Delayed access to conscious processing in multiple sclerosis: reduced cortical activation and impaired structural connectivity

Although multiple sclerosis (MS) is frequently accompanied by visuo-cognitive impairment, especially functional brain mechanisms underlying this impairment are still not well understood. Consequently, we used a functional MRI (fMRI) backward masking task to study visual information processing stratifying unconscious and conscious in MS. Specifically, 30 persons with MS (pwMS) and 34 healthy controls (HC) were shown target stimuli followed by a mask presented 8-150 ms later and had to compare the target to a reference stimulus. Retinal integrity (via optical coherence tomography), optic tract integrity (visual evoked potential; VEP) and whole brain structural connectivity (probabilistic tractography) were assessed as complementary structural brain integrity markers. On a psychophysical level, pwMS reached conscious access later than HC (50 vs. 16 ms, p < .001). The delay increased with disease duration (p < .001, β = .37) and disability (p < .001, β = .24), but did not correlate with conscious information processing speed (Symbol digit modality test, β = .07, p = .817). No association was found for VEP and retinal integrity markers. Moreover, pwMS were characterized by decreased brain activation during unconscious processing compared with HC. No group differences were found during conscious processing. Finally, a complementary structural brain integrity analysis showed that a reduced fractional anisotropy in corpus callosum and an impaired connection between right insula and primary visual areas was related to delayed conscious access in pwMS. Our study revealed slowed conscious access to visual stimulus material in MS and a complex pattern of functional and structural alterations coupled to unconscious processing of/delayed conscious access to visual stimulus material in MS

The Argument from Brain Damage Vindicated

It has long been known that brain damage has important negative effects on one’s mental life and even eliminates one’s ability to have certain conscious experiences. It thus stands to reason that when all of one’s brain activity ceases upon death, consciousness is no longer possible and so neither is an afterlife. It seems clear that human consciousness is dependent upon functioning brains. This essay reviews some of the overall neurological evidence from brain damage studies and concludes that our argument from brain damage has been vindicated by such overwhelming evidence. It also puts forth a more mature philosophical rationale against an afterlife and counters several replies to the argument. 1. Philosophical Background -- 2. The Dependence of Consciousness on the Brain: Some Preliminary Evidence -- 3. Brain Damage, Lesion Studies, and the Localization of Mental Function - 3.1 Perception - 3.2 Awareness, Comprehension, and Recognition - 3.3 Memory - 3.4 Personality - 3.5 Language - 3.6 Emotion - 3.7 Decision-Making - 3.8 Social Cognition and Theory of Mind - 3.9 Moral Judgment and Empathy - 3.10 Neurological Disorders and Disease - 3.11 The Unity of Consciousness -- 4. Objections and Replies - 4.1 Souls, Minds, and Energy Fields - 4.2 The Instrument Theory - 4.3 The Embodied Soul Alone is Affected -- 5. Conclusio

Polypharmacy in patients with Multiple Sclerosis: effects on fatigue, perceived cognition, and objective cognitive performance

Title from PDF of title page, viewed on June 24, 2013Thesis advisor: Jared M. BruceVitaIncludes bibliographic references (pages 60-82)Thesis (M.A.)--Dept. of Psychology. University of Missouri--Kansas City. 2013OBJECTIVE: Many individuals with multiple sclerosis (MS) take multiple medications on a regular basis, also referred to as polypharmacy. In other patient populations, polypharmacy has been associated with fatigue and cognitive dysfunction. However, no study has examined polypharmacy in MS. We explored the association between polypharmacy, fatigue, and cognition in a group of participants with MS. METHODS: Data for this study were collected as part of a larger investigation examining medication adherence in MS. The sample included 86 patients with MS and 20 healthy controls. We assessed objective cognitive functioning, self-reported cognition, and self-reported fatigue. In addition, a list of patients' medications was obtained at the time of testing. Polypharmacy was classified using a cutoff of 5 or more daily medications. RESULTS: Approximately 33% of the MS sample had polypharmacy. After controlling for age, disease duration, and disability, MS patients with polypharmacy reported more memory problems, processing speed difficulties, and fatigue than MS patients without polypharmacy, F(1, 79) = 13.09, p = .001 and F(1, 79) = 7.33, p < .01, F(1, 79) = 10.45, p < .01, respectively. MS patients with polypharmacy also exhibited worse prospective memory performance than patients without polypharmacy, F(1, 77) = 12.67, p = .001. CONCLUSIONS: This is the first study to examine the association between fatigue, cognition, and polypharmacy in MS patients. Results suggest that researchers should account for polypharmacy and medication effects when conducting studies examining fatigue and cognition in MS. Similarly, clinicians and patients should carefully weigh the costs and benefits of prescribing multiple medications, as these may contribute to iatrogenic fatigue and cognitive problems.Overview -- Review of literature -- Method -- Results -- Discussion -- Appendi

Attention, inhibition and food: a neuroscientific investigation of eating disorders and obesity

Eating disorders (ED, i.e. anorexia nervosa, bulimia and binge eating) and obesity have been linked to attentional biases for and altered inhibition of responses to food stimuli. However, these two groups of patients have rarely been investigated together in the same studies. The goal of this study is to fill this gap in the literature by investigating subliminal visual processing of food stimuli and response inhibition in both ED patients and overweight/obese participants. Seventy-four participants (25 ED patients, 24 overweight and obese, and 25 healthy controls) were enrolled in this study. Subliminal processing of food and non-food stimuli was measured with a breaking continuous flash suppression (bCFS) task, while impulsivity was measured with a Go/No-Go task. Among participants with ED symptoms, higher BMI predicted faster awareness in the bCFS task, especially of food images compared to non-food images, and shorter RTs to food Go cues in the Go/No-Go task. Altered subliminal processing of and heightened attention for food stimuli was found in patients who suffered from both dysfunctional eating habits and obesity. These results demonstrate the need to also include obese participants in future studies on processing biases in ED patients, to better understand attentional biases for food.Obesity has been linked to low performance in the attention and impulsivity domains. Obese individuals, compared with healthy-weight participants, exhibit increased attentional bias to food cues. Notably, the prefrontal cortex plays a central role in cognitive control over food choices and is less active in obese individuals. By using direct current stimulation (tDCS), the study investigated the role of the right dorsolateral prefrontal cortex (dlPCF) in subliminal visual processing of, and in the inhibition of responses to food pictures, in individuals with healthy vs. obese body mass index (BMI). Obese individuals were expected to show a subliminal food bias and reduced inhibition. Moreover, modulation of the dlPFC by tDCS was expected to impact on this pattern. In a within-subject design, fifty-three participants with a BMI ranging from 17 to 34 received in separate sessions, anodal, cathodal, or sham tDCS over the right dlPCF. Subliminal processing was measured with a breaking Continuous Flash Suppression task (bCFS), and inhibition was assessed with a Go/No-Go task. In both tasks, food-related and unrelated pictures were presented. Data were analyzed using Linear Mixed Models (LMMs). In the bCFS task, a higher BMI led to longer detection times for both food and nonfood pictures [p = 0.02]. In the Go/No-Go task, higher BMI led to slower responses in food Go trials [p = 0.02]. Anodal stimulation resulted in shorter detection times in the bCFS task in all participants [p < 0.001], but especially in those with higher BMI [p = 0.01]. Cathodal stimulation did not interact with participants\u2019 BMI in neither the bCFS nor the Go/No-go tasks. The results indicates that an attentional bias for food is not present at a subliminal level of processing, and that it might be present only at a late stage of attentive processing. The study also revealed that obesity might be associated with a generally increased threshold of perceptual awareness. This association has never been reported before. Moreover, these findings indicate that anodal stimulation improves attentional performance of all participants, especially in those with higher BMIs, and particularly at a subliminal level. This is in accordance with the evidence of reduced dlPFC activity in obesity and, more generally, in eating disorders.Food is a salient stimulus and as such it is preferentially attended. From early stages of stimulus processing, obesity and eating disorders influence attention and inhibition towards food. Subliminal processing of food is also altered in individuals with a high BMI and ED symptoms, and a higher BMI has been linked to a higher threshold for visual awareness. In this study we explore the neural correlates of suppression and inhibition of food and non-food stimuli. Fifty-three participants completed a breaking Continuous Flash Suppression (bCFS) task and a Go/No-Go task with food and non-food stimuli. We collected whole-brain structural magnetic resonance images and used voxel-based morphometry to measure grey matter (GM) density. We find that higher GM density in visual (left calcarine and occipital cortex) and reward areas (bilateral caudate nuclei) is associated with longer suppression times in the bCFS task, while higher GM density in control areas is associated to shorter suppression times in the bCFS task (left frontal gyrus) and faster reaction times in the Go/No-Go task (left frontal pole). Higher hypothalamic and lower postcentral cortex GM density are associated with higher Body Mass Index and more severe self-reported eating disorder symptoms. Moreover, some areas in the reward and control circuit (left orbitofrontal cortex, left insula, right dorsolateral prefrontal cortex, bilateral temporal areas) are differentially correlated to suppression times in participants with a high BMI. In conclusion, the reward and control circuits are involved in subliminal processing, and altered suppression times are associated with morphological alterations of these regions

White matter damage impairs access to consciousness in multiple sclerosis

International audienc

Corrélats neuronaux de la conscience : apport de l'étude des modèles lésionnels du système nerveux central et périphérique

La conscience correspond à l'ensemble de capacités cognitives qui permettent à un individu d'acquérir et de partager son savoir avec autrui. D'un point de vue théorique, on peut distinguer deux composantes élémentaires dans ce concept: un niveau (i.e. vigilance) et un contenu (i.e. informations intégrées par l'individu). À son tour, le contenu conscient, fait référence à l'élaboration des notions distinctes de soi et du monde extérieur. En suivant une demarche anatomoclinique, centrée sur l'étude des modèles lésionnels du système nerveux central et périphérique, nous avons eu pour objectif la caractérisation des substrats neuronaux de chacune de ces composantes. Premièrement, nous nous sommes intéressés aux mécanismes impliqués dans l'emergence d'un contenu conscient à partir d'un niveau de conscience. Pour cela nous avons étudié de manière comparative en TEP H2O15 les cartes de débit sanguin cérébral au repos et lors d'une stimulation proprioceptive, chez des sujets sains et des patients en état neurologique végétatif (ENV). Nos résultats soulignent le rôle de la Formation Réticulée Activatrice Ascendante (FRAA) dans le maintien du niveau de conscience et du Cortex Postéro-Médian (CPM) dans l'élaboration de son contenu. Une deconnexion fonctionnelle entre ces structures semble associée au tableau clinique d'ENV. Ces éléments sont en accord avec les modèles théoriques qui corrèlent l'apparition de la conscience à la diffusion synchrone des informations au sein d'un réseau neuronal distribué. De manière complémentaire, nous avons étudié les processus liés à l'élaboration de la notion de soi à partir des representations motrices. À l'aide d'un modèle de déafférentation périphérique par anesthésie locorégionale (ALR), nous avons caractérisé dans ce contexte un ensemble d'illusions peceptives analogues à celles décrites chez les patients amputés. En effet, l'ALR semble être à l'origine de distorsions perceptives de taille/forme, de posture et de mouvement, dont l'apparition est corrélée avec la survenue du déficit proprioceptif. Parallèlement, nous avons analysé les performances des sujets sains bénéficiant d'une ALR du membre supérieur au décours d'une tâche de reconnaissance bimanuelle. Les résultats obtenus suggèrent que (i) la reconnaissance bimanuelle implique la simulation mentale des mouvements des mains, (ii) les representations centrales sous-jacentes sont modifiées rapidement par l'ALR, (iii) le substrat neuronal de l'image du corps recruté par cette tâche est capable d'intègrer des informations polymodales. Nos résultats apportent des éléments nouveaux concernant l'activité cérébrale résiduelle des sujets cérébrolésé et soulignent l'importance des connexions cérébrales nécessaires à l'élaboration d'une expérience consciente. L'étude du phénomène de membre fantôme induit par l'ALR constitue une approche originale des mécanismes impliqués dans l'émergence de la notion de soi. Cette procédure, actuellement dédiée à un usage exclusivement anesthésique, pourrait constituer dans un avenir proche, un nouvel outil de modulation thérapeutique des phénomènes de plasticité cérébrale adaptativeConsciousness is a multifaceted concept, which can be divided in two main components: arousal (i.e. level of consciousness) and awareness (i.e. the contents of consciousness). In turn, awareness can be divided in two elementary units: external and self-awareness. Here, we propose that disorders of consciouness, associated to brain or peripheral nervous injuries, are a privileged way to investigate the links between these components and their related neural mechanisms. On the basis of H2 O15 PET measurement of cerebral blood flow during rest or during a sensory stimulus, we comparatively analysed the level of interplay which exists between arousal and awareness in healthy subjects and in severely brain-injured patients in a vegetative state. Our results highlighted the role of two major areas: the Ascending Reticular Activating System (ARAS), and the Posteromedial cortex (PMC): one allowing conscious access to external stimuli and the another one, allowing self-referential processes. We demonstrated for the first time, that the Ascending Reticular Activating System (ARAS), whose activity was functionally correlated to that of the PMC in controls, showed no functional correlation with it in PVS patients. This data emphasizes the functional link between cortices and brainstem in the genesis of perceptual awareness and strengthens the hypothesis that consciousness is based on a widespread neural network. Otherwise, we studied generation and updating of self-awareness from peripheral inputs in a model of acute deafferentation induced by regional anesthesia (RA). First, we described that RA induces a set of perceptual illusion that are similar to the phantom limb sensations identified in amputees. RA-induced size, shape, postural and kinesthetic misperceptions for which the onset seems strongly related to an alteration of proprioception. Second, we used a visual left/right hand judgement task, implicitly recruiting motor imagery processes in patients receiving upper limb RA. Results suggest that (i) the right/left judgement task involves mental simulation of hand movements, (ii) the underlying mental representations and their neural substrates are subject to acute alterations following RA, (iii) brain regions supporting body image representations are modulated in a cross-modal way. Our data provide new insights about residual brain activity in severely brain-injured patients and the elaboration of a content of consciousness from a level of arousal. Looking at the phantom limb phenomena induced by RA, constitutes a novel approach to the study of the Self, and could pave the way to further studies assessing RA modulation of afferent inputs in the neurorehabilitation contex