Memory and cognition in schizophrenia.

Episodic memory deficits are consistently documented as a core aspect of cognitive dysfunction in schizophrenia patients, present from the onset of the illness and strongly associated with functional disability. Over the past decade, research using approaches from experimental cognitive neuroscience revealed disproportionate episodic memory impairments in schizophrenia (Sz) under high cognitive demand relational encoding conditions and relatively unimpaired performance under item-specific encoding conditions. These specific deficits in component processes of episodic memory reflect impaired activation and connectivity within specific elements of frontal-medial temporal lobe circuits, with a central role for the dorsolateral prefrontal cortex (DLPFC), relatively intact function of ventrolateral prefrontal cortex and variable results in the hippocampus. We propose that memory deficits can be understood within the broader context of cognitive deficits in Sz, where impaired DLPFC-related cognitive control has a broad impact across multiple cognitive domains. The therapeutic implications of these findings are discussed

Monitoring of Single-Cell Responses in the Optic Tectum of Adult Zebrafish with Dextran-Coupled Calcium Dyes Delivered via Local Electroporation

Kassing V, Engelmann J, Kurtz R. Monitoring of Single-Cell Responses in the Optic Tectum of Adult Zebrafish with Dextran-Coupled Calcium Dyes Delivered via Local Electroporation. PLoS ONE. 2013;8(5): e62846.The zebrafish (Danio rerio) has become one of the major animal models for in vivo examination of sensory and neuronal computation. Similar to Xenopus tadpoles neural activity in the optic tectum, the major region controlling visually guided behavior, can be examined in zebrafish larvae by optical imaging. Prerequisites of these approaches are usually the transparency of larvae up to a certain age and the use of two-photon microscopy. This principle of fluorescence excitation was necessary to suppress crosstalk between signals from individual neurons, which is a critical issue when using membrane-permeant dyes. This makes the equipment to study neuronal processing costly and limits the approach to the study of larvae. Thus there is lack of knowledge about the properties of neurons in the optic tectum of adult animals. We established a procedure to circumvent these problems, enabling in vivo calcium imaging in the optic tectum of adult zebrafish. Following local application of dextran-coupled dyes single-neuron activity of adult zebrafish can be monitored with conventional widefield microscopy, because dye labeling remains restricted to tens of neurons or less. Among the neurons characterized with our technique we found neurons that were selective for a certain pattern orientation as well as neurons that responded in a direction-selective way to visual motion. These findings are consistent with previous studies and indicate that the functional integrity of neuronal circuits in the optic tectum of adult zebrafish is preserved with our staining technique. Overall, our protocol for in vivo calcium imaging provides a useful approach to monitor visual responses of individual neurons in the optic tectum of adult zebrafish even when only widefield microscopy is available. This approach will help to obtain valuable insight into the principles of visual computation in adult vertebrates and thus complement previous work on developing visual circuits

Quantitative pretreatment VOI analysis of liver metastases 99mTc-MAA SPECT/CT and FDG PET/CT in relation with treatment response to SIRT

Using quantitive VOI analysis, the percentage Tc-99m-MAA uptake and SUVmax and mean values of liver metastases obtained prior to SIRT were related to treatment response using both a lesion-based and clinical dichotomous approach. Based on the VOI % of Tc-99m-MAA activity, the estimated Y-90-microspheres activity/cc (MBq/cc) was calculated from the effective dose injected. Baseline VOI FDG PET SUVmean and max values and estimated MBq/cc values were related to treatment response using a lesion-based approach (% change in SUVmean >= 50%) and a clinical dichotomous approach. Fifteen treatment sessions were analyzed (13 patients). Using the lesion-based approach (12 treatment sessions) 40 lesions responded and 37 did not. SUVmax and mean values proved significantly different between non-responding and responding lesions; 18:6 (SD 10.8) versus 13.5 (SD 8.4) for SUVmax (p = 0.02) and 11.4 (SD 3.8) versus 6.3 (SD 4.5) for SUVmean (p = 0.002). Using the clinical dichotomous approach (15 treatment sessions / 11 responding), 91 lesions were analyzed; 57 responded. VOI volumes and estimated Y-90-loaded glass microspheres activity (MBq/cc) did not differ between responders and non responders; 24 cc (SD 27) versus 21 cc (SD 21 cc) (p = 0.4) and 1.95 MBq/cc (SD 1.1 MBq/cc) versus 1.90 MB/cc (SD 2.7 MBq/cc) (p = 0.92). On the contrary, SUVmax and mean values proved significantly different between responders and non-responders; 23.7 (SD 9.8) versus 9.4 (SD 3.8) for SUVmax (p = 0.0001) and 13.1 (SD 8.1) versus 4.9 (SD 1.4) for SUVmean. Conclusion: These findings suggest that in patients presenting with high baseline SUVmax and mean values, the administration of higher activities or alternatively, other potentially more useful treatment options might be considered

Mental rotation meets the motion aftereffect: the role of hV5/MT+ in visual mental imagery

A growing number of studies show that visual mental imagery recruits the same brain areas as visual perception. Although the necessity of hV5/MT+ for motion perception has been revealed by means of TMS, its relevance for motion imagery remains unclear. We induced a direction-selective adaptation in hV5/MT+ by means of an MAE while subjects performed a mental rotation task that elicits imagined motion. We concurrently measured behavioral performance and neural activity with fMRI, enabling us to directly assess the effect of a perturbation of hV5/MT+ on other cortical areas involved in the mental rotation task. The activity in hV5/MT+ increased as more mental rotation was required, and the perturbation of hV5/MT+ affected behavioral performance as well as the neural activity in this area. Moreover, several regions in the posterior parietal cortex were also affected by this perturbation. Our results show that hV5/MT+ is required for imagined visual motion and engages in an interaction with parietal cortex during this cognitive process

Laminar fMRI: applications for cognitive neuroscience

The cortex is a massively recurrent network, characterized by feedforward and feedback connections between brain areas as well as lateral connections within an area. Feedforward, horizontal and feedback responses largely activate separate layers of a cortical unit, meaning they can be dissociated by lamina-resolved neurophysiological techniques. Such techniques are invasive and are therefore rarely used in humans. However, recent developments in high spatial resolution fMRI allow for non-invasive, in vivo measurements of brain responses specific to separate cortical layers. This provides an important opportunity to dissociate between feedforward and feedback brain responses, and investigate communication between brain areas at a more fine- grained level than previously possible in the human species. In this review, we highlight recent studies that successfully used laminar fMRI to isolate layer-specific feedback responses in human sensory cortex. In addition, we review several areas of cognitive neuroscience that stand to benefit from this new technological development, highlighting contemporary hypotheses that yield testable predictions for laminar fMRI. We hope to encourage researchers with the opportunity to embrace this development in fMRI research, as we expect that many future advancements in our current understanding of human brain function will be gained from measuring lamina-specific brain responses