Using Bayesian Dynamic Borrowing to Maximize the Use of Existing Data: A Case-Study.

Bayesian Dynamic Borrowing (BDB) designs are being increasingly used in clinical drug development. These methods offer a mathematically rigorous and robust approach to increase efficiency and strengthen evidence by integrating existing trial data into a new clinical trial. The regulatory acceptability of BDB is evolving and varies between and within regulatory agencies. This paper describes how BDB can be used to design a new randomised clinical trial including external data to supplement the planned sample size and discusses key considerations related to data re-use and BDB in drug development programs. A case-study illustrating the planning and evaluation of a BDB approach to support registration of a new medicine with the Center for Drug Evaluation in China will be presented. Key steps and considerations for the use of BDB will be discussed and evaluated, including how to decide whether it is appropriate to borrow external data, which external data can be re-used, the weight to put on the external data and how to decide if the new study has successfully demonstrated treatment benefit.

Action-specific feature processing in the human cortex: An fMRI study.

Sensorimotor integration involves feedforward and reentrant processing of sensory input. Grasp-related motor activity precedes and is thought to influence visual object processing. Yet, while the importance of reentrant feedback is well established in perception, the top-down modulations for action and the neural circuits involved in this process have received less attention. Do action-specific intentions influence the processing of visual information in the human cortex? Using a cue-separation fMRI paradigm, we found that action-specific instruction processing (manual alignment vs. grasp) became apparent only after the visual presentation of oriented stimuli, and occurred as early as in the primary visual cortex and extended to the dorsal visual stream, motor and premotor areas. Further, dorsal stream area aIPS, known to be involved in object manipulation, and the primary visual cortex showed task-related functional connectivity with frontal, parietal and temporal areas, consistent with the idea that reentrant feedback from dorsal and ventral visual stream areas modifies visual inputs to prepare for action. Importantly, both the task-dependent modulations and connections were linked specifically to the object presentation phase of the task, suggesting a role in processing the action goal. Our results show that intended manual actions have an early, pervasive, and differential influence on the cortical processing of vision.

Perceptual-Cognitive Integration for Goal-Directed Action in Naturalistic Environments.

Real-world actions require one to simultaneously perceive, think, and act on the surrounding world, requiring the integration of (bottom-up) sensory information and (top-down) cognitive and motor signals. Studying these processes involves the intellectual challenge of cutting across traditional neuroscience silos, and the technical challenge of recording data in uncontrolled natural environments. However, recent advances in techniques, such as neuroimaging, virtual reality, and motion tracking, allow one to address these issues in naturalistic environments for both healthy participants and clinical populations. In this review, we survey six topics in which naturalistic approaches have advanced both our fundamental understanding of brain function and how neurologic deficits influence goal-directed, coordinated action in naturalistic environments. The first part conveys fundamental neuroscience mechanisms related to visuospatial coding for action, adaptive eye-hand coordination, and visuomotor integration for manual interception. The second part discusses applications of such knowledge to neurologic deficits, specifically, steering in the presence of cortical blindness, impact of stroke on visual-proprioceptive integration, and impact of visual search and working memory deficits. This translational approach-extending knowledge from lab to rehab-provides new insights into the complex interplay between perceptual, motor, and cognitive control in naturalistic tasks that are relevant for both basic and clinical research.

Integration of landmark and saccade target signals in macaque frontal cortex visual responses.

Visual landmarks influence spatial cognition and behavior, but their influence on visual codes for action is poorly understood. Here, we test landmark influence on the visual response to saccade targets recorded from 312 frontal and 256 supplementary eye field neurons in rhesus macaques. Visual response fields are characterized by recording neural responses to various target-landmark combinations, and then we test against several candidate spatial models. Overall, frontal/supplementary eye fields response fields preferentially code either saccade targets (40%/40%) or landmarks (30%/4.5%) in gaze fixation-centered coordinates, but most cells show multiplexed target-landmark coding within intermediate reference frames (between fixation-centered and landmark-centered). Further, these coding schemes interact: neurons with near-equal target and landmark coding show the biggest shift from fixation-centered toward landmark-centered target coding. These data show that landmark information is preserved and influences target coding in prefrontal visual responses, likely to stabilize movement goals in the presence of noisy egocentric signals.

Occipital and parietal cortex participate in a cortical network for transsaccadic discrimination of object shape and orientation.

Saccades change eye position and interrupt vision several times per second, necessitating neural mechanisms for continuous perception of object identity, orientation, and location. Neuroimaging studies suggest that occipital and parietal cortex play complementary roles for transsaccadic perception of intrinsic versus extrinsic spatial properties, e.g., dorsomedial occipital cortex (cuneus) is sensitive to changes in spatial frequency, whereas the supramarginal gyrus (SMG) is modulated by changes in object orientation. Based on this, we hypothesized that both structures would be recruited to simultaneously monitor object identity and orientation across saccades. To test this, we merged two previous neuroimaging protocols: 21 participants viewed a 2D object and then, after sustained fixation or a saccade, judged whether the shape or orientation of the re-presented object changed. We, then, performed a bilateral region-of-interest analysis on identified cuneus and SMG sites. As hypothesized, cuneus showed both saccade and feature (i.e., object orientation vs. shape change) modulations, and right SMG showed saccade-feature interactions. Further, the cuneus activity time course correlated with several other cortical saccade/visual areas, suggesting a 'functional network' for feature discrimination. These results confirm the involvement of occipital/parietal cortex in transsaccadic vision and support complementary roles in spatial versus identity updating.

Angular Correlations in the ß Decay of

We present the first measurement of the α-ß-ν angular correlation in the Gamow-Teller ß^{+} decay of ^{8}B. This was accomplished using the Beta-decay Paul Trap, expanding on our previous work on the ß^{-} decay of ^{8}Li. The ^{8}B result is consistent with the V-A electroweak interaction of the standard model and, on its own, provides a limit on the exotic right-handed tensor current relative to the axial-vector current of |C_{T}/C_{A}|^{2}<0.013 at the 95.5% confidence level. This represents the first high-precision angular correlation measurements in mirror decays and was made possible through the use of an ion trap. By combining this ^{8}B result with our previous ^{8}Li results, we demonstrate a new pathway for increased precision in searches for exotic currents.

A single-arm, multicenter, phase II trial of osimertinib in patients with epidermal growth factor receptor exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations.

BACKGROUND: For patients with stage IV non-small-cell lung cancer with epidermal growth factor receptor (EGFR) exon 19 deletions and exon 21 L858R mutations, osimertinib is the standard of care. Investigating the activity and safety of osimertinib in patients with EGFR exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations is of clinical interest. PATIENTS AND METHODS: Patients with stage IV non-small-cell lung cancer with confirmed EGFR exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations were eligible. Patients were required to have measurable disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate organ function. Patients were required to be EGFR tyrosine kinase inhibitor-naive. The primary objective was objective response rate, and secondary objectives were progression-free survival, safety, and overall survival. The study used a two-stage design with a plan to enroll 17 patients in the first stage, and the study was terminated after the first stage due to slow accrual. RESULTS: Between May 2018 and March 2020, 17 patients were enrolled and received study therapy. The median age of patients was 70 years (interquartile range 62-76), the majority were female (n = 11), had a performance status of 1 (n = 10), and five patients had brain metastases at baseline. The objective response rate was 47% [95% confidence interval (CI) 23% to 72%], and the radiographic responses observed were partial response (n = 8), stable disease (n = 8), and progressive disease (n = 1). The median progression-free survival was 10.5 months (95% CI 5.0-15.2 months), and the median OS was 13.8 months (95% CI 7.3-29.2 months). The median duration on treatment was 6.1 months (range 3.6-11.9 months), and the most common adverse events (regardless of attribution) were diarrhea, fatigue, anorexia, weight loss, and dyspnea. CONCLUSIONS: This trial suggests osimertinib has activity in patients with these uncommon EGFR mutations.

Parietofrontal oscillations show hand-specific interactions with top-down movement plans.

To generate a hand-specific reach plan, the brain must integrate hand-specific signals with the desired movement strategy. Although various neurophysiology/imaging studies have investigated hand-target interactions in simple reach-to-target tasks, the whole brain timing and distribution of this process remain unclear, especially for more complex, instruction-dependent motor strategies. Previously, we showed that a pro/anti pointing instruction influences magnetoencephalographic (MEG) signals in frontal cortex that then propagate recurrently through parietal cortex (Blohm G, Alikhanian H, Gaetz W, Goltz HC, DeSouza JF, Cheyne DO, Crawford JD. NeuroImage 197: 306-319, 2019). Here, we contrasted left versus right hand pointing in the same task to investigate 1) which cortical regions of interest show hand specificity and 2) which of those areas interact with the instructed motor plan. Eight bilateral areas, the parietooccipital junction (POJ), superior parietooccipital cortex (SPOC), supramarginal gyrus (SMG), medial/anterior interparietal sulcus (mIPS/aIPS), primary somatosensory/motor cortex (S1/M1), and dorsal premotor cortex (PMd), showed hand-specific changes in beta band power, with four of these (M1, S1, SMG, aIPS) showing robust activation before movement onset. M1, SMG, SPOC, and aIPS showed significant interactions between contralateral hand specificity and the instructed motor plan but not with bottom-up target signals. Separate hand/motor signals emerged relatively early and lasted through execution, whereas hand-motor interactions only occurred close to movement onset. Taken together with our previous results, these findings show that instruction-dependent motor plans emerge in frontal cortex and interact recurrently with hand-specific parietofrontal signals before movement onset to produce hand-specific motor behaviors.NEW & NOTEWORTHY The brain must generate different motor signals depending on which hand is used. The distribution and timing of hand use/instructed motor plan integration are not understood at the whole brain level. Using MEG we show that different action planning subnetworks code for hand usage and integrating hand use into a hand-specific motor plan. The timing indicates that frontal cortex first creates a general motor plan and then integrates hand specificity to produce a hand-specific motor plan.

Integration of allocentric and egocentric visual information in a convolutional/multilayer perceptron network model of goal-directed gaze shifts.

Allocentric (landmark-centered) and egocentric (eye-centered) visual codes are fundamental for spatial cognition, navigation, and goal-directed movement. Neuroimaging and neurophysiology suggest these codes are initially segregated, but then reintegrated in frontal cortex for movement control. We created and validated a theoretical framework for this process using physiologically constrained inputs and outputs. To implement a general framework, we integrated a convolutional neural network (CNN) of the visual system with a multilayer perceptron (MLP) model of the sensorimotor transformation. The network was trained on a task where a landmark shifted relative to the saccade target. These visual parameters were input to the CNN, the CNN output and initial gaze position to the MLP, and a decoder transformed MLP output into saccade vectors. Decoded saccade output replicated idealized training sets with various allocentric weightings and actual monkey data where the landmark shift had a partial influence (R 2 = 0.8). Furthermore, MLP output units accurately simulated prefrontal response field shifts recorded from monkeys during the same paradigm. In summary, our model replicated both the general properties of the visuomotor transformations for gaze and specific experimental results obtained during allocentric-egocentric integration, suggesting it can provide a general framework for understanding these and other complex visuomotor behaviors.

Iris and Ciliary Body Melanocytomas Are Defined by Solitary GNAQ Mutation Without Additional Oncogenic Alterations.

OBJECTIVE: To analyze the genetic features of melanocytomas and melanomas of the anterior uvea and assess the value of molecular testing for diagnosis and prognostication. DESIGN: Retrospective case-control study. SUBJECTS: Patients with melanocytoma (n = 16) and melanoma (n = 19) of the anterior uvea. METHODS: Targeted next-generation sequencing was performed on formalin-fixed, paraffin-embedded tumor tissue from anterior uveal melanocytic tumors and correlated with clinicopathologic features. MAIN OUTCOME MEASURES: Presence or absence of accompanying oncogenic alterations beyond GNAQ/GNA11 and their association with histologic features and local recurrence. RESULTS: Hotspot missense mutations in GNAQ/GNA11 were identified in 91% (32/35) of all cases. None of the melanocytomas with or without atypia demonstrated chromosomal imbalances or additional oncogenic variants beyond GNAQ mutation, and none recurred over a median follow-up of 36 months. Additional alterations identified in a subset of melanomas include mutations in BAP1 (n = 3), EIF1AX (n = 4), SRSF2 (n = 1), PTEN (n = 1), and EP300 (n = 1); monosomy 3p (n = 6); trisomy 6p (n = 3); trisomy 8q (n = 2); and an ultraviolet mutational signature (n = 5). Local recurrences were limited to melanomas, all of which demonstrated oncogenic alterations in addition to GNAQ/GNA11 (n = 5). A single melanoma harboring GNAQ and BAP1 mutations and monosomy 3 was the only tumor that metastasized. CONCLUSIONS: In this study, anterior segment uveal melanocytomas did not display oncogenic alterations beyond GNAQ/GNA11. Therefore, they are genetically similar to uveal nevi rather than uveal melanoma based on their molecular features known from the literature. Molecular testing can be performed on borderline cases to aid risk stratification and clinical management decisions.

Action planning modulates the representation of object features in human fronto-parietal and occipital cortex.

The visual cortex has been extensively studied to investigate its role in object recognition but to a lesser degree to determine how action planning influences the representation of objects' features. We used functional MRI and pattern classification methods to determine if during action planning, object features (orientation and location) could be decoded in an action-dependent way. Sixteen human participants used their right dominant hand to perform movements (Align or Open reach) towards one of two 3D-real oriented objects that were simultaneously presented and placed on either side of a fixation cross. While both movements required aiming towards target location, Align but not Open reach movements required participants to precisely adjust hand orientation. Therefore, we hypothesized that if the representation of object features is modulated by the upcoming action, pre-movement activity pattern would allow more accurate dissociation between object features in Align than Open reach tasks. We found such dissociation in the anterior and posterior parietal cortex, as well as in the dorsal premotor cortex, suggesting that visuomotor processing is modulated by the upcoming task. The early visual cortex showed significant decoding accuracy for the dissociation between object features in the Align but not Open reach task. However, there was no significant difference between the decoding accuracy in the two tasks. These results demonstrate that movement-specific preparatory signals modulate object representation in the frontal and parietal cortex, and to a lesser extent in the early visual cortex, likely through feedback functional connections.

Pyridostigmine bromide elicits progressive and chronic impairments in the cholinergic anti-inflammatory pathway in the prefrontal cortex and hippocampus of male rats.

Gulf War Illness (GWI) is a multi-symptom illness that continues to affect over 250,000 American Gulf War veterans. The causes of GWI remain equivocal; however, prophylactic use of the acetylcholinesterase inhibitor pyridostigmine bromide (PB), and the stress of combat have been identified as two potential causative factors. Both PB and stress alter acetylcholine (ACh), which mediates both cognition and anti-inflammatory responses. As inflammation has been proposed to contribute to the cognitive deficits and immune dysregulation in GWI, the goal of this study was to determine the long-term effects of PB and stress on the cholinergic anti-inflammatory pathway in the central nervous system and periphery. We used our previously established rat model of GWI and in vivo microdialysis to assess cholinergic neurochemistry in the prefrontal cortex (PFC) and hippocampus following a mild immune challenge (lipopolysaccharide; LPS). We then examined LPS-induced changes in inflammatory markers in PFC and hippocampal homogenates. We found that PB treatment produces a long-lasting potentiation of the cholinergic response to LPS in both the PFC and hippocampus. Interestingly, this prolonged effect of PB treatment enhancing cholinergic responses to LPS was accompanied by paradoxical increases in the release of pro-inflammatory cytokines in these brain regions. Collectively, these findings provide evidence that neuroinflammation resulting from dysregulation of the cholinergic anti-inflammatory pathway is a mechanistic mediator in the progression of the neurochemical and neurocognitive deficits in GWI and more broadly suggest that dysregulation of this pathway may contribute to neuroinflammatory processes in stress-related neurological disorders.

Occipital cortex is modulated by transsaccadic changes in spatial frequency: an fMRI study.

Previous neuroimaging studies have shown that inferior parietal and ventral occipital cortex are involved in the transsaccadic processing of visual object orientation. Here, we investigated whether the same areas are also involved in transsaccadic processing of a different feature, namely, spatial frequency. We employed a functional magnetic resonance imaging paradigm where participants briefly viewed a grating stimulus with a specific spatial frequency that later reappeared with the same or different frequency, after a saccade or continuous fixation. First, using a whole-brain Saccade > Fixation contrast, we localized two frontal (left precentral sulcus and right medial superior frontal gyrus), four parietal (bilateral superior parietal lobule and precuneus), and four occipital (bilateral cuneus and lingual gyri) regions. Whereas the frontoparietal sites showed task specificity, the occipital sites were also modulated in a saccade control task. Only occipital cortex showed transsaccadic feature modulations, with significant repetition enhancement in right cuneus. These observations (parietal task specificity, occipital enhancement, right lateralization) are consistent with previous transsaccadic studies. However, the specific regions differed (ventrolateral for orientation, dorsomedial for spatial frequency). Overall, this study supports a general role for occipital and parietal cortex in transsaccadic vision, with a specific role for cuneus in spatial frequency processing.

Reconciling Assumptions in Bottom-Up and Top-Down Approaches for Estimating Aerosol Emission Rates From Wildland Fires Using Observations From FIREX-AQ.

Accurate fire emissions inventories are crucial to predict the impacts of wildland fires on air quality and atmospheric composition. Two traditional approaches are widely used to calculate fire emissions: a satellite-based top-down approach and a fuels-based bottom-up approach. However, these methods often considerably disagree on the amount of particulate mass emitted from fires. Previously available observational datasets tended to be sparse, and lacked the statistics needed to resolve these methodological discrepancies. Here, we leverage the extensive and comprehensive airborne in situ and remote sensing measurements of smoke plumes from the recent Fire Influence on Regional to Global Environments and Air Quality (FIREX-AQ) campaign to statistically assess the skill of the two traditional approaches. We use detailed campaign observations to calculate and compare emission rates at an exceptionally high-resolution using three separate approaches: top-down, bottom-up, and a novel approach based entirely on integrated airborne in situ measurements. We then compute the daily average of these high-resolution estimates and compare with estimates from lower resolution, global top-down and bottom-up inventories. We uncover strong, linear relationships between all of the high-resolution emission rate estimates in aggregate, however no single approach is capable of capturing the emission characteristics of every fire. Global inventory emission rate estimates exhibited weaker correlations with the high-resolution approaches and displayed evidence of systematic bias. The disparity between the low-resolution global inventories and the high-resolution approaches is likely caused by high levels of uncertainty in essential variables used in bottom-up inventories and imperfect assumptions in top-down inventories.

Postoperative delirium in patients with head and neck oral cancer in the West of Scotland.

Our aims were to determine the prevalence and association of postoperative delirium (POD) in head and neck (H&N) cancer patients undergoing free flap reconstruction at the oral and maxillofacial surgery (OMFS) unit, Queen Elizabeth University Hospital (QEUH) Glasgow, and to assess whether these determinants can be modified to optimise patient care and reduce the occurrence of POD. Delirium remains an important problem in the postoperative care of patients undergoing major H&N surgery, and early detection and management improve overall outcomes. The patient database containing details of the preoperative physical status (including alcohol misuse, chronic comorbidity, and physiological status) of 1006 patients who underwent major H&N surgery with free-flap repair at the QEUH from 2009-2019, was analysed. Factors associated with delirium were studied, identifying univariate associations as well as multivariate models to determine independent risk factors. The incidence of POD was 7.5% (75/1006; 53 male:22 female; mean (SD) age 65.41 (13.16) years). POD was strongly associated with pre-existing medical comorbidities, excess alcohol, smoking, a prolonged surgical operating time (more than 700 minutes), tracheostomy, blood transfusion, and bony free flaps. Those with POD were at an increased risk of postoperative wound and lung complications, and were more likely to require a hospital stay of more than 21 days. Presurgical assessment should identify risk factors to optimise the diagnosis and treatment of POD, and will enhance patient care by reducing further medical and surgical complications, and overall hospital stay.

Parietal Cortex Integrates Saccade and Object Orientation Signals to Update Grasp Plans.

Coordinated reach-to-grasp movements are often accompanied by rapid eye movements (saccades) that displace the desired object image relative to the retina. Parietal cortex compensates for this by updating reach goals relative to current gaze direction, but its role in the integration of oculomotor and visual orientation signals for updating grasp plans is unknown. Based on a recent perceptual experiment, we hypothesized that inferior parietal cortex (specifically supramarginal gyrus [SMG]) integrates saccade and visual signals to update grasp plans in additional intraparietal/superior parietal regions. To test this hypothesis in humans (7 females, 6 males), we used a functional magnetic resonance paradigm, where saccades sometimes interrupted grasp preparation toward a briefly presented object that later reappeared (with the same/different orientation) just before movement. Right SMG and several parietal grasp regions, namely, left anterior intraparietal sulcus and bilateral superior parietal lobule, met our criteria for transsaccadic orientation integration: they showed task-dependent saccade modulations and, during grasp execution, they were specifically sensitive to changes in object orientation that followed saccades. Finally, SMG showed enhanced functional connectivity with both prefrontal saccade regions (consistent with oculomotor input) and anterior intraparietal sulcus/superior parietal lobule (consistent with sensorimotor output). These results support the general role of parietal cortex for the integration of visuospatial perturbations, and provide specific cortical modules for the integration of oculomotor and visual signals for grasp updating.SIGNIFICANCE STATEMENT How does the brain simultaneously compensate for both external and internally driven changes in visual input? For example, how do we grasp an unstable object while eye movements are simultaneously changing its retinal location? Here, we used fMRI to identify a group of inferior parietal (supramarginal gyrus) and superior parietal (intraparietal and superior parietal) regions that show saccade-specific modulations during unexpected changes in object/grasp orientation, and functional connectivity with frontal cortex saccade centers. This provides a network, complementary to the reach goal updater, that integrates visuospatial updating into grasp plans, and may help to explain some of the more complex symptoms associated with parietal damage, such as constructional ataxia.

A Causal Role of Area hMST for Self-Motion Perception in Humans.

Previous studies in the macaque monkey have provided clear causal evidence for an involvement of the medial-superior-temporal area (MST) in the perception of self-motion. These studies also revealed an overrepresentation of contraversive heading. Human imaging studies have identified a functional equivalent (hMST) of macaque area MST. Yet, causal evidence of hMST in heading perception is lacking. We employed neuronavigated transcranial magnetic stimulation (TMS) to test for such a causal relationship. We expected TMS over hMST to induce increased perceptual variance (i.e., impaired precision), while leaving mean heading perception (accuracy) unaffected. We presented 8 human participants with an optic flow stimulus simulating forward self-motion across a ground plane in one of 3 directions. Participants indicated perceived heading. In 57% of the trials, TMS pulses were applied, temporally centered on self-motion onset. TMS stimulation site was either right-hemisphere hMST, identified by a functional magnetic resonance imaging (fMRI) localizer, or a control-area, just outside the fMRI localizer activation. As predicted, TMS over area hMST, but not over the control-area, increased response variance of perceived heading as compared with noTMS stimulation trials. As hypothesized, this effect was strongest for contraversive self-motion. These data provide a first causal evidence for a critical role of hMST in visually guided navigation.

Allocentric representations for target memory and reaching in human cortex.

The use of allocentric cues for movement guidance is complex because it involves the integration of visual targets and independent landmarks and the conversion of this information into egocentric commands for action. Here, we focus on the mechanisms for encoding reach targets relative to visual landmarks in humans. First, we consider the behavioral results suggesting that both of these cues influence target memory, but are then transformed-at the first opportunity-into egocentric commands for action. We then consider the cortical mechanisms for these behaviors. We discuss different allocentric versus egocentric mechanisms for coding of target directional selectivity in memory (inferior temporal gyrus versus superior occipital gyrus) and distinguish these mechanisms from parieto-frontal activation for planning egocentric direction of actual reach movements. Then, we consider where and how the former allocentric representations of remembered reach targets are converted into the latter egocentric plans. In particular, our recent neuroimaging study suggests that four areas in the parietal and frontal cortex (right precuneus, bilateral dorsal premotor cortex, and right presupplementary area) participate in this allo-to-ego conversion. Finally, we provide a functional overview describing how and why egocentric and landmark-centered representations are segregated early in the visual system, but then reintegrated in the parieto-frontal cortex for action.

Neuromagnetic signatures of the spatiotemporal transformation for manual pointing.

Movement planning involves transforming the sensory signals into a command in motor coordinates. Surprisingly, the real-time dynamics of sensorimotor transformations at the whole brain level remain unknown, in part due to the spatiotemporal limitations of fMRI and neurophysiological recordings. Here, we used magnetoencephalography (MEG) during pro-/anti-wrist pointing to determine (1) the cortical areas involved in transforming visual signals into appropriate hand motor commands, and (2) how this transformation occurs in real time, both within and across the regions involved. We computed sensory, motor, and sensorimotor indices in 16 bilateral brain regions for direction coding based on hemispherically lateralized de/synchronization in the α (7-15 Hz) and ß (15-35 Hz) bands. We found a visuomotor progression, from pure sensory codes in 'early' occipital-parietal areas, to a temporal transition from sensory to motor coding in the majority of parietal-frontal sensorimotor areas, to a pure motor code, in both the α and ß bands. Further, the timing of these transformations revealed a top-down pro/anti cue influence that propagated 'backwards' from frontal through posterior cortical areas. These data directly demonstrate a progressive, real-time transformation both within and across the entire occipital-parietal-frontal network that follows specific rules of spatial distribution and temporal order.

The Vascular Behavioral and Cognitive Disorders criteria for vascular cognitive disorders: a validation study.

BACKGROUND AND PURPOSE: The Vascular Behavioral and Cognitive Disorders (VASCOG) criteria for vascular cognitive disorders were published in 2014, but their concurrent and predictive validity have not been examined. METHODS: Participants (N = 165, aged 49-86 years) were from Sydney Stroke Study, a longitudinal study of post-stroke cognitive impairment and dementia. Diagnoses using the National Institute of Neurological Disorders and Stroke - Association Internationale pour la Recherché et l'Enseignement en Neurosciences (NINDS-AIREN), the Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC) and the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), criteria for vascular dementia (VaD) were made by consensus at multidisciplinary case conferences. Diagnoses for mild vascular cognitive disorder (mVCD) and VaD using VASCOG, DSM-5 and the Vascular Impairment of Cognition Classification Consensus Study (VICCCS) criteria were made by two study authors. Agreement levels between criteria sets were examined using Cohen's kappa (κ). The ability of VaD diagnoses to predict mortality over 10 years and of mVCD to predict dementia over 5 years was investigated. RESULTS: The VASCOG criteria yielded rates of mVCD slightly lower than for DSM-5 and VICCCS. VaD rates were similar for all criteria, although slightly lower for DSM-IV. Agreement between the VASCOG, VICCCS and DSM-5 criteria was excellent for VaD and mVCD (κ = 0.83-1.0), but lower for VaD between VASCOG and the other criteria (κ = 0.47-0.63). VaD-based mortality predictions were similar for the VASCOG, VICCCS and DSM-5 criteria, and higher than those for other criteria. The prediction of incident dementia within 5 years from mVCD was slightly lower with VASCOG criteria than with DSM-5 and VICCCS criteria. CONCLUSIONS: The VASCOG criteria have greater sensitivity, modest concurrent validity and better predictive validity than older criteria for VaD, but are comparable to DSM-5 and VICCCS criteria. Their operationalization and inclusion of a mild VCD category make them useful for clinical and research applications.