Contributions of memory circuits to language: The declarative/procedural model

The structure of the brain and the nature of evolution suggest that, despite its uniqueness, language likely depends on brain systems that also subserve other functions. The declarative/procedural (DP) model claims that the mental lexicon of memorized word-specific knowledge depends on the largely temporal-lobe substrates of declarative memory, which underlies the storage and use of knowledge of facts and events. The mental grammar, which subserves the rule-governed combination of lexical items into complex representations, depends on a distinct neural system. This system, which is composed of a network of specific frontal, basal-ganglia, parietal and cerebellar structures, underlies procedural memory, which supports the learning and execution of motor and cognitive skills, especially those involving sequences. The functions of the two brain systems, together with their anatomical, physiological and biochemical substrates, lead to specific claims and predictions regarding their roles in language. These predictions are compared with those of other neurocognitive models of language. Empirical evidence is presented from neuroimaging studies of normal language processing, and from developmental and adult-onset disorders. It is argued that this evidence supports the DP model. It is additionally proposed that "language" disorders, such as specific language impairment and non-fluent and fluent aphasia, may be profitably viewed as impairments primarily affecting one or the other brain system. Overall, the data suggest a new neurocognitive framework for the study of lexicon and grammar

The role of pre-supplementary motor area in spatial vector transformation: evidence from Parkinson's disease

This thesis investigated the role of the supplementary motor area (SMA) in visuospatial processing using Parkinson’s disease (PD) patients as a model of pre-supplementary motor area (pre-SMA) dysfunction. The vector transformation hypothesis assumes that visuospatial transformation deficits in PD are a result of impairments in calculating vectors or co-ordinate remapping with a reference frame. These vector transformation processes were investigated in spatial normalisation during mental rotation and showed that PD patients demonstrate slower image normalisation rates indicative of a deficit compares with controls. It was then investigated how far these deficits extend to other vector transformation tasks such as abstract grid navigation. PD patients were less accurate than controls and these deficits were independent of spatial short term memory and serial processing suggesting that PD is associated with spatial transformation deficits. Comparisons of visual vector transformation and auditory vector transformation showed that PD patients were less accurate at visual vector transformation than auditory vector transformation suggesting that vector transformation processes may be more sensitive to the visual domain. The final study was a pilot study to investigate the feasibility of using a cognitive vector transformation task to remediate symptoms of bradykinesia in PD. Modest improvements in movement velocity following the vector transformation task but no significant change in movement velocity following a control task suggests that vector transformation can be used for therapeutic gain

Premotor and prefrontal contributions to modulating upper limb somatosensory input into non-primary motor areas

Upper limb motor control requires the use and integration of afferent somatosensory input from peripheral receptors to help plan and prepare movements. Cortical surface electroencephalography can be used to measure the earliest relay and processing of mixed somatosensory input in primary (SI) and secondary somatosensory (SII) cortices using parietal somatosensory evoked potentials (SEPs) that occur 20 to 100 milliseconds (ms) after median nerve stimulation. Moreover, somatosensory input into non-primary motor areas, such as premotor cortex (PMC) and supplementary motor area (SMA), can be measured by frontal N30 and N60 SEPs. Therefore, frontal N30 and N60 SEPs may provide an important neurophysiological link between somatosensory processing and upper limb motor control. Both PMC and SMA have intracortical connections with primary motor cortex (M1) and prefrontal cortex (PFC) as well as intercortical connections with their contralateral representations. However, it is not fully understood how somatosensory input in non-primary motor areas, represented by frontal SEPs, are modulated in the cortex by contralateral PMC and ipsilateral PFC. A modulatory role of contralateral M1 but not contralateral premotor areas on somatosensory input into non-primary motor areas has been established through contralateral movement paradigms. Furthermore, a modulatory role of the ipsilateral PFC on somatosensory input into non-primary motor areas has been identified through prefrontal lesion patients but it is unclear how PFC functionally modulates this somatosensory input during movement. Thus, the current thesis aimed to evaluate the contributions of the ipsilateral PFC as well as contralateral PMC on somatosensory processing in non-primary motor areas as well as SI/SII. SEP modulations were examined using experimental manipulations of top-down attention and cued contralateral movements to evaluate PFC and PMC contributions, respectively. In addition, continuous theta burst stimulation, a specific type of inhibitory non-invasive transcranial magnetic stimulation technique, was applied over PMC and PFC to evaluate their specific contributions to modulating somatosensory input into non-primary motor areas and SI/SII during a cued movement task. Understanding frontal SEP modulations and their association with upper limb motor control will have important applications for understanding dysfunctional upper limb motor control in various neurological disorders such as Parkinson’s disease (PD) that are known to have irregular frontal SEPs. The main findings from Chapters 2 and 3 revealed that frontal N30 and N60 SEPs were decreased during early response selection and increased during the late stages of preparing finger sequences to attended somatosensory input. In contrast, SI/SII input represented by parietal P50 and P100 SEPs were increased with attention. The main results of Chapter 4 showed that N30 and N60 SEPs were decreased and increased after transiently decreasing excitability in left PMC and right PFC, respectively. Collectively, the results of this thesis revealed temporally-specific modulations of somatosensory input into non-primary motor areas during contralateral upper limb movements that are a result of changes in activity in a network that includes the right PFC and left PMC

Contribution à l'étude des liens entre conscience et déglutition

Following severe brain injuries (e.g., traumatic or anoxic brain injury, stroke), a small proportion of patients will remain in an altered state of consciousness. Patients with prolonged (> 28 days post-insult) disorders of consciousness (DOC) can open their eyes (sometimes showing electrophysiological sleep/wake cycles) and the majority no longer need invasive ventilation. However, most of them receive artificial feeding, suggesting that consciousness affects swallowing capacities. The aim of this thesis is to contribute to the study of the links between consciousness and swallowing. The hypotheses are that swallowing capacities are linked to level of consciousness, and that the presence of some components of swallowing constitutes a possible sign of consciousness. Based on a literature review, we show that the sequencing of the components of swallowing falls on a continuum of voluntary to reflex behaviors. Components of the oral phase may be considered as voluntary behaviors because they are controllable and suppressible (although largely automated), components of the pharyngeal phase as somatic reflexes, and components of the esophageal phase as autonomic reflexes. The triggering of the swallowing reflex inhabits the border region between voluntary behaviors and somatic reflexes, while the opening of the upper esophageal sphincter divides somatic from autonomic reflexes. If voluntary behaviors are considered possible signs of consciousness, the presence of components of the oral phase of swallowing should be considered as revealing conscious behaviors. Moreover, we show that a range of cortical areas (mainly the primary sensorimotor cortex, premotor cortex and supplementary motor area, anterior part of the cingulate cortex, insula and cerebellum) are involved in both volitional and non-volitional swallowing tasks. In two retrospective studies analyzing swallowing in patients with DOC diagnosed by means of repeated behavioral assessment and neuroimaging, we demonstrate that almost all such patients present at least one dysfunction in the oral and/or pharyngeal phase. Patients who do not show behavioral signs of consciousness (unresponsive wakefulness syndrome – UWS) do not present an efficient oral phase of swallowing allowing oral feeding with solid food. Consequently, the preservation of components of the oral phase of swallowing should be considered as a sign of consciousness and be one of the diagnostic criteria for consciousness. The absence of an efficient oral phase of swallowing in patients with UWS and its presence in only a small proportion of minimally conscious (MCS) patients explain why no “typical” patients with UWS (i.e., with behavioral and neuroimaging assessments pointing in the same direction) can be fed entirely orally while no patients with MCS can eat ordinary textured food. Furthermore, in the studied group, level of consciousness is linked to components of the pharyngeal phase (reflected by the absence of a tracheostomy, pharyngo-laryngeal secretions or saliva aspiration) and to the cough reflex. Indeed, more patients with MCS than UWS present efficient spontaneous saliva management and a cough reflex, although these components are present in some patients with UWS. For that reason, these components seem to represent cortically mediated behavior but do not constitute signs of consciousness as such. Finally, this work highlights the lack of appropriate tools to assess and treat swallowing for patients with DOC. A protocol study for the validation of a swallowing assessment tool for patients with DOC is therefore proposed

FMRI evidence of memory representations of somatosensory stimuli in the human brain

Distinct brain regions process innocuous vibration and cutaneous heat pain. The role of these areas in the perception of pain is still a matter of debate; and the role of these areas in the mediation of memory of somatosensory stimuli is uncertain and has not been studied with brain imaging in healthy human volunteers. All experiments described here, involved an experimental design, which included a delayed-discrimination paradigm and functional magnetic resonance imaging (fMRI). In manuscript #1, we aimed at unraveling the cerebral correlates of attention and spatial localization of innocuous vibrotactile stimuli applied to the right volar surface of the forearm. In this study, we report that increased degrees of attention to the vibrotactile stimuli were associated with heightened levels of activation in several brain areas. In manuscript #2, we investigated the short-term memory for sensory aspects (intensity and location) of cutaneous heat pain delivered to two areas (thenar and hypothenar eminences) of the palm of the right hand. In this experiment, the memory and control trials were presented in blocks, whereby the subjects could predict what trials were going to follow. This study revealed that the presentation of painful stimuli evoked activation in different brain regions than those activated during the online maintenance (interstimulus interval or ISI) of the intensity and spatial features of those stimuli; a process, which I will refer to short-term memory. In manuscript #3, we investigated again short-term memory for sensory aspects of heat pain (as in manuscript #2), but in this case, the memory and control trials were presented in a randomized order. In this study, we found that the perception and short-term memory of pain were processed by a comparable network of areas. The predictability of the memory and control trials may have contributed to these findings.La vibration inoffensive ainsi que la chaleur douloureuse cutanée sont traitées pardifférentes régions du cerveau. Le rôle de ces régions dans la perception de la douleurest controversé; et le rôle de ces régions dans la mémoire des stimuli somatosensorielsest incertain et n'a jamais encore été étudié en imagerie cérébrale chez des sujetshumains sains. Le design expérimental de toutes les études décrites ici comprenait unparadigme de 'delayed-discrimination' et l'imagerie par résonance magnétiquefonctionnelle (IRMf). L'étude #1 visait à élucider les corrélats cérébraux de l'attention etde la localisation spatiale des stimuli vibrotactiles inoffensifs présentés à la faceantérieure de l'avant-bras droit. Dans cette étude, nous avons trouvé que des degrésélevés d'attention portée aux stimuli vibrotactiles étaient associés à des niveaux accrusd'activation dans plusieurs zones du cerveau. Dans l'étude #2, nous avons enquêté surla mémoire à court-terme des caractéristiques sensorielles (intensité et emplacement)de la chaleur douloureuse cutanée présentée à deux endroits (éminences thénar ethypothénar) de la paume de la main droite. Dans cette étude, les essais mémoire etcontrôle étaient présentés en bloc, ou de sorte que les participants pouvaient prévoir dequel type serait le prochain essai. Cette étude a révélé que la présentation des stimulidouloureux a évoqué une activation de différentes régions cérébrales que celles quiétaient activées lors de la rétention de l'intensité et de l'emplacement des stimulationsdurant l'intervalle inter-stimuli (liS); un processus que je qualifierai de mémoire à courtterme.Dans l'étude #3, nous avons également enquêté sur la 'mémoire à court-termedes aspects sensoriels de la chaleur douloureuse (tout comme dans l'étude #2), maisdans ce cas, les essais mémoire et contrôle étaient présentés de façon aléatoire. Danscette étude, nous avons trouvé que la perception de la douleur ainsi que la mémoire àcourt-terme de la douleur étaient traitées par un réseau de régions semblable. Laprévisibilité des essais mémoire et contrôle peut avoir contribué à ce résultat

Cognitive Assessment and Rehabilitation of subjects with Traumatic Brain Injury

This thesis regards the study and the development of new cognitive assessment and rehabilitation techniques of subjects with traumatic brain injury (TBI). In particular, this thesis i) provides an overview about the state of art of this new assessment and rehabilitation technologies, ii) suggests new methods for the assessment and rehabilitation and iii) contributes to the explanation of the neurophysiological mechanism that is involved in a rehabilitation treatment. Some chapters provide useful information to contextualize TBI and its outcome; they describe the methods used for its assessment/rehabilitation. The other chapters illustrate a series of experimental studies conducted in healthy subjects and TBI patients that suggest new approaches to assessment and rehabilitation. The new proposed approaches have in common the use of electroencefalografy (EEG). EEG was used in all the experimental studies with a different purpose, such as diagnostic tool, signal to command a BCI-system, outcome measure to evaluate the effects of a treatment, etc. The main achieved results are about: i) the study and the development of a system for the communication with patients with disorders of consciousness. It was possible to identify a paradigm of reliable activation during two imagery task using EEG signal or EEG and NIRS signal; ii) the study of the effects of a neuromodulation technique (tDCS) on EEG pattern. This topic is of great importance and interest. The emerged founding showed that the tDCS can manipulate the cortical network activity and through the research of optimal stimulation parameters, it is possible move the working point of a neural network and bring it in a condition of maximum learning. In this way could be possible improved the performance of a BCI system or to improve the efficacy of a rehabilitation treatment, like neurofeedback

Intentional inhibition of actions in humans

A crucial component of human behavioural flexibility is the capacity to inhibit actions at the last moment before action execution. This behavioural inhibition is often not an immediate reaction to external stimuli, but rather an endogenous ‘free’ decision. Knowledge about such ‘intentional inhibition’ is currently limited, with most research focused on stimulus-driven inhibition. This thesis will examine intentional inhibition, using several different experimental approaches. The behavioural experiments reported in the initial chapters found that intentional inhibition directly alters sensory processing during decision-making. In addition, there were unique effects of prior event sequences on subsequent decisions to either act or inhibit. Brain imaging methods using EEG and fMRI showed distinct neural mechanisms associated with intentional inhibition, which did not apply to rule-based inhibition. Work with Tourette syndrome patients indicated that the intentional inhibition of involuntary motor tics affects brain activity associated with voluntary actions. Furthermore, attentional manipulation strategies were shown to be highly effective in reducing tics, which may open up alternative behavioural treatment approaches for tic disorders. This thesis concludes by demonstrating that intentional inhibition is a bona fide cognitive function worth studying. It also develops a cognitive model in which behavioural inhibition varies along a continuum from ‘instructed inhibition’ to ‘intentional inhibition’. This model may be useful as a guide for future work

Cognitive flexibility in obsessive-compulsive disorder and major depression: Functional neuroimaging studies on reversal learning and task switching

Veltman, D.J. [Promotor]Uylings, H.B.M. [Promotor]Nielen, M.M.A. [Copromotor