Neural correlates of the energetic value of food during visual processing and response inhibition.

Previous research showed that human brain regions involved in reward and cognitive control are responsive to visually presented food stimuli, in particular high-energy foods. However, it is still to be determined whether the preference towards high-energy foods depends on their higher energy density (kcal/gram), or is based on the difference in energy content of the food items (total amount of kcal). Here we report the results of an fMRI study in which normal-weight healthy participants processed food images during a one-back task or were required to inhibit their response towards food stimuli during a Go/No-Go task. High-energy density (HD) and low-energy density (LD) foods were matched for energy content displayed. Food-related kitchen objects (OBJ) were used as control stimuli. The lateral occipital complex and the orbitofrontal cortex showed consistent higher activity in response to HD than LD foods, both during visual processing and response inhibition. This result suggests that images of HD foods, even when the amount of food shown is not associated with a higher energy content, elicit preferential visual processing - possibly involving attentional processes - and trigger a response from the reward system. We conclude that the human brain is able to distinguish food energy densities of food items during both active visual processing and response inhibition.

How brain response and eating habits modulate food energy estimation.

The estimates we do of the energy content of different foods tend to be inaccurate, depending on several factors. The elements influencing such evaluation are related to the differences in the portion size of the foods shown, their energy density (kcal/g), but also to individual differences of the estimators, such as their body-mass index (BMI) or eating habits. Within this context the contribution of brain regions involved in food-related decisions to the energy estimation process is still poorly understood. Here, normal-weight and overweight/obese women with restrained or non-restrained eating habits, received anodal transcranial direct current stimulation (AtDCS) to modulate the activity of the left dorsolateral prefrontal cortex (dlPFC) while they performed a food energy estimation task. Participants were asked to judge the energy content of food images, unaware that all foods, for the quantity presented, shared the same energy content. Results showed that food energy density was a reliable predictor of their energy content estimates, suggesting that participants relied on their knowledge about the food energy density as a proxy for estimating food energy content. The neuromodulation of the dlPFC interacted with individual differences in restrained eating, increasing the precision of the energy content estimates in participants with higher scores in the restrained eating scale. Our study highlights the importance of eating habits, such as restrained eating, in modulating the activity of the left dlPFC during food appraisal.

Intermittent alien hand syndrome and callosal apraxia in multiple sclerosis: implications for interhemispheric communication.

We report a case of a 47-year-old woman with 35-year history of multiple sclerosis, who showed alien hand signs, a rare behavioural disorder that involves unilateral goal-directed movements that are contrary to the individual's intention. Alien hand syndrome has been described in multiple sclerosis (MS) only occasionally and is generally suggestive of callosal disconnection. The patient presented also with bilateral limb apraxia and left hand agraphia, raising the possibility of cortical dysfunction or disconnection, in addition to corpus callosum and white matter involvement. Her specific pattern of symptoms supports the role of the corpus callosum in interhemispheric communication for complex as well as fine motor activities and may indicate that it can serve as both an inhibitory and excitatory function depending on task demands.

The Brief Neuropsychological Screening (BNS): valuation of its clinical validity.

The assessment of functional and cognitive efficiency of acute brain injured patients represents a relevant innovation in the rehabilitative approach to stroke patients. Indeed, the identification of severe cognitive difficulties early in the recovery process can be an important prognostic factor for the evolution of the disorders themselves. The aim of the present study was to describe a new diagnostic tool that rapidly assesses the cognitive efficiency of acute patients suffering from a cerebral vascular accident. The Brief Neuropsychological Screening (BNS) has been designed for the detection of either the presence or absence of damage in different cognitive areas, with particular emphasis to those most frequently occurring after a stroke, such as aphasia, apraxia, agnosia or eminattention. Data from 250 normal adult subjects and from a group of 150 acute cerebrovascular inpatients are also presented that confirm the validity of the BNS in discriminating acute patients affected by cognitive impairments from those free of cognitive disruption, and supports its prognostic value in predicting cognitive recovery over time.

Differential regulation of mu- and m-calpain in rat hearts perfused with Ca2+ and cAMP.

Reversible interconversion between calpastatin I and calpastatin II, the phosphorylated form of the inhibitor, has been induced in rat heart perfused with the combination Ca2+/A23187 ionophore or with cAMP. In the presence of the ionophore and increasing concentrations of Ca2+, calpastatin II is converted into calpastatin I; whereas the reverse reaction is induced by the addition of cAMP. Both interconversions leave substantially unmodified the amount of calpastatin I which inhibits mu-calpain with higher efficiency and accordingly keeps the proteinase in an permanent inactive state. On the contrary, expression of m-calpain activity is significantly repressed or alternatively largely augmented as a result of a profound increase or decrease in the level of calpastatin II induced by perfusion with cAMP or with Ca2+/ionophore respectively. Taken together our results demonstrate that bidirectional interconversion can take place in rat heart cells and through this mechanism the activity of m-calpain can be efficiently controlled. Ca2+ ions and cAMP are temptatively proposed as the natural stimuli responsible for the modulation of this overall process. Experimental evidences are provided indicating that the transition to the active form of mu-calpain involves association to the plasma membrane, a process competitively antagonized by calpastatin I; thus suggesting that interaction with one or the other ligand can affect the intracellular ratio between inactive and active mu-calpain forms.

Modulation of calpastatin specificity in rat tissues by reversible phosphorylation and dephosphorylation.

Two calpastatins, with Mr 110 KD and named calpastatin I and II, have been isolated from rat heart and kidney and displayed distinct inhibitory efficiency with mu- and m-calpain, respectively, as those isolated from rat skeletal muscle. Whereas the level of calpastatin I always exceeds that of mu-calpain, the level of calpastatin II appears to be more closely correlated to the level of m-calpain. As previously shown for skeletal muscle, the two inhibitor proteins can be interconverted by a phosphorylation-dephosphorylation reaction; the enzyme responsible for phosphate incorporation in calpastatin I is now identified in c-AMP dependent protein kinase A. In rat erythrocytes, containing a single calpain form, the single low Mr calpastatin form does not undergo reversible phosphorylation and is equally efficient in respect to typical mu- and m-calpain. The presence of two interconvertible calpastatin forms provides the cells with a highly sensitive mechanism of regulation of the Ca(2+)-dependent proteolytic system.

Site-directed activation of calpain is promoted by a membrane-associated natural activator protein.

Human erythrocytes contain a calpain activator protein with a molecular mass of approx. 40 kDa. The activator is present in association with the plasma membrane and promotes expression of calpain activity at a concentration of Ca2+ close to physiological values. The initial step of the activating mechanism involves association of the activator with calpain, followed by autoproteolytic activation of the proteinase in the presence of 1 microM Ca2+, at a rate identical to that induced by 1 mM Ca2+. In a reconstituted system, the activator binds to erythrocyte membranes, but not to phospholipid vesicles, suggesting the participation of an intrinsic membrane protein(s). In its membrane-associated form the activator selectively binds calpain, thus favouring interaction of the proteinase with the inner surface of plasma membranes. These results further confirm the importance of a natural activator protein in promoting intracellular activation of calpain under physiological conditions through a site-directed mechanism, which explains the high specificity of the proteinase for membrane of cytoskeletal proteins.

Different susceptibility of red cell membrane proteins to calpain degradation.

The presence of low levels of calpastatin activity in erythrocytes of hypertensive rats affects regulation of calpain activity so it is highly susceptible to activation within physiological fluctuations in [Ca2+]. Under identical conditions, in red cells of normotensive rats, calpain activation is efficiently controlled by the high levels of calpastatin activity, and a progressive increase in proteinase activity can only be observed in parallel with a decrease in the level of calpastatin. In intact erythrocytes from hypertensive rats exposed to small variations in [Ca2+], degradation of anion transport protein (band 3) and Ca(2+)-ATPase appears as a primary event indicating that these two transmembrane proteins are probably early recognized as targets of intracellular calpain activity. Furthermore, band 3 protein seems to be structurally modified in erythrocytes from hypertensive rats, as indicated by its increased susceptibility to degradation in the presence of 10-50 microM Ca2+. In addition, when exposed to progressive and limited increases in [Ca2+], erythrocytes from hypertensive rats, but not those from normotensive rats, show a high degree of fragility that can be restored to normal values by inhibition of calpain. These results indicate that, within fluctuations in [Ca2+] close to physiological values, regulation of calpain activity is efficiently accomplished in normal erythrocytes but is completely lost in cells from hypertensive animals. Regulation is of critical importance in maintaining normal structural and functional properties of selective red cell membrane and cytoskeletal proteins, among which band 3 and Ca(2+)-ATPase appear to be the substrates with highest susceptibility to digestion by calpain.

Respiratory burst in activated neutrophils is directly correlated to the intracellular level of protein kinase C.

The production of superoxide anion in human and rat neutrophils is directly correlated to the level of protein kinase C. Such correlation has been established on a comparative basis by analysis of neutrophils from normal and hypertensive subjects, characterized by an increased amount of protein kinase C, and of neutrophils from normal and genetically hypertensive rats characterized by low amounts of the kinase. Protein kinase C activity in all these different populations of neutrophils is modulated by specific inhibitors in an identical dose-dependent fashion which results in a linearly correlated decrease in O2- production. Taken together, these results provide a direct demonstration that in neutrophils the intracellular level of protein kinase C represents one of the determinants of the rate and extent of O2- production.