SLV330, a cannabinoid CB1 receptor antagonist,ameliorates deficits in the T-maze,object recognition and Social Recognition Tasks in rodents

Cannabinoid CB₁ receptor (CB₁R) signaling has been suggested to play an important role in the regulation of memory and cognition. In the present study, our aim was to investigate whether the CB₁R antagonist SLV330 (doses ranging from 0.3 to 10 mg/kg, given orally, p.o.) could ameliorate impairments in distinct aspects of cognition using different disruption models in both mice and rats. Effects of SLV330 were tested on working memory deficits in the T-maze Continuous Alternation Task (T-CAT) in mice; episodic memory deficits in the Object Recognition Task (ORT) and Social Recognition Task (SRT) in rats. The acetylcholinesterase inhibitor (AChEI) donepezil (Aricept®, approved for symptomatic treatment of Alzheimer’s disease) and nicotine were used as reference compounds.SLV330 markedly improved aging and scopolamine-induced memory deficits in the T-CAT in mice with a lowest effective dose (LED) of 1 mg/kg p.o., while reversing the cognitive dysfunction induced by the N-methyl-d-aspartate (NMDA) antagonist dizocilpine (MK-801) only at the middle dose of 3 mg/kg. In the ORT, we have found that combined administration of subthreshold doses of SLV330 (1 mg/kg, p.o.) and the AChEI donepezil (0.1 mg/kg, p.o.), that had no discernable effects on performance when given alone, enhanced memory performance in Wistar rats with deficits induced by the muscarinic antagonist scopolamine, suggestive of additive synergistic effects of SLV330 and donepezil on cognitive impairment. Finally, SLV330 was found to have cognition enhancing properties in a time delay paradigm in the SRT at a LED dose of 3 mg/kg (p.o.).In conclusion, the CB₁R antagonist SLV330 was found to clearly improve memory in several preclinical models for cognitive impairment.     

Auditory verbal hallucinations: Dialoguing between the cognitive sciences and phenomenology

Auditory verbal hallucinations (AVHs) are a highly complex and rich phenomena, and this has a number of important clinical, theoretical and methodological implications. However, until recently, this fact has not always been incorporated into the experimental designs and theoretical paradigms used by researchers within the cognitive sciences. In this paper, we will briefly outline two recent examples of phenomenologically informed approaches to the study of AVHs taken from a cognitive science perspective. In the first example, based on Larøi and Woodward (Harv Rev Psychiatry 15:109–117, 2007), it is argued that reality monitoring studies examining the cognitive underpinnings of hallucinations have not reflected the phenomenological complexity of AVHs in their experimental designs and theoretical framework. The second example, based on Jones (Schizophr Bull, in press, 2010), involves a critical examination of the phenomenology of AVHs in the context of two other prominent cognitive models: inner speech and intrusions from memory. It will be shown that, for both examples, the integration of a phenomenological analysis provides important improvements both on a methodological, theoretical and clinical level. This will be followed by insights and critiques from philosophy and clinical psychiatry—both of which offer a phenomenological alternative to the empiricist–rationalist conceptualisation of AVHs inherent to the cognitive sciences approach. Finally, the paper will conclude with ideas as to how the cognitive sciences may integrate these latter perspectives into their methodological and theoretical programmes.     

Automatic quantity processing in 5-year olds and adults

In this study adults performed numerical and physical size judgments on a symbolic (Arabic numerals) and non-symbolic (groups of dots) size congruity task. The outcomes would reveal whether a size congruity effect (SCE) can be obtained irrespective of notation. Subsequently, 5-year-old children performed a physical size judgment on both tasks. The outcomes will give a better insight in the ability of 5-year-olds to automatically process symbolic and non-symbolic numerosities. Adult performance on the symbolic and non-symbolic size congruity tasks revealed a SCE for numerical and physical size judgments, indicating that the non-symbolic size congruity task is a valid indicator for automatic processing of non-symbolic numerosities. Physical size judgments on both tasks by children revealed a SCE only for non-symbolic notation, indicating that the lack of a symbolic SCE is not related to the mathematical or cognitive abilities required for the task but instead to an immature association between the number symbol and its meaning.     

Right-hemisphere reading in a case of developmental deep dyslexia

The right-hemisphere hypothesis of deep dyslexia has received support from functional imaging studies of acquired deep dyslexia following damage to the left cerebral hemisphere, but no imaging studies of cases of developmental deep dyslexia, in which brain damage is not suspected, have been reported. In this paper, we report the first evidence of right hyperactivation in an adult case of developmental deep dyslexia. Hyperactivation was observed in the right inferior frontal cortex during functional magnetic resonance imaging (fMRI) of the oral reading of imageable content words and nonwords to which imageable lexical responses were frequently made. No evidence of right hyperactivation was observed in the oral reading of function words, nor during the naming of imageable words in response to pictured objects. The results reveal strategic and selective use of right-hemisphere functions for particular types of written stimuli. We propose that children with developmental deep dyslexia compensate for their lack of phonological skills by accessing right-hemisphere imageable associations that provide a mnemonic for linking written forms to spoken names.     

Somatosensory processes subserving perception and action

The functions of the somatosensory system are multiple. We use tactile input to localize and experience the various qualities of touch, and proprioceptive information to determine the position of different parts of the body with respect to each other, which provides fundamental information for action. Further, tactile exploration of the characteristics of external objects can result in conscious perceptual experience and stimulus or object recognition. Neuroanatomical studies suggest parallel processing as well as serial processing within the cerebral somatosensory system that reflect these separate functions, with one processing stream terminating in the posterior parietal cortex (PPC), and the other terminating in the insula. We suggest that, analogously to the organisation of the visual system, somatosensory processing for the guidance of action can be dissociated from the processing that leads to perception and memory. In addition, we find a second division between tactile information processing about external targets in service of object recognition and tactile information processing related to the body itself. We suggest the posterior parietal cortex subserves both perception and action, whereas the insula principally subserves perceptual recognition and learning.     

Cross-domain semantic priming in normal subjects and a prosopagnosic patient

Cross-domain semantic priming of person recognition (from face primes to name targets at 500msecs SOA) is investigated in normal subjects and a brain-injured patient (PH) with a very severe impairment of overt face recognition ability. Experiment 1 demonstrates equivalent semantic priming effects for normal subjects from face primes to name targets (cross-domain priming) and from name primes to name targets (within-domain priming). Experiment 2 demonstrates cross-domain semantic priming effects from face primes that PH cannot recognize overtly. Experiment 3 shows that cross-domain semantic priming effects can be found for normal subjects when target names are repeated across all conditions. This (repeated targets) method is then used in Experiment 4 to establish that PH shows equivalent semantic priming to normal subjects from face primes which he is very poor at identifying overtly and from name primes which he can identify overtly. These findings demonstrate that automatic aspects of face recognition can remain intact even when all sense of overt recognition has been lost.     

On the usefulness of 'what' and 'where' pathways in vision

The primate visual brain is classically portrayed as a large number of separate 'maps', each dedicated to the processing of specific visual cues, such as colour, motion or faces and their many features. In order to understand this fractionated architecture, the concept of cortical 'pathways' or 'streams' was introduced. In the currently prevailing view, the different maps are organised hierarchically into two major pathways, one involved in recognition and memory (the ventral stream or 'what' pathway) and the other in the programming of action (the dorsal stream or 'where' pathway). In this review, we question this heuristically influential but potentially misleading linear hierarchical pathway model and argue instead for a 'patchwork' or network model.