Deleterious Effects of a Low Amount of Ethanol on LTP-Like Plasticity in Human Cortex

Ingesting ethanol (EtOH) at low doses during social drinking is a common human behavior for its facilitating effects on social interactions. However, low-dose EtOH may have also detrimental effects that so far are underexplored. Here we sought to test the effects of low-dose EtOH on long-term potentiation (LTP)-like plasticity in human motor cortex. Previous cellular experiments showed that low-dose EtOH potentiates extrasynaptic GABAAR and reduces NMDAR-mediated currents, processes that would limit the expression of LTP. Paired associative transcranial magnetic stimulation (PAS_LTP) was employed in nine healthy subjects for induction of LTP-like plasticity, indexed by a long-term increase in motor-evoked potential input–output curves. Synaptic α1-GABAAR function was measured by saccadic peak velocity (SPV). Very low doses of EtOH (resulting in blood concentrations of <5 mM) suppressed LTP-like plasticity but did not affect SPV when compared with a placebo condition. In contrast, 1 mg of alprazolam, a classical benzodiazepine, or 10 mg of zolpidem, a non-benzodiazepine hypnotic, decreased SPV but did not significantly affect LTP-like plasticity when compared with placebo. This double dissociation of low-dose EtOH vs alprazolam/zolpidem effects is best explained by the putatively high affinity of EtOH but not alprazolam/zolpidem to extrasynaptic GABAARs and to NMDARs. Findings suggest that enhancement of extrasynaptic GABAAR-mediated tonic inhibition and/or reduction of NMDAR-mediated neurotransmission by EtOH blocks LTP-like plasticity in human cortex at very low doses that are easily reached during social drinking. Therefore, low-dose EtOH may jeopardize LTP-dependent processes, such as learning and memory formation.     

Visualization of the amygdalo–hippocampal border and its structural variability by 7T and 3T magnetic resonance imaging

The amygdala and the hippocampus are two adjacent structures in the medial temporal lobe that have been broadly investigated in functional and structural neuroimaging due to their central importance in sensory perception, emotion, and memory. Exact demarcation of the amygdalo‐hippocampal border (AHB) is, however, difficult in conventional structural imaging. Recent evidence suggests that, due to this difficulty, functional activation sites with high probability of being located in the hippocampus may erroneously be assigned to the amygdala, and vice versa. In the present study, we investigated the potential of ultra‐high‐field magnetic resonance imaging (MRI) in single sessions for detecting the AHB in humans. We show for the first time the detailed structure of the AHB as it can be visualized in T1‐weighted 7T in vivo images at 0.5‐mm³ isotropic resolution. Compared to data acquired at 3T, 7T images revealed considerably more structural detail in the AHB region. Thus, we observed a striking inter‐hemispheric and interindividual variability of the exact anatomical configuration of the AHB that points to the necessity of individual imaging of the AHB as a prerequisite for accurate anatomical assignment in this region. The findings of the present study demonstrate the usefulness of ultra‐high‐field structural MRI to resolve anatomical ambiguities of the human AHB. Highly accurate morphometric and functional investigations in this region at 7T may allow addressing such hitherto unexplored issues as whether the structural configuration of the AHB is related to functional differences in amygdalo‐hippocampal interaction. Hum Brain Mapp 35:4316–4329, 2014. © 2014 Wiley Periodicals, Inc .     

Functional characterization of genetic polymorphisms identified in the human cytochrome P450 4F12 (CYP4F12) promoter region

The human cytochrome CYP4F12 has been shown to be active toward inflammatory mediators and exogenous compounds such as antihistaminic drugs. In the present study, we report the first investigation of polymorphisms in the human CYP4F12 gene. A screening for sequence variations in the 5'-flanking region was performed by a Polymerase Chain Reaction-Single Strand Conformational Polymorphism (PCR-SSCP) strategy, using DNA samples from 53 unrelated French individuals of Caucasian origin. Several polymorphisms were identified, comprising a large deletion located in intron 1 (CYP4F12*v1), two isolated substitutions -402G>A (CYP4F12*v3) and -188 T>C (CYP4F12*v4) and nine combined mutations, -474T>C, -279A>C, -224A>G, -173G>A, -145C>G, -140T>C, -126T>C, -56T>C, and -21T>G (CYP4F12*v2). Considering the nature and location of the polymorphisms characterizing the CYP4F12*v1 and *v2, the functional relevance of those two allelic variants was further examined by transfecting different cell lines with constructs of the related region of the CYP4F12/luciferase reporter gene. Both alleles lead to a significant decrease of CYP4F12 gene expression in HepG2 cell line and, therefore, are likely to determine interindividual differences in CYP4F12 gene expression.     

Alpha synchronization during auditory spatial short-term memory

Recent studies have suggested an active role of cortical alpha oscillations for cognitive functions including short-term memory. We used magnetoencephalography to assess alpha activity during an auditory spatial delayed matching-to-sample task compared with a nonmemory control condition. In the memory task, participants had to memorize the lateralization angle of a noise stimulus S1 and compare it with another lateralized sound S2 presented after an 800-ms delay phase. Whereas alpha desynchronization following S1 was observed over superior temporal areas under both conditions, only the memory task was accompanied by posterior parietal alpha synchronization during the subsequent delay period. The findings are consistent with the notion of alpha activity reflecting active inhibition of interfering processes during memory maintenance of spatial sounds.     

Distinct gamma-band components reflect the short-term memory maintenance of different sound lateralization angles

Oscillatory activity in human electro- or magnetoencephalogram has been related to cortical stimulus representations and their modulation by cognitive processes. Whereas previous work has focused on gamma-band activity (GBA) during attention or maintenance of representations, there is little evidence for GBA reflecting individual stimulus representations. The present study aimed at identifying stimulus-specific GBA components during auditory spatial short-term memory. A total of 28 adults were assigned to 1 of 2 groups who were presented with only right- or left-lateralized sounds, respectively. In each group, 2 sample stimuli were used which differed in their lateralization angles (15 degrees or 45 degrees) with respect to the midsagittal plane. Statistical probability mapping served to identify spectral amplitude differences between 15 degrees versus 45 degrees stimuli. Distinct GBA components were found for each sample stimulus in different sensors over parieto-occipital cortex contralateral to the side of stimulation peaking during the middle 200-300 ms of the delay phase. The differentiation between "preferred" and "nonpreferred" stimuli during the final 100 ms of the delay phase correlated with task performance. These findings suggest that the observed GBA components reflect the activity of distinct networks tuned to spatial sound features which contribute to the maintenance of task-relevant information in short-term memory.     

Behavioral relevance of gamma-band activity for short-term memory-based auditory decision-making

Oscillatory activity in the gamma-band range has been established as a correlate of cognitive processes, including perception, attention and memory. Only a few studies, however, have provided evidence for an association between gamma-band activity (GBA) and measures of behavioral performance. Here we focused on the comparison between sample and test stimuli S1 and S2 during an auditory spatial short-term memory task. Applying statistical probability mapping to magnetoencephalographic recordings from 28 human subjects, we identified GBA components distinguishing nonidentical from identical S1–S2 pairs. This activity was found at frequencies between 65 and 90 Hz and was localized over posterior cortical regions contralateral to the hemifield in which the stimuli were presented. The 10 best task performers showed higher amplitudes of this GBA component than the 10 worst performers. This group difference was most pronounced between about 150 and 300 ms after stimulus onset. Apparently the decision about whether test stimuli matched the stored representation of previously presented sample sounds relied partly on the oscillatory activation of networks representing differences between both stimuli. This result could be replicated by reanalyzing the combined data from two previous studies assessing short-term memory for sound duration and sound lateralization, respectively. Similarly to our main study, GBA amplitudes to nonmatching vs. matching S1–S2 pairs were higher in good performers than poor performers. The present findings demonstrate the behavioral relevance of GBA.