Connectivity of the Cingulate Sulcus Visual Area (CSv) in Macaque Monkeys.

In humans, the posterior cingulate cortex contains an area sensitive to visual cues to self-motion. This cingulate sulcus visual area (CSv) is structurally and functionally connected with several (multi)sensory and (pre)motor areas recruited during locomotion. In nonhuman primates, electrophysiology has shown that the cingulate cortex is also related to spatial navigation. Recently, functional MRI in macaque monkeys identified a cingulate area with similar visual properties to human CSv. In order to bridge the gap between human and nonhuman primate research, we examined the structural and functional connectivity of putative CSv in three macaque monkeys adopting the same approach as in humans based on diffusion MRI and resting-state functional MRI. The results showed that putative monkey CSv connects with several visuo-vestibular areas (e.g., VIP/FEFsem/VPS/MSTd) as well as somatosensory cortex (e.g., dorsal aspects of areas 3/1/2), all known to process sensory signals that can be triggered by self-motion. Additionally, strong connections are observed with (pre)motor areas located in the dorsal prefrontal cortex (e.g., F3/F2/F1) and within the anterior cingulate cortex (e.g., area 24). This connectivity pattern is strikingly reminiscent of that described for human CSv, suggesting that the sensorimotor control of locomotion relies on similar organizational principles in human and nonhuman primates.

Hyperexcitability of brain stem pathways in cerebral palsy.

Individuals with cerebral palsy (CP) experience impairments in the control of head and neck movements, suggesting dysfunction in brain stem circuitry. To examine if brain stem circuitry is altered in CP, we compared reflexes evoked in the sternocleidomastoid (SCM) muscle by trigeminal nerve stimulation in adults with CP and in age/sex-matched controls. Increasing the intensity of trigeminal nerve stimulation produced progressive increases in the long-latency suppression of ongoing SCM electromyography in controls. In contrast, participants with CP showed progressively increased facilitation around the same reflex window, suggesting heightened excitability of brain stem pathways. We also examined if there was altered activation of cortico-brain stem pathways in response to prenatal injury of the brain. Motor-evoked potentials (MEPs) in the SCM that were conditioned by a prior trigeminal afferent stimulation were more facilitated in CP compared with controls, especially in ipsilateral MEPs that are likely mediated by corticoreticulospinal pathways. In some participants with CP, but not in controls, a combined trigeminal nerve and cortical stimulation near threshold intensities produced large, long-lasting responses in both the SCM and biceps brachii muscles. We propose that the enhanced excitatory responses evoked from trigeminal and cortical inputs in CP are produced by heightened excitability of brain stem circuits, resulting in the augmented activation of reticulospinal pathways. Enhanced activation of reticulospinal pathways in response to early injury of the corticospinal tract may provide a compensated activation of the spinal cord or, alternatively, contribute to impairments in the precise control of head and neck functions. NEW & NOTEWORTHY This is the first study to show that in adults with spastic cerebral palsy, activation of brain stem circuits by cortical and/or trigeminal afferents produces excitatory responses in anterior neck muscles compared with inhibitory responses in age/sex-matched controls. This may reflect a more excitable reticulospinal tract in response to early brain injury to provide a compensated activation of postural muscles. On the other hand, a hyperexcitable brain stem may contribute to impairments in the precise control of head and neck functions.

Three changes to reduce the loss of dual degree trainees from OMFS national specialty selection in the UK: evidence based proposals.

The training pathway for oral and maxillofacial surgery (OMFS) has remained relatively stable for around 30 years. Circumstances surrounding the training pathway have changed including the priorities of individuals considering entering OMFS training. Run-through Specialty Training (ST1) OMFS posts (which include core surgical training) are oversubscribed while direct entry to Specialty Training (ST3) OMFS specialty recruitment rounds have unfilled posts, including places declined by appointable candidates. As part of a project to refine and improve OMFS recruitment and retention, data drawn from the British Association of Oral and Maxillofacial Surgeons (BAOMS) and the OMFS National Selection administering Deanery, Health Education England South West were scrutinised. Numbers of students starting second undergraduate degrees (medicine or dentistry) to pursue an OMFS career are increasing. Of a total of 43 candidates deemed appointable at OMFS ST1 selection but not offered an available post, 16 did not subsequently apply for ST3 selection. In the period studied (2015-20), of a total of 116 unfilled ST3 posts, 39 remained vacant because appointable candidates declined the available posts (33%). Appropriate changes to the current national selection processes could help address the perceived OMFS ST recruitment problems. By increasing the number of available ST1 posts, widening the window during which appointable candidates can continue into training and increasing prior experience recognition (including creating benchmarking processes prior to ST). These three clear, fair and transparent changes could reduce the current levels of attrition.

The confounding effect of response amplitude on MVPA performance measures.

Multi-voxel pattern analysis (MVPA) is proving very powerful in the analysis of fMRI timeseries data, yielding surprising sensitivity, in many different contexts, to the response characteristics of neurons in a given brain region. However, MVPA yields a metric (classification performance) that does not readily lend itself to quantitative comparisons across experimental conditions, brain regions or people. This is because performance is influenced by a number of factors other than the sensitivity of neurons to the experimental manipulation. One such factor that varies widely but has been largely ignored in MVPA studies is the amplitude of the response being decoded. In a noisy system, it is expected that measured classification performance will decline with declining response amplitude, even if the underlying neuronal specificity is constant. We document the relationship between response amplitude and classification performance in the context of orientation decoding in the visual cortex. Flickering sine gratings were presented at each of two orthogonal orientations in a block design (multivariate experiment) or an event-related design (univariate experiment). Response amplitude was manipulated by varying stimulus contrast. Orientation classification performance in retinotopically defined occipital area V1 increased approximately linearly with the logarithm of stimulus contrast. As expected, univariate response amplitude also increased with contrast. Similar results were obtained in V2, V3 and V3A. Plotting classification performance against response amplitude gave a function with a compressive non-linearity that was well fit by a power function. Knowledge of this function potentially allows adjustment of classification performance to take account of the effect of response size, making comparisons across brain areas, categories or people more meaningful.

Malignant transformation in a cohort of patients with oral epithelial dysplasia.

Oral epithelial dysplasia (OED) is often diagnosed in oral potentially malignant disorders (OPMD) and carries an increased risk of malignant transformation. Currently, the reported risk of malignant transformation for OED varies. Here we present the risk in a cohort of 150 patients with OED at a specialist centre. In this cohort 2.6%, 4.1%, and 29.2% cases of mild, moderate, and severe OED, respectively, progressed to oral squamous cell carcinoma at the dysplastic site, while a small number developed a malignant lesion elsewhere. Moreover, 17 patients experienced an increase in grade of dysplasia and two showed histological resolution of their lesions.

Errors in interpretation of neck levels in postoperative pathological specimens.

Accurate orientation of pathological specimens is of fundamental importance, and specimens that are divided postoperatively may be misinterpreted. We asked surgeons and pathologists to identify boundaries between nodal levels on a clinical photograph of a neck dissection specimen. Few participants were able to identify the boundaries between levels accurately, with several important errors where a marked level contained none of the relevant anatomical tissue. Most errors were in level I, and the number decreased towards level IV. Errors were made by both pathologists and surgeons. The boundaries of level IIA were consistently overestimated, which may have implications for previous studies that evaluated patterns of nodal spread.

Involvement of the jaw bones in systemic mastocytosis.

Systemic mastocytosis is characterised by proliferation of mast cells and infiltration of organs. Severe bony pain may result from release of chemical mediators from mast cells and affected patients are at an increased risk of anaphylaxis. Traditional analgesics such as non-steroidal anti-inflammatory agents and opioids are contraindicated. Diagnosis is based on presentation, biopsy of bone marrow, and magnetic resonance imaging of the affected area. In the head and neck, the disease may present as facial pain, localised osteomyelitis, oral sinus formation, and oral ulceration. Treatment is with histamine antagonists and bisphosphonates to control symptoms. An adrenaline pen is provided for use in case of anaphylaxis.

Substrate binding and catalysis in heme peroxidases.

Peroxidase-catalysed reactions are being analysed at an increasingly advanced level of structural and mechanistic sophistication. A significant development in this respect has been the long-anticipated solution of crystal structures for several plant peroxidases and a fungal peroxidase complexed to benzhydroxamic acid. New insights into peroxide binding and catalysis have been obtained through site-directed mutagenesis, a technique also crucial to recent progress in understanding the diversity of substrate interaction sites associated with peroxidases from different sources.

Crystal structures of pristine and oxidatively processed lignin peroxidase expressed in Escherichia coli and of the W171F variant that eliminates the redox active tryptophan 171. Implications for the reaction mechanism.

The heme enzyme lignin peroxidase (LiP) from the white rot fungus Phanerochaete chrysosporium contains a solvent exposed redox active tryptophan residue (Trp171) that carries a unique hydroxy group stereo-specifically attached to its C(beta) atom. A Trp171Phe mutant has no activity at all towards the substrate veratryl alcohol. The mechanism of veratryl alcohol oxidation involving beta-hydroxy-Trp171 is largely unknown. Here, we present the first crystal structures of LiP isozyme H8 at high resolution in its pristine non-hydroxylated form, of the C(beta)-hydroxylated form, and of the Trp171Phe mutant using recombinantly expressed and refolded protein produced from Escherichia coli. As a consequence, all structures are unglycosylated. Structural changes in response to the mutation are marginal and allow us to attribute the complete lack of activity exclusively to the absence of the redox active indole side-chain. The origin of the stereospecificity of the Trp171 hydroxylation can be explained on structural grounds. A reaction mechanism involving Trp171 is proposed and the possible function of the modification is discussed. Another important result regarding the ongoing debate on the co-ordination state of the heme iron in the resting state is that the iron is six co-ordinate in all cases the data being collected at room temperature. The mean distance from the iron to the distal water ligand is 2.18(+/-0.08) A. The radical scavenger orcinol was found to decrease radiation damage to the crystals, during data collection at room temperature.

Motion detection in human vision: a unifying approach based on energy and features.

Most studies of human motion perception have been based on the implicit assumption that the brain has only one motion-detection system, or at least that only one is operational in any given instance. We show, in the context of direction perception in spatially filtered two-frame random-dot kinematograms, that two quite different mechanisms operate simultaneously in the detection of such patterns. One mechanism causes reversal of the perceived direction (reversed-phi motion) when the image contrast is reversed between frames, and is highly dependent on the spatial-frequency content of the image. These characteristics are both signatures of detection based on motion energy. The other mechanism does not produce reversed-phi motion and is unaffected by spatial filtering. This appears to involve the tracking of unsigned complex spatial features. The perceived direction of a filtered dot pattern typically reflects a mixture of the two types of behaviour in any given instance. Although both types of mechanism have previously been invoked to explain the perception of motion of different types of image, the simultaneous involvement of two mechanisms in the detection of the same simple rigid motion of a pattern suggests that motion perception in general results from a combination of mechanisms working simultaneously on different principles in the same circumstances.

Stereoscopic and contrast-defined motion in human vision.

There is considerable evidence for the existence of a specialized mechanism in human vision for detecting moving contrast modulations and some evidence for a mechanism for detecting moving stereoscopic depth modulations. It is unclear whether a single second-order motion mechanism detects both types of stimulus or whether they are detected separately. We show that sensitivity to stereo-defined motion resembles that to contrast-defined motion in two important ways. First, when a missing-fundamental disparity waveform is moved in steps of 0.25 cycles, its perceived direction tends to reverse. This is a property of both luminance-defined and contrast-defined motion and is consistent with independent detection of motion at different spatial scales. Second, thresholds for detecting the direction of a smoothly drifting sinusoidal disparity modulation are much higher than those for detecting its orientation. This is a property of contrast-modulated gratings but not luminance-modulated gratings, for which the two thresholds are normally identical. The results suggest that stereo-defined and contrast-defined motion stimuli are detected either by a common mechanism or by separate mechanisms sharing a common principle of operation.

Comparison of the effects of Alzheimer's disease, normal aging and scopolamine on human transient visual evoked potentials.

Transient visual evoked potentials elicited by the onset of a patterned stimulus were recorded in patients suffering from Alzheimer's disease (AD), in healthy elderly controls and in healthy young individual. The latencies and amplitudes of both the components studied were adversely affected by normal aging and one of the components, CI, but not the other, CII, showed further deterioration in AD. These changes occurred over a range of stimulus contrast levels. The changes found in AD, but not those seen in normal aging, could be mimicked by administration of the cholinergic antagonist scopolamine to young volunteers.

Specific oculomotor deficits after amylobarbitone.

Five healthy volunteers received a single oral dose of amylobarbitone sodium (200 mg) and placebo in a double blind randomized fashion. Peak velocity of horizontal saccadic eye movements, saccade duration and smooth pursuit velocity were measured at intervals up to 6 h after drug administration. The active treatment produced a statistically significant decrease of both saccadic and smooth pursuit eye velocity. The maximum effect was observed 2 h after drug administration. The effect on peak saccadic velocity was still statistically significant 6 h after treatment. The maximum impairment in eye movement performance ranged between 25 and 29%. These results demonstrate that both saccadic and smooth pursuit systems are unable to generate the required eye velocity under the influence of a therapeutic dose of amylobarbitone sodium.

Effect of amphetamine on saccadic and smooth pursuit eye movements.

Healthy volunteers received single oral or intravenous doses of d-amphetamine sulphate (15 mg) and placebo in a double blind randomized design. Peak velocity of horizontal saccadic eye movements, saccade duration, saccade reaction time and smooth pursuit velocity were measured at intervals up to 1 h (IV) and 6 h (oral) after drug administration. Amphetamine produced no significant effect on saccadic and smooth-pursuit eye movements after oral administration. However, intravenous amphetamine abolished the effect of fatigue on saccadic movements and significantly (P less than 0.01) shortened saccadic reaction time.

Nelson's syndrome after Cushing's disease in childhood: a continuing problem.

Nelson's syndrome--progressive cutaneous hyperpigmentation with x-ray film evidence of an expanding pituitary tumor--is now a well-recognized sequela of bilateral adrenalectomy for Cushing's disease. It is estimated to occur in 8% to 38% of adults. Because Cushing's disease is rare in children, a higher incidence of Nelson's syndrome has not been suggested until recently. Although transsphenoidal operation is now the treatment of choice for Cushing's disease, children who have undergone bilateral adrenalectomy remain at risk for the development of Nelson's syndrome. A review of our experience and the literature indicates that the incidence of Nelson's syndrome after the treatment of Cushing's disease is higher in children than in adults. In our six children who underwent adrenalectomy between 8 and 17 years of age, four developed Nelson's syndrome at 2, 6, 10, and 12 years after adrenalectomy. Two of these patients remain well at 6 and 9 years after treatment with external irradiation. One patient treated with external irradiation developed recurrence at 5 years and required total hypophysectomy. The fourth patient required total hypophysectomy followed by external irradiation. Of the 37 patients reviewed and analyzed, the mean age at diagnosis of Cushing's disease was 12 years, with a mean interval of 8.4 years between adrenalectomy and Nelson's syndrome. Information regarding treatment for Nelson's syndrome was known in 24 patients and included pituitary irradiation (four patients), pituitary operation (11 patients), pituitary irradiation followed by operation (six patients), and pituitary operation followed by irradiation (three patients).

The effect of exercise on plasma somatomedin-C/insulinlike growth factor I concentrations.

Because inadequate intake of energy or protein causes reduction in the plasma concentrations of somatomedin-C/insulinlike growth factor I (Sm-C/IGF-I), we have completed studies to determine whether the energy deficit induced by vigorous exercise sustained for 1 week would also be associated with a reduction in this peptide. When six healthy, exercise-conditioned males were fed a diet consisting of 35 kcal/kg ideal body weight (IBW) and 1.0 g protein/kg and exercised so that 14.1 to 16.3 kcal/kg of energy was expended each day, their plasma Sm-C/IGF-I concentrations declined from a mean basal value of 1.15 +/- 0.78 U/mL (1 +/- SD) to 0.62 +/- 0.41 U/mL during the last two days of a seven-day exercise period (P less than .05). This decrease in Sm-C/IFG-I occurred almost entirely in the first four days of the study period. After 3 weeks for reacclimation, the calorie intake of each volunteer was reduced by the same number of calories as had been expended in the form of exercise during each day of the exercise week (mean of 15.1 kcal/kg IBW/d). On this regimen the mean plasma Sm-C/IGF-I declined from 1.12 +/- 0.57 U/mL, to 0.69 +/- 0.37 U/mL on the last two days of dietary restriction. The magnitude of fall with dietary restriction was not significantly different from that observed during exercise. During the last three days of the exercise period the mean daily nitrogen balance was -1.60 +/- 1.70 g/d, while this value was -3.50 +/- 1.73 g/d during the last three days of dietary restriction (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Attentional suppression of activity in the human visual cortex.

We have used fMRI to examine the nature of the changes that occur in the human visual cortex when an observer attends to a particular location in the visual image. Previous studies have shown that the magnitude of the response to a visual stimulus is increased when the observer attends to the stimulus. We show that, in addition, attention to a particular location results in a widespread suppression of activity levels at all other locations. This suggests that a key mechanism of attentional modulation may be that spontaneous (baseline) levels of neural activity are adjusted in a position-dependent manner across the entire visual field.

Sensitivity of complex cells in cat striate cortex to relative motion.

Sensitivity of 95 complex cells to relative motion between oriented bars and textured backgrounds was investigated monocularly in the striate cortex of lightly anesthetized, paralyzed cats. Cells were classified conventionally. Those in deep layers were either direction-selective, or strongly preferred one direction of motion, and responded well to background texture motion alone: backgrounds potentiated the response to the bar in the cell's preferred direction when moved in phase, or in the opposite direction when moved in antiphase; other combinations depressed the level of response compared with that for the bar alone. The majority of direction-selective or strongly direction-biased cells in superficial layers behaved similarly. The most interesting superficial-layer cells were bidirectional or weakly direction-biased, and recorded closer to the cortical surface than the direction-selective neurons. A majority showed preference for relative motion, some for antiphase, others for in-phase motion, regardless of the absolute direction of motion across the receptive field, which could not be accounted for on the basis of separate responses to bars and backgrounds alone. Three of the superficial-layer direction-selective cells also showed preference for antiphase relative motion. In a few complex cells from superficial laminae, backgrounds were either without influence on responses to oriented stimuli, or purely suppressive. Visual backgrounds against which objects are perceived are usually neither featureless nor motionless: the results suggest that most complex cells in striate cortex are sensitive to the context in which objects are seen and susceptible to relationships between objects and their backgrounds in relative motion.