Language impairments in ALS/MND (Amyotrophic Lateral Sclerosis/Motor Neuron Disease)

Paolo Bongioanni §, Giancarlo Buoiano C§, Marzia Magoni § § Neuroscience Dpt., Univ. Of Pisa, Italy c Corresponding author: Giancarlo Buoiano Via del Morello 8 Bargecchia I-55040 Corsanico (LU) email: [email protected] Language impairments in Amyotrophic Lateral Sclerosis/Motor Neuron Disease (ALS/MND) Abstract We review 6 papers on Motor Neuron Disease (MND) and language impairments. ALS/MND (Amyotrophic Lateral Sclerosis/MND) is an wide-ranging term used to cover several derangements of the motor neurons. ALS/MND brings to progressive degeneration of the motor neurons. The motor neurons control the muscles that consent us to move and act. Until some years ago, ALS/MND was thought not to affect language and higher-order cognitive functions, but at present it is acknowledged that about 3-5% of patients affected by ALS/MND show cognitive impairments. Up to date, it is not possible to establish whether this subgroup is affected by ALS/MND and Fronto-Temporal Dementia (FTD) or FTD/Aphasia syndrome or whether FTD/aphasia syndrome can be, in some cases, a consequence of ALS/MND. Furthermore, it is not clear whether MND/FTD syndrome brings to language breakdown or whether MND/Aphasia can be considered a self-standing syndrome. Lexical category-specific impairments affect more often than not verbs, while nouns appear to be by some means preserved. The verbs deficit is remarkable because it can place a new light on the link between actions, verbal and cognitive imagery, and ideomotor praxis. Language impairments detected in ALS/MND point largely to frontal and frontostriatal damages. Actually functional neuroimaging studies show reduced frontal activation. Alterations in Broca’s area, DorsoLateral PreFrontal Cortex (DLPFC) and fronto-striatal circuit have been all reported in ALS/MND: several functional studies link Broca’s area to syntactic processing and DLPFC to verbs production as well as language Short Term Memory (STM). A basic issue is the link between action and verbs and, as a result, between action syntax and speech syntax. This connection would be involved in the origin of language: it would be evolved passing from action to speech syntax. According to our point of view, verbs are pivotal in this system. In short, when actions are missing, verbs, ideomotor praxis and their neurocorrelates would deteriorate. A longitudinal study on the effect of massive motor derangement on the verb degeneration is at present carried out by our research group, so to date this is a working hypothesis waiting for further evidence. Keywords: ALS/MND, syntax, verbs, action, fronto-striatal circuit

Perception of Real-World Without a Language

Perception of Real-World Without a Language Gian Carlo Buoiano C§, Mario Betti * and Paolo Bongioanni § §Neuroscience Dpt., University of Pisa; *CESER Center of Mental Health (Lucca), Italy C Corresponding author: Giancarlo Buoiano Via del Morello 8 Bargecchia I-55040 Corsanico (LU) Italy e-mail: [email protected] Abstract The aim of this study is to show how real-world knowledge works without language. Lelio is a 76-year-old man who has been profoundly deaf since birth like his mother and brothers. In the clinical history, Lelio’s father was reported as affected by an unspecified “cerebropathy”. Lelio’s two brothers had a relatively normal life. Lelio is illiterate like his mother and brothers: therefore Lelio grew up in a rather atypical relational context, developing a pathological affection for his mother and communicating through non-linguistically structured gestures. When his mother died Lelio was 31 and had some bursts of violence. In 1956 he was admitted in a psychiatric hospital with the diagnosis of “phrenastenia due to cerebropathy, microcephalia, deafness and mutism and probable epileptic crises”. During the 35-year hospitalization, there were no attempts to teach him “to read the lips” or use a structured sign language and, consequently, read and write. Since 1997 he has been living with his adoptive family. For these reasons, Lelio is a subject totally deprived of language. Apparently, he is unable to indicate a temporal sequence, but can understand simple gestures for “before” and “after”. Simple gestures of this kind are related to his needs and might constitute a primitive form of deictic communication not inserted in a linguistic network of relations: they could be a clue for the existence of an elementary form of temporal communication. Lelio can only produce signs linked to his immediate needs. We administered him a Comprehensive Test of Non-verbal Intelligence (CTONI)1 and a color categorization test. Lelio performed in two of three subtests closely to pre-school and pre-linguistic children who have not yet fully developed their frontal lobes. We found that categorical, contextual and abstract reasoning are highly impaired in the total absence of a structured language. However, a crucial point to clear up is whether his cognitive impairments are mainly due to a reduced brain function or primarily to the total lack of language. One hypothesis is that his deafness and reduced brain function have blocked the development of any form of language, thus severely worsening his cognitive abilities. Since the present study has been carried out on a single case, it waits for further evidence. For these reasons, Lelio is a subject totally deprived of language, at least in the conventional sense. At the moment he attends a group of Theatre Therapy. In this group he uses some very simple gestures to communicate with the others. We have video-recorded Lelio and analysed these signs. They are highly iconic and deictic: i.e., he has a sign for “cat” (two raised fingers on the ears) a sign for “umbrella” (the gesture to open an umbrella), a sign for “toilette” (a raised finger). He doesn’t seem capable of indicating a temporal sequence, but he seems to understand simple gestures for “before” and “after”. He does not produce any sign that is not linked to his immediate needs. The cognitive evolution of the subject leaves open an interpretation according to which the passage from the imagistic way of thinking to the alphanumeric way of reasoning is missing. This lack can be seen as the basis that reveal an archaic and primitive thinking, where the objects are always seen in their concrete and functional perspective and Lelio’s way of thinking could precisely be of this kind

Prosody and Broca's Aphasia: An acoustic analysis

studio seprimentale acustico su soggetti afasici di Broc

Effects of Global Warming on Patients with Dementia, Motor Neuron or Parkinson’s Diseases: A Comparison among Cortical and Subcortical Disorders

Exposure to global warming can be dangerous for health and can lead to an increase in the prevalence of neurological diseases worldwide. Such an effect is more evident in populations that are less prepared to cope with enhanced environmental temperatures. In this work, we extend our previous research on the link between climate change and Parkinson's disease (PD) to also include Alzheimer's Disease and other Dementias (AD/D) and Amyotrophic Lateral Sclerosis/Motor Neuron Diseases (ALS/MND). One hundred and eighty-four world countries were clustered into four groups according to their climate indices (warming and annual average temperature). Variations between 1990 and 2016 in the diseases' indices (prevalence, deaths, and disability-adjusted life years) and climate indices for the four clusters were analyzed. Unlike our previous work on PD, we did not find any significant correlation between warming and epidemiological indices for AD/D and ALS/MND patients. A significantly lower increment in prevalence in countries with higher temperatures was found for ALS/MND patients. It can be argued that the discordant findings between AD/D or ALS/MND and PD might be related to the different features of the neuronal types involved and the pathophysiology of thermoregulation. The neurons of AD/D and ALS/MND patients are less vulnerable to heat-related degeneration effects than PD patients. PD patients' substantia nigra pars compacta (SNpc), which are constitutively frailer due to their morphology and function, fall down under an overwhelming oxidative stress caused by climate warming

Divergent targets of glycolysis and oxidative phosphorylation result in additive effects of metformin and starvation in colon and breast cancer

Emerging evidence demonstrates that targeting energy metabolism is a promising strategy to fight cancer. Here we show that combining metformin and short-term starvation markedly impairs metabolism and growth of colon and breast cancer. The impairment in glycolytic flux caused by starvation is enhanced by metformin through its interference with hexokinase II activity, as documented by measurement of 18F-fluorodeoxyglycose uptake. Oxidative phosphorylation is additively compromised by combined treatment: metformin virtually abolishes Complex I function; starvation determines an uncoupled status of OXPHOS and amplifies the activity of respiratory Complexes II and IV thus combining a massive ATP depletion with a significant increase in reactive oxygen species. More importantly, the combined treatment profoundly impairs cancer glucose metabolism and virtually abolishes lesion growth in experimental models of breast and colon carcinoma. Our results strongly suggest that energy metabolism is a promising target to reduce cancer progression

Pointing in cervical dystonia patients

IntroductionThe normal hemispheric balance can be altered by the asymmetric sensorimotor signal elicited by Cervical Dystonia (CD), leading to motor and cognitive deficits.MethodsDirectional errors, peak velocities, movement and reaction times of pointing towards out-of-reach targets in the horizontal plane were analysed in 18 CD patients and in 11 aged-matched healthy controls.ResultsCD patients displayed a larger scatter of individual trials around the average pointing direction (variable error) than normal subjects, whatever the arm used, and the target pointed. When pointing in the left hemispace, all subjects showed a left deviation (constant error) with respect to the target position, which was significantly larger in CD patients than controls, whatever the direction of the abnormal neck torsion could be. Reaction times were larger and peak velocities lower in CD patients than controls.DiscussionDeficits in the pointing precision of CD patients may arise from a disruption of motor commands related to the sensorimotor imbalance, from a subtle increase in shoulder rigidity or from a reduced agonists activation. Their larger left bias in pointing to left targets could be due to an increased right parietal dominance, independently upon the direction of head roll/jaw rotation which expands the left space representation and/or increases left spatial attention. These deficits may potentially extend to tracking and gazing objects in the left hemispace, leading to reduced skills in spatial-dependent motor and cognitive performance

First pass perfusion MRI identifies microvascular anatomical damage in patients with hypertrophic cardiomyopathy

Introduction Sudden death (SD) and progressive left ventricular (LV) impairment are serious possible consequences occurring in patients with hypertrophic cardiomyopathy (HCM). Interstitial fibrosis and scarring are associated with progressive LV dysfunction and with markers of SD, and are usually associated with small-vessel disease and a reduction of the number of vessels related to interstitial fibrosis and scarring