Neural correlates of cognitive control of reaching movements in the dorsal premotor cortex of rhesus monkeys

Mirabella G, Pani P, Ferraina S. Neural correlates of cognitive control of reaching movements in the dorsal premotor cortex of rhesus monkeys. J Neurophysiol 106: 1454-1466, 2011. First published June 22, 2011; doi: 10.1152/jn.00995.2010.-Canceling a pending movement is a hallmark of voluntary behavioral control because it allows us to quickly adapt to unattended changes either in the external environment or in our thoughts. The countermanding paradigm allows the study of inhibitory processes of motor acts by requiring the subject to withhold planned movements in response to an infrequent stop-signal. At present the neural processes underlying the inhibitory control of arm movements are mostly unknown. We recorded the activity of single units in the rostral and caudal portion of the dorsal premotor cortex (PMd) of monkeys trained in a countermanding reaching task. We found that among neurons with a movement-preparatory activity, about one-third exhibit a modulation before the behavioral estimate of the time it takes to cancel a planned movement. Hence these neurons exhibit a pattern of activity suggesting that PMd plays a critical role in the brain networks involved in the control of arm movement initiation and suppression.Mirabella G, Pani P, Ferraina S. Neural correlates of cognitive control of reaching movements in the dorsal premotor cortex of rhesus monkeys. J Neurophysiol 106: 1454-1466, 2011. First published June 22, 2011; doi: 10.1152/jn.00995.2010.-Canceling a pending movement is a hallmark of voluntary behavioral control because it allows us to quickly adapt to unattended changes either in the external environment or in our thoughts. The countermanding paradigm allows the study of inhibitory processes of motor acts by requiring the subject to withhold planned movements in response to an infrequent stop-signal. At present the neural processes underlying the inhibitory control of arm movements are mostly unknown. We recorded the activity of single units in the rostral and caudal portion of the dorsal premotor cortex (PMd) of monkeys trained in a countermanding reaching task. We found that among neurons with a movement-preparatory activity, about one-third exhibit a modulation before the behavioral estimate of the time it takes to cancel a planned movement. Hence these neurons exhibit a pattern of activity suggesting that PMd plays a critical role in the brain networks involved in the control of arm movement initiation and suppression

Neuronal dynamics of signal selective motor plan cancellation in the macaque dorsal premotor cortex

Primates adopt various strategies to interact with the environment. Yet, no study has examined the effects of behavioural strategies with regard to how movement inhibition is implemented at the neuronal level. We used a modified version of the stop-task by adding an extra signal – termed the Ignore signal – capable of influencing the inhibition of movements only within a specific strategy. We simultaneously recorded multisite neuronal activity from the dorsal premotor (PMd) cortex of macaque monkeys during the task and applied a state-space approach. As a result, we found that movement generation is characterized by neuronal dynamics that evolve between subspaces. When the movement is halted, this evolution is arrested and inverted. Conversely, when the Ignore signal is presented, inversion of the evolution is observed briefly and only when a specific behavioural strategy is adopted. Moreover, neuronal signatures during the inhibitory process were predictive of how PMd processes inhibitory signals, allowing the classification of the resulting behavioural strategy. Our data further corroborate the PMd as a critical node in movement inhibition

Visuomotor transformations underlying arm movements toward visual targets: a neural network model of cerebral cortical operations

We propose a biologically realistic neural network that computes coordinate transformations for the command of arm reaching movements in 3-D space. This model is consistent with anatomical and physiological data on the cortical areas involved in the command of these movements. Studies of the neuronal activity in the motor (Georgopoulos et al., 1986; Schwartz et al., 1988; Caminiti et al., 1990a) and premotor (Caminiti et al., 1990b, 1991) cortices of behaving monkeys have shown that the activity of individual arm-related neurons is broadly tuned around a preferred direction of movements in 3-D space. Recent data demonstrate that in both frontal areas (Caminiti et al., 1990a,b, 1991) these cell preferred directions rotate with the initial position of the arm. Furthermore, the rotation of the population of preferred directions precisely corresponds to the rotation of the arm in space. The neural network model computes the motor command by combining the visual information about movement trajectory with the kinesthetic information concerning the orientation of the arm in space. The appropriate combination, learned by the network from spontaneous movement, can be approximated by a bilinear operation that can be interpreted as a projection of the visual information on a reference frame that rotates with the arm. This bilinear combination implies that neural circuits converging on a single neuron in the motor and premotor cortices can learn and generalize the appropriate command in a 2-D subspace but not in the whole 3-D space. However, the uniform distribution of cell preferred directions in these frontal areas can explain the computation of the correct solution by a population of cortical neurons. The model is consistent with the existing neurophysiological data and predicts how visual and somatic information can be combined in the different processing steps of the visuomotor transformation subserving visual reaching

Jejunal perforation in gallstone ileus – a case series

<p>Abstract</p> <p>Introduction</p> <p>Gallstone ileus is an uncommon complication of cholelithiasis but an established cause of mechanical bowel obstruction in the elderly. Perforation of the small intestine proximal to the obstructing gallstone is rare, and only a handful of cases have been reported. We present two cases of perforation of the jejunum in gallstone ileus, and remarkably in one case, the gallstone ileus caused perforation of a jejunal diverticulum and is to the best of our knowledge the first such case to be described.</p> <p>Case presentations</p> <p><b>Case 1</b></p> <p>A 69 year old man presented with two days of vomiting and central abdominal pain. He underwent laparotomy for small bowel obstruction and was found to have a gallstone obstructing the mid-ileum. There was a 2 mm perforation in the anti-mesenteric border of the dilated proximal jejunum. The gallstone was removed and the perforated segment of jejunum was resected.</p> <p><b>Case 2</b></p> <p>A 68 year old man presented with a four day history of vomiting and central abdominal pain. Chest and abdominal radiography were unremarkable however a subsequent CT scan of the abdomen showed aerobilia. At laparotomy his distal ileum was found to be obstructed by an impacted gallstone and there was a perforated diverticulum on the mesenteric surface of the mid-jejunum. An enterolithotomy and resection of the perforated small bowel was performed.</p> <p>Conclusion</p> <p>Gallstone ileus remains a diagnostic challenge despite advances in imaging techniques, and pre-operative diagnosis is often delayed. Partly due to the elderly population it affects, gallstone ileus continues to have both high morbidity and mortality rates. On reviewing the literature, the most appropriate surgical intervention remains unclear.</p> <p>Jejunal perforation in gallstone ileus is extremely rare. The cases described illustrate two quite different causes of perforation complicating gallstone ileus. In the first case, perforation was probably due to pressure necrosis caused by the gallstone. The second case was complicated by the presence of a perforated jejunal diverticulum, which was likely to have been secondary to the increased intra-luminal pressure proximal to the obstructing gallstone.</p> <p>These cases should raise awareness of the complications associated with both gallstone ileus, and small bowel diverticula.</p

NH2-truncated human tau induces deregulated mitophagy in neurons by aberrant recruitment of Parkin and UCHL-1: implications in Alzheimer's disease.

Disarrangement in functions and quality control of mitochondria at synapses are early events in Alzheimer's disease (AD) pathobiology. We reported that a 20-22 kDa NH2-tau fragment mapping between 26 and 230 amino acids of the longest human tau isoform (aka NH2htau): (i) is detectable in cellular and animal AD models, as well in synaptic mitochondria and cerebrospinal fluids (CSF) from human AD subjects; (ii) is neurotoxic in primary hippocampal neurons; (iii) compromises the mitochondrial biology both directly, by inhibiting the ANT-1-dependent ADP/ATP exchange, and indirectly, by impairing their selective autophagic clearance (mitophagy). Here, we show that the extensive Parkin-dependent turnover of mitochondria occurring in NH2htau-expressing post-mitotic neurons plays a pro-death role and that UCHL-1, the cytosolic Ubiquitin-C-terminal hydrolase L1 which directs the physiological remodeling of synapses by controlling ubiquitin homeostasis, critically contributes to mitochondrial and synaptic failure in this in vitro AD model. Pharmacological or genetic suppression of improper mitophagy, either by inhibition of mitochondrial targeting to autophagosomes or by shRNA-mediated silencing of Parkin or UCHL-1 gene expression, restores synaptic and mitochondrial content providing partial but significant protection against the NH2htau-induced neuronal death. Moreover, in mitochondria from human AD synapses, the endogenous NH2htau is stably associated with Parkin and with UCHL-1. Taken together, our studies show a causative link between the excessive mitochondrial turnover and the NH2htau-induced in vitro neuronal death, suggesting that pathogenetic tau truncation may contribute to synaptic deterioration in AD by aberrant recruitment of Parkin and UCHL-1 to mitochondria making them more prone to detrimental autophagic clearance

Natural orifice surgery: initial clinical experience

Natural orifice translumenal endoscopic surgery (NOTES) has moved quickly from preclinical investigation to clinical implementation. However, several major technical problems limit clinical NOTES including safe access, retraction and dissection of the gallbladder, and clipping of key structures. This study aimed to identify challenges and develop solutions for NOTES during the initial clinical experience. Under an Institutional Review Board (IRB)-approved protocol, patients consented to a natural orifice operation for removal of either the gallbladder or the appendix via either the vagina or the stomach using a single umbilical trocar for safety and assistance. Nine transvaginal cholecystectomies, one transgastric appendectomy, and one transvaginal appendectomy have been completed to date. All but one patient were discharged on postoperative day 1 as per protocol. No complications occurred. The limited initial evidence from this study demonstrates that NOTES is feasible and safe. The addition of an umbilical trocar is a bridge allowing safe performance of NOTES procedures until better instruments become available. The addition of a flexible long grasper through the vagina and a flexible operating platform through the stomach has enabled the performance of NOTES in a safe and easily reproducible manner. The use of a uterine manipulator has facilitated visualization of the cul de sac in women with a uterus to allow for safe transvaginal access

Visual Stability and the Motion Aftereffect: A Psychophysical Study Revealing Spatial Updating

Eye movements create an ever-changing image of the world on the retina. In particular, frequent saccades call for a compensatory mechanism to transform the changing visual information into a stable percept. To this end, the brain presumably uses internal copies of motor commands. Electrophysiological recordings of visual neurons in the primate lateral intraparietal cortex, the frontal eye fields, and the superior colliculus suggest that the receptive fields (RFs) of special neurons shift towards their post-saccadic positions before the onset of a saccade. However, the perceptual consequences of these shifts remain controversial. We wanted to test in humans whether a remapping of motion adaptation occurs in visual perception

A competitive integration model of exogenous and endogenous eye movements

We present a model of the eye movement system in which the programming of an eye movement is the result of the competitive integration of information in the superior colliculi (SC). This brain area receives input from occipital cortex, the frontal eye fields, and the dorsolateral prefrontal cortex, on the basis of which it computes the location of the next saccadic target. Two critical assumptions in the model are that cortical inputs are not only excitatory, but can also inhibit saccades to specific locations, and that the SC continue to influence the trajectory of a saccade while it is being executed. With these assumptions, we account for many neurophysiological and behavioral findings from eye movement research. Interactions within the saccade map are shown to account for effects of distractors on saccadic reaction time (SRT) and saccade trajectory, including the global effect and oculomotor capture. In addition, the model accounts for express saccades, the gap effect, saccadic reaction times for antisaccades, and recorded responses from neurons in the SC and frontal eye fields in these tasks. © The Author(s) 2010

Neural correlates of cognitive control of reaching movements in the dorsal premotor cortex of rhesus monkeys

3Mirabella G, Pani P, Ferraina S. Neural correlates of cognitive control of reaching movements in the dorsal premotor cortex of rhesus monkeys. J Neurophysiol 106: 1454-1466, 2011. First published June 22, 2011; doi: 10.1152/jn.00995.2010.-Canceling a pending movement is a hallmark of voluntary behavioral control because it allows us to quickly adapt to unattended changes either in the external environment or in our thoughts. The countermanding paradigm allows the study of inhibitory processes of motor acts by requiring the subject to withhold planned movements in response to an infrequent stop-signal. At present the neural processes underlying the inhibitory control of arm movements are mostly unknown. We recorded the activity of single units in the rostral and caudal portion of the dorsal premotor cortex (PMd) of monkeys trained in a countermanding reaching task. We found that among neurons with a movement-preparatory activity, about one-third exhibit a modulation before the behavioral estimate of the time it takes to cancel a planned movement. Hence these neurons exhibit a pattern of activity suggesting that PMd plays a critical role in the brain networks involved in the control of arm movement initiation and suppression.restrictedrestrictedGiovanni Mirabella; P. Pani; Stefano FerrainaMirabella, Giovanni; Pani, P.; Ferraina, Stefan