Giovanni de Marco

Cerebral peritumoral oedema study: Does a single dynamic MR sequence assessing perfusion and permeability can help to differentiate glioblastoma from metastasis?

Our purpose was to differentiate glioblastoma from metastasis using a single dynamic MR sequence to assess perfusion and permeability parameters. 24 patients with glioblastoma or cerebral metastasis with peritumoral oedema were recruited and explored with a 3T MR unit. Post processing used DPTools software. Regions of interest were drawn around contrast enhancement to assess relative cerebral blood volume and permeability parameters. Around the contrast enhancement Glioblastoma present high rCBV with modification of the permeability, metastasis present slight modified rCBV without modification of permeability. In conclusion, peritumoral T2 hypersignal exploration associating morphological MR and functional MR parameters can help to differentiate cerebral metastasis from glioblastoma.

Mathematical modeling of energy metabolism and hemodynamics of WHO grade II gliomas using in vivo MR data.

Therapeutic management of low-grade gliomas (LGG) is a challenge because they have undergone anaplastic transformation with variable delay. Today, only progressive volume growth on successive MRI allows an in vivo monitoring of this evolution. On the other hand, multinuclear spectroscopy and perfusion available during MRI may also provide assessment of metabolic changes underlying morphological modifications. To overcome this drawback, we developed a mathematical model of the metabolism and the hemodynamic of gliomas, based on a physiological model previously published, and including the MR parameters. This allows us to suggest that some specific profiles of metabolic and hemodynamic changes would be good indicators of potential anaplastic transformation.

Exploration and Identification of Cortico-Cerebellar-Brainstem Closed Loop During a Motivational-Motor Task: an fMRI Study

The cerebellum is involved not only in motor coordination, training, and memory, but also in cognition and emotion. Lobule VI in particular belongs to sensorimotor, salience, and executive cerebellar networks. This study aims to determine whether lobule VI would constitute an integrative interface between motor and cognitive/emotional circuits during a motor task with verbal encouragement, likely in conjunction with the basal ganglia (reward and motivational system). We used fMRI to identify specific recruitment of cerebellar and striatal systems during physical performance using two motor tasks with and without encouragement. We found that: (i) Force results were higher during verbal encouragement than during basal condition in all participants. (ii) The anterior part of the right lobule VI was activated by motor execution in both tasks, while its posterior part was specifically activated by verbal encouragement. (iii) The closed-connectivity loop maintained motivation induced by verbal encouragement between cerebral and cerebellar through the red nucleus and striatal network. Therefore, right lobule VI is a hub-controlling sensorimotor and motivates aspects of motor performance in relation with the red nucleus and the ventral striatum. These results could have important implications for extrapyramidal and multisystem degenerative diseases.

fMRI Randomized Study of Mental and Motor Task Performance and Cortisol Levels to Potentiate Cortisol as a New Diagnostic Biomarker

Cortisol is an important hormone in the protective stress response system, the Hypothalamus-Pituitary-Adrenal (HPA-axis). It becomes especially salient in immune suppression syndromes such as multiple sclerosis and Cushing’s disease. Fatigue is a common symptom and mental and motor tasks are difficult and labored. The role of cortisol is mental and motor tasks and the recruitment of key brain regions in completion of these tasks is explored together with functional magnetic resonance imaging in healthy participants. Cortisol levels were found to be higher and had greater reduction in levels during mental versus motor tasks. Recruitment of brain-stem and hypothalamus regions, important in cortisol activity, was affected differently. At low cortisol levels, mental task participants had less activity in the regions than their physical task counterparts. When cortisol levels were higher, wider spread recruitment of these brain regions was seen in the mental task participants, and for the physical task participants, the spread was at comparative low levels of cortisol. It is concluded that cortisol is implicated in these brain regions supporting the Thompson Cortisol Hypothesis and that brain region recruitment is likely to be dependent upon factors including cortisol levels as well as perception of stress in the task. It is suggested that mental tasks are perceived more stressful than physical but demand higher cortisol levels to promote wider spread brain region activity. Implication for neurological disease includes the use of cortisol in the proposed development of a potential new diagnostic biomarker for early detection of neurological sequelae.

Development of EMG Indicators for Measuring and Analyzing Pre-motor Activity on Muscles

In sport, it is well known that mental preparation to a physical effort increases drastically the performance. In this paper, we present a study that aims to evaluate the effect of movement preparation during pre-motor activity on the EMG signal. We considered the existence/no-existence of preparation and preparation duration as indicators. The results of this study performed on different muscles of the forearm show: i) female are sensitive to preparation warning whereas male are not sensitive, ii) contrary to deep muscles, superficial muscles are affected by preparation warning.

Collaboration of Cerebello-Rubral and Cerebello-Striatal Loops in a Motor Preparation Task

In this study, we used fMRI to identify brain regions associated with concentration (sustained attention) during a motor preparation task. In comparison with a non-concentration task, increased activities were observed (Pu2009<u20090.05, FWE-corrected P values) in cerebellar lobules VI and VII, motor cortex, pre-supplementary motor area (pre-SMA), thalamus, red nucleus (RN), and caudate nucleus (CN). Moreover, analysis of effective connectivity inter-areal (psychophysiological interactions) showed that during preparation, concentration-related brain activity increase was dependent on Cerebello-thalamo-pre-SMA-RN and Pre-SMA-CN-thalamo-M1 loops. We postulate that, while pre-SMA common to both loops is specifically involved in the movement preparation and readiness for voluntary movement through the striatum, the cerebellar lobule VI in conjunction with RN, likely through a cerebellar-rubro-olivary-cerebellar loop, might be implicated in concentration-related optimization of upcoming motor performances.

Extrapyramidal deficits in ALS: a combined biomechanical and neuroimaging study

IntroductionExtrapyramidal deficits are poorly characterised in amyotrophic lateral sclerosis (ALS) despite their contribution to functional disability, increased fall risk and their quality-of-life implications. Given the concomitant pyramidal and cerebellar degeneration in ALS, the clinical assessment of extrapyramidal features is particularly challenging.ObjectiveThe comprehensive characterisationxa0of postural instability in ALS using standardised clinical assessments, gait analyses and computational neuroimaging tools in a prospective study design.MethodsParameters of gait initiation in the anticipatory postural adjustment phase (APA) and execution phase (EP) were evaluated in ALS patients with and without postural instability and healthy controls. Clinical and gait analysis parameters were interpreted in the context of brain imaging findings.ResultsALS patients with postural instability exhibit impaired gait initiation with an altered APA phase, poor dynamic postural control and significantly decreased braking index. Consistent with their clinical profile, “unsteady” ALS patients have reduced caudate and brain stem volumes compared to “steady” ALS patients.InterpretationOur findings highlight that the ALS functional rating scale (ALSFRS-r) does not account for extrapyramidal deficits, which are major contributors to gait impairment in a subset of ALS patients. Basal ganglia degeneration in ALS does not only contribute to cognitive and behavioural deficits, but also adds to the heterogeneity of motor disability.

Neural mechanisms associated with treatment decision making: an fMRI study

HighlightsEnhanced effective connectivity between OFC and VS is associated with the likehood of taking medications.Enhanced effective connectivity between OFC, insula and amygdala is associated with the likehood of refusing treatment.Participants demonstrated increased skin conductance response prior to making riskier treatment decisions.Neural and physiological results mirrored behavioral data and fit within a behavioral economic theoretical framework. Abstract Great progress has been made in understanding how people make financial decisions. However, there is little research on how people make health and treatment choices. Our study aimed to examine how participants weigh benefits (reduction in disease progression) and probability of risk (medications’ side effects) when making hypothetical treatment decisions, and to identify the neural networks implicated in this process. Fourteen healthy participants were recruited to perform a treatment decision probability discounting task using MRI. Behavioral responses and skin conductance responses (SCRs) were measured. A whole brain analysis were performed to compare activity changes between mild and severe medications’ side effects conditions. Then, orbitofrontal cortex (OFC), ventral striatum (VS), amygdala and insula were chosen for effective connectivity analysis. Behavioral data showed that participants are more likely to refuse medication when side effects are high and efficacy is low. SCRs values were significantly higher when people made medication decisions in the severe compared to mild condition. Functionally, OFC and VS were activated in the mild condition and were associated with increased likehood of choosing to take medication (higher area under the curve AUC side effects/efficacy). These regions also demonstrated an increased effective connectivity when participants valued treatment benefits. By contrast, the OFC, insula and amygdala were activated in the severe condition and were associated with and increased likelihood to refuse treatment. These regions showed enhanced effective connectivity when participants were confronted with increased side effects severity. This is the first study to examine the behavioral and neural bases of medical decision making.

The Click Test: A Novel Tool to Quantify the Age-Related Decline of Fast Motor Sequencing of the Thumb

BACKGROUNDnThe thumb plays a critical role for manual tasks during the activities of daily life and the incidence of neurological or musculoskeletal disorders affecting the voluntary movements of the thumb is high in the elderly. There is currently no tool to assess repetitive motor sequencing of the thumb during ageing.nnnOBJECTIVESnTo report a novel procedure (the Click Test) assessing the effects of ageing on fast motor sequencing of the thumb.nnnMETHODnHealthy subjects (n = 252; mean age +/- SD: 49.76 +/- 19.97 years; range: 19-89 years; F/M: 151/101) were asked to perform fast repeated flexion/extension movements of the thumb using a mechanical counter.nnnRESULTSnMotor performances (assessed by the number of clicks during 3 time periods: 15, 30 and 45 sec), significantly decreased as a function of age for both the dominant (age effect; p< 0.0001 for 15, 30 and 45 sec) and the non-dominant hand (p<0.0001 for 15, 30 and 45 sec). The number of clicks was significantly higher in males (gender effect; p<0.001) and was higher on the dominant side as compared to the non-dominant side (handedness effect: p<0.001). The Click Test is characterized by high repeatability (coefficients of variation from 3.20 to 4.47%), excellent intra-rater reliability (intra-class coefficients ICC ranging from 0.89 to 0.98), high inter-rater reproducibility (Pearsons product correlation ranging from 0.85 to 0.96), high internal consistency (Cronbach alpha coefficient=0.95) and is highly correlated in terms of relative performances with the box and block test and the 9-hole peg test (positive linear correlation with the results of the box and block test: p<0.001 for 15, 30 and 45 sec for both the dominant and the non-dominant hand; negative linear correlation with the results of the 9-hole peg test: p<0.001 for 15, 30 and 45 sec for both the dominant and the non-dominant hand).nnnCONCLUSIONnThe Click Test is an entirely novel and very low cost tool to reliably discriminate the ageing effects upon the performances during fast repetitive motor sequencing of the thumb. The potential clinical and research applications for motor functions are multiple, especially in acute and chronic neurological disorders affecting the thumb as well as in the field of rheumatology and orthopedics.