Cerebellar Contribution to Context Processing in Extinction Learning and Recall.

Whereas acquisition of new associations is considered largely independent of the context, context dependency is a hallmark of extinction of the learned associations. The hippocampus and the prefrontal cortex are known to be involved in context processing during extinction learning and recall. Although the cerebellum has known functional and anatomic connections to the hippocampus and the prefrontal cortex, cerebellar contributions to context processing of extinction have rarely been studied. In the present study, we reanalyzed functional brain imaging data (fMRI) of previous work investigating context effects during extinction in a cognitive associative learning paradigm in 28 young and healthy subjects (Lissek et al. Neuroimage. 81:131-3, 2013). In that study, event-related fMRI analysis did not include the cerebellum. The 3 T fMRI dataset was reanalyzed using a spatial normalization method optimized for the cerebellum. Data of seven participants had to be excluded because the cerebellum had not been scanned in full. Cerebellar activation related to context change during extinction learning was most prominent in lobule Crus II bilaterally (p < 0.01, t > 2.53; partially corrected by predetermined cluster size). No significant cerebellar activations were observed related to context change during extinction retrieval. The posterolateral cerebellum appears to contribute to context-related processes during extinction learning, but not (or less) during extinction retrieval. The cerebellum may support context learning during extinction via its connections to the hippocampus. Alternatively, the cerebellum may support the shifting of attention to the context via its known connections to the dorsolateral prefrontal cortex. Because the ventromedial prefrontal cortex (vmPFC) is critically involved in context-related processes during extinction retrieval, and there are no known connections between the cerebellum and the vmPFC, the cerebellum may be less important during extinction recall.

E-cadherin, actin, microtubules and FAK dominate different spheroid formation phases and important elements of tissue integrity.

Spheroids resemble features of tissues and serve as model systems to study cell-cell and cell-ECM interactions in non-adhesive three-dimensional environments. Although it is generally accepted that mature spheroids resemble tissue properties very well, no studies relate different phases in the spheroid formation processes that contribute to tissue integrity. Tissue integrity involves the cellular processes adhesion formation, adhesion reinforcement, rearrangement as well as proliferation. They maintain the structure and function of tissues and, upon dysregulation, contribute to malignancy. We investigated spheroid formation dynamics in cell lines of different metastatic potential. We dissected spheroid formation into phases of aggregation, compaction and growth to identify the respective contributions of E-cadherin, actin, microtubules and FAK. E-cadherin, actin and microtubules drive the first two phases. Microtubules and FAK are involved in the proliferation phase. FAK activity correlates with the metastatic potential of the cells. A robust computational model based on a very large number of experiments reveals the temporal resolution of cell adhesion. Our results provide novel hypotheses to unveil the general mechanisms that contribute to tissue integrity.

Impaired learning of a color reversal task after NMDA receptor blockade in the pigeon (Columba livia) associative forebrain (neostriatum caudolaterale).

The neostriatum caudolaterale (NCL) in the pigeon (Columba livia) forebrain is a multisensory associative area and a functional equivalent to the mammalian prefrontal cortex (PFC). To investigate the role of N-methyl-D-aspartate (NMDA) receptors in the NCL for learning flexibility, the authors trained pigeons in a color reversal task while locally blocking NMDA receptors with D,L-2-2-amino-5-phosphonovalerate (AP-5). Controls received saline injections. AP-5-treated pigeons made significantly more errors and showed significantly stronger perseveration in a learning strategy applied by both groups but were unimpaired in initial learning. Results indicate that NMDA receptors in the NCL are necessary for efficient performance in this PFC-sensitive task, and that they are involved in extinction of obsolete information rather than in acquiring new information.

Sports and brain morphology - a voxel-based morphometry study with endurance athletes and martial artists.

Physical exercises and motor skill learning have been shown to induce changes in regional brain morphology, this has been demonstrated for various activities and tasks. Also individuals with special skills show differences in regional brain morphology. This has been indicated for professional musicians, London taxi drivers, as well as for athletes like dancers, golfers and judokas. However little is known about whether sports with different metabolic profiles (aerobic vs. anaerobic) are associated with different patterns of altered brain morphology. In this cross-sectional study we investigated two groups of high-performance athletes, one group performing sports that are thought to be mainly aerobic, and one group performing sports known to have intermittent phases of anaerobic metabolism. Using high-resolution structural imaging and voxel-based morphometry (VBM), we investigated a group of 26 male athletes consisting of 13 martial artists and 13 endurance athletes as well as a group of non-exercising men (n=13). VBM analyses revealed higher gray matter (GM) volumes in the supplementary motor area/dorsal premotor cortex (BA 6) in both athlete groups as compared to the control group. In addition, endurance athletes showed significantly higher GM volume in the medial temporal lobe (MTL), specifically in the hippocampus and parahippocampal gyrus, which was not seen in the martial arts group. Our data suggest that high-performance sports are associated with changes in regional brain morphology in areas implicated in motor planning and motor learning. In addition high-level endurance sports seem to affect MTL structures, areas that have previously been shown to be modulated by aerobic exercise.

Bilateral somatosensory cortex disinhibition in complex regional pain syndrome type I.

OBJECTIVE: In a previous study, we found bilateral disinhibition in the motor cortex of patients with complex regional pain syndrome (CRPS). This finding suggests a complex dysfunction of central motor-sensory circuits. The aim of our present study was to assess possible bilateral excitability changes in the somatosensory system of patients with CRPS. METHODS: We measured paired-pulse suppression of somatosensory evoked potentials in 21 patients with unilateral CRPS I involving the hand. Eleven patients with upper limb pain of non-neuropathic origin and 21 healthy subjects served as controls. Innocuous paired-pulse stimulation of the median nerve was either performed at the affected and the unaffected hand, or at the dominant hand of healthy controls, respectively. RESULTS: We found a significant reduction of paired-pulse suppression in both sides of patients with CRPS, compared with control patients and healthy control subjects. CONCLUSION: These findings resemble our findings in the motor system and strongly support the hypothesis of a bilateral complex impairment of central motor-sensory circuits in CRPS I.