A pilot study of closed-loop neuromodulation for treatment-resistant post-traumatic stress disorder.

The neurophysiological mechanisms in the human amygdala that underlie post-traumatic stress disorder (PTSD) remain poorly understood. In a first-of-its-kind pilot study, we recorded intracranial electroencephalographic data longitudinally (over one year) in two male individuals with amygdala electrodes implanted for the management of treatment-resistant PTSD (TR-PTSD) under clinical trial NCT04152993. To determine electrophysiological signatures related to emotionally aversive and clinically relevant states (trial primary endpoint), we characterized neural activity during unpleasant portions of three separate paradigms (negative emotional image viewing, listening to recordings of participant-specific trauma-related memories, and at-home-periods of symptom exacerbation). We found selective increases in amygdala theta (5-9 Hz) bandpower across all three negative experiences. Subsequent use of elevations in low-frequency amygdala bandpower as a trigger for closed-loop neuromodulation led to significant reductions in TR-PTSD symptoms (trial secondary endpoint) following one year of treatment as well as reductions in aversive-related amygdala theta activity. Altogether, our findings provide early evidence that elevated amygdala theta activity across a range of negative-related behavioral states may be a promising target for future closed-loop neuromodulation therapies in PTSD.

Selective transfer of visual working memory training on Chinese character learning.

Previous research has shown a systematic relationship between phonological working memory capacity and second language proficiency for alphabetic languages. However, little is known about the impact of working memory processes on second language learning in a non-alphabetic language such as Mandarin Chinese. Due to the greater complexity of the Chinese writing system we expect that visual working memory rather than phonological working memory exerts a unique influence on learning Chinese characters. This issue was explored in the present experiment by comparing visual working memory training with an active (auditory working memory training) control condition and a passive, no training control condition. Training induced modulations in language-related brain networks were additionally examined using functional magnetic resonance imaging in a pretest-training-posttest design. As revealed by pre- to posttest comparisons and analyses of individual differences in working memory training gains, visual working memory training led to positive transfer effects on visual Chinese vocabulary learning compared to both control conditions. In addition, we found sustained activation after visual working memory training in the (predominantly visual) left infero-temporal cortex that was associated with behavioral transfer. In the control conditions, activation either increased (active control condition) or decreased (passive control condition) without reliable behavioral transfer effects. This suggests that visual working memory training leads to more efficient processing and more refined responses in brain regions involved in visual processing. Furthermore, visual working memory training boosted additional activation in the precuneus, presumably reflecting mental image generation of the learned characters. We, therefore, suggest that the conjoint activity of the mid-fusiform gyrus and the precuneus after visual working memory training reflects an interaction of working memory and imagery processes with complex visual stimuli that fosters the coherent synthesis of a percept from a complex visual input in service of enhanced Chinese character learning.

The impact of auditory working memory training on the fronto-parietal working memory network.

Working memory training has been widely used to investigate working memory processes. We have shown previously that visual working memory benefits only from intra-modal visual but not from across-modal auditory working memory training. In the present functional magnetic resonance imaging study we examined whether auditory working memory processes can also be trained specifically and which training-induced activation changes accompany theses effects. It was investigated whether working memory training with strongly distinct auditory materials transfers exclusively to an auditory (intra-modal) working memory task or whether it generalizes to a (across-modal) visual working memory task. We used adaptive n-back training with tonal sequences and a passive control condition. The memory training led to a reliable training gain. Transfer effects were found for the (intra-modal) auditory but not for the (across-modal) visual transfer task. Training-induced activation decreases in the auditory transfer task were found in two regions in the right inferior frontal gyrus. These effects confirm our previous findings in the visual modality and extents intra-modal effects in the prefrontal cortex to the auditory modality. As the right inferior frontal gyrus is frequently found in maintaining modality-specific auditory information, these results might reflect increased neural efficiency in auditory working memory processes. Furthermore, task-unspecific (amodal) activation decreases in the visual and auditory transfer task were found in the right inferior parietal lobule and the superior portion of the right middle frontal gyrus reflecting less demand on general attentional control processes. These data are in good agreement with amodal activation decreases within the same brain regions on a visual transfer task reported previously.

Separating intra-modal and across-modal training effects in visual working memory: an fMRI investigation.

Working memory training is a useful tool to examine dissociations between specific working memory processes. Although current models propose a distinction between modality-specific working memory processes, to our knowledge no study has directly examined the effects of visual versus auditory working memory training. Functional magnetic resonance imaging was used to investigate whether visual working memory processes can be trained specifically and whether those effects can be separated from across-modal training effects. We found decidedly larger training gains after visual working memory training compared with auditory or no training on a visual 2-back task. These effects were accompanied by specific training-related decreases in the right middle frontal gyrus arising from visual training only. Likewise, visual and auditory training led to decreased activations in the superior portion of the right middle frontal gyrus and the right posterior parietal lobule. We infer that the combination of effects resulted from increased neural efficiency of intra-modal (visual) processes on the one hand and of across-modal (general control) processes on the other hand. Therefore, visual processes of working memory can be trained specifically, and these effects can be functionally dissociated from alterations in general control processes common to both working memory trainings.