Pragmatic language disorder in Parkinson's disease and the potential effect of cognitive reserve

It is known that patients with Parkinson\u2019s Disease (PD) may show deficits in several areas of cognition, including speech and language abilities. One domain of particular interest is pragmatics, which refers to the capacity of using language in context for a successful communication. Several studies showed that some specific aspects of pragmatics \u2013 both in production and in comprehension \u2013 might be impaired in patients with PD. However, a clear picture of pragmatic abilities in PD is still missing, as most of the existing studies focused on specific aspects of the pragmatic competence rather than on sketching a complete pragmatic profile. Moreover, little is known on the potential role of protective factors in compensating the decline of communicative skills as the disease progresses. The present study has two aims: (1) to provide a complete picture of pragmatic abilities in patients with PD, by using a comprehensive battery (Assessment of Pragmatic Abilities and Cognitive Substrates, APACS) and by investigating the relationship with other aspects of cognitive functioning (e.g., working memory and Theory of Mind) and (2) to investigate whether Cognitive Reserve, i.e., the resilience to cognitive impairment provided by life experiences and activities, may compensate for the progressive pragmatic deficits in PD. We found that patients with PD, compared to healthy matched controls, had worse performance in discourse production and in the description of scenes, and that these impairments were tightly correlated with the severity of motor impairment, suggesting reduced intentionality of engaging in a communicative exchange. Patients with PD showed also an impairment in comprehending texts and humor, suggesting a problem in inferring from stories, which was related to general cognitive impairment. Notably, we did not find any significant difference between patients and controls in figurative language comprehension, a domain that is commonly impaired in other neurodegenerative diseases. This might be indicative of a specific profile of pragmatic impairment in patients with PD, worth of further investigation. Finally, Cognitive Reserve measures showed a high degree of association with pragmatic comprehension abilities, suggesting that the modification of life-styles could be a good candidate for compensating the possible problems in understanding the pragmatic aspects of language experienced by patients with PD

A new clinical tool for assessing numerical abilities in neurological diseases: numerical activities of daily living

The aim of this study was to build an instrument, the numerical activities of daily living (NADL), designed to identify the specific impairments in numerical functions that may cause problems in everyday life. These impairments go beyond what can be inferred from the available scales evaluating activities of daily living in general, and are not adequately captured by measures of the general deterioration of cognitive functions as assessed by standard clinical instruments like the MMSE and MoCA. We assessed a control group (n = 148) and a patient group affected by a wide variety of neurological conditions (n = 175), with NADL along with IADL, MMSE, and MoCA. The NADL battery was found to have satisfactory construct validity and reliability, across a wide age range. This enabled us to calculate appropriate criteria for impairment that took into account age and education. It was found that neurological patients tended to overestimate their abilities as compared to the judgment made by their caregivers, assessed with objective tests of numerical abilities

Role of positron emission tomography (PET) in advanced stage non-small cell lung cancer patients treated with cisplatin-based doublets

n/

Theta and alpha oscillations as signatures of internal and external attention to delayed intentions: A magnetoencephalography (MEG) study

Background: Remembering to execute delayed intentions (i.e., prospective memory, PM) entails the allocation of internal and external attention. These processes are crucial for rehearsing PM intentions in memory and for monitoring the presence of the PM cue in the environment, respectively. Aim: The study took advantage of the excellent spatial and temporal resolution of magnetoencephalography (MEG) to delineate the neural mechanisms of the memory and monitoring processes underlying PM. Method: The spatio-temporal dynamic of theta and alpha oscillations were explored in 21 participants in two PM tasks compared to a baseline condition (i.e., a lexical decision task with no PM instruction). The PM tasks varied for the load of internally-directed attention (Retrospective-load task) vs externally-directed attention (Monitoring-load task). Results: Increase in theta activity was observed in the Retrospective-load task, and was particularly expressed in the regions of the Default Mode Network, such as in medial temporal regions, precuneus, posterior cingulate cortex and medial prefrontal cortex. Alpha decrease was the most relevant feature of the Monitoring-load task, and it was expressed over bilateral occipital, occipito-parietal and fronto-temporal regions, as well as over left dorsal fronto-parietal regions. Conclusions: Theta and alpha oscillations are strictly associated with the direction of attention during the PM tasks. In particular, theta increase is linked to internal attention necessary for maintaining the intention active in working memory, whereas alpha decrease supports the external attention for detecting the PM cue in the environment

Cortical gamma-synchrony measured with magnetoencephalography is a marker of clinical status and predicts clinical outcome in stroke survivors.

Background: The outcome of stroke survivors is difficult to anticipate. While the extent of the anatomical brain lesion is only poorly correlated with the prognosis, functional measures of cortical synchrony, brain networks and cortical plasticity seem to be good predictors of clinical recovery. In this field, gamma (>30 Hz) cortical synchrony is an ideal marker of brain function, as it plays a crucial role for the integration of information, it is an indirect marker of Glutamate/GABA balance and it directly estimates the reserve of parvalbulin-positive neurons, key players in synaptic plasticity. In this study we measured gamma synchronization driven by external auditory stimulation with magnetoencephalography and tested whether it was predictive of the clinical outcome in stroke survivors undergoing intensive rehabilitation in a tertiary rehabilitation center. Material and methods: Eleven stroke survivors undergoing intensive rehabilitation were prospectively recruited. Gamma synchrony was measured non-invasively within one month from stroke onset with magnetoencephalography, both at rest and during entrainment with external 40 Hz amplitude modulated binaural sounds. Lesion location and volume were quantitatively assessed through a high-resolution anatomical MRI. Barthel index (BI) and Functional Independence Measure (FIM) scales were measured at the beginning and at the end of the admission to the rehabilitation unit. Results: The spatial distribution of cortical gamma synchrony was altered, and the physiological right hemispheric dominance observed in healthy controls was attenuated or lost. Entrained gamma synchronization (but not resting state gamma synchrony) showed a very high correlation with the clinical status at both admission and discharge (both BI and FIM). Neither clinical status nor gamma synchrony showed a correlation with lesion volume. Conclusions: Cortical gamma synchrony related to auditory entrainment can be reliably measured in stroke patients. Gamma synchrony is strongly associated with the clinical outcome of stroke survivors undergoing rehabilitation

Bilateral transcranial direct current stimulation reshapes resting-state brain networks: A Magnetoencephalography assessment

Transcranial direct current stimulation (tDCS) can noninvasively induce brain plasticity, and it is potentially useful to treat patients affected by neurological conditions. However, little is known about tDCS effects on resting-state brain networks, which are largely involved in brain physiological functions and in diseases. In this randomized, sham-controlled, double-blind study on healthy subjects, we have assessed the effect of bilateral tDCS applied over the sensorimotor cortices on brain and network activity using a whole-head magnetoencephalography system. Bilateral tDCS, with the cathode (−) centered over C4 and the anode (+) centered over C3, reshapes brain networks in a nonfocal fashion. Compared to sham stimulation, tDCS reduces left frontal alpha, beta, and gamma power and increases global connectivity, especially in delta, alpha, beta, and gamma frequencies. The increase of connectivity is consistent across bands and widespread. These results shed new light on the effects of tDCS and may be of help in personalizing treatments in neurological disorders

Breakthrough pain in oncology: a longitudinal study.

Abstract CONTEXT: Existing studies on breakthrough pain (BP) have reported different prevalence rates because of different settings, populations, and assessment methods. These studies have used cross-sectional designs, and the relationship of BP with analgesic treatment has not been evaluated. OBJECTIVES: The aim of this study was to longitudinally assess BP in cancer patients admitted to oncology units. METHODS: A consecutive sample of patients admitted to oncology centers was selected. At admission (T0), three months after admission (T3), and six months after admission (T6), data on background pain and BP were recorded. BP was assessed in terms of its intensity, duration, number of episodes, onset with movement, spontaneous relief after stopping activity, limitation of physical activity, and effectiveness of analgesics. RESULTS: Three hundred two patients completed the study. At T0, T3, and T6, 39%, 38%, and 33% patients, respectively, had continuous pain (P=0.294). Pain intensity significantly decreased (P=0.004 and 0.027 at T3 and T6, respectively). Most patients had BP at T0 (87.1%), T3 (80.9%), and T6 (73.2%), and there was a significant decrease in the prevalence of BP over time (P=0.016). Of 149 patients with BP, pain on movement was recorded in 43.6%, 43.4%, and 32.4% at T0, T3, and T6, respectively (P=0.228). Pain spontaneously decreased or ceased when stopping physical activity in 66%, 56%, and 62% at T0, T3, and T6, respectively (P=0.537). Pain on movement strongly limited physical activity in most patients. CONCLUSION: These data expand current information about BP and underline the need for a longitudinal assessment of a phenomenon that is invariably dependent on stage of disease, patient, and therapeutic factors

Production of subject-verb agreement, tense, mood, and negation in Italian agrammatic aphasia

Impaired (morpho)syntactic production is the hallmark of agrammatic aphasia. Several hypotheses have been proposed to account for agrammatic production, which often make different predictions. The Distributed Morphology Hypothesis (DMH) (Wang et al., 2014) posits that categories involving inflectional alternations are impaired in agrammatism. The Tense Underspecification Hypothesis (TUH) (Wenzlaff & Clahsen, 2004, 2005) states that what is impaired (\u201cunderspecified\u201d) is tense; subject-verb agreement and mood are well-preserved. The Interpretable Features\u2019 Impairment Hypothesis (IFIH) (Fyndanis et al., 2012) predicts categories involving integration processes (e.g., tense, mood, negation) to be more impaired than categories that do not involve integration processes (e.g., agreement). The Tree Pruning Hypothesis (TPH) (Friedmann & Grodzinsky, 1997) states that the syntactic tree is pruned at a specific node, usually tense, with all nodes/categories above the pruning site deleted/inaccessible and all nodes below intact. To reliably test these accounts, one should test agrammatic speakers on a wide range of (morpho)syntactic phenomena/categories. In this study, we investigate the ability of Italian-speaking agrammatic individuals to produce subject-verb agreement, tense, mood, and sentential negation. A sentence completion task (SCT) tapping agreement and tense, a SCT assessing mood, and a constituent ordering task tapping negation were administered to eight native speakers of Italian with chronic agrammatic aphasia and eight controls. Results are presented in Table 1. The control group performed better than the aphasic group on all four conditions. Both groups showed similar patterns of performance, with better performance on agreement and tense than on mood. Negation was better preserved than agreement, tense, and mood in the aphasic group, but in the control group negation was not different from any other category. At the individual level, five agrammatic participants exhibited the same pattern of performance (agreement/tense/negation>mood). At the group level, the results of the agrammatic participants are not consistent with any of the hypotheses discussed here. Contrary to the TUH, participants performed better on tense than on mood. The DMH cannot explain the observed, selective impairment of categories involving inflectional alternations (tense/agreement>mood). Results do not support the TPH, as the higher the category in the syntactic hierarchy (Neg>T(future/past)>M) (Cinque, 1999; Zanuttini, 2001), the better the performance of agrammatic participants. Lastly, results are at odds with the IFIH, because negation (+integration processes) is better preserved than agreement (-integration processes). Analogous results are observed at the individual level. None of the available hypotheses can account for the patterns of performance of all the agrammatic participants. Their results, together with the production results of other agrammatic speakers in the literature, show that all possible patterns can be observed in agrammatism, and that a unitary account of the disorder is unlikely to succeed. We suggest that subject-specific characteristics (e.g., site/type/volume of brain damage, type/severity of language impairment, education, age) and language-specific properties of functional categories (e.g., syntactic hierarchy, interpretability/involvement of integration processes, frequency) may interact in determining the way in which (morpho)syntactic impairments manifest themselves across agrammatic speakers and languages

Prediction of rehabilitation induced motor recovery after stroke using a multi-dimensional and multi-modal approach

Background: Stroke is a debilitating disease affecting millions of people worldwide. Despite the survival rate has significantly increased over the years, many stroke survivors are left with severe impairments impacting their quality of life. Rehabilitation programs have proved to be successful in improving the recovery process. However, a reliable model of sensorimotor recovery and a clear identification of predictive markers of rehabilitation-induced recovery are still needed. This article introduces the cross-modality protocols designed to investigate the rehabilitation treatment’s effect in a group of stroke survivors. Methods/design: A total of 75 stroke patients, admitted at the IRCCS San Camillo rehabilitation Hospital in Venice (Italy), will be included in this study. Here, we describe the rehabilitation programs, clinical, neuropsychological, and physiological/imaging [including electroencephalography (EEG), transcranial magnetic stimulation (TMS), and magnetic resonance imaging (MRI) techniques] protocols set up for this study. Blood collection for the characterization of predictive biological biomarkers will also be taken. Measures derived from data acquired will be used as candidate predictors of motor recovery. Discussion/summary: The integration of cutting-edge physiological and imaging techniques, with clinical and cognitive assessment, dose of rehabilitation and biological variables will provide a unique opportunity to define a predictive model of recovery in stroke patients. Taken together, the data acquired in this project will help to define a model of rehabilitation induced sensorimotor recovery, with the final aim of developing personalized treatments promoting the greatest chance of recovery of the compromised functions