News and Commercials: Binding Deficits for Complex Information in Schizophrenia.

Memory for complex content is severely impaired in patients with schizophrenia spectrum disorders, which might make processing of daily information such as news and commercials particularly challenging. The goal of the present study was to assess the impairment of everyday memory in patients with schizophrenia. Healthy controls (HC) and patients with schizophrenia (SZ) were asked to watch a selection of six news segments and six commercials and complete a recognition task on the content of these video clips. All participants completed a neuropsychological test battery comprising measures of attention, working and episodic memory, and executive function. The total number of correctly recognized items was significantly lower in the SZ group. In contrast, the number of false recognitions was alike in both news and commercials paradigm. We conclude that memory in patients with schizophrenia is more prone to omissions than distortions for complex everyday stimuli. The results offer further support for impaired binding in SZ patients. Memory in SZ suffices to reject false multi-feature items on grounds of identifying at least one feature as incorrect but does not suffice to recall all features of a complex item and affirm it as correct.

Caudate nucleus and insular activation during a pain suppression paradigm comparing thermal and electrical stimulation.

Pain modulation is an integral function of the nervous system. It is needed to adapt to chronic stimuli. To gain insights into pain suppression mechanisms, two studies concerning the suppression of the feeling of pain with different stimulation modalities (heat vs. electrical stimuli) but using the same stimulation paradigms were compared: 15 subjects each had been stimulated on both hands under the instruction to suppress the feeling of pain. Anterior insula and DLPFC activation was seen in both single modality studies and seems to be a common feature of pain suppression, as it is absent in the interaction analyses presented here. During the task to suppress the feeling of pain, there were no consistent activations stronger under thermostimulation. But during electrostimulation, there was significantly stronger activation than during thermal stimulation in the caudate nucleus bilaterally and in the contralateral posterior insula. This may be attributed to the higher sensory-discriminative content and more demand on subjective rating and suppression of the painful electrical stimulus, compared to thermostimulation. The caudate nucleus seems to play an important role not only in the motor system but also in the modulation of the pain experience.

Graded cutaneous electrical vs thermal stimulation in humans shows different insular and cingulate cortex activation.

Pain can result from various sensory input modalities. To elucidate the differences of cortical responses to graded electrical and thermal stimulation, functional magnetic resonance imaging (fMRI) results of two studies using the same stimulation paradigms but different modalities with 15 healthy subjects each are compared. During painful electrical stimulation contralateral dorsal posterior insula and ventral posterior anterior cingulate cortex (ACC) activated more. During thermal stimulation, there was more activation in ipsilateral primary motor area (MI)/primary sensory area (SI) complex and premotor areas as well as dorsal posterior ACC. Thus electrostimulation preferably activates structures of the lateral pain projection system resulting in contralateral dorsal posterior insula and ventral posterior ACC activation. During thermal stimulation, more dorsal areas of the posterior ACC activated. The activation of ipsilateral MI/SI complex and premotor areas may be attributed to the slower perception of thermal stimuli and resulting re-evaluation. This has to be taken into account in the interpretation of other cross-modality studies as well.

The 3'-UTR of the mRNA coding for the major protein kinase C substrate MARCKS contains a novel CU-rich element interacting with the mRNA stabilizing factors HuD and HuR.

The expression of the major protein kinase C substrate MARCKS (myristoylated alanine-rich C kinase substrate) is controlled by the stability of its mRNA. While the MARCKS mRNA is long living in quiescent fibroblasts (t1/2 = 14 h), its half-life time is drastically reduced (t1/2 = 2 h) in cells treated with phorbol esters to activate protein kinase C (PKC) or treated with growth factors. In a first step to study the underlying mechanism we identified both a cis-element on the MARCKS mRNA and the corresponding trans-acting factors. Fusing the complete 3'-UTR or specific regions of the 3'-UTR of the MARCKS gene to a luciferase reporter gene caused a drastic decrease in luciferase expression to as low as 5-10% of controls. This down-regulation was a result of destabilization of the chimeric transcript as shown by RNA run-off and Northern blot-assays. By RNase/EMSA and UV-cross-linking experiments, we identified a stretch of 52 nucleotides [(CUUU)11(U)8] in the 3'-UTR of the MARCKS mRNA specifically recognized by two RNA-binding proteins, HuD and HuR. These trans-acting factors are members of the ELAV gene family and bind the MARCKS CU-rich sequence with high affinity. Overexpression of HuD and HuR in murine fibroblasts caused a striking stabilization of the endogenous MARCKS mRNA even under conditions when the MARCKS mRNA is normally actively degraded, i.e. after treating cells with phorbol ester. These data imply, that the identified CU-rich cis-element of the MARCKS 3'-UTR is involved in conferring instability to mRNAs and that members of the ELAV gene family oppose this effect. Based on its structural and functional properties, the (CUUU)11(U)8 sequence described here can be grouped into class III of AU-rich elements.