Recovering meaning: left prefrontal cortex guides controlled semantic retrieval

Prefrontal cortex plays a central role in mnemonic control, with left inferior prefrontal cortex (LIPC) mediating control of semantic knowledge. One prominent theory posits that LIPC does not mediate semantic retrieval per se, but rather subserves the selection of task-relevant knowledge from amidst competing knowledge. The present event-related fMRI study provides evidence for an alternative hypothesis: LIPC guides controlled semantic retrieval irrespective of whether retrieval requires selection against competing representations. With selection demands held constant, LIPC activation increased with semantic retrieval demands and with the level of control required during retrieval. LIPC mediates a top-down bias signal that is recruited to the extent that the recovery of meaning demands controlled retrieval. Selection may reflect a specific instantiation of this mechanism.     

Auditory and action semantic features activate sensory-specific perceptual brain regions

Traditionally, concepts were considered propositional, amodal, and verbal in nature (for review, see ). Recent findings, however, suggest that conceptual knowledge is divisible into different types (L. Wu and L.W. Barsalou, personal communication, ) and that each type may be linked to specific sensory and motor processes. This implies that sensory processing regions of the brain may also process concepts. In fact, there is some neuroimaging evidence that conceptual information does activate perceptual brain regions and that there is a correspondence between knowledge type and the region being activated. In the following experiment, using a training technique developed in previous studies, participants verbally learned associations between novel objects and conceptual features. The objective was to create objects that were associated with features from only one knowledge type, something that does not occur with common objects. During a visual task that did not require retrieval of learned associations, the superior temporal gyrus, which responds well to sounds, was preferentially activated by objects associated with auditory features (e.g., buzzes). Likewise, the posterior superior temporal sulcus, which responds well to motion, was preferentially activated by objects associated with "action" features (e.g., hops). These findings support the theory that knowledge is grounded in perception.     

Right prefrontal activity reflects the ability to overcome sleepiness during working memory tasks: a functional near-infrared spectroscopy study

It has been speculated that humans have an inherent ability to overcome sleepiness that counteracts homeostatic sleep pressure. However, it remains unclear which cortical substrate activities are involved in the ability to overcome sleepiness during the execution of cognitive tasks. Here we sought to confirm that this ability to overcome sleepiness in task execution improves performance on cognitive tasks, showing activation of neural substrates in the frontal cortex, by using a modified n-back (2- and 0-back) working memory task and functional near-infrared spectroscopy. The change in alertness was just correlated with performances on the 2-back task. Activity in the right prefrontal cortex changed depending on alertness changes on the 2- and 0-back tasks independently, which indicates that activity in this region clearly reflects the ability to overcome sleepiness; it may contribute to the function of providing sufficient activity to meet the task load demands. This study reveals characteristics of the ability to overcome sleepiness during the n-back working memory task which goes beyond the attention-control function traditionally proposed.     

Dissociable controlled retrieval and generalized selection mechanisms in ventrolateral prefrontal cortex

How does ventrolateral prefrontal cortex (VLPFC) control mnemonic processing? Alternative models propose that VLPFC guides top-down (controlled) retrieval of knowledge from long-term stores or selects goal-relevant products of retrieval from among competitors. A paucity of evidence supports a retrieval/selection distinction, raising the possibility that these models reduce to a common mechanism. Here, four manipulations varied semantic control demands during fMRI: judgment specificity, cue-target-associative strength, competitor dominance, and number of competitors. Factor analysis revealed evidence for a metafactor that accounted for common behavioral variance across manipulations and for functional variance in left mid-VLPFC. These data support a generalized control process that selects relevant knowledge from among competitors. By contrast, left anterior VLPFC and middle temporal cortex were sensitive to cue-target-associative strength, but not competition, consistent with a control process that retrieves knowledge stored in lateral temporal cortex. Distinct PFC mechanisms mediate top-down retrieval and postretrieval selection.     

Under-recruitment and nonselective recruitment: dissociable neural mechanisms associated with aging

Frontal contributions to cognitive decline in aging were explored using functional MRI. Frontal regions active in younger adults during self-initiated (intentional) memory encoding were under-recruited in older adults. Older adults showed less activity in anterior-ventral regions associated with controlled use of semantic information. Under-recruitment was reversed by requiring semantic elaboration suggesting it stemmed from difficulty in spontaneous recruitment of available frontal resources. In addition, older adults recruited multiple frontal regions in a nonselective manner for both verbal and nonverbal materials. Lack of selectivity was not reversed during semantically directed encoding even when under-recruitment was diminished. These findings suggest two separate forms of age-associated change in frontal cortex: under-recruitment and nonselective recruitment. The former is reversible and potentially amenable to cognitive training; the latter may reflect a less malleable change associated with cognitive decline in advanced aging.     

Common and distinct regions of defective-interfering RNAs of Sindbis virus

Defective-interfering (DI) particles are helper-dependent deletion mutants which interfere specifically with the replication of the homologous standard virus. Serial passaging of alphaviruses in cultured cells leads to the accumulation of DI particles whose genomic RNAs are heterogeneous in size and sequence composition. In an effort to examine the sequence organization of an individual DI RNA species generated from Sindbis virus, we isolated and sequenced a representative cDNA clone derived from a Sindbis DI RNA population. Our data showed that: (i) the 3' end of the DI RNA template was identical to the 50 nucleotides at the 3' end of the standard RNA; (ii) the majority (75%) of the DI RNA template was derived from the 1,200 5'-terminal nucleotides of the standard RNA and included repeats of these sequences; and (iii) the 5' end of the DI RNA template was not derived from the standard RNA, but is nearly identical to a cellular tRNAAsp (S. S. Monroe and S. Schlesinger, Proc. Natl. Acad. Sci. U.S.A. 80:3279-3283, 1983). We have also utilized restriction fragments from cloned DNAs to probe by blot hybridization for the presence of conserved sequences in several independently derived DI RNA populations. These studies indicated that: (i) a 51-nucleotide conserved sequence located close to the 5' end of several alphavirus RNAs was most likely retained in the DI RNAs; (ii) the junction region containing the 5' end of the subgenomic 26S mRNA was deleted from the DI RNAs; and (iii) the presence of tRNAAsp sequences was a common occurrence in Sindbis virus DI RNAs derived by passaging in chicken embryo fibroblasts.     

Heat regulation during exercise with controlled cooling

During heavy sustained exercise, when sweating is usually needed to dissipate the extra metabolic heat, controlled cooling caused heat loss to match total heat production with little sweating. The total heat produced and metabolic rate were varied independently by having subjects walk uphill and down. Heat loss was measured directly with a suit calorimeter; other measurements included metabolic energy from respiratory gas exchange and body temperatures. Thermoregulatory sweating was minimized by adjusting cooling in the calorimeter suit. Heat loss rose to match total heat, not metabolic rate, and there was a slow rise in rectal temperature. In the absence of major thermoregulatory response rectal temperature correlated most closely with total heat; it also correlated with the relative oxygen cost of exercise. Heat flow or heat content appeared to be the controlled variable and body temperature rise a secondary event resulting from thermal transport lag.     

Shift in the intrinsic excitability of medial prefrontal cortex neurons following training in impulse control and cued-responding tasks

Impulse control is an executive process that allows animals to inhibit their actions until an appropriate time. Previously, we reported that learning a simple response inhibition task increases AMPA currents at excitatory synapses in the prelimbic region of the medial prefrontal cortex (mPFC). Here, we examined whether modifications to intrinsic excitability occurred alongside the synaptic changes. To that end, we trained rats to obtain a food reward in a response inhibition task by withhold responding on a lever until they were signaled to respond. We then measured excitability, using whole-cell patch clamp recordings in brain slices, by quantifying action potentials generated by the injection of depolarizing current steps. Training in this task depressed the excitability of layer V pyramidal neurons of the prelimbic, but not infralimbic, region of the mPFC relative to behavioral controls. This decrease in maximum spiking frequency was significantly correlated with performance on the final session of the task. This change in intrinsic excitability may represent a homeostatic mechanism counterbalancing increased excitatory synaptic inputs onto those neurons in trained rats. Interestingly, subjects trained with a cue that predicted imminent reward availability had increased excitability in infralimbic, but not the prelimbic, pyramidal neurons. This dissociation suggests that both prelimbic and infralimbic neurons are involved in directing action, but specialized for different types of information, inhibitory or anticipatory, respectively.     

Prelimbic and infralimbic prefrontal cortex interact during fast network oscillations

Background

The medial prefrontal cortex has been implicated in a variety of cognitive and executive processes such as decision making and working memory. The medial prefrontal cortex of rodents consists of several areas including the prelimbic and infralimbic cortex that are thought to be involved in different aspects of cognitive performance. Despite the distinct roles in cognitive behavior that have been attributed to prelimbic and infralimbic cortex, little is known about neuronal network functioning of these areas, and whether these networks show any interaction during fast network oscillations.

Methodology/Principal Findings

Here we show that fast network oscillations in rat infralimbic cortex slices occur at higher frequencies and with higher power than oscillations in prelimbic cortex. The difference in oscillation frequency disappeared when prelimbic and infralimbic cortex were disconnected.

Conclusions/Significance

Our data indicate that neuronal networks of prelimbic and infralimbic cortex can sustain fast network oscillations independent of each other, but suggest that neuronal networks of prelimbic and infralimbic cortex are interacting during these oscillations.     

PLAD (personal lift assistive device) stiffness affects the lumbar flexion/extension moment and the posterior chain EMG during symmetrical lifting tasks

The PLAD (personal lift assistive device) was designed to reduce the lumbar moment during lifting and bending tasks via elastic elements. This investigation examined the effects of modulating the elastic stiffness. Thirteen men completed 90 lifts (15 kg) using 6 different PLAD stiffnesses in stoop, squat and freestyle lifting postures. The activity of 8 muscles were recorded (latissimus dorsi, thoracic and lumbar erector spinae, rectus abdominis, external oblique, gluteus maximus, biceps femoris and rectus femoris), 3D electromagnetic sensors tracked the motion of each segment and strain gauges measured the elastic tension. EMG data were rectified, filtered, normalized and integrated as a percentage of the lifting task. The highest PLAD tension elicited the greatest reduction in erector spinae activity (mean of thoracic and lumbar) in comparison to the no-PLAD condition for the stoop (37%), squat (38%), and freestyle (37%) lifts, while prompting comparable reductions in gluteus maximums and biceps femoris activity. The highest PLAD stiffness also elicited the greatest reduction in the integrated L4/L5 flexion moment for the stoop (19.0%), squat (18.4%) and freestyle (17.4%) lifts without changing peak lumbar flexion. Each increase in PLAD stiffness further reduced the muscle activity of the posterior chain and the dynamic lumbar moment.     

DC-SIGN interactions with human immunodeficiency virus: virus binding and transfer are dissociable functions

The C-type lectins DC-SIGN and DC-SIGNR capture and transfer human immunodeficiency virus (HIV) to susceptible cells, although the underlying mechanism is unclear. Here we show that DC-SIGN/DC-SIGNR-mediated HIV transmission involves dissociable binding and transfer steps, indicating that efficient virus transmission is not simply due to tethering of virus to the cell surface.     

Modulation of prefrontal cortex with anodal tDCS prevents post-exercise facilitation interference during dual task

In this study we aimed to investigate whether transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) reduces interference effects of a dual task (DT) on post-exercise facilitation (PEF) of the motor evoked potentials. Anodal tDCS reversed the DT interference on PEF after a non-fatiguing isometric contraction. We conclude that anodal DLPFC tDCS improves the ability to allocate attentional resources and modulates plastic adaptations across brain systems.     

Electromyogram and force fluctuation during different linearly varying isometric motor tasks

The purpose of this work was to verify if deviation from the mirror-like behaviour of the motor units activation strategy (MUAS) and de-activation strategy (MUDS) and the degree of the error of the motor control system, during consecutive linearly increasing–decreasing isometric tension tasks, depend on the maximum reached tension and/or on the rate of tension changes. In 12 male subjects the surface EMG and force produced by the first dorsal interosseus activity were recorded during two (a and b) trapezoid isometric contractions with different plateau (a: 50% maximal voluntary contraction (MVC) and b: 100% MVC) and rate of tension changes (a: 6.7% MVC/s and b: 13.3% MVC/s) during up-going (UGR) and down-going (DGR) ramps. Ten steps (ST) 6 s long at 5, 10, 20, 30, 40, 50, 60, 70, 80 and 90% MVC were also recorded. The root mean square (RMS) and mean frequency (MF) from EMG and the relative error of actual force output with respect to the target (% ERR) were computed. The EMG-RMS/% MVC and EMG-MF/% MVC relationships were not overlapped when the ST and DGR as well as the UGR and DGR data were compared. The % ERR/% MVC relationships during a and b contractions differed from ST data only below 20% MVC. It can be concluded that MUAS and MUDS are not mirroring one each other because MU recruitment or de-recruitment threshold may be influenced by the maximum effort and by the % MVC/s of UGR and DGR. The role of MUs mechanical and/or central nervous system hysteresis on force decrement control is discussed.     

Comparison of proteins synthesized by anterior and posterior regions of Dictyostelium discoideum pseudoplasmodia.

In migrating pseudoplasmodia of the cellular slime mold Dictyostelium discoideum, cells in approximately the anterior quarter of the structure give rise to stalk cells, while the remainder produce spore cells. Certain biochemical and structural components have been found to differ between cells occupying these two positions, indicating that some differentiation has already occurred by this stage. To evaluate the degree of this differentiation we have compared the proteins being synthesized in different regions of the pseudoplasmodia. Migrating pseudoplasmodia were labeled with [³⁵S]methionine and cut into five segments, and the labeled proteins were resolved by two-dimensional gel electrophoresis and visualized by autofluorography. Of 500 polypeptides detected, 57 showed regional variations in labeling. Nearly all of these differences in labeling occurred between the anterior fifth and posterior four-fifths of the pseudoplasmodia, indicating that by this stage a marked degree of differentiation has occurred between the two cell types.     

Hippocampal and ventral medial prefrontal activation during retrieval-mediated learning supports novel inference

Memory enables flexible use of past experience to inform new behaviors. Although leading theories hypothesize that this fundamental flexibility results from the formation of integrated memory networks relating multiple experiences, the neural mechanisms that support memory integration are not well understood. Here, we demonstrate that retrieval-mediated learning, whereby prior event details are reinstated during encoding of related experiences, supports participants' ability to infer relationships between distinct events that share content. Furthermore, we show that activation changes in a functionally coupled hippocampal and ventral medial prefrontal cortical circuit track the formation of integrated memories and successful inferential memory performance. These findings characterize the respective roles of these regions in retrieval-mediated learning processes that support relational memory network formation and inferential memory in the human brain. More broadly, these data reveal fundamental mechanisms through which memory representations are constructed into prospectively useful formats.     

Neuronal activity in the prefrontal cortex in rats with various typological features during emotional affect

Unit activity in the right and left prefrontal cortex was recorded in male Wistar rats after testing by the emotional resonance technique. Rats were divided in two groups by their reaction to the suffering cry of a partner. Rats from the group A ("altruists") escaped partner's crying, and those from the group E ("egoists") did not. Activity of neurons was analyzed in hungry rats, after feeding, during intracranial emotionally positive and negative stimulation, and during crying of the rat partner. Some differences in neural activity between A and E groups were revealed. In the hungry state the rate of neuronal discharges was higher in the A group. In both groups of animals the positive emotional stimulation was accompanied by more intensive neuronal reaction that the negative stimulation, but in the E group increase in the rate of neuronal discharges in both hemispheres was significantly more pronounced. Negative stimulation produced in both groups a significantly greater activation in the left hemisphere than in the right one while during the positive stimulation the neural activity was more intensive in the left hemisphere. The neuronal reaction to partner's crying was significantly higher in the A group in both hemispheres, while the neuronal activity in E group did not significantly change.