Metabolite profiles in the anterior cingulate cortex of depressed patients differentiate those taking N-acetyl-cysteine versus placebo

Background: Increased oxidative stress is thought to contribute to the pathophysiology of major depressive disorder (MDD), which is in part due to diminished levels of glutathione, the primary anti-oxidant of the brain. Oral administration of N-acetyl-cysteine (NAC) replenishes glutathione and has therefore been shown to reduce depressive symptoms. Proton magnetic spectroscopy (1H-MRS) that allows quantification of brain metabolites pertinent to both MDD and oxidative biology may provide some novel insights into the neurobiological effects of NAC, and in particular metabolite concentrations within the anterior cingulate cortex (ACC) are likely to be important given the key role of this region in the regulation of affect.

Objective: The aim of this study was to determine whether the metabolite profile of the ACC in MDD patients predicts treatment with adjunctive NAC versus placebo.

Methods: This study was nested within a multicentre, randomized, double-blind, placebo-controlled study of MDD participants treated with adjunctive NAC. Participants (n = 76) from one site completed the spectroscopy component at the end of treatment (12 weeks). Spectra from a single-voxel in the ACC were acquired and absolute concentrations of glutamate (Glu), glutamate-glutamine (Glx), N-acetyl-aspartate (NAA) and myo-inositol (mI) were obtained. Binary logistic regression analysis was performed to determine whether metabolite profiles could predict NAC versus placebo group membership.

Results: When predicting group outcome (NAC or placebo), Glx, NAA and mI were a significant model, and had 75% accuracy, while controlling for depression severity and sex. However, the Glu, NAA and mI profile was only predictive at a trend level, with 68.3% accuracy. For both models, the log of the odds of a participant being in the NAC group was positively related to NAA, Glx and Glu levels and negatively related to mI levels.

Conclusion: The finding of higher Glx and NAA levels being predictive of the NAC group provides preliminary support for the putative anti-oxidative role of NAC in MDD.

Different current intensities of anodal transcranial direct current stimulation do not differentially modulate motor cortex plasticity

Transcranial direct current stimulation (tDCS) is a noninvasive technique that modulates the excitability of neurons within the motor cortex (M1). Although the aftereffects of anodal tDCS on modulating cortical excitability have been described, there is limited data describing the outcomes of different tDCS intensities on intracortical circuits. To further elucidate the mechanisms underlying the aftereffects of M1 excitability following anodal tDCS, we used transcranial magnetic stimulation (TMS) to examine the effect of different intensities on cortical excitability and short-interval intracortical inhibition (SICI). Using a randomized, counterbalanced, crossover design, with a one-week wash-out period, 14 participants (6 females and 8 males, 22–45 years) were exposed to 10 minutes of anodal tDCS at 0.8, 1.0, and 1.2 mA. TMS was used to measure M1 excitability and SICI of the contralateral wrist extensor muscle at baseline, immediately after and 15 and 30 minutes following cessation of anodal tDCS. Cortical excitability increased, whilst SICI was reduced at all time points following anodal tDCS. Interestingly, there were no differences between the three intensities of anodal tDCS on modulating cortical excitability or SICI. These results suggest that the aftereffect of anodal tDCS on facilitating cortical excitability is due to the modulation of synaptic mechanisms associated with long-term potentiation and is not influenced by different tDCS intensities.

Corticomotor responses to attentionally demanding motor performance: a mini-review

Increased attentional demand has been shown to reduce motor performance, leading to increases in accidents, particularly in elderly populations. While these deficits have been well documented behaviorally, their cortical correlates are less well known. Increased attention has been shown to affect activity in prefrontal regions of the cortex. However there have been varying results within past research investigating corticomotor regions, mediating motor performance. This mini-review initially discusses past behavioral research, before moving to studies investigating corticomotor areas in response to changes in attention. Recent dual task studies have revealed a possible decline in the ability of older, but not younger, adults to activate inhibitory processes within the motor cortex, which may be correlated with poor motor performance, and thus accidents. A reduction in cortical inhibition may be caused by neurodegeneration within prefrontal regions of the cortex with age, rendering older adults less able to allocate attention to corticomotor regions.

Breakdown in central motor control can be attenuated by motor practice and neuro-modulation of the primary motor cortex

The performance of a repetitive index finger flexion–extension task at maximal voluntary rate (MVR) begins to decline just a few seconds into the task and we have previously postulated that this breakdown has a central origin. To test this hypothesis, we have combined two objectives; to determine whether motor practice can lessen the performance deterioration in an MVR task, and whether further gains can be achieved with a transcranial magnetic stimulation (TMS) protocol that increases corticomotor excitability (CME). Eleven right-handed subjects participated in a randomized crossover study design that consisted of a 15-min interventional TMS at I-wave periodicity (ITMS) and single-pulsed Sham intervention prior to six 10-s practice sets of a repetitive finger flexion–extension task at MVR. Motor-evoked potentials (MEPs) were recorded from the first dorsal interosseous muscle. The starting movement rate, and the percentage decline in rate by the end of the MVR were quantitated. Training of the MVR task improved the sustainability of the task by reducing the decline in movement rate. CME increased steadily after each training bout, and this increase was maintained up to 20 min after the last bout. ITMS further increased CME, and was associated with an increase in both the starting rate of the MVR task and its sustainability, when compared to Sham. The results implicate central motor processes in the performance and sustainability of the MVR task, and indicate that MVR kinematics can improve with short-term training and with non-invasive neuro-modulation.

N-Ethylmaleimide sensitive factor in the cortex of subjects with schizophrenia and bipolar I disorder

N-Ethylmaleimide sensitive factor (NSF) is a presynaptic protein that has been suggested to be differentially expressed in the cortex of schizophrenic subjects through both high-throughput proteomic and genomic screening studies. Thus, to expand upon these studies we measured NSF using Western blotting in four regions of the cortex (BA9, 10, 40 and 46), in a cohort comprising 20 schizophrenic subjects, 8 bipolar I disorder subjects, and 20 control subjects. There was no significant difference in NSF levels between diagnostic cohorts in any of the four cortical regions. These findings highlight the importance of validating findings from high-throughput screening studies and do not support changes in cortical NSF as being of significance in schizophrenia or bipolar 1 disorder.

Motor cortex excitability is not differentially modulated following skill and strength training

AIM: A single session of skill or strength training can modulate the primary motor cortex (M1), which manifests as increased corticospinal excitability (CSE) and decreased short-latency intra-cortical inhibition (SICI). We tested the hypothesis that both skill and strength training can propagate the neural mechanisms mediating cross-transfer and modulate the ipsilateral M1 (iM1). METHODS: Transcranial magnetic stimulation (TMS) measured baseline CSE and SICI in the contralateral motor cortex (cM1) and iM1. Participants completed 4 sets of unilateral training with their dominant arm, either visuomotor tracking, metronome-paced strength training (MPST), self-paced strength training (SPST) or control. Immediately post training, TMS was repeated in both M1s. RESULTS: Motor-evoked potentials (MEPs) increased and inhibition was reduced for skill and MPST training from baseline in both M1s. Self-paced strength training and control did not produce changes in CSE and SICI when compared to baseline in both M1s. After training, skill and MPST increased CSE and decreased SICI in cM1 compared to SPST and control. Skill and MPST training decreased SICI in iM1 compared to SPST and control post intervention; however, CSE in iM1 was not different across groups post training. CONCLUSION: Both skill training and MPST facilitated an increase in CSE and released SICI in iM1 and cM1 compared to baseline. Our results suggest that synchronizing to an auditory or a visual cue promotes neural adaptations within the iM1, which is thought to mediate cross transfer.

Intelligent line segment perception with cortex-like mechanisms

This paper proposes a novel general framework for line segment perception, which is motivated by a biological visual cortex, and requires no parameter tuning. In this framework, we design a model to approximate receptive fields of simple cells. More importantly, the structure of biological orientation columns is imitated by organizing artificial complex and hypercomplex cells with the same orientation into independent arrays. Besides, an interaction mechanism is implemented by a set of self-organization rules. Enlightened by the visual topological theory, the outputs of these artificial cells are integrated to generate line segments that can describe nonlocal structural information of images. Each line segment is evaluated quantitatively by its significance. The computation complexity is also analyzed. The proposed method is tested and compared to state-of-the-art algorithms on real images with complex scenes and strong noises. The experiments demonstrate that our method outperforms the existing methods in the balance between conciseness and completeness.