Anatomical Modularity of Verbal Working Memory? Functional Anatomical Evidence from a Famous Patient with Short-Term Memory Deficits.

Cognitive skills are the emergent property of distributed neural networks. The distributed nature of these networks does not necessarily imply a lack of specialization of the individual brain structures involved. However, it remains questionable whether discrete aspects of high-level behavior might be the result of localized brain activity of individual nodes within such networks. The phonological loop of working memory, with its simplicity, seems ideally suited for testing this possibility. Central to the development of the phonological loop model has been the description of patients with focal lesions and specific deficits. As much as the detailed description of their behavior has served to refine the phonological loop model, a classical anatomoclinical correlation approach with such cases falls short in telling whether the observed behavior is based on the functions of a neural system resembling that seen in normal subjects challenged with phonological loop tasks or whether different systems have taken over. This is a crucial issue for the cross correlation of normal cognition, normal physiology, and cognitive neuropsychology. Here we describe the functional anatomical patterns of JB, a historical patient originally described by Warrington et al. (1971), a patient with a left temporo-parietal lesion and selective short phonological store deficit. JB was studied with the H2(15)O PET activation technique during a rhyming task, which primarily depends on the rehearsal system of the phonological loop. No residual function was observed in the left temporo-parietal junction, a region previously associated with the phonological buffer of working memory. However, Broca's area, the major counterpart of the rehearsal system, was the major site of activation during the rhyming task. Specific and autonomous activation of Broca's area in the absence of afferent inputs from the other major anatomical component of the phonological loop shows that a certain degree of functional independence or modularity exists in this distributed anatomical-cognitive system

The effect of ethanol and nicotine on ER stress in human placental villous explants

Pregnant mothers continue smoking and drinking during pregnancy. To clarify the mechanisms of nicotine and ethanol toxicity during development, we have examined their effects on endoplasmic reticulum (ER) stress in human first trimester and term placental explants. First trimester and term human placental explants were treated with ethanol (2 ‰) or nicotine (15 µM), or their combination. The ER stress markers glucose regulated protein 78 (GRP78/BiP) and inositol requiring enzyme 1 α (IRE1α) were analyzed by immunoblotting. A statistically significant increase (p < 0.05) of GRP78/BiP by nicotine was noted in first trimester placental explants at 48 h, and in term placental explants at 24 h. Ethanol did not change protein expression of GRP78/BiP in either first trimester or term placental explants. IRE1α increased, although not statistically significantly, by all treatments in both first trimester and term placental explants. Thus, regardless of the known structural and functional differences in early and late placenta, both responded very similarly to the toxic compounds studied. These data support our earlier results in BeWo cells (Repo et al., 2014) implicating that nicotine induces ER stress in human placenta and may interfere with placental functions potentially disrupting fetal growth and development

Role of the macrophage migration inhibitory factor in the pathophysiology of pre-eclampsia

Proinflammatory cytokines are produced in pregnancy in response to the invading pathogens and/or nonmicrobial causes such as damage-associated molecules and embryonic semi-allogenic antigens. While inflammation is essential for a successful pregnancy, an excessive inflammatory response is implicated in several pathologies including pre-eclampsia (PE). This review focuses on the proinflammatory cytokine macrophage migration inhibitory factor (MIF), a critical regulator of the innate immune response and a major player of processes allowing normal placental development. PE is a severe pregnancy-related syndrome characterized by exaggerated inflammatory response and generalized endothelial damage. In some cases, usually of early onset, it originates from a maldevelopment of the placenta, and is associated with intrauterine growth restriction (IUGR) (placental PE). In other cases, usually of late onset, pre-pregnancy maternal diseases represent risk factors for the development of the disease (maternal PE). Available data suggest that low MIF production in early pregnancy could contribute to the abnormal placentation. The resulting placental hypoxia in later pregnancy could produce high release of MIF in maternal serum typical of placental PE. More studies are needed to understand the role of MIF, if any, in maternal PE

Hungry brains: A meta-analytical review of brain activation imaging studies on food perception and appetite in obese individuals

The dysregulation of food intake in chronic obesity has been explained by different theories. To assess their explanatory power, we meta-analyzed 22 brain-activation imaging studies. We found that obese individuals exhibit hyper-responsivity of the brain regions involved in taste and reward for food-related stimuli. Consistent with a Reward Surfeit Hypothesis, obese individuals exhibit a ventral striatum hyper-responsivity in response to pure tastes, particularly when fasting. Furthermore, we found that obese subjects display more frequent ventral striatal activation for visual food cues when satiated: this continued processing within the reward system, together with the aforementioned evidence, is compatible with the Incentive Sensitization Theory. On the other hand, we did not find univocal evidence in favor of a Reward Deficit Hypothesis nor for a systematic deficit of inhibitory cognitive control. We conclude that the available brain activation data on the dysregulated food intake and food-related behavior in chronic obesity can be best framed within an Incentive Sensitization Theory. Implications of these findings for a brain-based therapy of obesity are briefly discussed

Motor imagery training speeds up gait recovery and decreases the risk of falls in patients submitted to total knee arthroplasty

With Motor imagery (MI), movements are mentally rehearsed without overt actions; this procedure has been adopted in motor rehabilitation, primarily in brain-damaged patients. Here we rather tested the clinical potentials of MI in purely orthopaedic patients who, by definition, should maximally benefit of mental exercises because of their intact brain. To this end we studied the recovery of gait after total knee arthroplasty and evaluated whether MI combined with physiotherapy could speed up the recovery of gait and even limit the occurrence of future falls. We studied 48 patients at the beginning and by the end of the post-surgery residential rehabilitation program: half of them completed a specific MI training supported by computerized visual stimulation (experimental group); the other half performed a non-motoric cognitive training (control group). All patients also had standard physiotherapy. By the end of the rehabilitation, the experimental group showed a better recovery of gait and active knee flexion-extension movements, and less pain. The number of falls or near falls after surgery was significantly lower in the experimental group. These results show that MI can improve gait abilities and limit future falls in orthopaedic patients, without collateral risks and with limited costs

Chronic cigarette smoking enhances spontaneous release of tumour necrosis factor-α from alveolar macrophages of rats

Some biological effects of chronic cigarette smoking (two cigarettes for 2 h, daily for 4 months) in rats were evaluated. During the smoking period, body weight of smoker rats was always significantly lower than that of control rats. Immediately after the last smoking session the carboxyhaemoglobin concentration in the blood was about 8.5% and the polymorphonuclear cells in the bronchoalveolar fluid increased significantly. At the same time, enzymatic analyses on the supernatants of bronchoalveolar fluid revealed a significant increase of β-glucuronidase in the smoker group. Alveolar macrophages, collected 0, 8 and 24 h after the last smoking session, significantly increased the generation of superoxide anion and, after incubation for 24 h at 37° C in a humidified atmosphere, released significantly high amounts of TNF-α. When challenged with lipopolysaccharide, alveolar macrophages of smoker rats released much more TNF-α but, in such a case, TNF-α release was about one half of that observed in the control group. Peritoneal macrophages of both control and smoker rats were unable either to generate high levels of superoxide anion or to release significant amounts of TNF-α. The results clearly demonstrated the activated state of alveolar macrophages and the resting state of peritoneal macrophages

Effects of acute cigarette smoke exposure on macrophage kinetics and release of tumour necrosis factor α in rats

Some biological parameters before and after an acute episode of cigarette smoking in rats have been evaluated. The carboxyhaemoglobin levels depended either on the number of cigarettes, or on the time of exposure to cigarette smoke and returned to pre-smoking values in about 2 h. The evaluation of the kinetics of alveolar and peritoneal macrophages in rats after a smoking session of three cigarettes within an hour, indicated that alveolar macrophages in the bronchoalveolar lavage fluid significantly increased 8 h after the smoking, whereas the number of peritoneal macrophages remained practically constant. The incubation of these cells for various times at 37°C in a humidified atmosphere, resulted in a spontaneous release, 24 h thereafter, of variable amounts of tumour necrosis factor α (TNFα), which remained practically constant during the following days. Neither alveolar macrophages of control rats, nor peritoneal macrophages of both control and smoking rats were able to release TNFα. Moreover, after lipopolysaccharide induction of alveolar macrophages of both control and smoking rats, an increased release of TNFα was observed, indicating that these cells were in an active state

Enhanced activation of the left inferior frontal gyrus in deaf and dyslexic adults during rhyming

Hearing developmental dyslexics and profoundly deaf individuals both have difficulties processing the internal structure of words (phonological processing) and learning to read. In hearing non-impaired readers, the development of phonological representations depends on audition. In hearing dyslexics, many argue, auditory processes may be impaired. In congenitally profoundly deaf individuals, auditory speech processing is essentially absent. Two separate literatures have previously reported enhanced activation in the left inferior frontal gyrus in both deaf and dyslexic adults when contrasted with hearing non-dyslexics during reading or phonological tasks. Here, we used a rhyme judgement task to compare adults from these two special populations to a hearing non-dyslexic control group. All groups were matched on non-verbal intelligence quotient, reading age and rhyme performance. Picture stimuli were used since this requires participants to generate their own phonological representations, rather than have them partially provided via text. By testing well-matched groups of participants on the same task, we aimed to establish whether previous literatures reporting differences between individuals with and without phonological processing difficulties have identified the same regions of differential activation in these two distinct populations. The data indicate greater activation in the deaf and dyslexic groups than in the hearing non-dyslexic group across a large portion of the left inferior frontal gyrus. This includes the pars triangularis, extending superiorly into the middle frontal gyrus and posteriorly to include the pars opercularis, and the junction with the ventral precentral gyrus. Within the left inferior frontal gyrus, there was variability between the two groups with phonological processing difficulties. The superior posterior tip of the left pars opercularis, extending into the precentral gyrus, was activated to a greater extent by deaf than dyslexic participants, whereas the superior posterior portion of the pars triangularis extending into the ventral pars opercularis, was activated to a greater extent by dyslexic than deaf participants. Whether these regions play differing roles in compensating for poor phonological processing is not clear. However, we argue that our main finding of greater inferior frontal gyrus activation in both groups with phonological processing difficulties in contrast to controls suggests greater reliance on the articulatory component of speech during phonological processing when auditory processes are absent (deaf group) or impaired (dyslexic group). Thus, the brain appears to develop a similar solution to a processing problem that has different antecedents in these two populations

Uterine Gene Expression in the Live-Bearing Lizard, Chalcides ocellatus, Reveals Convergence of Squamate Reptile and Mammalian Pregnancy Mechanisms

Although the morphological and physiological changes involved in pregnancy in live-bearing reptiles are well studied, the genetic mechanisms that underlie these changes are not known. We used the viviparous African Ocellated Skink, Chalcides ocellatus, as a model to identify a near complete gene expression profile associated with pregnancy using RNA-Seq analyses of uterine transcriptomes. Pregnancy in C. ocellatus is associated with upregulation of uterine genes involved with metabolism, cell proliferation and death, and cellular transport. Moreover, there are clear parallels between the genetic processes associated with pregnancy in mammals and Chalcides in expression of genes related to tissue remodeling, angiogenesis, immune system regulation, and nutrient provisioning to the embryo. In particular, the pregnant uterine transcriptome is dominated by expression of proteolytic enzymes that we speculate are involved both with remodeling the chorioallantoic placenta and histotrophy in the omphaloplacenta. Elements of the maternal innate immune system are downregulated in the pregnant uterus, indicating a potential mechanism to avoid rejection of the embryo. We found a downregulation of major histocompatability complex loci and estrogen and progesterone receptors in the pregnant uterus. This pattern is similar to mammals but cannot be explained by the mammalian model. The latter finding provides evidence that pregnancy is controlled by different endocrinological mechanisms in mammals and reptiles. Finally, 88% of the identified genes are expressed in both the pregnant and the nonpregnant uterus, and thus, morphological and physiological changes associated with C. ocellatus pregnancy are likely a result of regulation of genes continually expressed in the uterus rather than the initiation of expression of unique genes