The nervous system continuously predicts the sensory consequences of self-generated actions. These predictions can be used to cancel self-generated sensory information. It has been hypothesized that ...this cancellation process may serve to increase the perceptual sensitivity to unpredicted external events. Here, we provide the first empirical evidence for this idea. Participants were required to detect coherent motion in a random dot motion display. The task was made more difficult by a set of superimposed distractor dots that had to be ignored. When these distractors moved congruently with an active arm movement, perceptual performance in detecting the coherent motion was superior compared to a condition in which the distractor motion did not match the arm movement. To test whether this difference was due to sensory cancellation of matching distractors, or to the attentional enhancement of non-matching distractors, we introduced a control condition without any overt movement. Our results indicate that improvements in the detection of visual motion are indeed caused by sensory cancellation of self-generated events. In conjunction with other recent results, our data therefore suggest that the nervous system is able to attenuate or facilitate self-generated visual stimuli in a task-dependent manner.
To ascertain the mechanisms of neuropsychiatric illnesses and their treatment, accurate and reliable imaging techniques are required; proton magnetic resonance spectroscopy ((1) H-MRS) can ...noninvasively measure glutamatergic function. Evidence suggests that aberrant glutamatergic signaling plays a role in numerous psychopathologies. Until recently, overlapping glutamatergic signals (glutamate, glutamine, and glutathione) could not easily be separated. However, the advent of novel pulse sequences and higher field magnetic resonance imaging (MRI) allows more precise resolution of overlapping glutamatergic signals, although the question of signal reliability remains undetermined.
At 7T MR, we acquired (1) H-MRS data from the medial pregenual anterior cingulate cortex of healthy volunteers (n = 26) twice on two separate days. An adapted echo time optimized point-resolved spectroscopy sequence, modified with the addition of a J-suppression pulse to attenuate N-acetyl-aspartate multiplet signals at 2.49 ppm, was used to excite and acquire the spectra. In-house software was used to model glutamate, glutamine, and glutathione, among other metabolites, referenced to creatine. Intraclass correlation coefficients (ICCs) were computed for within- and between-session measurements.
Within-session measurements of glutamate, glutamine, and glutathione were on average reliable (ICCs ≥0.7). As anticipated, ICCs for between-session values of glutamate, glutamine, and glutathione were slightly lower but nevertheless reliable (ICC >0.62). A negative correlation was observed between glutathione concentration and age (r(24) = -0.37; P < 0.05), and a gender effect was noted on glutamine and glutathione.
The adapted sequence provides good reliability to measure glutamate, glutamine, and glutathione signals.
The glutamatergic modulator ketamine has striking and rapid antidepressant effects in major depressive disorder (MDD), but its mechanism of action remains unknown. Proton magnetic resonance ...spectroscopy (1H-MRS) is the only non-invasive method able to directly measure glutamate levels in vivo; in particular, glutamate and glutamine metabolite concentrations are separable by 1H-MRS at 7T. This double-blind, placebo-controlled, crossover study that included 1H-MRS scans at baseline and at 24 h post ketamine and post-placebo infusions sought to determine glutamate levels in the pregenual anterior cingulate (pgACC) of 20 medication-free MDD subjects and 17 healthy volunteers (HVs) 24 h post ketamine administration, and to evaluate any other measured metabolite changes, correlates, or predictors of antidepressant response. Metabolite levels were compared at three scan times (baseline, post-ketamine, and post-placebo) in HVs and MDD subjects at 7T using a 1H-MRS sequence specifically optimized for glutamate. No significant between-group differences in 1H-MRS-measured metabolites were observed at baseline. Antidepressant response was not predicted by baseline glutamate levels. Our results suggest that any infusion-induced increases in glutamate at the 24-h post ketamine time point were below the sensitivity of the current technique; that these increases may occur in different brain regions than the pgACC; or that subgroups of MDD subjects may exist that have a differential glutamate response to ketamine.
The glutamatergic modulator ketamine has striking and rapid antidepressant effects in major depressive disorder (MDD), but its mechanism of action remains unknown. Proton magnetic resonance ...spectroscopy (1H-MRS) is the only non-invasive method able to directly measure glutamate levels in vivo; in particular, glutamate and glutamine metabolite concentrations are separable by 1H-MRS at 7T. This double-blind, placebo-controlled, crossover study that included
H-MRS scans at baseline and at 24 h post ketamine and post-placebo infusions sought to determine glutamate levels in the pregenual anterior cingulate (pgACC) of 20 medication-free MDD subjects and 17 healthy volunteers (HVs) 24 h post ketamine administration, and to evaluate any other measured metabolite changes, correlates, or predictors of antidepressant response. Metabolite levels were compared at three scan times (baseline, post-ketamine, and post-placebo) in HVs and MDD subjects at 7T using a
H-MRS sequence specifically optimized for glutamate. No significant between-group differences in
H-MRS-measured metabolites were observed at baseline. Antidepressant response was not predicted by baseline glutamate levels. Our results suggest that any infusion-induced increases in glutamate at the 24-h post ketamine time point were below the sensitivity of the current technique; that these increases may occur in different brain regions than the pgACC; or that subgroups of MDD subjects may exist that have a differential glutamate response to ketamine.
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