Quantitative susceptibility mapping of striatum in children and adults, and its association with working memory performance.

Quantitative susceptibility mapping (QSM) is a magnetic resonance imaging (MRI) technique in which the magnetic susceptibility characteristic of molecular and cellular components, including iron and myelin, is quantified. Rapid iron accumulation in subcortical nuclei and myelination of the white matter tracts are two important developmental processes that contribute to cognitive functions. Both also contribute to the magnetic susceptibility of the brain tissues. Here, we used the QSM as indirect measures of iron in subcortical nuclei and myelin in caudo-frontal white matter pathways. We included two groups of participants; 21 children aged 6-7years and 25 adults aged 21-40years. All subjects also performed tests estimating their visuo-spatial working memory capacity. Adults had higher magnetic susceptibility in all subcortical nuclei, compared to children. The magnetic susceptibility of these nuclei highly correlated with their previously reported iron content. Moreover, working memory performance correlated significantly with the magnetic susceptibility in caudate nucleus in both children and adults, while the correlation was not significant for gray matter density. QSM of white matter in the caudo-frontal tract also differed between children and adults, but did not correlate with working memory scores. These results indicate that QSM is a feasible technique to measure developmental aspects of changes in the striatum, possibly related to iron content that is relevant to cognition.

Transcranial Electric Stimulation Can Impair Gains during Working Memory Training and Affects the Resting State Connectivity.

Transcranial electric stimulation (tES) is a promising technique that has been shown to improve working memory (WM) performance and enhance the effect of cognitive training. However, experimental set up and electrode placement are not always determined based on neurofunctional knowledge about WM, leading to inconsistent results. Additional research on the effects of tES grounded on neurofunctional evidence is therefore necessary. Sixty young, healthy, volunteers, assigned to six different groups, participated in 5 days of stimulation or sham treatment. Twenty-five of these subjects also participated in MRI acquisition. We performed three experiments: In the first one, we evaluated tES using either direct current stimulation (tDCS) with bilateral stimulation of the frontal or parietal lobe; in the second one, we used the same tDCS protocol with a different electrode placement (i.e., supraorbital cathode); in the third one, we used alternating currents (tACS) of 35 Hz, applied bilaterally to either the frontal or parietal lobes. The behavioral outcome measure was the WM capacity (i.e., number of remembered spatial position) during the 5 days of training. In a subsample of subjects we evaluated the neural effects of tDCS by measuring resting state connectivity with functional MRI, before and after the 5 days of tDCS and visuo-spatial WM training. We found a significant impairment of WM training-related gains associated with parietal tACS and frontal tDCS. Five days of tDCS stimulation was also associated with significant change in resting state connectivity revealed by multivariate pattern analysis. None of the stimulation paradigms resulted in improved WM performance or enhanced WM training gains. These results show that tES can have negative effects on cognitive plasticity and affect resting-state functional connectivity.

Alpha7 nicotinic acetylcholine receptor agonists and PAMs as adjunctive treatment in schizophrenia. An experimental study.

Nicotine has been found to improve cognition and reduce negative symptoms in schizophrenia and a genetic and pathophysiological link between the α7 nicotinic acetylcholine receptors (nAChRs) and schizophrenia has been demonstrated. Therefore, there has been a large interest in developing drugs affecting the α7 nAChRs for schizophrenia. In the present study we investigated, in rats, the effects of a selective α7 agonist (PNU282987) and a α7 positive allosteric modulator (PAM; NS1738) alone and in combination with the atypical antipsychotic drug risperidone for their utility as adjunct treatment in schizophrenia. Moreover we also investigated their utility as adjunct treatment in depression in combination with the SSRI citalopram. We found that NS1738 and to some extent also PNU282987, potentiated a subeffective dose of risperidone in the conditioned avoidance response test. Both drugs also potentiated the effect of a sub-effective concentration of risperidone on NMDA-induced currents in pyramidal cells of the medial prefrontal cortex. Moreover, NS1738 and PNU282987 enhanced recognition memory in the novel object recognition test, when given separately. Both drugs also potentiated accumbal but not prefrontal risperidone-induced dopamine release. Finally, PNU282987 reduced immobility in the forced swim test, indicating an antidepressant-like effect. Taken together, our data support the utility of drugs targeting the α7 nAChRs, perhaps especially α7 PAMs, to potentiate the effect of atypical antipsychotic drugs. Moreover, our data suggest that α7 agonists and PAMs can be used to ameliorate cognitive symptoms in schizophrenia and depression.