Human Posterior Parietal Cortex Plans Where to Reach and What to Avoid

In this time-resolved functional magnetic resonance imaging (fMRI) study, we aimed to trace the neuronal correlates of covert planning processes that precede visually guided motor behavior. Specifically, we asked whether human posterior parietal cortex has prospective planning activity that can be distinguished from activity related to retrospective visual memory and attention. Although various electrophysiological studies in monkeys have demonstrated such motor planning at the level of parietal neurons, comparatively little support is provided by recent human imaging experiments. Rather, a majority of experiments highlights a role of human posterior parietal cortex in visual working memory and attention. We thus sought to establish a clear separation of visual memory and attention from processes related to the planning of goal-directed motor behaviors. To this end, we compared delayed-response tasks with identical mnemonic and attentional demands but varying degrees of motor planning. Subjects memorized multiple target locations, and in a random subset of trials targets additionally instructed (1) desired goals or (2) undesired goals for upcoming finger reaches. Compared with the memory/attention-only conditions, both latter situations led to a specific increase of preparatory fMRI activity in posterior parietal and dorsal premotor cortex. Thus, posterior parietal cortex has prospective plans for upcoming behaviors while considering both types of targets relevant for action: those to be acquired and those to be avoided

Restricting excessive cardiac action potential and QT prolongation: a vital role for IKs in human ventricular muscle

Background - Although pharmacological block of the slow, delayed rectifier potassium current (I-Ks) by chromanol 293B, L-735,821, or HMR-1556 produces little effect on action potential duration (APD) in isolated rabbit and dog ventricular myocytes, the effect of IKs block on normal human ventricular muscle APD is not known. Therefore, studies were conducted to elucidate the role of IKs in normal human ventricular muscle and in preparations in which both repolarization reserve was attenuated and sympathetic activation was increased by exogenous dofetilide and adrenaline. Methods and Results - Preparations were obtained from undiseased organ donors. Action potentials were measured in ventricular trabeculae and papillary muscles using conventional microelectrode techniques; membrane currents were measured in ventricular myocytes using voltage-clamp techniques. Chromanol 293B (10 mu mol/L), L-735,821 (100 nmol/L), and HMR-1556 (100 nmol/L and 1 mu mol/L) produced a < 12-ms change in APD while pacing at cycle lengths ranging from 300 to 5000 ms, whereas the I-Kr blockers sotalol and E-4031 markedly lengthened APD. In voltage-clamp experiments, L- 735,821 and chromanol 293B each blocked IKs in the presence of E-4031 to block IKr. The E-4031-sensitive current (I-Kr) at the end of a 150-ms-long test pulse to 30 mV was 32.9 +/- 6.7 pA (n = 8); the L-735,821-sensitive current (I-Ks) magnitude was 17.8 +/- 2.94 pA (n = 10). During a longer 500-ms test pulse, IKr was not substantially changed (33.6 +/- 6.1 pA; n = 8), and I-Ks was significantly increased (49.6 +/- 7.24 pA; n = 10). On application of an "action potential-like" test pulse, I-Kr increased as voltage became more negative, whereas I-Ks remained small throughout all phases of the action potential - like test pulse. In experiments in which APD was first lengthened by 50 nmol/L dofetilide and sympathetic activation was increased by 1 mu mol/L adrenaline, 1 mu mol/L HMR-1556 significantly increased APD by 14.7 +/- 3.2% (P < 0.05; n = 3). Conclusions - Pharmacological IKs block in the absence of sympathetic stimulation plays little role in increasing normal human ventricular muscle APD. However, when human ventricular muscle repolarization reserve is attenuated, IKs plays an increasingly important role in limiting action potential prolongation

Mechanical characterization of sol–gel epoxy-silylatedhyperbranched poly(ethyleneimine) coatings by meansof Depth Sensing Indentation methods

A series of hybrid epoxy-silica coatings were prepared from a synthesized hyperbranched poly(ethyleneimine) with ethoxysilyl groups at the chain ends and diglycidylether of bisphenol A in different proportions. The curing procedure was based in a first sol-gel reaction performed at 80 °C in a humid chamber followed by the anionic homopolymerization of epoxides initiated by 1-methylimidazole in an oven at 180 °C. The prepared coatings were characterized mechanically by means of Depth Sensing Indentation technique. The influence of physical ageing on indentation hardness has been evaluated. The kinetic of the delayed depth recovery has been analyzed using the phenomenological so-called Kohlrausch-Williams-Watts relaxation function. It has been found that silylated hyperbranched poly(ethyleneimine) improves simultaneously the mechanical coating performance and the elastic recovery.Postprint (author's final draft

Convulsant actions of 4-aminopyridine on the guinea-pig olfactory cortex slice

The effects of bath-applied 4-aminopyridine on neurones and extracellular potassium and calcium concentrations were recorded in slices of guinea-pig olfactory cortex. Neurones were orthodromically activated by stimulating the lateral olfactory tract. 4-Aminopyridine (3–10 μM) had the following effects: (1) an increase in the frequency and amplitude of spontaneous postsynaptic potentials: (2) a prolongation and oscillatory behaviour or orthodromically evoked postsynaptic potentials; (3) induction of spontaneous or stimulus-evoked seizure-type discharges which were accompanied by large rises in extracellular potassium and falls in calcium concentration; (4) a prolongation of the lateral olfactory tract population fibre spike. Prior to paroxysmal depolarization, membrane potential, input resistance and soma spike duration were unaffected. In the seconds before seizure discharges, a late hyperpolarizing potential (evoked by orthodromic stimulation) was reduced in amplitude or abolished. Diphenylhydantoin (50 μM) or magnesium ions (5 mM) prevented paroxysmal activity. Our results whow that 4-aminopyridine can produce seizure-type discharges in a brain slice preparation. The role of increased spontaneous potentials and possible loss of synaptic inhibition as causal factors for such discharges is discussed

Visual salience of the stop signal affects the neuronal dynamics of controlled inhibition

The voluntary control of movement is often tested by using the countermanding, or stop-signal task that sporadically requires the suppression of a movement in response to an incoming stop-signal. Neurophysiological recordings in monkeys engaged in the countermanding task have shown that dorsal premotor cortex (PMd) is implicated in movement control. An open question is whether and how the perceptual demands inherent the stop-signal affects inhibitory performance and their underlying neuronal correlates. To this aim we recorded multi-unit activity (MUA) from the PMd of two male monkeys performing a countermanding task in which the salience of the stop-signals was modulated. Consistently to what has been observed in humans, we found that less salient stimuli worsened the inhibitory performance. At the neuronal level, these behavioral results were subtended by the following modulations: when the stop-signal was not noticeable compared to the salient condition the preparatory neuronal activity in PMd started to be affected later and with a less sharp dynamic. This neuronal pattern is probably the consequence of a less efficient inhibitory command useful to interrupt the neural dynamic that supports movement generation in PMd

Moving beyond a limited follow-up in cost-effectiveness analyses of behavioral interventions

Background Cost-effectiveness analyses of behavioral interventions typically use a dichotomous outcome criterion. However, achieving behavioral change is a complex process involving several steps towards a change in behavior. Delayed effects may occur after an intervention period ends, which can lead to underestimation of these interventions. To account for such delayed effects, intermediate outcomes of behavioral change may be used in cost-effectiveness analyses. The aim of this study is to model cognitive parameters of behavioral change into a cost-effectiveness model of a behavioral intervention. Methods The cost-effectiveness analysis (CEA) of an existing dataset from an RCT in which an high-intensity smoking cessation intervention was compared with a medium-intensity intervention, was re-analyzed by modeling the stages of change of the Transtheoretical Model of behavioral change. Probabilities were obtained from the dataset and literature and a sensitivity analysis was performed. Results In the original CEA over the first 12 months, the high-intensity intervention dominated in approximately 58% of the cases. After modeling the cognitive parameters to a future 2nd year of follow-up, this was the case in approximately 79%. Conclusion This study showed that modeling of future behavioral change in CEA of a behavioral intervention further strengthened the results of the standard CEA. Ultimately, modeling future behavioral change could have important consequences for health policy development in general and the adoption of behavioral interventions in particular

Overlapping neural systems represent cognitive effort and reward anticipation

Anticipating a potential benefit and how difficult it will be to obtain it are valuable skills in a constantly changing environment. In the human brain, the anticipation of reward is encoded by the Anterior Cingulate Cortex (ACC) and Striatum. Naturally, potential rewards have an incentive quality, resulting in a motivational effect improving performance. Recently it has been proposed that an upcoming task requiring effort induces a similar anticipation mechanism as reward, relying on the same cortico-limbic network. However, this overlapping anticipatory activity for reward and effort has only been investigated in a perceptual task. Whether this generalizes to high-level cognitive tasks remains to be investigated. To this end, an fMRI experiment was designed to investigate anticipation of reward and effort in cognitive tasks. A mental arithmetic task was implemented, manipulating effort (difficulty), reward, and delay in reward delivery to control for temporal confounds. The goal was to test for the motivational effect induced by the expectation of bigger reward and higher effort. The results showed that the activation elicited by an upcoming difficult task overlapped with higher reward prospect in the ACC and in the striatum, thus highlighting a pivotal role of this circuit in sustaining motivated behavior

Effects of motor preparation and spatial attention on corticospinal excitability in a delayed-response paradigm

The preparation of motor responses during the delay period of an instructed delay task is associated with sustained neural firing in the primate premotor cortex. It remains unclear how and when such preparation-related premotor activity influences the motor output system. In this study, we tested modulation of corticospinal excitability using single-pulse transcranial magnetic stimulation (TMS) during a delayed-response task. At the beginning of the delay interval participants were either provided with no information, spatial attentional information concerning location but not identity of an upcoming imperative stimulus, or information regarding the upcoming response. Behavioral data indicate that participants used all information available to them. Only when information concerning the upcoming response was provided did corticospinal excitability show differential modulation for the effector muscle compared to other task-unrelated muscles. We conclude that modulation of corticospinal excitability reflects specific response preparation, rather than non-specific event preparation