical violations due to a disruption of syntactic unification operations, it instead predicts an increase in beta power for the object-relative clause condition because syntactic unification at the point of disambiguation becomes more demanding. We observed decreased beta power for both the agreement violation and object-relative clause conditions in typical left hemisphere language regions, which provides compelling support for the beta-maintenance hypothesis. Mid-frontal theta power effects were also present for grammatical violations and object-relative clause sentences, suggesting that violations and unexpected sentence interpretations are registered as conflicts by the brain's domain-general error detection system.</p

Seeking the neural basis of grammar : English noun and verb morphological processing investigated with rapid event-related fMRI and intracortical electrophysiology

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2003.Includes bibliographical references (v. 2, leaves 268-271).(cont.) the functionality of the fMRI data analysis and visualization tools used at Massachusetts General Hospital. I analyze and interpret an 18-subject fMRI experiment I ran using the new task design and software tools. Finally, I present preliminary findings on linguistic questions as well as the nature of fMRI signal, using direct Electrophysiological data recorded from electrodes implanted in the brains of two Epilepsy patients. These patients had electrodes implanted through or near classical language areas of their brains, as a necessary clinical step in locating and surgically removing the seizure-causing tissue. The main findings of this thesis are: 1.) Morphology alone can activate Broca's area, 2.) Other areas are involved, including BA47, anterior insula, and SMA, 3.) Broca's area and BA47 respond to application of abstract grammatical features, even without phonological manipulations, 4.) Morphophonological manipulation additionally recruits insula and SMA, 5.) While simply accessing nouns versus verbs may involve separable brain regions, inflectional processing of the two categories may be done by the same process, 6.) Regularly and Irregularly inflected verbs show a double dissociation of activation in frontal and medial regions, 7.) Processing of English noun more than verb morphology may rely on some contribution from number processing brain systems ...Inflectional morphology is the component of language concerned with changing a word's form to reflect context-specific meaning, such as the affixing of"-ed" for English verbs in the past tense, or adding "-s" in order to signal a noun's plural form. Although it is but one part of language, morphology may be useful as a model system for larger issues in language and cognition. Morphological processing touches on: the manipulation of memorized items (the vocabulary of words, and maybe word endings), the application and power of combinatorial rules (to generate correct forms, even of unknown words), and the binding of units of information into meaning. Morphology's relationship with other more traditional facets of language such as syntax (sentence structure) and semantics (meanings of individual words) is debated, as is the objective reality of grammatical categories (e.g. noun/verb) as well as combinatorial rules. Functional Magnetic Resonance Imaging (fMRI) is an exciting technique for peering into the brain and answering questions about its function. However, the technique has limited temporal and spatial resolution, and indexes the brain basis of cognition only indirectly, via blood response to cellular metabolism. In this thesis I propose a task for manipulating morphological production, embedded in a 2*2*3 design simultaneously varying grammatical class (nouns versus verbs), regularity of inflection (e.g. words like "walk" which take the stereotyped or regular ending "-ed", versus those like "bring" and "sing" which have idiosyncratic past tense forms), and three types of morphological task aimed to separate the assignment of grammatical features (e.g. present/past tense) from changes in word sound. I introduce and utilize software to extendby Nedim T. Sahin.S.M