Resting state functional magnetic resonance imaging reveals distinct brain activity in heavy cannabis users - a multi-voxel pattern analysis.

Chronic cannabis use can cause cognitive, perceptual and personality alterations, which are believed to be associated with regional brain changes and possible changes in connectivity between functional regions. This study aims to identify the changes from resting state functional magnetic resonance imaging scans. A two-level multi-voxel pattern analysis was proposed to classify male cannabis users from normal controls. The first level analysis works on a voxel basis and identifies clusters for the input of a second level analysis, which works on the functional connectivity between these regions. We found distinct clusters for male cannabis users in the middle frontal gyrus, precentral gyrus, superior frontal gyrus, posterior cingulate cortex, cerebellum and some other regions. Based on the functional connectivity of these clusters, a high overall accuracy rate of 84-88% in classification accuracy was achieved. High correlations were also found between the overall classification accuracy and Barrett Barrett Impulsiveness Scale factor scores of attention and motor. Our result suggests regional differences in the brains of male cannabis users that span from the cerebellum to the prefrontal cortex, which are associated with differences in functional connectivity.

From membrane phospholipid defects to altered neurotransmission: is arachidonic acid a nexus in the pathophysiology of schizophrenia?

Schizophrenia (SZ) is a devastating neuropsychiatric disorder affecting 1% of the general population, and is characterized by symptoms such as delusions, hallucinations, and blunted affect. While many ideas regarding SZ pathogenesis have been put forth, the majority of research has focused on neurotransmitter function, particularly in relation to altered dopamine activity. However, treatments based on this paradigm have met with only modest success, and current medications fail to alleviate symptoms in 30-60% of patients. An alternative idea postulated a quarter of a century ago by Feldberg (Psychol. Med. 6 (1976) 359) and Horrobin (Lancet 1 (1977) 936) involves the theory that SZ is associated in part with phospholipid/fatty acid abnormalities. Since then, it has been repeatedly shown that in both central and peripheral tissue, SZ patients demonstrate increased phospholipid breakdown and decreased levels of various polyunsaturated fatty acids (PUFAs), particularly arachidonic acid (AA). Given the diverse physiological function of membrane phospholipids and PUFAs, an elucidation of their role in SZ pathophysiology may provide novel strategies in the treatment of this disorder. The purpose of this review is to summarize the relevant data on membrane phospholipid/PUFA defects in SZ, the physiological consequence of altered AA signaling, and how they relate to the neurobiological manifestations of SZ and therapeutic outcome.

Neural correlates of artificial grammar learning.

Artificial grammar learning (AGL) is a form of nondeclarative memory that involves the nonconscious acquisition of abstract rules. While data from amnesic patients indicate that AGL does not depend on the medial temporal lobe, the neural basis of this type of memory is unknown and was therefore examined using event-related fMRI. Prior to scanning, participants studied letter strings constructed according to an artificial grammar. Participants then made grammaticality judgments about novel grammatical and nongrammatical strings while fMRI data were collected. The participants successfully acquired knowledge of the grammar, as evidenced by correct identification of the grammatical letter strings (57.4% correct; SE 1.9). During grammaticality judgments, widespread increases in activity were observed throughout the occipital, posterior temporal, parietal, and prefrontal cortical areas, reflecting the cognitive demands of the task. More specific analyses contrasting grammatical and nongrammatical strings identified greater activity in left superior occipital cortex and the right fusiform gyrus for grammatical stimuli. Increased activity was also observed in the left superior occipital and left angular gyrus for correct responses compared to incorrect. Comparing activity during grammaticality judgments versus a matched recognition control task again identified greater activation in the left angular gyrus. The network of areas exhibiting increased activity for grammatical stimuli appears to have more in common with studies examining word-form processing or mental calculation than the fluency effects previously reported for nondeclarative memory tasks such as priming and visual categorization. These results suggest that a novel nondeclarative memory mechanism supporting AGL exists in the left superior occipital and inferior parietal cortex.

Cannabis use is associated with schizotypy and attentional disinhibition.

While most neurochemical research into the pathogenesis of schizophrenia (SZ) has focused on the dopaminergic, glutamatergic, and serotonergic systems, the exact nature and cause of this disorder have proven intractable. Given the recent discovery and elucidation of the endogenous cannabinioid system, a re-examination of the cannabis-induced exacerbation hypothesis of SZ is warranted. The purpose of the present study was to assess whether current cannabis users exhibit personality correlates and neurocognitive deficits similar to those observed in SZ patients. 15 current cannabis users, 15 drug-free controls, and 10 past cannabis users were assessed on tasks which assess attentional inhibition, spatial working memory, olfactory identification, and schizotypal personality. Current cannabis users demonstrated deficits in attentional inhibition, decreased reaction time, and significantly higher scores on the schizotypal personality questionnaire (SPQ) compared with the non-using and past cannabis using groups. No group differences were found on the working memory or olfactory identification tasks. These results suggest that cannabis use can mimic attentional deficits seen in acute schizophrenia and is associated with schizotypal personality, thus setting the stage for a possible cannabinoid model of SZ.

Modulation of attentional inhibition by norepinephrine and cortisol after psychological stress.

Two of the most salient physiological responses to stress are increased norepinephrine (NE) and cortisol (CORT) activities. However, it is unclear how these neurochemical events affect cognition, especially attention. We examined the effects of mild psychological stress on selective attention, as assessed by the negative priming (NP) paradigm. Salivary measures of the stress hormone CORT and alpha-amylase (a correlate of NE) were assayed to probe the relationship between the stress response and attentional inhibition. Healthy subjects (N = 20) engaged in the attention task, which was then followed by 15 min of a stressful video game before a return to the attentional task. Baseline saliva samples were obtained before the experiment began, 1 min after the video-game stressor, and 20 min post-stress. Subjects showed a significant reduction in NP and a decrease in reaction time (RT) after the video game. Moreover, alpha-amylase levels increased significantly after the stressor, indicating the role of NE in the acute stress response. While CORT levels remained unchanged after stress, CORT correlated significantly with both NP scores and RT after the stressor. These results imply that mild psychological stress can significantly alter attentional processes. Given the increase in alpha-amylase and the correlation between attention and CORT after stress, it seems likely that attentional processes are under tight control by brain systems which mediate the fight-or-flight response.