Towards Optimization of Oscillatory Stimulation During Sleep.

BACKGROUND: Oscillatory rhythms during sleep, such as slow oscillations (SOs) and spindles and, most importantly, their coupling, are thought to underlie processes of memory consolidation. External slow oscillatory transcranial direct current stimulation (so-tDCS) with a frequency of 0.75 Hz has been shown to improve this coupling and memory consolidation; however, effects varied quite markedly between individuals, studies, and species. In this study, we aimed to determine how precisely the frequency of stimulation must match the naturally occurring SO frequency in individuals to best improve SO-spindle coupling. Moreover, we systematically tested stimulation durations necessary to induce changes. MATERIALS AND METHODS: We addressed these questions by comparing so-tDCS with individualized frequency to standardized frequency of 0.75 Hz in a within-subject design with 28 older participants during napping while stimulation train durations were systematically varied between 30 seconds, 2 minutes, and 5 minutes. RESULTS: Stimulation trains as short as 30 seconds were sufficient to modulate the coupling between SOs and spindle activity. Contrary to our expectations, so-tDCS with standardized frequency indicated stronger aftereffects regarding SO-spindle coupling than individualized frequency. Angle and variance of spindle maxima occurrence during the SO cycle were similarly modulated. CONCLUSIONS: In sum, short stimulation trains were sufficient to induce significant changes in sleep physiology, allowing for more trains of stimulation, which provides methodological advantages and possibly even larger behavioral effects in future studies. Regarding individualized stimulation frequency, further options of optimization need to be investigated, such as closed-loop stimulation, to calibrate stimulation frequency to the SO frequency at the time of stimulation onset. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT04714879.

Pre-loss grief experiences of adults when someone important to them is at end-of-life: A qualitative systematic review.

Pre-loss grief can be experienced by relatives before impending death; however, limited understanding exists about the impact of pre-loss grief on bereavement. This systematic review aimed to synthesize qualitative research evidence reporting adults' experiences of pre-loss grief within cancer care. Thirteen studies were selected, and three key themes identified. Findings indicate that relatives transitioned through lived experiences during end-stage cancer, and that meanings attached to these experiences influenced how they experienced pre-loss grief. Limited formal support was identified to navigate these experiences; however, context was seen as important, and skilled healthcare practitioners and physical environment were key to facilitating preparedness.

Pulmonary Tumor Thrombotic Microangiopathy: Case Report and Review of Literature.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare rapidly progressive fatal disease that is difficult to diagnosis antemortem. Activation of the coagulation cascade and fibrocellular intimal thickening caused by embolism of tumor cells into pulmonary vasculature leads to extensive pulmonary hypertension and eventually death. We describe a case of PTTM with association of a presumed lung adenocarcinoma primary. Although rare in nature, PTTM should be a considered diagnosis with chronic dyspnea of unknown origin, severe pulmonary hypertension coupled with right-side heart failure, in the absence of pulmonary embolism.

Electrophysiological Evidence for Early and Interactive Symbol Access and Rule Processing in Retrieving and Combining Language Constructions.

The human brain stores an immense repertoire of linguistic symbols (morphemes, words) and combines them into a virtually unlimited set of well-formed strings (phrases, sentences) that serve as efficient communicative tools. Communication is hampered, however, if strings include meaningless items (e.g., "pseudomorphemes"), or if the rules for combining string elements are violated. Prior research suggests that, when participants attentively process sentences in a linguistic task, syntactic processing can occur quite early, but lexicosemantic processing, or any interaction involving this factor, is manifest later in time (ca. 400 msec or later). In contrast, recent evidence from passive speech perception paradigms suggests early processing of both combinatorial (morphosyntactic) and storage-related (lexicosemantic) properties. A crucial question is whether these parallel processes might also interact early in processing. Using ERPs in an orthogonal design, we presented spoken word strings to participants while they were distracted from incoming speech to obtain information about automatic language processing mechanisms unaffected by task-related strategies. Stimuli were either (1) well-formed miniconstructions (short pronoun-verb sentences), (2) "unstored" strings containing a pseudomorpheme, (3) "ill-combined" strings violating subject-verb agreement rules, or (4) double violations including both types of errors. We found that by 70-210 msec after the onset of the phrase-final syllable that disambiguated the strings, interactions of lexicosemantic and morphosyntactic deviance were evident in the ERPs. These results argue against serial processing of lexical storage, morphosyntactic combination and their interaction, and in favor of early, simultaneous, and interactive processing of symbols and their combinatorial structures.

External noise removed from magnetoencephalographic signal using independent component analyses of reference channels.

BACKGROUND: Many magnetoencephalographs (MEG) contain, in addition to data channels, a set of reference channels positioned relatively far from the head that provide information on magnetic fields not originating from the brain. This information is used to subtract sources of non-neural origin, with either geometrical or least mean squares (LMS) methods. LMS methods in particular tend to be biased toward more constant noise sources and are often unable to remove intermittent noise. NEW METHOD: To better identify and eliminate external magnetic noise, we propose performing ICA directly on the MEG reference channels. This in most cases produces several components which are clear summaries of external noise sources with distinct spatio-temporal patterns. We present two algorithms for identifying and removing such noise components from the data which can in many cases significantly improve data quality. RESULTS: We performed simulations using forward models that contained both brain sources and external noise sources. First, traditional LMS-based methods were applied. While this removed a large amount of noise, a significant portion still remained. In many cases, this portion could be removed using the proposed technique, with little to no false positives. COMPARISON WITH EXISTING METHOD(S): The proposed method removes significant amounts of noise to which existing LMS-based methods tend to be insensitive. CONCLUSIONS: The proposed method complements and extends traditional reference based noise correction with little extra computational cost and low chances of false positives. Any MEG system with reference channels could profit from its use, particularly in labs with intermittent noise sources.

Congruency of Separable Affix Verb Combinations Is Linearly Indexed by the N400.

Separable affix verbs consist of a stem and a derivational affix, which, in some languages can appear together or in discontinuous, distributed form, e.g., German "aufgreifen" and "greifen … auf" ["up-pick(ing)" and "pick … up"]. Certain stems can combine with only certain affixes. However, many such combinations are evaluated not as clearly correct or incorrect, but frequently take an intermediate status with participants rating them ambiguously. Here, we mapped brain responses to combinations of verb stems and affixes realized in short sentences, including more and less common particle verbs, borderline acceptable combinations and clear violations. Event-related potential responses to discontinuous particle verbs were obtained for five affixes re-combined with 10 verb stems, situated within short, German sentences, i.e., "sie en es ," English: "they it ." The congruity of combinations was assessed both with behavioral ratings of the stimuli and corpus-derived probability measures. The size of a frontal N400 correlated with the degree of incongruency between stem and affix, as assessed by both measures. Behavioral ratings performed better than corpus-derived measures in predicting N400 magnitudes, and a combined model performed best of all. No evidence for a discrete, right/wrong effect was found. We discuss methodological implications and integrate the results into past research on the N400 and neurophysiological studies on separable-affix verbs, generally.

Spread the word: MMN brain response reveals whole-form access of discontinuous particle verbs.

The status of particle verbs such as rise (…) up as either lexically stored or combinatorially assembled is an issue which so far has not been settled decisively. In this study, we use the mismatch negativity (MMN) brain response to observe neurophysiological responses to discontinuous particle verbs. The MMN can be used to distinguish between whole-form storage and combinatorial processes, as it is enhanced to stored words compared to unknown pseudowords, whereas combinatorially legal strings elicit a reduced MMN relative to ungrammatical ones. Earlier work had found larger MMNs to congruent than to incongruent verb-particle combinations when particle and verb appeared as adjacent elements, thus suggesting whole-form storage at least in this case. However, it is still possible that particle verbs discontinuously spread out across a sentence would elicit the combinatorial, grammar-violation response pattern instead. Here, we tested the brain signatures of discontinuous verb-particle combinations, orthogonally varying congruence and semantic transparency. The results show for the first time brain indices of whole-form storage for discontinuous constituents, thus arguing in favour of access to whole-form-stored lexical elements in the processing of particle verbs, irrespective of their semantic opacity. Results are discussed in the context of linguistic debates about the status of particle verbs as words, lexical elements or syntactically generated combinations. The explanation of the pattern of results within a neurobiological language model is highlighted.

Early neurophysiological indices of second language morphosyntax learning.

Humans show variable degrees of success in acquiring a second language (L2). In many cases, morphological and syntactic knowledge remain deficient, although some learners succeed in reaching nativelike levels, even if they begin acquiring their L2 relatively late. In this study, we use psycholinguistic, online language proficiency tests and a neurophysiological index of syntactic processing, the syntactic mismatch negativity (sMMN) to local agreement violations, to compare behavioural and neurophysiological markers of grammar processing between native speakers (NS) of English and non-native speakers (NNS). Variable grammar proficiency was measured by psycholinguistic tests. When NS heard ungrammatical word sequences lacking agreement between subject and verb (e.g. *we kicks), the MMN was enhanced compared with syntactically legal sentences (e.g. he kicks). More proficient NNS also showed this difference, but less proficient NNS did not. The main cortical sources of the MMN responses were localised in bilateral superior temporal areas, where, crucially, source strength of grammar-related neuronal activity correlated significantly with grammatical proficiency of individual L2 speakers as revealed by the psycholinguistic tests. As our results show similar, early MMN indices to morpho-syntactic agreement violations among both native speakers and non-native speakers with high grammar proficiency, they appear consistent with the use of similar brain mechanisms for at least certain aspects of L1 and L2 grammars.

Neurophysiological evidence for whole form retrieval of complex derived words: a mismatch negativity study.

Complex words can be seen as combinations of elementary units, decomposable into stems and affixes according to morphological rules. Alternatively, complex forms may be stored as single lexical entries and accessed as whole forms. This study uses an event-related potential brain response capable of indexing both whole-form retrieval and combinatorial processing, the Mismatch Negativity (MMN), to investigate early brain activity elicited by morphologically complex derived words in German. We presented complex words consisting of stems "sicher" (secure), or "sauber" (clean) combined with abstract nominalizing derivational affixes -heit or -keit, to form either congruent derived words: "Sicherheit" (security) and "Sauberkeit" (cleanliness), or incongruent derived pseudowords: *"Sicherkeit", and *"Sauberheit". Using this orthogonal design, it was possible to record brain responses for -heit and -keit in both congruent and incongruent contexts, therefore balancing acoustic variance. Previous research has shown that incongruent combinations of symbols elicit a stronger MMN than congruent combinations, but that single words or constructions stored as whole forms elicit a stronger MMN than pseudowords or non-existent constructions. We found that congruent derived words elicited a stronger MMN than incongruent derived words, beginning about 150 ms after perception of the critical morpheme. This pattern of results is consistent with whole-form storage of morphologically complex derived words as lexical units, or mini-constructions. Using distributed source localization methods, the MMN enhancement for well-formed derivationally complex words appeared to be most prominent in the left inferior anterior-temporal, bilateral superior parietal and bilateral post-central, supra-marginal areas. In addition, neurophysiological results reflected the frequency of derived forms, thus providing further converging evidence for whole form storage and against a combinatorial mechanism.

Early activation of Broca's area in grammar processing as revealed by the syntactic mismatch negativity and distributed source analysis.

Though activation of Broca's region in the combinatorial processing of symbols (language, music) has been revealed by neurometabolic studies, most previous neurophysiological research found the earliest grammar indices in the temporal cortex, with inferior-frontal generators becoming active at relatively late stages. We use the attention- and task-free syntactic mismatch negativity (sMMN) event-related potential (ERP) to measure rapid and automatic sensitivity of the human brain to grammatical information in participants' native language (French). Further, sources underlying the MMN were estimated by applying the Parametrical Empirical Bayesian (PEB) approach, with the Multiple Sparse Priors (MSP) technique. Results showed reliable grammar-related activation focused on Broca's region already in the 150-190 ms time window, providing robust documentation of its involvement in the first stages of syntactic processing.