Predicted utility modulates working memory fidelity in the brain.

The predicted utility of information stored in working memory (WM) is hypothesized to influence the strategic allocation of WM resources. Prior work has shown that when information is prioritized, it is remembered with greater precision relative to other remembered items. However, these paradigms often complicate interpretation of the effects of predicted utility on item fidelity due to a concurrent memory load. Likewise, no fMRI studies have examined whether the predicted utility of an item modulates fidelity in the neural representation of items during the memory delay without a concurrent load. In the current study, we used fMRI to investigate whether predicted utility influences fidelity of WM representations in the brain. Using a generative model multivoxel analysis approach to estimate the quality of remembered representations across predicted utility conditions, we observed that items with greater predicted utility are maintained in memory with greater fidelity, even when they are the only item being maintained. Further, we found that this pattern follows a parametric relationship where more predicted utility corresponded to greater fidelity. These precision differences could not be accounted for based on a redistribution of resources among already-remembered items. Rather, we interpret these results in terms of a gating mechanism that allows for pre-allocation of resources based on predicted value alone. This evidence supports a theoretical distinction between resource allocation that occurs as a result of load and resource pre-allocation that occurs as a result of predicted utility.

Attention and Default Mode Network Assessments of Meditation Experience during Active Cognition and Rest.

Meditation experience has previously been shown to improve performance on behavioral assessments of attention, but the neural bases of this improvement are unknown. Two prominent, strongly competing networks exist in the human cortex: a dorsal attention network, that is activated during focused attention, and a default mode network, that is suppressed during attentionally demanding tasks. Prior studies suggest that strong anti-correlations between these networks indicate good brain health. In addition, a third network, a ventral attention network, serves as a "circuit-breaker" that transiently disrupts and redirects focused attention to permit salient stimuli to capture attention. Here, we used functional magnetic resonance imaging to contrast cortical network activation between experienced focused attention Vipassana meditators and matched controls. Participants performed two attention tasks during scanning: a sustained attention task and an attention-capture task. Meditators demonstrated increased magnitude of differential activation in the dorsal attention vs. default mode network in a sustained attention task, relative to controls. In contrast, there were no evident attention network differences between meditators and controls in an attentional reorienting paradigm. A resting state functional connectivity analysis revealed a greater magnitude of anticorrelation between dorsal attention and default mode networks in the meditators as compared to both our local control group and a n = 168 Human Connectome Project dataset. These results demonstrate, with both task- and rest-based fMRI data, increased stability in sustained attention processes without an associated attentional capture cost in meditators. Task and resting-state results, which revealed stronger anticorrelations between dorsal attention and default mode networks in experienced mediators than in controls, are consistent with a brain health benefit of long-term meditation practice.

Identification of Visual Attentional Regions of the Temporoparietal Junction in Individual Subjects using a Vivid, Novel Oddball Paradigm.

The Temporoparietal Junction (TPJ) of the cerebral cortex is a functionally heterogeneous region that also exhibits substantial anatomical variability across individuals. As a result, the precise functional organization of TPJ remains controversial. One or more regions within TPJ support visual attention processes, but the "attention TPJ" is difficult to functionally observe in individual subjects, and thus is typically identified by averaging across a large group of subjects. However, group-averaging also blurs localization and can obscure functional organization. Here, we develop and test an individual-subject approach to identifying attentional TPJ. This paradigm employs novel oddball images with a strong visual drive to produce robust TPJ responses in individuals. Vivid, novel oddballs drive responses in two TPJ regions bilaterally, a posterior region centered in posterior Superior Temporal Sulcus (TPJSTS) and an anterior region in ventral Supramarginal Gyrus (TPJSMG). Although an attentional reorienting task fails to drive TPJ activation in individuals, group analysis of the attentional reorienting contrast reveals recruitment of right TPJSTS, but not right TPJSMG. Similarly, right TPJSTS, as identified in individual subjects by the vivid, novel oddball contrast, is activated by attentional reorienting, but right TPJSMG is not. These findings advance an individual-subject based approach to understanding the functional organization of TPJ.

Topographic Cortico-cerebellar Networks Revealed by Visual Attention and Working Memory.

Substantial portions of the cerebellum appear to support non-motor functions; however, previous investigations of cerebellar involvement in cognition have revealed only a coarse degree of specificity. Although somatotopic maps have been observed within cerebellum, similar precision within cortico-cerebellar networks supporting non-motor functions has not previously been reported. Here, we find that human cerebellar lobule VIIb/VIIIa differentially codes key aspects of visuospatial cognition. Ipsilateral visuospatial representations were observed during both a visual working memory and an attentionally demanding visual receptive field-mapping fMRI task paradigm. Moreover, within lobule VIIb/VIIIa, we observed a functional dissociation between spatial coding and visual working memory processing. Visuospatial representations were found in the dorsomedial portion of lobule VIIb/VIIIa, and load-dependent visual working memory processing was shifted ventrolaterally. A similar functional gradient for spatial versus load processing was found in posterior parietal cortex. This cerebral cortical organization was well predicted by functional connectivity with spatial and load regions of cerebellar lobule VIIb/VIIIa. Collectively, our findings indicate that recruitment by visuospatial attentional functions within cerebellar lobule VIIb/VIIIa is highly specific. Furthermore, the topographic arrangement of these functions is mirrored in frontal and parietal cortex. These findings motivate a closer examination of cortico-cerebellar functional specialization across a broad range of cognitive domains.

Functional Evidence for a Cerebellar Node of the Dorsal Attention Network.

UNLABELLED: The "dorsal attention network" or "frontoparietal network" refers to a network of cortical regions that support sustained attention and working memory. Recent work has demonstrated that cortical nodes of the dorsal attention network possess intrinsic functional connections with a region in ventral cerebellum, in the vicinity of lobules VII/VIII. Here, we performed a series of task-based and resting-state fMRI experiments to investigate cerebellar participation in the dorsal attention network in humans. We observed that visual working memory and visual attention tasks robustly recruit cerebellar lobules VIIb and VIIIa, in addition to canonical cortical dorsal attention network regions. Across the cerebellum, resting-state functional connectivity with the cortical dorsal attention network strongly predicted the level of activation produced by attention and working memory tasks. Critically, cerebellar voxels that were most strongly connected with the dorsal attention network selectively exhibited load-dependent activity, a hallmark of the neural structures that support visual working memory. Finally, we examined intrinsic functional connectivity between task-responsive portions of cerebellar lobules VIIb/VIIIa and cortex. Cerebellum-to-cortex functional connectivity strongly predicted the pattern of cortical activation during task performance. Moreover, resting-state connectivity patterns revealed that cerebellar lobules VIIb/VIIIa group with cortical nodes of the dorsal attention network. This evidence leads us to conclude that the conceptualization of the dorsal attention network should be expanded to include cerebellar lobules VIIb/VIIIa. SIGNIFICANCE STATEMENT: The functional participation of cerebellar structures in nonmotor cortical networks remains poorly understood and is highly understudied, despite the fact that the cerebellum possesses many more neurons than the cerebral cortex. Although visual attention paradigms have been reported to activate cerebellum, many researchers have largely dismissed the possibility of a cerebellar contribution to attention in favor of a motor explanation, namely, eye movements. The present study demonstrates that a cerebellar subdivision (mainly lobules VIIb/VIIIa), which exhibits strong intrinsic functional connectivity with the cortical dorsal attention network, also closely mirrors a myriad of cortical dorsal attention network responses to visual attention and working memory tasks. This evidence strongly supports a reconceptualization of the dorsal attention network to include cerebellar lobules VIIb/VIIIa.

Current Strategies in Anesthesia and Analgesia for Total Knee Arthroplasty.

Total knee arthroplasty is associated with substantial postoperative pain that may impair mobility, reduce the ability to participate in rehabilitation, lead to chronic pain, and reduce patient satisfaction. Traditional general anesthesia with postoperative epidural and patient-controlled opioid analgesia is associated with an undesirable adverse-effect profile, including postoperative nausea and vomiting, hypotension, urinary retention, respiratory depression, delirium, and an increased infection rate. Multimodal anesthesia--incorporating elements of preemptive analgesia, neuraxial perioperative anesthesia, peripheral nerve blockade, periarticular injections, and multimodal oral opioid and nonopioid medications during the perioperative and postoperative periods--can provide superior pain control while minimizing opioid-related adverse effects, improving patient satisfaction, and reducing the risk of postoperative complications.

Ordering of neuronal apoptosis signaling: a superoxide burst precedes mitochondrial cytochrome c release in a growth factor deprivation model.

Axonal injury to retinal ganglion cells, a defined central neuron, induces a burst of intracellular superoxide anion that precedes externalization of membrane phosphatidylserine and subsequent apoptotic cell death. Dismutation of superoxide prevents the signal and delays loss of these cells, consistent with superoxide being necessary for transduction of the axotomy signal. However, phosphatidylserine externalization is a relatively late step in apoptosis, and it is possible that the superoxide burst is not an early axotomy signal but rather a result of cytochrome c release from the mitochondrial inner membrane with consequent accumulation of reduced intermediates. Other possibilities are that both superoxide generation and cytochrome c release are induced in parallel by axotomy, or that cytochrome c release potentiates the effect of the superoxide burst. To distinguish these various possibilities, serum-deprived neuronal retinal cells were assayed in vitro for superoxide elevation and release of cytochrome c from mitochondria, and the distribution of these two markers across a large number of cells used to model the temporal ordering of events. Based on this model of factor-dependent cell death, superoxide precedes, and possibly potentiates, cytochrome c release, and thus the former is likely an early signal for certain types of neuronal apoptosis in the central nervous system.

Incidence of late rectal and urinary toxicities after three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for localized prostate cancer.

PURPOSE: To report the incidence and predictors of treatment-related toxicity at 10 years after three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) for localized prostate cancer. METHODS AND MATERIALS: Between 1988 and 2000, 1571 patients with stages T1-T3 prostate cancer were treated with 3D-CRT/IMRT with doses ranging from 66 to 81 Gy. The median follow-up was 10 years. Posttreatment toxicities were all graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events. RESULTS: The actuarial likelihood at 10 years for the development of Grade>or=2 GI toxicities was 9%. The use of IMRT significantly reduced the risk of gastrointestinal (GI) toxicities compared with patients treated with conventional 3D-CRT (13% to 5%; p<0.001). Among patients who experienced acute symptoms the 10-year incidence of late toxicity was 42%, compared with 9% for those who did not experience acute symptoms (p<0.0001). The 10-year incidence of late Grade>or=2 genitourinary (GU) toxicity was 15%. Patients treated with 81 Gy (IMRT) had a 20% incidence of GU symptoms at 10 years, compared with a 12% for patient treated to lower doses (p=0.01). Among patients who had developed acute symptoms during treatment, the incidence of late toxicity at 10 years was 35%, compared with 12% (p<0.001). The incidence of Grade 3 GI and GU toxicities was 1% and 3%, respectively. CONCLUSIONS: Serious late toxicity was unusual despite the delivery of high radiation dose levels in these patients. Higher doses were associated with increased GI and GU Grade 2 toxicities, but the risk of proctitis was significantly reduced with IMRT. Acute symptoms were a precursor of late toxicities in these patients.