A brief real-time fNIRS-informed neurofeedback training of the prefrontal cortex changes brain activity and connectivity during subsequent working memory challenge.

Working memory (WM) represents a building-block of higher cognitive functions and a wide range of mental disorders are associated with WM impairments. Initial studies have shown that several sessions of functional near-infrared spectroscopy (fNIRS) informed real-time neurofeedback (NF) allow healthy individuals to volitionally increase activity in the dorsolateral prefrontal cortex (DLPFC), a region critically involved in WM. For the translation to therapeutic or neuroenhancement applications, however, it is critical to assess whether fNIRS-NF success transfers into neural and behavioral WM enhancement in the absence of feedback. We therefore combined single-session fNIRS-NF of the left DLPFC with a randomized sham-controlled design (N = 62 participants) and a subsequent WM challenge with concomitant functional MRI. Over four runs of fNIRS-NF, the left DLPFC NF training group demonstrated enhanced neural activity in this region, reflecting successful acquisition of neural self-regulation. During the subsequent WM challenge, we observed no evidence for performance differences between the training and the sham group. Importantly, however, examination of the fMRI data revealed that - compared to the sham group - the training group exhibited significantly increased regional activity in the bilateral DLPFC and decreased left DLPFC - left anterior insula functional connectivity during the WM challenge. Exploratory analyses revealed a negative association between DLPFC activity and WM reaction times in the NF group. Together, these findings indicate that healthy individuals can learn to volitionally increase left DLPFC activity in a single training session and that the training success translates into WM-related neural activation and connectivity changes in the absence of feedback. This renders fNIRS-NF as a promising and scalable WM intervention approach that could be applied to various mental disorders.

Cortical and subcortical microstructure integrity changes after repetitive transcranial magnetic stimulation therapy in cocaine use disorder and relates to clinical outcomes.

Cocaine use disorder (CUD) is a worldwide public health condition that is suggested to induce pathological changes in macrostructure and microstructure. Repetitive transcranial magnetic stimulation (rTMS) has gained attention as a potential treatment for CUD symptoms. Here, we sought to elucidate whether rTMS induces changes in white matter (WM) microstructure in frontostriatal circuits after 2 weeks of therapy in patients with CUD and to test whether baseline WM microstructure of the same circuits affects clinical improvement. This study consisted of a 2-week, parallel-group, double-blind, randomized controlled clinical trial (acute phase) (sham [n = 23] and active [n = 27]), in which patients received two daily sessions of rTMS on the left dorsolateral prefrontal cortex (lDLPFC) as an add-on treatment. T1-weighted and high angular resolution diffusion-weighted imaging (DWI-HARDI) at baseline and 2 weeks after served to evaluate WM microstructure. After active rTMS, results showed a significant increase in neurite density compared with sham rTMS in WM tracts connecting lDLPFC with left and right ventromedial prefrontal cortex (vmPFC). Similarly, rTMS showed a reduction in orientation dispersion in WM tracts connecting lDLPFC with the left caudate nucleus, left thalamus, and left vmPFC. Results also showed a greater reduction in craving Visual Analogue Scale (VAS) after rTMS when baseline intra-cellular volume fraction (ICVF) was low in WM tracts connecting left caudate nucleus with substantia nigra and left pallidum, as well as left thalamus with substantia nigra and left pallidum. Our results evidence rTMS-induced WM microstructural changes in fronto-striato-thalamic circuits and support its efficacy as a therapeutic tool in treating CUD. Further, individual clinical improvement may rely on the patient's individual structural connectivity integrity.

Positive effects of brisk walking and Tai Chi on cognitive function in older adults: An fNIRS study.

Exercise has shown to have beneficial effects on cognition in older adults. The purpose of this study was to investigate the cortical hemodynamic responses during the word-color Stroop test (WCST) prior and after acute walking and Tai Chi exercise by functional near-infrared spectroscopy (fNIRS). Twenty participants (9 males, mean age 62.8 ± 5.2), first underwent a baseline WCST test, after which they took three WCST tests in a randomized order, (a) after sitting rest (control), (b) after 6 minutes performing Tai Chi Quan, and (c) after a bout of 6 minutes brisk walking. During these four WCST tests cortical hemodynamic changes in the prefrontal area were monitored with fNIRS. Both brisk walking and Tai Chi enhanced hemodynamic activity during the Stroop incongruent tasks, leading to improved cognitive performance (quicker reaction time). Brisk walking induced a greater hemodynamic activity in the right dorsolateral prefrontal cortex (DLPFC) and ventrolateral prefrontal cortex (VLPFC) area, whereas Tai Chi induced a greater bilateral hemodynamic activity in the DLPFC and VLPFC areas. The present study provided empirical evidence of enhanced hemodynamic response in task- specific regions of the brain that can be achieved by a mere six minutes of brisk walking or Tai Chi in older adults.

Mechanisms underlying fNIRS-neurofeedback over the prefrontal cortex for participants with binge-eating disorder.

OBJECTIVE: Despite the increasing popularity of neurofeedback (NF), aiming at voluntary modulation of dysfunctional prefrontal cortex (PFC) signals in the treatment of binge-eating disorder (BED) and/or overweight, mechanisms remain poorly understood. METHODS: Based on a randomized-controlled trial offering 12 food-specific real-time functional near-infrared spectroscopy (rtfNIRS)-NF sessions to participants with BED (n = 22), this preregistered study examined (1) online regulation success as predictor for offline regulation success, defined by PFC signals during regulation versus watch, and subjective regulation success, and (2) changes in loss of control (LOC) eating after vs. before and across 12 rtfNIRS-NF-sessions. RESULTS: Higher online regulation success expectedly predicted better subjective, but worse offline regulation success. LOC eating decreased after vs. before, but not over rtfNIRS-NF-sessions, and was not associated with subjective or offline regulation success. CONCLUSIONS: The association between online and subjective regulation success confirmed the presumed mechanism of operant conditioning underlying rtfNIRS-NF-learning. The contrary association between online and offline regulation indicated differential PFC involvement upon subtraction of automatic food-specific responses from regulation signals for offline success. Decreased LOC eating after food-specific rtfNIRS-NF-sessions suggested the potential of NF in BED treatment. SIGNIFICANCE: Results may guide the optimization of future NF studies in larger samples with BED.

In situ fNIRS measurements during cognitive behavioral emotion regulation training in rumination-focused therapy: A randomized-controlled trial.

Repetitive negative thinking (RNT), including rumination, plays a key role in various psychopathologies. Although several psychotherapeutic treatments have been developed to reduce RNT, the neural correlates of those specific treatments and of psychotherapy in general are largely unknown. Functional near-infrared spectroscopy (fNIRS) offers the potential to investigate the neural correlates of psychotherapeutic techniques in situ. Therefore, in this study we investigated the efficacy and neural correlates of a fNIRS adapted Mindfulness-based Emotion Regulation Training (MBERT) for the treatment of depressive rumination in 42 subjects with major depressive disorder (MDD) in a cross-over designed randomized controlled trial. Using psychometric measures, subjective ratings and fNIRS, we analyzed in situ changes in depressive symptom severity, ruminative thoughts and cortical activity in the Cognitive Control Network (CCN). Our results show that MBERT is effective in treating depressive symptoms and rumination. On a neural level, we found consistently higher cortical activation during emotion regulation training compared to control trials in the bilateral inferior frontal gyrus (IFG) and dorsolateral prefrontal cortex (DLPFC). Furthermore, cortical oxygenation decreased from session to session in the bilateral DLPFC. The relevance of the results for the psychotherapeutic treatment of MDD as well as further necessary investigations are discussed.

High-Resolution Tractography Protocol to Investigate the Pathways between Human Mediodorsal Thalamic Nucleus and Prefrontal Cortex.

Animal studies have established that the mediodorsal nucleus (MD) of the thalamus is heavily and reciprocally connected with all areas of the prefrontal cortex (PFC). In humans, however, these connections are difficult to investigate. High-resolution imaging protocols capable of reliably tracing the axonal tracts linking the human MD with each of the PFC areas may thus be key to advance our understanding of the variation, development, and plastic changes of these important circuits, in health and disease. Here, we tested in adult female and male humans the reliability of a new reconstruction protocol based on in vivo diffusion MRI to trace, measure, and characterize the fiber tracts interconnecting the MD with 39 human PFC areas per hemisphere. Our protocol comprised the following three components: (1) defining regions of interest; (2) preprocessing diffusion data; and, (3) modeling white matter tracts and tractometry. This analysis revealed largely separate PFC territories of reciprocal MD-PFC tracts bearing striking resemblance with the topographic layout observed in macaque connection-tracing studies. We then examined whether our protocol could reliably reconstruct each of these MD-PFC tracts and their profiles across test and retest sessions. Results revealed that this protocol was able to trace and measure, in both left and right hemispheres, the trajectories of these 39 area-specific axon bundles with good-to-excellent test-retest reproducibility. This protocol, which has been made publicly available, may be relevant for cognitive neuroscience and clinical studies of normal and abnormal PFC function, development, and plasticity.SIGNIFICANCE STATEMENT Reciprocal MD-PFC interactions are critical for complex human cognition and learning. Reliably tracing, measuring and characterizing MD-PFC white matter tracts using high-resolution noninvasive methods is key to assess individual variation of these systems in humans. Here, we propose a high-resolution tractography protocol that reliably reconstructs 39 area-specific MD-PFC white matter tracts per hemisphere and quantifies structural information from diffusion MRI data. This protocol revealed a detailed mapping of thalamocortical and corticothalamic MD-PFC tracts in four different PFC territories (dorsal, medial, orbital/frontal pole, inferior frontal) showing structural connections resembling those observed in tracing studies with macaques. Furthermore, our automated protocol revealed high test-retest reproducibility and is made publicly available, constituting a step forward in mapping human MD-PFC circuits in clinical and academic research.

Macroscopic resting state model predicts theta burst stimulation response: A randomized trial.

Repetitive transcranial magnetic stimulation (rTMS) is a promising alternative therapy for treatment-resistant depression, although its limited remission rate indicates room for improvement. As depression is a phenomenological construction, the biological heterogeneity within this syndrome needs to be considered to improve the existing therapies. Whole-brain modeling provides an integrative multi-modal framework for capturing disease heterogeneity in a holistic manner. Computational modelling combined with probabilistic nonparametric fitting was applied to the resting-state fMRI data from 42 patients (21 women), to parametrize baseline brain dynamics in depression. All patients were randomly assigned to two treatment groups, namely active (i.e., rTMS, n = 22) or sham (n = 20). The active treatment group received rTMS treatment with an accelerated intermittent theta burst protocol over the dorsomedial prefrontal cortex. The sham treatment group underwent the identical procedure but with the magnetically shielded side of the coil. We stratified the depression sample into distinct covert subtypes based on their baseline attractor dynamics captured by different model parameters. Notably, the two detected depression subtypes exhibited different phenotypic behaviors at baseline. Our stratification could predict the diverse response to the active treatment that could not be explained by the sham treatment. Critically, we further found that one group exhibited more distinct improvement in certain affective and negative symptoms. The subgroup of patients with higher responsiveness to treatment exhibited blunted frequency dynamics for intrinsic activity at baseline, as indexed by lower global metastability and synchrony. Our findings suggested that whole-brain modeling of intrinsic dynamics may constitute a determinant for stratifying patients into treatment groups and bringing us closer towards precision medicine.

Self-deception: Distorted metacognitive process in ambiguous contexts.

As one of the commonly used folk psychological concepts, self-deception has been intensively discussed yet is short of solid ground from cognitive neuroscience. Self-deception is a biased cognitive process of information to obtain or maintain a false belief that could be both self-enhancing or self-diminishing. Study 1 (N = 152) captured self-deception by adopting a modified numerical discrimination task that provided cheating opportunities, quantifying errors in predicting future performance (via item-response theory model), and measuring the belief of how good they are at solving the task (i.e., self-efficacy belief). By examining whether self-efficacy belief is based upon actual ability (true belief) or prediction errors (false belief), Study 1 showed that self-deception occurred in the effortless (easier access to answer cues) rather than effortful (harder access to answer cues) cheating opportunity conditions, suggesting high ambiguity in attributions facilitates self-deception. Studies 2 and 3 probed the neural source of self-deception, linking self-deception with the metacognitive process. Both studies replicated behavioral results from Study 1. Study 2 (ERP study; N = 55) found that the amplitude of frontal slow wave significantly differed between participants with positive/self-enhancing and negative/self-diminishing self-deceiving tendencies in incorrect predictions while remaining similar in correct predictions. Study 3 (functional magnetic resonance imaging study; N = 33) identified self-deceiving associated activity in the anterior medial prefrontal cortex and showed that effortless cheating context increased cheating behaviors that further facilitated self-deception. Our findings suggest self-deception is a false belief associated with a distorted metacognitive mental process that requires ambiguity in attributions of behaviors.

Neural and functional validation of fMRI-informed EEG model of right inferior frontal gyrus activity.

The right inferior frontal gyrus (rIFG) is a region involved in the neural underpinning of cognitive control across several domains such as inhibitory control and attentional allocation process. Therefore, it constitutes a desirable neural target for brain-guided interventions such as neurofeedback (NF). To date, rIFG-NF has shown beneficial ability to rehabilitate or enhance cognitive functions using functional Magnetic Resonance Imaging (fMRI-NF). However, the utilization of fMRI-NF for clinical purposes is severely limited, due to its poor scalability. The present study aimed to overcome the limited applicability of fMRI-NF by developing and validating an EEG model of fMRI-defined rIFG activity (hereby termed "Electrical FingerPrint of rIFG"; rIFG-EFP). To validate the computational model, we employed two experiments in healthy individuals. The first study (n = 14) aimed to test the target engagement of the model by employing rIFG-EFP-NF training while simultaneously acquiring fMRI. The second study (n = 41) aimed to test the functional outcome of two sessions of rIFG-EFP-NF using a risk preference task (known to depict cognitive control processes), employed before and after the training. Results from the first study demonstrated neural target engagement as expected, showing associated rIFG-BOLD signal changing during simultaneous rIFG-EFP-NF training. Target anatomical specificity was verified by showing a more precise prediction of the rIFG-BOLD by the rIFG-EFP model compared to other EFP models. Results of the second study suggested that successful learning to up-regulate the rIFG-EFP signal through NF can reduce one's tendency for risk taking, indicating improved cognitive control after two sessions of rIFG-EFP-NF. Overall, our results confirm the validity of a scalable NF method for targeting rIFG activity by using an EEG probe.

The increased inter-brain neural synchronization in prefrontal cortex between simulated patient and acupuncturist during acupuncture stimulation: Evidence from functional near-infrared spectroscopy hyperscanning.

The patient-acupuncturist interaction was a critical influencing factor for acupuncture effects but its mechanism remains unclear. This study aimed to examine the inter-brain mechanism of patient-acupuncturist dyad during acupuncture stimulation in a naturalistic clinical setting. Seventy healthy subjects (simulated "patients") were randomly assigned to two groups and received verum acupuncture group or sham acupuncture by one acupuncturist. Functional near-infrared spectroscopy hyperscanning was used to simultaneously record the neural responses of "patient"-acupuncturist dyad during acupuncture stimulation in each group. The results showed that inter-brain neural synchronization (INS) in the prefrontal cortex (PFC) of "patient"-acupuncturist dyad was significantly increased during verum but not sham acupuncture stimuli, and positively correlated with the needling sensations of "patients." Granger causality analysis demonstrated that there were no significant differences in INS direction between the "patient" and the acupuncturist. This study identified the increase of INS between "patient" and acupuncturist, and suggested that PFC was important to the interaction of "patient"-acupuncturist dyad.

Thalamic regulation of frontal interactions in human cognitive flexibility.

Interactions across frontal cortex are critical for cognition. Animal studies suggest a role for mediodorsal thalamus (MD) in these interactions, but the computations performed and direct relevance to human decision making are unclear. Here, inspired by animal work, we extended a neural model of an executive frontal-MD network and trained it on a human decision-making task for which neuroimaging data were collected. Using a biologically-plausible learning rule, we found that the model MD thalamus compressed its cortical inputs (dorsolateral prefrontal cortex, dlPFC) underlying stimulus-response representations. Through direct feedback to dlPFC, this thalamic operation efficiently partitioned cortical activity patterns and enhanced task switching across different contingencies. To account for interactions with other frontal regions, we expanded the model to compute higher-order strategy signals outside dlPFC, and found that the MD offered a more efficient route for such signals to switch dlPFC activity patterns. Human fMRI data provided evidence that the MD engaged in feedback to dlPFC, and had a role in routing orbitofrontal cortex inputs when subjects switched behavioral strategy. Collectively, our findings contribute to the emerging evidence for thalamic regulation of frontal interactions in the human brain.

Antidepressant chronotherapeutics normalizes prefrontal 1H-MRS glutamate in bipolar depression.

BACKGROUND: Dysfunctional glutamatergic neurotransmission has been proposed both, as a biological underpinning of mood disorder and as a target for rapid-acting antidepressant treatments. Total sleep deprivation and light therapy (TSD + LT) can prompt antidepressant response in drug-resistant bipolar depression. Here we explored the effects of TSD + LT on dorsolateral prefrontal cortex (DLPFC) glutamate and/or glutamine+glutamate (Glx) levels. METHODS: We studied single voxel 1H-MRS measures of DLPFC Glu and Glx levels of 48 healthy participants and 55 inpatients with a major depressive episode in course of Bipolar Disorder, a subset of which (N = 23) underwent three cycles of repeated TSD + LT and were evaluated before and after treatment. Treatment effects of mood and on Glu and Glx concentrations were analyzed in the context of the Generalized Linear Model (GLM), correcting for age, sex and ongoing lithium treatment. RESULTS: Higher concentration of Glu (adjusted Z = -2189, p = 0,0285) and Glx (adjusted Z = -3,13, p = 0,0017) were observed in BD patients compared to HC. Treatment caused a significant rapid reduction of depressive symptom severity over time (F = 63.98, p < 0.01). Change in depression levels after TSD + LT treatment was significantly influenced by delta change in Glu levels (LR χ2 = 4.619, p = 0.0316) and in Glx levels (LR χ2 = 4.486, p = 0.0341). CONCLUSION: A reduction in Glu and Glx levels associated with depression could contribute to the mechanism of action of TSD + LT, directly acting on glutamatergic neurons, or to the interaction between the glutamatergic system and dopamine (DA) and serotonin (5-HT) levels, known to be targeted by TSD. This is in line with several studies showing a glutamatergic modulation effects of antidepressants and mood stabilizing agents. This finding deepens our understanding of antidepressant effect of chronoterapeutics.

Long-term Meditation Training Is Associated with Enhanced Subjective Attention and Stronger Posterior Cingulate-Rostrolateral Prefrontal Cortex Resting Connectivity.

Mindfulness meditation has been shown to increase resting-state functional connectivity (rsFC) between the posterior cingulate cortex (PCC) and dorsolateral prefrontal cortex (DLPFC), which is thought to reflect improvements in shifting attention to the present moment. However, prior research in long-term meditation practitioners lacked quantitative measures of attention that would provide a more direct behavioral correlate and interpretational anchor for PCC-DLPFC connectivity and was inherently limited by small sample sizes. Moreover, whether mindfulness meditation primarily impacts brain function locally, or impacts the dynamics of large-scale brain networks, remained unclear. Here, we sought to replicate and extend prior findings of increased PCC-DLPFC rsFC in a sample of 40 long-term meditators (average practice = 3759 hr) who also completed a behavioral assay of attention. In addition, we tested a network-based framework of changes in interregional connectivity by examining network-level connectivity. We found that meditators had stronger PCC-rostrolateral prefrontal cortex (RLPFC) rsFC, lower connector hub strength across the default mode network, and better subjective attention, compared with 124 meditation-naive controls. Orienting attention positively correlated with PCC-RLPFC connectivity and negatively correlated with default mode network connector hub strength. These findings provide novel evidence that PCC-RLPFC rsFC may support attention orienting, consistent with a role for RLPFC in the attention shifting component of metacognitive awareness that is a core component of mindfulness meditation training. Our results further demonstrate that long-term mindfulness meditation may improve attention and strengthen the underlying brain networks.

Nx4 Modulated Resting-State Functional Connectivity Between Amygdala and Prefrontal Cortex in a Placebo-Controlled, Crossover Trial.

Background: The basic functional organization of the resting brain, assessed as resting-state functional connectivity (rsFC), can be affected by previous stress experience and it represents the basis on which subsequent stress experience develops. Notably, the rsFC between the amygdala and the cortical regions associated with emotion regulation and anxiety are affected during stress. The multicomponent drug Neurexan® (Nx4) has previously demonstrated a reduction in amygdala activation in an emotional face matching task and it ameliorated stress-related symptoms. We, thus, investigated the effect of Nx4 on rsFC of the amygdala before stress induction compared with baseline in mildly to moderately stressed participants. Methods: In a randomized, placebo-controlled, double-blind, crossover trial 39 participants received a single dose of placebo or Nx4. Resting-state functional magnetic resonance imaging scans were performed pre-dose and 40 to 60 min post-dose, before any stress induction. First, highly connected functional hubs were identified by global functional connectivity density (gFCD) analysis. Second, by using a seed-based approach, rsFC maps of the left centromedial amygdala (CeMA) were created. The effect of Nx4 on both was evaluated. Results: The medial prefrontal cortex was identified as a relevant functional hub affected by Nx4 in an explorative whole brain gFCD analysis. Using the seed-based approach, we then demonstrated that Nx4 significantly enhanced the negative connectivity between the left CeMA and two cortical regions: the dorsolateral and medial prefrontal cortices. Conclusions: In a resting-state condition, Nx4 reduced the prefrontal cortex gFCD and strengthened the functional coupling between the amygdala and the prefrontal cortex that is relevant for emotion regulation and the stress response. Further studies should elaborate whether this mechanism represents enhanced regulatory control of the amygdala at rest and, consequently, to a diminished susceptibility to stress. ClinicalTrials.gov ID: NCT02602275.

Four-Week Mentalizing Imagery Therapy for Family Dementia Caregivers: A Randomized Controlled Trial with Neural Circuit Changes.

INTRODUCTION: Family caregivers of patients with dementia suffer a high burden of depression and reduced positive emotions. Mentalizing imagery therapy (MIT) provides mindfulness and guided imagery skills training to improve balanced mentalizing and emotion regulation. OBJECTIVE: Our aims were to test the hypotheses that MIT for family caregivers would reduce depression symptoms and improve positive psychological traits more than a support group (SG), and would increase dorsolateral prefrontal cortex (DLPFC) connectivity and reduce subgenual anterior cingulate cortex (sgACC) connectivity. METHODS: Forty-six caregivers participated in a randomized controlled trial comparing a 4-week MIT group (n = 24) versus an SG (n = 22). Resting state neuroimaging was obtained at baseline and post-group in 28 caregivers, and questionnaires completed by all participants. The primary outcome was change in depression; secondary measures included anxiety, mindfulness, self-compassion, and well-being. Brain networks with participation of DLPFC and sgACC were identified. Connectivity strengths of DLPFC and sgACC with respective networks were determined with dual regression. DLPFC connectivity was correlated with mindfulness and depression outcomes. RESULTS: MIT significantly outperformed SG in improving depression, anxiety, mindfulness, self-compassion, and well-being, with moderate to large effect sizes. Relative to SG, participants in MIT showed significant increases in DLPFC connectivity - exactly replicating pilot study results - but no change in sgACC. DLPFC connectivity change correlated positively with mindfulness and negatively with depression change. CONCLUSIONS: In this trial, MIT was superior to SG for reducing depression and anxiety symptoms and improving positive psychological traits. Neuroimaging results suggested that strengthening DLPFC connectivity with an emotion regulation network might be mechanistically related to MIT effects.

Structural brain correlates of burnout severity in medical professionals: A voxel-based morphometric study.

Occupational burnout has become a pervasive problem, especially among medical professionals who are highly vulnerable to burnout. Since the beginning of the COVID-19 pandemic, medical professionals have faced greater levels of stress. It is critical to increase our understanding of the neurobiological mechanisms of burnout among medical professionals for the benefit of healthcare systems. Therefore, in this study, we investigated structural brain correlates of burnout severity in medical professionals using a voxel-based morphometric technique. Nurses in active service underwent structural magnetic resonance imaging. Two core dimensions of burnout, namely, emotional exhaustion and depersonalization, were assessed using self-reported psychological questionnaires. Levels of emotional exhaustion were found to be negatively correlated with gray matter (GM) volumes in the bilateral ventromedial prefrontal cortex (vmPFC) and left insula. Moreover, levels of depersonalization were negatively correlated with GM volumes in the left vmPFC and left thalamus. Altogether, these findings contribute to a better understanding of the neural mechanisms of burnout and may provide helpful insights for developing effective interventions for medical professionals.

A neural signature for combined action observation and motor imagery? An fNIRS study into prefrontal activation, automatic imitation, and self-other perceptions.

INTRODUCTION: Research indicates that both observed and imagined actions can be represented in the brain as two parallel sensorimotor representations. One proposal is that higher order cognitive processes would align these two hypothetical action simulations. METHODS: We investigated this hypothesis using an automatic imitation paradigm, with functional near-infrared spectroscopy recordings over the prefrontal cortex during different motor simulation states. On each trial, participants (n = 14) observed a picture of a rhythmical action (instructed action) followed by a distractor movie showing the same or different action. Participants then executed the instructed action. Distractor actions were manipulated to be fast or slow, and instructions were manipulated during distractor presentation: action observation (AO), combined action observation and motor imagery (AO+MI) and observe to imitate (intentional imitation). A pure motor imagery (MI) condition was also included. RESULTS: Kinematic analyses showed that although distractor speed effects were significant under all instructions (shorter mean cycle times in execution for fast compared to slow trials), this imitation bias was significantly stronger for combined AO+MI than both AO and MI, and stronger for intentional imitation than the other three automatic imitation conditions. In the left prefrontal cortex, cerebral oxygenation was significantly greater for combined AO+MI than all other instructions. Participants reported that their representation of the self overlapped with the observed model significantly more during AO+MI than AO. CONCLUSION: Left prefrontal activation may therefore be a neural signature of AO+MI, supporting attentional switching between concurrent representations of self (MI, top-down) and other (AO, bottom-up) to increase imitation and perceived closeness.

Prefronto-thalamic tract injury and cognitive outcome according to external ventricular drainage location in stroke patients.

OBJECTIVES: We investigated the characteristics of prefronto-thalamic tract (PF-TT) injuries in stroke patients using diffusion tensor tractography (DTT) and assessing cognitive outcome according to location of the external ventricular drainage (EVD). METHODS: Forty-five consecutive stroke patients who underwent EVD and 24 control subjects were recruited. The patients were classified into three groups: group A (EVD on the lesion or one side, 17 patients), group B (EVD on the hemisphere opposite to the lesion, 12 patients), and group C (EVD on both sides, 16 patients). Mini-Mental State Examination (MMSE) results were performed at the beginning (average 2.27 months from onset) and end (average 4.19 months from onset) of rehabilitation. Three parts of the PF-TT (dorsolateral PF-TT[DLPF-TT], ventrolateral PF-TT[VLPF-TT], orbitofronto-thalamic tract[OF-TT]) were reconstructed and the fractional anisotropy (FA) and tract volume (TV) measurements were obtained. RESULTS: With the EVD on the stroke-affected side, the values of FA and TV of all three parts of the PF-TTs in three patient groups were lower than those of the control group (p < 0.05). With the EVD on the unaffected side, the FA values of the DLPF-TT in groups B and C and the OF-TT in group C were lower than those of the control group (p < 0.05). There was no difference in initial MMSE score among three patient groups; however, group A had a higher mean follow-up MMSE score than that of groups B and C (p < 0.05). CONCLUSIONS: Patients who underwent EVD of the affected hemisphere showed better results in terms of the PF-TT injury and cognitive outcome than patients who underwent EVD through the unaffected hemisphere or through both hemispheres.

Neurometabolic patterns of an "at risk for mental disorders" syndrome involve abnormalities in the thalamus and anterior midcingulate cortex.

BACKGROUND: The ultra-high risk (UHR) paradigm allows the investigation of individuals at increased risk of developing psychotic or other mental disorders with the aim of making prevention and early intervention as specific as possible in terms of the individual outcome. METHODS: Single-session 1H-/31P-Chemical Shift Imaging of thalamus, prefrontal (DLPFC) and anterior midcingulate (aMCC) cortices was applied to 69 UHR patients for psychosis and 61 matched healthy controls. N-acetylaspartate (NAA), glutamate/glutamine complex (Glx), energy (PCr, ATP) and phospholipid metabolites were assessed, analysed by ANOVA (or ANCOVA [with covariates]) and correlated with symptomatology (SCL-90R). RESULTS: The thalamus showed decreased NAA, inversely correlated with self-rated aggressiveness, as well as increased PCr, and altered phospholipid breakdown. While the aMCC showed a pattern of NAA decrease and PCr increase, the DLPFC showed PCr increase only in the close-to-psychosis patient subgroup. There were no specific findings in transition patients. CONCLUSION: The results do not support the notion of a specific pre-psychotic neurometabolic pattern, but likely reflect correlates of an "at risk for mental disorders syndrome". This includes disturbed neuronal (mitochondrial) metabolism in the thalamus and aMCC, with emphasis on left-sided structures, and altered PL remodeling across structures.