On the speech envelope in the cortical tracking of speech.

The synchronization between the speech envelope and neural activity in auditory regions, referred to as cortical tracking of speech (CTS), plays a key role in speech processing. The method selected for extracting the envelope is a crucial step in CTS measurement, and the absence of a consensus on best practices among the various methods can influence analysis outcomes and interpretation. Here, we systematically compare five standard envelope extraction methods the absolute value of Hilbert transform (absHilbert), gammatone filterbanks, heuristic approach, Bark scale, and vocalic energy), analyzing their impact on the CTS. We present performance metrics for each method based on the recording of brain activity from participants listening to speech in clear and noisy conditions, utilizing intracranial EEG, MEG and EEG data. As expected, we observed significant CTS in temporal brain regions below 10 Hz across all datasets, regardless of the extraction methods. In general, the gammatone filterbanks approach consistently demonstrated superior performance compared to other methods. Results from our study can guide scientists in the field to make informed decisions about the optimal analysis to extract the CTS, contributing to advancing the understanding of the neuronal mechanisms implicated in CTS.

Prefrontal cortex hemodynamic activity during a test of lower extremity functional muscle strength in children with cerebral palsy: A functional near-infrared spectroscopy study.

Children with cerebral palsy (CP) exhibit impaired motor control and significant muscle weakness due to a brain lesion. However, studies that assess the relationship between brain activity and performance on dynamic functional muscle strength assessments in CP are needed. The aim of this study was to determine the effect of a progressive lateral step-up test on prefrontal cortex (PFC) hemodynamic activity in children with CP. Fourteen ambulatory children with spastic CP (Gross Motor Function Classification System level I; 5-11 y) and 14 age- and sex-matched typically developing control children completed a progressive lateral step-up test at incremental step heights (0, 10, 15 and 20 cm) using their non-dominant lower limb. Hemodynamic activity in the PFC was assessed using non-invasive, portable functional neuroimaging (functional near-infrared spectroscopy). Children with CP completed fewer repetitions at each step height and exhibited lower PFC hemodynamic activity across step heights compared to controls. Lower PFC activation in CP was maintained after statistically controlling for the number of repetitions completed at each step height. PFC hemodynamic activity was not associated with LSUT task performance in children with CP, but a positive relationship was observed in controls at the most challenging 20 cm step height. The results suggest there is an altered PFC recruitment pattern in children with CP during a highly dynamic test of functional strength. Further studies are needed to explore the mechanisms underlying the suppressed PFC activation observed in children with CP compared to typically developing children.

How do we make progress in phenotyping patients with lower urinary tract such as overactive bladder and underactive detrusor, including using urine markers and microbiome data, to personalize therapy? ICI-RS 2023-Part 2.

INTRODUCTION: Overactive bladder (OAB) and underactive bladder (UAB) could be associated with metabolic syndrome, affective disorders, sex hormone deficiency, changes in urinary microbiota, functional gastrointestinal disorders, or autonomic nervous system dysfunction. OBJECTIVES: The aim of this Think Tank was to provide a guide on how to investigate OAB and/or detrusor underactivity (DU) patients to better clarify the underlying pathophysiology and possibly personalize the treatment. METHODS: A compendium of discussion based on the current evidence related to phenotyping patients with OAB or DU using urodynamic tests, functional neuro-imaging, urinary markers, and microbiome. RESULTS AND CONCLUSIONS: The article emphasizes the critical significance of adopting a comprehensive yet tailored approach to phenotyping patients with lower urinary tract (LUT) symptoms, such as OAB and UAB. The intricate interplay between the LUT and various factors, metabolic, neurological, psychological, and gastrointestinal can define unique LUT profiles, enabling personalized therapies to replace the one-size-fits-all approach.

Sex differences in anhedonia in bipolar depression: a resting-state fMRI study.

Previous studies about anhedonia symptoms in bipolar depression (BD) ignored the unique role of gender on brain function. This study aims to explore the regional brain neuroimaging features of BD with anhedonia and the sex differences in these patients. The resting-fMRI by applying fractional amplitude of low-frequency fluctuation (fALFF) method was estimated in 263 patients with BD (174 high anhedonia [HA], 89 low anhedonia [LA]) and 213 healthy controls. The effects of two different factors in patients with BD were analyzed using a 3 (group: HA, LA, HC) × 2 (sex: male, female) ANOVA. The fALFF values were higher in the HA group than in the LA group in the right medial cingulate gyrus and supplementary motor area. For the sex-by-group interaction, the fALFF values of the right hippocampus, left medial occipital gyrus, right insula, and bilateral medial cingulate gyrus were significantly higher in HA males than in LA males but not females. These results suggested that the pattern of high activation could be a marker of anhedonia symptoms in BD males, and the sex differences should be considered in future studies of BD with anhedonia symptoms.

Using neuroimaging to assess brain activity and areas associated with surgical skills: a systematic review.

BACKGROUND: Surgical skills acquisition is under continuous development due to the emergence of new technologies, and there is a need for assessment tools to develop along with these. A range of neuroimaging modalities has been used to map the functional activation of brain networks while surgeons acquire novel surgical skills. These have been proposed as a method to provide a deeper understanding of surgical expertise and offer new possibilities for the personalized training of future surgeons. With studies differing in modalities, outcomes, and surgical skills there is a need for a systematic review of the evidence. This systematic review aims to summarize the current knowledge on the topic and evaluate the potential use of neuroimaging in surgical education. METHODS: We conducted a systematic review of neuroimaging studies that mapped functional brain activation while surgeons with different levels of expertise learned and performed technical and non-technical surgical tasks. We included all studies published before July 1st, 2023, in MEDLINE, EMBASE and WEB OF SCIENCE. RESULTS: 38 task-based brain mapping studies were identified, consisting of randomized controlled trials, case-control studies, and observational cohort or cross-sectional studies. The studies employed a wide range of brain mapping modalities, including electroencephalography, functional magnetic resonance imaging, positron emission tomography, and functional near-infrared spectroscopy, activating brain areas involved in the execution and sensorimotor or cognitive control of surgical skills, especially the prefrontal cortex, supplementary motor area, and primary motor area, showing significant changes between novices and experts. CONCLUSION: Functional neuroimaging can reveal how task-related brain activity reflects technical and non-technical surgical skills. The existing body of work highlights the potential of neuroimaging to link task-related brain activity patterns with the individual level of competency or improvement in performance after training surgical skills. More research is needed to establish its validity and usefulness as an assessment tool.

Resting-state functional connectivity and cognitive performance in aging adults with cognitive decline: A data-driven multivariate pattern analysis.

BACKGROUND: Cognitive impairments occur on a continuous spectrum in multiple cognitive domains showing individual variability of the deteriorating patterns; however, often, cognitive domains are studied separately. METHODS: The present study investigated aging individual variations of cognitive abilities and related resting-state functional connectivity (rsFC) using data-driven approach. Cognitive and neuroimaging data were obtained from 62 elderly outpatients with cognitive decline. Principal component analysis (PCA) was conducted on the cognitive data to determine patterns of cognitive performance, then data-driven whole-brain connectome multivariate pattern analysis (MVPA) was applied on the neuroimaging data to discover neural regions associated with the cognitive characteristic. RESULTS: The first component (PC1) delineated an overall decline in all domains of cognition, and the second component (PC2) represented a compensatory relationship within basic cognitive functions. MVPA indicated rsFC of the cerebellum lobule VIII and insula with the default-mode network, frontoparietal network, and salience network inversely correlated with PC1 scores. Additionally, PC2 score was related to rsFC patterns with temporal pole and occipital cortex. CONCLUSIONS: The featured primary cognitive characteristic depicted the importance of the cerebellum and insula connectivity patterns in of the general cognitive decline. The findings also discovered a secondary characteristic that communicated impaired interactions within the basic cognitive function, which was independent from the impairment severity.

Arterial Spin Labeling Magnetic Resonance Imaging for Acute Disorders of Consciousness in the Intensive Care Unit.

BACKGROUND: To investigate patients with disorders of consciousness (DoC) for residual awareness, guidelines recommend quantifying glucose brain metabolism using positron emission tomography. However, this is not feasible in the intensive care unit (ICU). Cerebral blood flow (CBF) assessed by arterial spin labeling magnetic resonance imaging (ASL-MRI) could serve as a proxy for brain metabolism and reflect consciousness levels in acute DoC. We hypothesized that ASL-MRI would show compromised CBF in coma and unresponsive wakefulness states (UWS) but relatively preserved CBF in minimally conscious states (MCS) or better. METHODS: We consecutively enrolled ICU patients with acute DoC and categorized them as being clinically unresponsive (i.e., coma or UWS [≤ UWS]) or low responsive (i.e., MCS or better [≥ MCS]). ASL-MRI was then acquired on 1.5 T or 3 T. Healthy controls were investigated with both 1.5 T and 3 T ASL-MRI. RESULTS: We obtained 84 ASL-MRI scans from 59 participants, comprising 36 scans from 35 patients (11 women [31.4%]; median age 56 years, range 18-82 years; 24 ≤ UWS patients, 12 ≥ MCS patients; 32 nontraumatic brain injuries) and 48 scans from 24 healthy controls (12 women [50%]; median age 50 years, range 21-77 years). In linear mixed-effects models of whole-brain cortical CBF, patients had 16.2 mL/100 g/min lower CBF than healthy controls (p = 0.0041). However, ASL-MRI was unable to discriminate between ≤ UWS and ≥ MCS patients (whole-brain cortical CBF: p = 0.33; best hemisphere cortical CBF: p = 0.41). Numerical differences of regional CBF in the thalamus, amygdala, and brainstem in the two patient groups were statistically nonsignificant. CONCLUSIONS: CBF measurement in ICU patients using ASL-MRI is feasible but cannot distinguish between the lower and the upper ends of the acute DoC spectrum. We suggest that pilot testing of diagnostic interventions at the extremes of this spectrum is a time-efficient approach in the continued quest to develop DoC neuroimaging markers in the ICU.

Spontaneous brain activity abnormalities in migraine: A meta-analysis of functional neuroimaging.

Neuroimaging studies have demonstrated that migraine is accompanied by spontaneous brain activity alterations in specific regions. However, these findings are inconsistent, thus hindering our understanding of the potential neuropathology. Hence, we performed a quantitative whole-brain meta-analysis of relevant resting-state functional imaging studies to identify brain regions consistently involved in migraine. A systematic search of studies that investigated the differences in spontaneous brain activity patterns between migraineurs and healthy controls up to April 2022 was conducted. We then performed a whole-brain voxel-wise meta-analysis using the anisotropic effect size version of seed-based d mapping software. Complementary analyses including jackknife sensitivity analysis, heterogeneity test, publication bias test, subgroup analysis, and meta-regression analysis were conducted as well. In total, 24 studies that reported 31 datasets were finally eligible for our meta-analysis, including 748 patients and 690 controls. In contrast to healthy controls, migraineurs demonstrated consistent and robust decreased spontaneous brain activity in the angular gyrus, visual cortex, and cerebellum, while increased activity in the caudate, thalamus, pons, and prefrontal cortex. Results were robust and highly replicable in the following jackknife sensitivity analysis and subgroup analysis. Meta-regression analyses revealed that a higher visual analog scale score in the patient sample was associated with increased spontaneous brain activity in the left thalamus. These findings provided not only a comprehensive overview of spontaneous brain activity patterns impairments, but also useful insights into the pathophysiology of dysfunction in migraine.

Functional and structural network changes related with cognition in semantic dementia longitudinally.

Longitudinal changes in the white matter/functional brain networks of semantic dementia (SD), as well as their relations with cognition remain unclear. Using a graph-theoretic method, we examined the neuroimaging (T1, diffusion tensor imaging, functional MRI) network properties and cognitive performance in processing semantic knowledge of general and six modalities (i.e., object form, color, motion, sound, manipulation and function) from 31 patients (at two time points with an interval of 2 years) and 20 controls (only at baseline). Partial correlation analyses were carried out to explore the relationships between the network changes and the declines of semantic performance. SD exhibited aberrant general and modality-specific semantic impairment, and gradually worsened over time. Overall, the brain networks showed a decreased global and local efficiency in the functional network organization but a preserved structural network organization with a 2-year follow-up. With disease progression, both structural and functional alterations were found to be extended to the temporal and frontal lobes. The regional topological alteration in the left inferior temporal gyrus (ITG.L) was significantly correlated with general semantic processing. Meanwhile, the right superior temporal gyrus and right supplementary motor area were identified to be associated with color and motor-related semantic attributes. SD manifested disrupted structural and functional network pattern longitudinally. We proposed a hub region (i.e., ITG.L) of semantic network and distributed modality-specific semantic-related regions. These findings support the hub-and-spoke semantic theory and provide targets for future therapy.

Neuroimaging in early-treated phenylketonuria patients and clinical outcome: A systematic review.

Lacking direct neuropathological data, neuroimaging exploration has become the most powerful tool to give insight into pathophysiological alterations of early-treated PKU (ETPKU) patients. We conducted a systematic review of neuroimaging studies in ETPKU patients to explore 1) the occurrence of consistent neuroimaging alterations; 2) the relationship between them and neurological and cognitive disorders; 3) the contribution of neuroimaging in the insight of neuropathological background of ETPKU subjects; 4) whether brain neuroimaging may provide additional information in the monitoring of the disease course. Thirty-eight studies met the inclusion criteria for the full-text review, including morphological T1/T2 sequences, diffusion brain imaging (DWI/DTI) studies, brain MRI volumetric, functional neuroimaging studies, neurotransmission and brain energetic imaging studies. Non-progressive brain white matter changes were the most frequent and precocious alterations. As confirmed in hundreds of young adults with ETPKU, they affect over 90% of ETPKU patients. Consistent correlations are emerging between microstructural alteration (as detected by DWI/DTI) and metabolic control, which have also been confirmed in a few interventional trials. Volumetric studies detected later and less consistent cortical and subcortical grey matter alterations, which seem to be influenced by the patient's age and metabolic control. The few functional neuroimaging studies so far showed preliminary but interesting data about cortical activation patterns, skill performance, and brain connectivity. Further research is mandatory in these more complex areas. Recurrent methodological limitations include restricted sample sizes concerning the clinical variability of the disease, large age-range, variable measures of metabolic control, and prevalence of cross-sectional rather than longitudinal interventional studies.

Association of Changes in Neural Targets and Dietary Outcomes among Patients with Comorbid Obesity and Depression: Post hoc Analysis of ENGAGE-2 Mechanistic Clinical Trial.

BACKGROUND: Disruptions in brain circuits that regulate cognition and emotion can hinder dietary change and weight loss among individuals with obesity and depression. OBJECTIVE: The study aimed to investigate whether changes in brain targets in the cognitive control, negative affect, and positive affect circuits after 2-mo problem-solving therapy (PST) predict changes in dietary outcomes at 2 and 6 mo. METHODS: Adults with obesity and depression from an academic health system were randomly assigned to receive PST (7-step problem-solving and behavioral activation strategies) over 2 mo or usual care. Seventy participants (mean age = 45.9 ± 11.6 y; 75.7% women, 55.7% Black, 17.1% Hispanic, 20.0% White; mean BMI = 36.5 ± 5.3 kg/m2; mean Patient Health Questionnaire-9 depression score = 12.7 ± 2.8) completed functional MRI and 24-h food recalls. Ordinary least square regression analyses were performed. RESULTS: Among intervention participants, increased left dorsal lateral prefrontal cortex (dLPFC) activity of the cognitive control circuit at 2 mo was associated with increased diet quality (ß: 0.20; 95% CI: -0.02, 0.42) and decreased calories (ß: -0.19; 95% CI: -0.33, -0.04), fat levels (ß: -0.22; 95% CI: -0.39, -0.06), and high-sugar food intake (ß: -0.18; 95% CI: -0.37, 0.01) at 6 mo. For the negative affect circuit, increased right dLPFC-amygdala connectivity at 2 mo was associated with increased diet quality (ß: 0.32; 95% CI: -0.93, 1.57) and fruit and vegetable intake (ß: 0.38; 95% CI: -0.75, 1.50) and decreased calories (ß: -0.37; 95% CI: -1.29, 0.54), fat levels (ß: -0.37; 95% CI: -1.50, 0.76), sodium concentrations (ß: -0.36; 95% CI: -1.32, 0.60), and alcohol intake (ß: -0.71; 95% CI: -2.10, 0.68) at 2 but not at 6 mo. The usual care group showed opposing associations. The 95% CIs of all between-group differences did not overlap the null, suggesting a significant treatment effect. CONCLUSIONS: Among adults with obesity and depression who underwent PST compared with those under usual care, improved dLPFC-amygdala regulation of negative affective brain states predicted dietary improvements at 2 mo, whereas improvements in dLPFC-based cognitive control predicted dietary improvements at 6 mo. These findings warrant confirmatory studies. This trial was at clinicaltrials.gov as NCT03841682.

Task-based functional magnetic resonance imaging prediction of postsurgical cognitive outcomes in temporal lobe epilepsy: A systematic review, meta-analysis, and new data.

Task-based functional magnetic resonance imaging (tfMRI) has developed as a common alternative in epilepsy surgery to the intracarotid amobarbital procedure, also known as the Wada procedure. Prior studies have implicated tfMRI as a comparable predictor of postsurgical cognitive outcomes. However, the predictive validity of tfMRI has not been established. This preregistered systematic review and meta-analysis (CRD42020183563) synthesizes the literature predicting postsurgical cognitive outcomes in temporal lobe epilepsy (TLE) using tfMRI. The PubMed and PsycINFO literature databases were queried for English-language articles published between January 1, 2009 and December 31, 2020 associating tfMRI laterality indices or symmetry of task activation with outcomes in TLE. Their references were reviewed for additional relevant literature, and unpublished data from our center were incorporated. Nineteen studies were included in the meta-analysis. tfMRI studies predicted postsurgical cognitive outcomes in left TLE ( ρ ̂ = -.27, 95% confidence interval [CI] = -.32 to -.23) but not right TLE ( ρ ̂ = -.02, 95% CI = -.08 to .03). Among studies of left TLE, language tfMRI studies were more robustly predictive of postsurgical cognitive outcomes ( ρ ̂ = -.27, 95% CI = -.33 to -.20) than memory tfMRI studies ( ρ ̂ = -.27, 95% CI = -.43 to -.11). Further moderation by cognitive outcome domain indicated language tfMRI predicted confrontation naming ( ρ ̂ = -.32, 95% CI = -.41 to -.22) and verbal memory ( ρ ̂ = -.26, 95% CI = -.35 to -.17) outcomes, whereas memory tfMRI forecasted only verbal memory outcomes ( ρ ̂ = -.37, 95% CI = -.57 to -.18). Surgery type, birth sex, level of education, age at onset, disease duration, and hemispheric language dominance moderated study outcomes. Sensitivity analyses suggested the interval of postsurgical follow-up, and reporting and methodological practices influenced study outcomes as well. These findings intimate tfMRI is a modest predictor of outcomes in left TLE that should be considered in the context of a larger surgical workup.

Structural and functional multilayer network analysis in restless legs syndrome patients.

The combination of brain structural and functional connectivity offers complementary insights into its organisation. Multilayer network analysis explores various relationships across different layers within a single system. We aimed to investigate changes in the structural and functional multilayer network in 69 patients with primary restless legs syndrome (RLS) compared with 50 healthy controls. Participants underwent diffusion tensor imaging (DTI) and resting state-functional magnetic resonance imaging (rs-fMRI) using a three-tesla MRI scanner. We constructed a structural connectivity matrix derived from DTI using a DSI program and made a functional connectivity matrix based on rs-fMRI using an SPM program and CONN toolbox. A multilayer network analysis, using BRAPH program, was then conducted to assess the connectivity patterns in both groups. At the global level, significant differences there were between the patients with RLS and healthy controls. The average multiplex participation was lower in patients with RLS than in healthy controls (0.804 vs. 0.821, p = 0.042). Additionally, several regions showed significant differences in the nodal level in multiplex participation between patients with RLS and healthy controls, particularly the frontal and temporal lobes. The regions affected included the inferior frontal gyrus, medial orbital gyrus, precentral gyrus, rectus gyrus, insula, superior and inferior temporal gyrus, medial and lateral occipitotemporal gyrus, and temporal pole. These results represent evidence of diversity in interactions between structural and functional connectivity in patients with RLS, providing a more comprehensive understanding of the brain network in RLS. This may contribute to a precise diagnosis of RLS, and aid the development of a biomarker to track treatment effectiveness.

Mental workload classification using convolutional neural networks based on fNIRS-derived prefrontal activity.

BACKGROUND: Functional near-infrared spectroscopy (fNIRS) is a tool to assess brain activity during cognitive testing. Despite its usefulness, its feasibility in assessing mental workload remains unclear. This study was to investigate the potential use of convolutional neural networks (CNNs) based on functional near-infrared spectroscopy (fNIRS)-derived signals to classify mental workload in individuals with mild cognitive impairment. METHODS: Spatial images by constructing a statistical activation map from the prefrontal activity of 120 subjects with MCI performing three difficulty levels of the N-back task (0, 1, and 2-back) were used for CNNs. The CNNs were evaluated using a 5 and 10-fold cross-validation method. RESULTS: As the difficulty level of the N-back task increased, the accuracy decreased and prefrontal activity increased. In addition, there was a significant difference in the accuracy and prefrontal activity across the three levels (p's < 0.05). The accuracy of the CNNs based on fNIRS-derived spatial images evaluated by 5 and 10-fold cross-validation in classifying the difficulty levels ranged from 0.83 to 0.96. CONCLUSION: fNIRS could also be a promising tool for measuring mental workload in older adults with MCI despite their cognitive decline. In addition, this study demonstrated the feasibility of the classification performance of the CNNs based on fNIRS-derived signals from the prefrontal cortex.

The role of early functional neuroimaging in predicting neurodevelopmental outcomes in neonatal encephalopathy.

Reliably assessing the early neurodevelopmental outcomes in infants with neonatal encephalopathy (NE) is of utmost importance to advise parents and implement early and personalized interventions. We aimed to evaluate the accuracy of neuroimaging modalities, including functional magnetic resonance imaging (fMRI) in predicting neurodevelopmental outcomes in NE. Eighteen newborns with NE due to presumed perinatal asphyxia (PA) were included in the study, 16 of whom underwent therapeutic hypothermia. Structural magnetic resonance imaging (MRI), and fMRI during passive visual, auditory, and sensorimotor stimulation were acquired between the 10th and 14th day of age. Clinical follow-up protocol included visual and auditory evoked potentials and a detailed neurodevelopmental evaluation at 12 and 18 months of age. Infants were divided according to sensory and neurodevelopmental outcome: severe, moderate disability, or normal. Structural MRI findings were the best predictor of severe disability with an AUC close to 1.0. There were no good predictors to discriminate between moderate disability versus normal outcome. Nevertheless, structural MRI measures showed a significant correlation with the scores of neurodevelopmental assessments. During sensorimotor stimulation, the fMRI signal in the right hemisphere had an AUC of 0.9 to predict absence of cerebral palsy (CP). fMRI measures during auditory and visual stimulation did not predict sensorineural hearing loss or cerebral visual impairment. CONCLUSION: In addition to structural MRI, fMRI with sensorimotor stimulation may open the gate to improve the knowledge of neurodevelopmental/motor prognosis if proven in a larger cohort of newborns with NE. WHAT IS KNOWN: • Establishing an early, accurate neurodevelopmental prognosis in neonatal encephalopathy remains challenging. • Although structural MRI has a central role in neonatal encephalopathy, advanced MRI modalities are gradually being explored to optimize neurodevelopmental outcome knowledge. WHAT IS NEW: • Newborns who later developed cerebral palsy had a trend towards lower fMRI measures in the right sensorimotor area during sensorimotor stimulation. • These preliminary fMRI results may improve future early delineation of motor prognosis in neonatal encephalopathy.

Speech processing in voice-hearers: Bridging the gap between empirical research and clinical implications.

Individuals who hear voices (i.e. auditory verbal hallucinations) have been reported to exhibit a range of difficulties when listening to and processing the speech of other people. These speech processing challenges are observed even in the absence of hearing voices; however, some appear to be exacerbated during periods of acute symptomology. In this advisory piece, key findings from pertinent empirical research into external speech processing in voice-hearers are presented with the intention of informing healthcare professionals. It is the view that through a better understanding of the speech processing deficits faced by individuals who hear voices, more effective communication with such patients can be had.

Understanding, detecting, and stimulating consciousness recovery in the ICU.

Coma is a medical and socioeconomic emergency. Although underfunded, research on coma and disorders of consciousness has made impressive progress. Lesion-network-mapping studies have delineated the precise brainstem regions that consistently produce coma when damaged. Functional neuroimaging has revealed how mechanisms like "communication through coherence" and "inhibition by gating" work in synergy to enable cortico-cortical processing and how this information transfer is disrupted in brain injury. On the cellular level, break-down of intracellular communication between the layer 5 pyramidal cell soma and the apical dendritic part impairs dendritic information integration, with up-stream effects on microcircuits in local neuronal populations and on large-scale fronto-parietal networks, which correlates with loss of consciousness. A breakthrough in clinical concepts occurred when fMRI, and later EEG, studies revealed that 15% of clinically unresponsive patients in acute and chronic settings are in fact awake and aware, as shown by their command following abilities revealed by brain activation during motor and locomotion imagery tasks. This condition is now termed "cognitive motor dissociation." Furthermore, epidemiological data on coma were literally non-existent until recently because of difficulties related to case ascertainment with traditional methods, but crowdsourcing of family observations enabled the first estimates of how frequent coma is in the general population (pooled annual incidence of 201 coma cases per 100,000 population in the UK and the USA). Diagnostic guidelines on coma and disorders of consciousness by the American Academy of Neurology and the European Academy of Neurology provide ambitious clinical frameworks to accommodate these achievements. As for therapy, a broad range of medical and non-medical treatment options is now being tested in increasingly larger trials; in particular, amantadine and transcranial direct current stimulation appear promising in this regard. Major international initiatives like the Curing Coma Campaign aim to raise awareness for coma and disorders of consciousness in the public, with the ultimate goal to make more brain-injured patients recover consciousness after a coma. To highlight all these accomplishments, this paper provides a comprehensive overview of recent progress and future challenges related to understanding, detecting, and stimulating consciousness recovery in the ICU.

Longitudinal Change in Brain Functional Connectivity with Herpes Zoster Patients: Neuroimaging Case Series.

The exact mechanism involved in the development of postherpetic neuralgia (PHN) is not yet known. The objective of this study was to evaluate longitudinal functional connectivity (FC) changes in the neuroimaging case series of patients with acute herpes zoster (HZ). Cases: This study included five patients who had symptoms of HZ. Functional magnetic resonance imaging was conducted at enrollment and 3 months to determine FC changes. Of the five patients, three developed PHN. In the PHN subjects, the FC of the left superior frontal gyrus (SFG) and the right inferior frontal gyrus (IFG) were activated. The left SFG is known to contribute to higher cognitive functions and working memory. The right IFG is associated with pain processing and empathy for pain. Conclusions: Although only a few patients were enrolled in this study, the PHN could be affected by pain itself, as well as pain memory and psychological aspects such as empathy for pain.

Unlocking Hidden Awareness: Repurposing fMRI to Detect Levels of Consciousness.

Determining the state of consciousness in patients with disorders of consciousness is a challenging task because for someone to be deemed conscious, both wakefulness and awareness are required. Awareness has traditionally been assessed by examining physical responsiveness but in 2010, Monti et al. explored how using fMRI to measure brain activity in humans could help reclassify the state of consciousness in these patients. The findings, published in The New England Journal of Medicine, show that some brain regions are active when patients respond to an imagery or communication task. This is a seminal study because it demonstrates that patients who behaviourally appear to be in a vegetative or minimally conscious state may still have residual brain functions that would not be apparent from a clinical examination alone. Notably, it exemplified how fMRI can be repurposed as a communication tool for this subset of aware, but 'locked in', patients who appear unresponsive. From an educator's perspective, this paper is valuable because it is relevant to a broad audience, both introductory and advanced level undergraduate students. It introduces key concepts in cognitive and clinical neuroscience and encourages students to consider the connections between social issues and technology development in neuroscience. Finally, educators may use this paper to discuss and debate the nature of consciousness and the ethical implications that the use of fMRI for determining consciousness may have on medical ethics.

Evidence suggesting common mechanisms underlie contralateral and ipsilateral negative BOLD responses in the human visual cortex.

The task-evoked positive BOLD response (PBR) to a unilateral visual hemi-field stimulation is often accompanied by robust and sustained contralateral as well as ipsilateral negative BOLD responses (NBRs) in the visual cortex. The signal characteristics and the neural and/or vascular mechanisms that underlie these two types of NBRs are not completely understood. In this paper, we investigated the properties of these two types of NBRs. We first demonstrated the linearity of both NBRs with respect to stimulus duration. Next, we showed that the hemodynamic response functions (HRFs) of the two NBRs were similar to each other, but significantly different from that of the PBR. Moreover, the subject-wise expressions of the two NBRs were tightly coupled to the degree that the correlation between the two NBRs was significantly higher than the correlation between each NBR and the PBR. However, the activation patterns of the two NBRs did not show a high level of interhemispheric spatial similarity, and the functional connectivity between them was not different than the interhemispheric functional connectivity between the NBRs and PBR. Finally, while attention did modulate both NBRs, the attention-related changes in their HRFs were similar. Our findings suggest that the two NBRs might be generated through common neural and/or vascular mechanisms involving distal/deep brain regions that project to the two hemispheres.