Learning of object-in-context sequences in freely-moving macaques.

Flexible learning is a hallmark of primate cognition, which arises through interactions with changing environments. Studies of the neural basis for this flexibility are typically limited by laboratory settings that use minimal environmental cues and restrict interactions with the environment, including active sensing and exploration. To address this, we constructed a 3-D enclosure containing touchscreens on its walls, for studying cognition in freely moving macaques. To test flexible learning, two monkeys completed trials consisting of a regular sequence of object selections across four touchscreens. On each screen, the monkeys had to select by touching the sole correct object item ('target') among a set of four items, irrespective of their positions on the screen. Each item was the target on exactly one screen of the sequence, making correct performance conditioned on the spatiotemporal sequence rule across screens. Both monkeys successfully learned multiple 4-item sets (N=14 and 22 sets), totaling over 50 and 80 unique, conditional item-context memoranda, with no indication of capacity limits. The enclosure allowed freedom of movements leading up to and following the touchscreen interactions. To determine whether movement economy changed with learning, we reconstructed 3D position and movement dynamics using markerless tracking software and gyroscopic inertial measurements. Whereas general body positions remained consistent across repeated sequences, fine head movements varied as monkeys learned, within and across sequence sets, demonstrating learning set or "learning to learn". These results demonstrate monkeys' rapid, capacious, and flexible learning within an integrated, multisensory 3-D space. Furthermore, this approach enables the measurement of continuous behavior while ensuring precise experimental control and behavioral repetition of sequences over time. Overall, this approach harmonizes the design features that are needed for electrophysiological studies with tasks that showcase fully situated, flexible cognition.

Cholinergic modulation of response properties and orientation tuning of neurons in primary visual cortex of anaesthetized Marmoset monkeys.

Cortical processing is strongly influenced by the actions of neuromodulators such as acetylcholine (ACh). Early studies in anaesthetized cats argued that acetylcholine can cause a sharpening of orientation tuning functions and an improvement of the signal-to-noise ratio (SNR) of neuronal responses in primary visual cortex (V1). Recent in vitro studies have demonstrated that acetylcholine reduces the efficacy of feedback and intracortical connections via the activation of muscarinic receptors, and increases the efficacy of feed-forward connections via the activation of nicotinic receptors. If orientation tuning is mediated or enhanced by intracortical connections, high levels of acetylcholine should diminish orientation tuning. Here we investigate the effects of acetylcholine on orientation tuning and neuronal responsiveness in anaesthetized marmoset monkeys. We found that acetylcholine caused a broadening of the orientation tuning in the majority of cells, while tuning functions became sharper in only a minority of cells. Moreover, acetylcholine generally facilitated neuronal responses, but neither improved signal-to-noise ratio, nor reduced trial-to-trial firing rate variance systematically. Acetylcholine did however, reduce variability of spike occurrences within spike trains. We discuss these findings in the context of dynamic control of feed-forward and lateral/feedback connectivity by acetylcholine.

Acetylcholine dynamically controls spatial integration in marmoset primary visual cortex.

Recent in vitro studies have shown that acetylcholine (ACh) selectively reduces the efficacy of lateral cortical connections via a muscarinic mechanism, while boosting the efficacy of thalamocortical/feed-forward connections via a nicotinic mechanism. This suggests that high levels of ACh should reduce center-surround interactions of neurons in primary visual cortex, making cells more reliant on feed-forward information. In line with this hypothesis, we show that local iontophoretic application of ACh in primate primary visual cortex reduced the extent of spatial integration, assessed by recording a neurons' length tuning. When ACh was externally applied, neurons' preferred length shifted toward shorter bars, showing reduced impact of the extra-classical receptive field. We fitted a difference and a ratio of Gaussian model to these data to determine the underlying mechanisms of this dynamic change of spatial integration. These models assume overlapping summation and suppression areas with different widths and gains to be responsible for spatial integration and size tuning. ACh significantly reduced the extent of the summation area, but had no significant effect on the extent of the suppression area. In line with previous studies, we also show that applying ACh enhanced the response in the majority of cells, especially in the later (sustained) part of the response. These findings are similar to effects of attention on neuronal activity. The natural release of ACh is strongly linked with states of arousal and attention. Our results may therefore be relevant to the neurobiological mechanism of attention.

Amifostine in combination with erythropoietin and G-CSF promotes multilineage hematopoiesis in patients with myelodysplastic syndrome.

Ineffective hematopoiesis leading to profound cytopenias represents a major clinical problem in the management of patients with myelodysplastic syndrome (MDS). The aminothiol amifostine has shown to promote multilineage hematopoiesis both in vivo and in vitro in patients with MDS. We have treated 10 patients with 250 mg/m2 amifostine thrice weekly in combination with erythropoietin for 4 consecutive weeks followed by 2 weeks observation. Responding patients received the same 6 week schedule, while nonresponder received G-CSF in addition to erythropoietin and amifostine during the second treatment course. All patients experienced single or multilineage hematologic improvement, but only 2 reached transfusion independency. Moreover, response was durable only in a minority of patients and thus additional studies are warranted to further define the potential interaction of amifostine and growth factors.

99Tcm-tetrofosmin scintigraphy in Hodgkin's disease.

The aim of this study was to assess the suitability of 99Tcm-tetrofosmin (tetrofosmin) scintigraphy as a diagnostic modality in patients with Hodgkin's disease. Fourteen untreated patients with biopsy proven Hodgkin's disease (clinical stage Ia-IVb) were investigated. Post-treatment investigations were also done in 7 of the 14 patients. Focal pathological tetrofosmin uptake was seen in 42 site in the pre-treatment studies. Computed tomography identified 36 pathological regions. The tumour-to-background ratio ranged from 1.44 to 2.17 (mean 1.63). Follow-up studies demonstrated a response to treatment, in that there was a reduction in, or complete disappearance of, localized tetrofosmin uptake in regions previously pathological, and a decrease in tumour-to-background ratios. Tetrofosmin appears suitable for the localization of lymphomatous lesions, especially supradiaphragmatic ones, and for the follow-up of therapeutic response.