In the absence of external stimuli or task demands, correlations in spontaneous brain activity (functional connectivity) reflect patterns of anatomical connectivity. Hence, resting-state functional ...connectivity has been used as a proxy measure for structural connectivity and as a biomarker for brain changes in disease. To relate changes in functional connectivity to physiological changes in the brain, it is important to understand how correlations in functional connectivity depend on the physical integrity of brain tissue. The causal nature of this relationship has been called into question by patient data suggesting that decreased structural connectivity does not necessarily lead to decreased functional connectivity. Here we provide evidence for a causal but complex relationship between structural connectivity and functional connectivity: we tested interhemispheric functional connectivity before and after corpus callosum section in rhesus monkeys. We found that forebrain commissurotomy severely reduced interhemispheric functional connectivity, but surprisingly, this effect was greatly mitigated if the anterior commissure was left intact. Furthermore, intact structural connections increased their functional connectivity in line with the hypothesis that the inputs to each node are normalized. We conclude that functional connectivity is likely driven by corticocortical white matter connections but with complex network interactions such that a near-normal pattern of functional connectivity can be maintained by just a few indirect structural connections. These surprising results highlight the importance of network-level interactions in functional connectivity and may cast light on various paradoxical findings concerning changes in functional connectivity in disease states.
An operando electrochemical stage for the transmission electron microscope has been configured to form a “Li battery” that is used to quantify the electrochemical processes that occur at the anode ...during charge/discharge cycling. Of particular importance for these observations is the identification of an image contrast reversal that originates from solid Li being less dense than the surrounding liquid electrolyte and electrode surface. This contrast allows Li to be identified from Li-containing compounds that make up the solid-electrolyte interphase (SEI) layer. By correlating images showing the sequence of Li electrodeposition and the evolution of the SEI layer with simultaneously acquired and calibrated cyclic voltammograms, electrodeposition, and electrolyte breakdown processes can be quantified directly on the nanoscale. This approach opens up intriguing new possibilities to rapidly visualize and test the electrochemical performance of a wide range of electrode/electrolyte combinations for next generation battery systems.
Much of our behavior is guided by rules. Although human prefrontal cortex (PFC) and anterior cingulate cortex (ACC) are implicated in implementing rule-guided behavior, the crucial contributions made ...by different regions within these areas are not yet specified. In an attempt to bridge human neuropsychology and nonhuman primate neurophysiology, we report the effects of circumscribed lesions to macaque orbitofrontal cortex (OFC), principal sulcus (PS), superior dorsolateral PFC, ventrolateral PFC, or ACC sulcus, on separable cognitive components of a Wisconsin Card Sorting Test (WCST) analog. Only the PS lesions impaired maintenance of abstract rules in working memory; only the OFC lesions impaired rapid reward-based updating of representations of rule value; the ACC sulcus lesions impaired active reference to the value of recent choice-outcomes during rule-based decision-making.
We used inhibitory DREADDs (designer receptors exclusively activated by designer drugs) to reversibly disrupt dorsolateral prefrontal cortex (dlPFC) function in male rhesus monkeys. Monkeys were ...tested on a spatial delayed response task to assess working memory function after intramuscular injection of either clozapine-
-oxide (CNO) or vehicle. CNO injections given before DREADD transduction were without effect on behavior. rAAV5/hSyn-hM4Di-mCherry was injected bilaterally into the dlPFC of five male rhesus monkeys, to produce neuronal expression of the inhibitory (Gi-coupled) DREADD receptor. We quantified the percentage of DREADD-transduced cells using stereological analysis of mCherry-immunolabeled neurons. We found a greater number of immunolabeled neurons in monkeys that displayed CNO-induced behavioral impairment after DREADD transduction compared with monkeys that showed no behavioral effect after CNO. Even in monkeys that showed reliable effects of CNO on behavior after DREADD transduction, the number of prefrontal neurons transduced with DREADD receptor was on the order of 3% of total prefrontal neurons counted. This level of histological analysis facilitates our understanding of behavioral effects, or lack thereof, after DREADD vector injection in monkeys. It also implies that a functional silencing of a relatively small fraction of dlPFC neurons, albeit in a widely distributed area, is sufficient to disrupt spatial working memory.
Cognitive domains such as working memory and executive function are mediated by the dorsolateral prefrontal cortex (dlPFC). Impairments in these domains are common in neurodegenerative diseases as well as normal aging. The present study sought to measure deficits in a spatial delayed response task following activation of viral-vector transduced inhibitory DREADD (designer receptor exclusively activated by designer drug) receptors in rhesus macaques and compare this to the level of transduction in dlPFC using stereology. We found a significant relationship between the extent of DREADD transduction and the magnitude of behavioral deficit following administration of the DREADD actuator compound clozapine-
-oxide (CNO). These results demonstrate it will be critical to validate transduction to ensure DREADDs remain a powerful tool for neuronal disruption.
Anatomical and functional studies of the prefrontal cortex (PFC) have identified multiple PFC subregions. We argue that the PFC is involved in cognitive functions exceeding the sum of specific ...functions attributed to its subregions. These can be revealed either by lesions of the whole PFC, or more specifically by selective disconnection of the PFC from certain types of information (for example, visual) allowing the investigation of PFC function in toto . Recent studies in macaque monkeys using the latter approach lead to a second conclusion: that the PFC, as a whole, could be fundamentally specialized for representing events that are extended in time. The representation of temporally complex events might underlie PFC involvement in general intelligence, decision-making, and executive function.
Using Pacific benthic foraminiferal δ
O and Mg/Ca records, we derive a Cenozoic (66 Ma) global mean sea level (GMSL) estimate that records evolution from an ice-free Early Eocene to Quaternary ...bipolar ice sheets. These GMSL estimates are statistically similar to "backstripped" estimates from continental margins accounting for compaction, loading, and thermal subsidence. Peak warmth, elevated GMSL, high CO
, and ice-free "Hothouse" conditions (56 to 48 Ma) were followed by "Cool Greenhouse" (48 to 34 Ma) ice sheets (10 to 30 m changes). Continental-scale ice sheets ("Icehouse") began ~34 Ma (>50 m changes), permanent East Antarctic ice sheets at 12.8 Ma, and bipolar glaciation at 2.5 Ma. The largest GMSL fall (27 to 20 ka; ~130 m) was followed by a >40 mm/yr rise (19 to 10 ka), a slowing (10 to 2 ka), and a stillstand until ~1900 CE, when rates began to rise. High long-term CO
caused warm climates and high sea levels, with sea-level variability dominated by periodic Milankovitch cycles.
The geologic record provides constraints on the rates, amplitudes, and mechanisms controlling globally averaged (eustatic) and relative (eustatic plus subsidence/uplift) changes of sea level on ...various time scales. On geological time scales, global sea level changes are tied primarily to long-term (10⁷–10⁸-year scale) tectonism and short-term (10³–10⁶-year scale) changes in continental ice volume, though recent studies also illustrate the importance of tectonism on 10⁶-year time scales. The history of 10⁶-year scale eustatic changes has been controversial; the most widely used sea level curves agree with independently derived estimates with regard to the ages of sea level falls, but depart significantly from more recent studies with regard to amplitudes. We present a 180-million-year history of sea level changes. A global sea level rise of 120 m followed the Last Glacial Maximum, with rates that exceeded 10 times the modern rate of rise (> 40 mm yr⁻¹ versus ~ 3 mm yr⁻¹). The "ice ages" of the past 2.6 million years were due to growth/decay of large Northern Hemisphere ice sheets. Those of the past 780,000 years caused sea level changes that were large (> 100 m) and paced primarily by the ~100,000 year eccentricity cycle; smaller changes (typically < 60 m) prior to this time were paced primarily by the 41,000-year tilt cycle. The growth and decay of a continental-scale ice sheet in Antarctica caused 50–60-m variations on the 10⁶-year scale beginning ~ 33.5 million years ago. Prior to this time, Earth had been a warm, high-CO₂ "greenhouse" world that was largely ice-free back to 260 million years ago, though recent evidence suggests that 15–25-m sea level changes may have been caused by the growth and decay of small, ephemeral continental ice sheets.
Background
The Glasgow Benefit Inventory (GBI) is a validated, generic patient‐recorded outcome measure widely used in otolaryngology to report change in quality of life post‐intervention.
Objectives ...of review
To date, no systematic review has made (i) a quality assessment of reporting of Glasgow Benefit Inventory outcomes; (ii) a comparison between Glasgow Benefit Inventory outcomes for different interventions and objectives; (iii) an evaluation of subscales in describing the area of benefit; (iv) commented on its value in clinical practice and research.
Type of review
Systematic review.
Search strategy
‘Glasgow Benefit Inventory’ and ‘GBI’ were used as keywords to search for published, unpublished and ongoing trials in PubMed, EMBASE, CINAHL and Google in addition to an ISI citation search for the original validating Glasgow Benefit Inventory paper between 1996 and January 2015.
Evaluation method
Papers were assessed for study type and quality graded by a predesigned scale, by two authors independently. Papers with sufficient quality Glasgow Benefit Inventory data were identified for statistical comparisons. Papers with <50% follow‐up were excluded.
Results
A total of 118 eligible papers were identified for inclusion. A national audit paper (n = 4325) showed that the Glasgow Benefit Inventory gave a range of scores across the specialty, being greater for surgical intervention than medical intervention or ‘reassurance’. Fourteen papers compared one form of surgery versus another form of surgery. In all but one study, there was no difference between the Glasgow Benefit Inventory scores (or of any other outcome). The most likely reason was lack of power. Two papers took an epidemiological approach and used the Glasgow Benefit Inventory scores to predict benefit. One was for tonsillectomy where duration of sore throat episodes and days with fever were identified on multivariate analysis to predict benefit albeit the precision was low. However, the traditional factor of number of episodes of sore throat was not predictive. The other was surgery for chronic rhinosinusitis where those with polyps on univariate analysis had greater benefit than those without. Forty‐three papers had a response rate of >50% and gave sufficient Glasgow Benefit Inventory total and subscales for meta‐analysis. For five of the 11 operation categories (vestibular schwannoma, tonsillectomy, cochlear implant, middle ear implant and stapes surgery) that were most likely to have a single clear clinical objective, score data had low‐to‐moderate heterogeneity. The value in the Glasgow Benefit Inventory having both positive and negative scores was shown by an overall negative score for the management of vestibular schwannoma. The other six operations gave considerable heterogeneity with rhinoplasty and septoplasty giving the greatest percentages (98% and 99%) most likely because of the considerable variations in patient selection. The data from these operations should not be used for comparative purposes. Five papers also reported the number of patients that had no or negative benefit, a potentially a more clinically useful outcome to report. Glasgow Benefit Inventory subscores for tonsillectomy were significantly different from ear surgery suggesting different areas of benefit
Conclusions
The Glasgow Benefit Inventory has been shown to differentiate the benefit between surgical and medical otolaryngology interventions as well as ‘reassurance’. Reporting benefit as percentages with negative, no and positive benefit would enable better comparisons between different interventions with varying objectives and pathology. This could also allow easier evaluation of factors that predict benefit. Meta‐analysis data are now available for comparison purposes for vestibular schwannoma, tonsillectomy, cochlear implant, middle ear implant and stapes surgery. Fuller report of the Glasgow Benefit Inventory outcomes for non‐surgical otolaryngology interventions is encouraged.
To examine the generality of cholinergic involvement in visual memory in primates, we trained macaque monkeys either on an object-in-place scene learning task or in delayed nonmatching-to-sample ...(DNMS). Each monkey received either selective cholinergic depletion of inferotemporal cortex (including the entorhinal cortex and perirhinal cortex) with injections of the immunotoxin ME20.4-saporin or saline injections as a control and was postoperatively retested. Cholinergic depletion of inferotemporal cortex was without effect on either task. Each monkey then received fornix transection because previous studies have shown that multiple disconnections of temporal cortex can produce synergistic impairments in memory. Fornix transection mildly impaired scene learning in monkeys that had received saline injections but severely impaired scene learning in monkeys that had received cholinergic lesions of inferotemporal cortex. This synergistic effect was not seen in monkeys performing DNMS. These findings confirm a synergistic interaction in a macaque monkey model of episodic memory between connections carried by the fornix and cholinergic input to the inferotemporal cortex. They support the notion that the mnemonic functions tapped by scene learning and DNMS have dissociable neural substrates. Finally, cholinergic depletion of inferotemporal cortex, in this study, appears insufficient to impair memory functions dependent on an intact inferotemporal cortex.
PDF
