Prenatal Protein Malnutrition Leads to Hemispheric Differences in the Extracellular Concentrations of Norepinephrine, Dopamine and Serotonin in the Medial Prefrontal Cortex of Adult Rats

Exposure to prenatal protein malnutrition (PPM) leads to a reprogramming of the brain, altering executive functions involving the prefrontal cortex (PFC). In this study we used in vivo microdialysis to assess the effects of PPM on extracellular concentrations of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) bilaterally in the ventral portion of the medial prefrontal cortex (vmPFC; ventral prelimbic and infralimbic cortices) of adult Long-Evans rats. Female Long-Evans rats were fed either a low protein (6%) or adequate protein diet (25%) prior to mating and throughout pregnancy. At birth, all litters were culled and fostered to dams fed a 25% (adequate) protein diet. At 120 days of age, 2 mm microdialysis probes were placed into left and right vmPFC. Basal extracellular concentrations of NE, DA, and 5-HT were determined over a 1-h period using HPLC. In rats exposed to PPM there was a decrease in extracellular concentrations of NE and DA in the right vmPFC and an increase in the extracellular concentration of 5-HT in the left vmPFC compared to controls (prenatally malnourished: N = 10, well-nourished: N = 20). Assessment of the cerebral laterality of extracellular neurotransmitters in the vmPFC showed that prenatally malnourished animals had a significant shift in laterality from the right to the left hemisphere for NE and DA but not for serotonin. In a related study, these animals showed cognitive inflexibility in an attentional task. In animals in the current study, NE levels in the right vmPFC of well-nourished animals correlated positively with performance in an attention task, while 5-HT in the left vmPFC of well-nourished rats correlated negatively with performance. These data, in addition to previously published studies, suggest a long-term reprogramming of the vmPFC in rats exposed to PPM which may contribute to attention deficits observed in adult animals exposed to PPM

Facilitation paradoxale induite par la perturbation de la fonction visuo-spatiale: revisiter «l’effet Sprague»

International audienceThe ‘Sprague Effect’ described in the seminal paper of James Sprague (Science 153:1544 e1547, 1966a) is an unexpected paradoxical effect in which a second brain lesion reversed functional deficits induced by an earlier lesion. It was observed initially in the cat where severe and permanent contralateral visually guided attentional deficits generated by the ablation of large areas of the visual cortex were reversed by the subsequent removal of the superior colliculus (SC) opposite to the cortical lesion or by the splitting of the collicular commissure. Physiologically, this effect has been explained in several ways-most notably by the reduction of the functional inhibition of the ipsilateral SC by the contralateral SC, and the restoration of normal interactions between cortical and midbrain structures after ablation. In the present review, we aim at reappraising the ‘Sprague Effect’ by critically analyzing studies that have been conducted in the feline and human brain. Moreover, we assess applications of the ‘Sprague Effect’ in the rehabilitation of visually guided atten- tional impairments by using non-invasive therapeutic approaches such as transcranial magnetic stimulation (TMS) and transcranial direct-current stimulation (tDCS). We also review theoretical models of the effect that emphasize the inhibition and balancing be- tween the two hemispheres and show implications for lesion inference approaches. Last, we critically review whether the resulting inter-hemispheric rivalry theories lead toward an efficient rehabilitation of stroke in humans. We conclude by emphasizing key challenges in the field of ‘Sprague Effect’ applications in order to design better therapies for brain-damaged patients.L’effet Sprague décrit dans le document fondateur de James Sprague (Science 153: 1544 e1547, 1966a) est un effet paradoxal inattendu dans lequel une deuxième lésion cérébrale inversait les déficits fonctionnels induits par une lésion antérieure. Il a été observé initialement chez le chat où les déficits attentionnels controlatéraux sévères et permanents générés par l'ablation de grandes zones du cortex visuel ont été inversés par l'ablation ultérieure du colliculus supérieur (SC) opposé à la lésion corticale ou par la division de la commissure colliculaire. Physiologiquement, cet effet a été expliqué de plusieurs façons, notamment par la réduction de l'inhibition fonctionnelle de la SC ipsilatérale par la SC controlatérale et la restauration des interactions normales entre les structures corticales et du mésencéphale après l'ablation. Dans la présente revue, nous visons à réévaluer «l’effet Sprague» en analysant de manière critique les études qui ont été menées sur le cerveau félin et humain. De plus, nous évaluons les applications de «l’effet Sprague» dans la réadaptation des troubles de l’attention guidés visuellement en utilisant des approches thérapeutiques non invasives telles que la stimulation magnétique transcrânienne (TMS) et la stimulation transcrânienne à courant continu (tDCS). Nous passons également en revue les modèles théoriques de l'effet qui mettent l'accent sur l'inhibition et l'équilibre entre les deux hémisphères et montrent les implications pour les approches d'inférence des lésions. Enfin, nous examinons de manière critique si les théories de rivalité interhémisphérique qui en résultent conduisent à une réhabilitation efficace de l'AVC chez l'homme. Nous concluons en mettant l’accent sur les principaux défis dans le domaine des applications de «l’effet Sprague» afin de concevoir de meilleures thérapies pour les patients atteints de lésions cérébrales

Revisiting 'brain modes' in a new computational era: approaches for the characterization of brain-behavioural associations.

International audienceThe study of brain-function relationships is undergoing a conceptual and methodological transformation due to the emergence of network neuroscience and the development of multivariate methods for lesion-deficit inferences. Anticipating this process, in 1998 Godefroy and co-workers conceptualized the potential of four elementary typologies of brain-behaviour relationships named 'brain modes' (unicity, equivalence, association, summation) as building blocks able to describe the association between intact or lesioned brain regions and cognitive processes or neurological deficits. In the light of new multivariate lesion inference and network approaches, we critically revisit and update the original theoretical notion of brain modes, and provide real-life clinical examples that support their existence. To improve the characterization of elementary units of brain-behavioural relationships further, we extend such conceptualization with a fifth brain mode (mutual inhibition/masking summation). We critically assess the ability of these five brain modes to account for any type of brain-function relationship, and discuss past versus future contributions in redefining the anatomical basis of human cognition. We also address the potential of brain modes for predicting the behavioural consequences of lesions and their future role in the design of cognitive neurorehabilitation therapies

Reply: Inhibition between human brain areas or methodological artefact?

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Investigation of brain iron in anorexia nervosa, a quantitative susceptibility mapping study

Abstract Background Anorexia nervosa (AN) is a potentially fatal psychiatric condition, associated with structural brain changes such as gray matter volume loss. The pathophysiological mechanisms for these changes are not yet fully understood. Iron is a crucial element in the development and function of the brain. Considering the systemic alterations in iron homeostasis in AN, we hypothesized that brain iron would be altered as a possible factor associated with structural brain changes in AN. Methods In this study, we used quantitative susceptibility mapping (QSM) magnetic resonance imaging to investigate brain iron in current AN (c-AN) and weight-restored AN compared with healthy individuals. Whole-brain voxel wise comparison was used to probe areas with possible group differences. Further, the thalamus, caudate nucleus, putamen, nucleus accumbens, hippocampus, and amygdala were selected as the regions of interest (ROIs) for ROI-based comparison of mean QSM values. Results Whole-brain voxel-wise and ROI-based comparison of QSM did not reveal any differences between groups. Exploratory analyses revealed a correlation between higher regional QSM (higher iron) and lower body mass index, higher illness severity, longer illness duration, and younger age at onset in the c-AN group. Conclusions This study did not find evidence of altered brain iron in AN compared to healthy individuals. However, the correlations between clinical variables and QSM suggest a link between brain iron and weight status or biological processes in AN, which warrants further investigation