Resting-state brain activity as a biomarker of chronic pain impairment and a mediator of its association with pain resilience.

Past cross-sectional chronic pain studies have revealed aberrant resting-state brain activity in regions involved in pain processing and affect regulation. However, there is a paucity of longitudinal research examining links of resting-state activity and pain resilience with changes in chronic pain outcomes over time. In this prospective study, we assessed the status of baseline (T1) resting-state brain activity as a biomarker of later impairment from chronic pain and a mediator of the relation between pain resilience and impairment at follow-up. One hundred forty-two adults with chronic musculoskeletal pain completed a T1 assessment comprising a resting-state functional magnetic resonance imaging scan based on regional homogeneity (ReHo) and self-report measures of demographics, pain characteristics, psychological status, pain resilience, pain severity, and pain impairment. Subsequently, pain impairment was reassessed at a 6-month follow-up (T2). Hierarchical multiple regression and mediation analyses assessed relations of T1 ReHo and pain resilience scores with changes in pain impairment. Higher T1 ReHo values in the right caudate nucleus were associated with increased pain impairment at T2, after controlling for all other statistically significant self-report measures. ReHo also partially mediated associations of T1 pain resilience dimensions with T2 pain impairment. T1 right caudate nucleus ReHo emerged as a possible biomarker of later impairment from chronic musculoskeletal pain and a neural mechanism that may help to explain why pain resilience is related to lower levels of later chronic pain impairment. Findings provide empirical foundations for prospective extensions that assess the status of ReHo activity and self-reported pain resilience as markers for later impairment from chronic pain and targets for interventions to reduce impairment. PRACTITIONER POINTS: Resting-state markers of impairment: Higher baseline (T1) regional homogeneity (ReHo) values, localized in the right caudate nucleus, were associated with exacerbations in impairment from chronic musculoskeletal pain at a 6-month follow-up, independent of T1 demographics, pain experiences, and psychological factors. Mediating role of ReHo values: ReHo values in the right caudate nucleus also mediated the relationship between baseline pain resilience levels and later pain impairment among participants. Therapeutic implications: Findings provide empirical foundations for research extensions that evaluate (1) the use of resting-state activity in assessment to identify people at risk for later impairment from pain and (2) changes in resting-state activity as biomarkers for the efficacy of treatments designed to improve resilience and reduce impairment among those in need.

Laparoscopic caudate lobe resections: How I do it: tips and pitfalls (with video).

BACKGROUND: The caudate lobe (S1) of the liver, due to its deep central position, presents a formidable challenge for laparoscopic resection. Historical skepticism about laparoscopic approaches has been overshadowed by advancements in technology and technique, with recent studies showing comparable outcomes to open surgery. METHODS: This paper introduces the "Easy First" technique and the Sextet strategies for laparoscopic hepatic caudate lobectomy. The strategies include meticulous preoperative planning, optimal trocar placement, and team positioning, tailored to the anatomical complexities of the caudate lobe. RESULTS: With a 0% conversion and mortality rate, our series demonstrates the safety of the "Easy First" technique. The Sextet strategies have been instrumental in navigating the technical challenges, emphasizing the importance of patient selection and surgeon expertise. CONCLUSION: The "Easy First" technique, with its structured approach and the Sextet strategies, offers a replicable method for laparoscopic caudate lobectomy. It underscores the need for stringent patient selection, advanced technical skill, and high-volume center expertise to ensure procedural success and patient safety.

Erratum: Resting state functional connectivity of the rat claustrum.

[This corrects the article DOI: 10.3389/fnana.2019.00022.].

Effects of long-term antipsychotic medication on brain instability in first-episode schizophrenia patients: a resting-state fMRI study.

Early initiation of antipsychotic treatment plays a crucial role in the management of first-episode schizophrenia (FES) patients, significantly improving their prognosis. However, limited attention has been given to the long-term effects of antipsychotic drug therapy on FES patients. In this research, we examined the changes in abnormal brain regions among FES patients undergoing long-term treatment using a dynamic perspective. A total of 98 participants were included in the data analysis, comprising 48 FES patients, 50 healthy controls, 22 patients completed a follow-up period of more than 6 months with qualified data. We processed resting-state fMRI data to calculate coefficient of variation of fractional amplitude of low-frequency fluctuations (CVfALFF), which reflects the brain regional activity stability. Data analysis was performed at baseline and after long-term treatment. We observed that compared with HCs, patients at baseline showed an elevated CVfALFF in the supramarginal gyrus (SMG), parahippocampal gyrus (PHG), caudate, orbital part of inferior frontal gyrus (IOG), insula, and inferior frontal gyrus (IFG). After long-term treatment, the instability in SMG, PHG, caudate, IOG, insula and inferior IFG have ameliorated. Additionally, there was a positive correlation between the decrease in dfALFF in the SMG and the reduction in the SANS total score following long-term treatment. In conclusion, FES patients exhibit unstable regional activity in widespread brain regions at baseline, which can be ameliorated with long-term treatment. Moreover, the extent of amelioration in SMG instability is associated with the amelioration of negative symptoms.

Predictors associated with the rate of progression of nigrostriatal degeneration in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) manifests as a wide variety of clinical phenotypes and its progression varies greatly. However, the factors associated with different disease progression remain largely unknown. METHODS: In this retrospective cohort study, we enrolled 113 patients who underwent 18F-FP-CIT PET scan twice. Given the negative exponential progression pattern of dopamine loss in PD, we applied the natural logarithm to the specific binding ratio (SBR) of two consecutive 18F-FP-CIT PET scans and conducted linear mixed model to calculate individual slope to define the progression rate of nigrostriatal degeneration. We investigated the clinical and dopamine transporter (DAT) availability patterns associated with the progression rate of dopamine depletion in each striatal sub-region. RESULTS: More symmetric parkinsonism, the presence of dyslipidemia, lower K-MMSE total score, and lower anteroposterior gradient of the mean putaminal SBR were associated with faster progression rate of dopamine depletion in the caudate nucleus. More symmetric parkinsonism and lower anteroposterior gradient of the mean putaminal SBR were associated with faster depletion of dopamine in the anterior putamen. Older age at onset, more symmetric parkinsonism, the presence of dyslipidemia, and lower anteroposterior gradient of the mean putaminal SBR were associated with faster progression rate of dopamine depletion in the posterior putamen. Lower striatal mean SBR predicted the development of LID, while lower mean SBR in the caudate nuclei predicted the development of dementia. DISCUSSION: Our results suggest that the evaluation of baseline clinical features and patterns of DAT availability can predict the progression of PD and its prognosis.

Perihepatic caudate lobe haematoma originating from a pancreatic pseudoaneurysm: a diagnostic dilemma.

Despite advances in diagnostic imaging and interventional techniques, pancreatic pseudoaneurysms remain a life-threatening complication of pancreatitis. Presentation varies among patients and may include intra-abdominal, retroperitoneal, or gastrointestinal bleeding and bleeding into the pancreatic or common bile duct. We present a unique case of a 74-year-old man with a history of heavy alcohol consumption who presented with a haematoma surrounding the caudate lobe of the liver. Initially, alcoholic cirrhosis and a ruptured hepatocellular carcinoma were suspected. Therefore, transarterial embolization (TAE) of the caudate branch of the hepatic artery was performed. However, 3 months later, the patient experienced abdominal pain with a lesser sac haematoma and a seemingly interconnected pancreatic cyst. One month later, a pseudoaneurysm appeared in the pancreatic cyst. TAE was successfully performed for the pseudoaneurysm, and the patient showed no signs of recurrence during the 1-year follow-up.

Transcranial sonography of subcortical structures in tic/tourette disorder.

Functional neuroimaging studies demonstrate disinhibition of the cortico-striatal-thalamo-cortical circuit. However, structural imaging studies revealed conflicting results, some suggesting smaller volumes of the caudate nucleus (CN) in children with Gilles de la Tourette syndrome (TS). Here we wanted to find out whether transcranial sonography (TCS) detects alterations of raphe nuclei, substantia nigra, lenticular nucleus (LN), or CN in children with Tic disorder or TS (TIC/TS).The study included 25 treatment-naive children (age: 12.2 ± 2.5 years) with a DSM-V based diagnosis of Tic disorder or TS (10 subjects), without other psychiatric or neurologic diagnosis, and 25 healthy controls (age: 12.17 ± 2.57 years), matched for age and sex. Parental rating of behavioral, emotional abnormalities, somatic complaints and social competencies of the participants were assessed using the Child Behavior Check List (CBCL/4-18R). TCS of deep brain structures was conducted through the preauricular acoustic bone windows using a 2.5-MHz phased-array ultrasound system. Fisher's exact test and Mann-Whitney-U test were used for comparisons between TIC/TS patients and healthy volunteers. The number of participants with hyperechogenic area of left CN in the TIC/TS sample was increased, compared to the healthy control group. TIC/TS patients with hyperechogenic CN showed an increased occurrence of thought- and obsessive-compulsive problems. This TCS study revealed pathologic structural changes in CN, its higher occurrence in TIC/TS compared to healthy controls and the relation to comorbidity of thought problems. Further research should focus on the molecular cause of these alterations, probably the disturbed iron metabolism.

Endoscopic Ultrasound Guided Radiofrequency Ablation for Caudate Lobe Hepatocellular Carcinoma: A New Paradigm in Endohepatology.

Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is a promising technique for treating small left hepatic lesions, particularly where ablation via percutaneous route is deemed to be technically difficult. Herein, we report a case of a 64-year-old cirrhotic patient with caudate lobe hepatocellular carcinoma (HCC) who underwent EUS-RFA, resulting in complete ablation of the tumor and also review the related literature.

Differential regulation of G protein-coupled receptor-associated proteins in the caudate and the putamen of cynomolgus macaques following chronic ethanol drinking.

The dorsal striatum is composed of the caudate nucleus and the putamen in human and non-human primates. These two regions receive different cortical projections and are functionally distinct. The caudate is involved in the control of goal-directed behaviors, while the putamen is implicated in habit learning and formation. Previous reports indicate that ethanol differentially influences neurotransmission in these two regions. Because neurotransmitters primarily signal through G protein-coupled receptors (GPCRs) to modulate neuronal activity, the present study aimed to determine whether ethanol had a region-dependent impact on the expression of proteins that are involved in the trafficking and function of GPCRs, including G protein subunits and their effectors, protein kinases, and elements of the cytoskeleton. Western blotting was performed to examine protein levels in the caudate and the putamen of male cynomolgus macaques that self-administered ethanol for 1 year under free access conditions, along with control animals that self-administered an isocaloric sweetened solution under identical operant conditions. Among the 18 proteins studied, we found that the levels of one protein (PKCß) were increased, and 13 proteins (Gαi1/3, Gαi2, Gαo, Gß1γ, PKCα, PKCε, CaMKII, GSK3ß, ß-actin, cofilin, α-tubulin, and tubulin polymerization promoting protein) were reduced in the caudate of alcohol-drinking macaques. However, ethanol did not alter the expression of any proteins examined in the putamen. These observations underscore the unique vulnerability of the caudate nucleus to changes in protein expression induced by chronic ethanol exposure. Whether these alterations are associated with ethanol-induced dysregulation of GPCR function and neurotransmission warrants future investigation.

Excessive left anterior hippocampal and caudate activation in schizophrenia underlie cognitive underperformance in a virtual navigation task.

We used a virtual navigation paradigm in a city environment to assess neuroanatomical correlates of cognitive deficits in schizophrenia spectrum disorders (SSD). We studied a total of N = 36 subjects: 18 with SSD and 18 matched unaffected controls. Participants completed 10 rapid, single-trial navigation tasks within the virtual city while undergoing functional magnetic resonance imaging (fMRI). All trials tested ability to find different targets seen earlier, during the passive viewing of a path around different city blocks. SSD patients had difficulty finding previously-encountered targets, were less likely to find novel shortcuts to targets, and more likely to attempt retracing of the path observed during passive viewing. Based on a priori region-of-interest analyses, SSD participants had hyperactivation of the left hippocampus when passively viewing turns, hyperactivation of the left caudate when finding targets, and hypoactivation of a focal area of the dorsolateral prefrontal cortex when targets were initially shown during passive viewing. We propose that these brain-behaviour relations may bias or reinforce stimulus-response navigation approaches in SSD and underlie impaired performance when allocentric spatial memory is required, such as when forming efficient shortcuts. This pattern may extend to more general cognitive impairments in SSD that could be used to design remediation strategies.

The well-worn route revisited: Striatal and hippocampal system contributions to familiar route navigation.

Classic research has shown a division in the neuroanatomical structures that support flexible (e.g., short-cutting) and habitual (e.g., familiar route following) navigational behavior, with hippocampal-caudate systems associated with the former and putamen systems with the latter. There is, however, disagreement about whether the neural structures involved in navigation process particular forms of spatial information, such as associations between constellations of cues forming a cognitive map, versus single landmark-action associations, or alternatively, perform particular reinforcement learning algorithms that allow the use of different spatial strategies, so-called model-based (flexible) or model-free (habitual) forms of learning. We sought to test these theories by asking participants (N = 24) to navigate within a virtual environment through a previously learned, 9-junction route with distinctive landmarks at each junction while undergoing functional magnetic resonance imaging (fMRI). In a series of probe trials, we distinguished knowledge of individual landmark-action associations along the route versus knowledge of the correct sequence of landmark-action associations, either by having absent landmarks, or "out-of-sequence" landmarks. Under a map-based perspective, sequence knowledge would not require hippocampal systems, because there are no constellations of cues available for cognitive map formation. Within a learning-based model, however, responding based on knowledge of sequence would require hippocampal systems because prior context has to be utilized. We found that hippocampal-caudate systems were more active in probes requiring sequence knowledge, supporting the learning-based model. However, we also found greater putamen activation in probes where navigation based purely on sequence memory could be planned, supporting models of putamen function that emphasize its role in action sequencing.

Identification of patients with internet gaming disorder via a radiomics-based machine learning model of subcortical structures in high-resolution T1-weighted MRI.

It is of vital importance to establish an objective and reliable model to facilitate the early diagnosis and intervention of internet gaming disorder (IGD). A total of 133 patients with IGD and 110 healthy controls (HCs) were included. We extracted radiomic features of subcortical structures in high-resolution T1-weighted MRI. Different combinations of four feature selection methods (analysis of variance, Kruskal-Wallis, recursive feature elimination and relief) and ten classification algorithms were used to identify the most robust combined models for distinguishing IGD patients from HCs. Furthermore, a nomogram incorporating radiomic signatures and independent clinical factors was developed. Calibration curve and decision curve analyses were used to evaluate the nomogram. The combination of analysis of variance selector and logistic regression classifier identified that the radiomic model constructed with 20 features from the right caudate nucleus and amygdala showed better IGD screening performance. The radiomic model produced good areas under the curves (AUCs) in the training, validation and test cohorts (AUCs of 0.961, 0.903 and 0.895, respectively). In addition, sex, internet addiction test scores and radiomic scores were included in the nomogram as independent risk factors for IGD. Analysis of the correction curve and decision curve showed that the clinical-radiomic model has good reliability (C-index: 0.987). The nomogram incorporating radiomic features of subcortical structures and clinical characteristics achieved satisfactory classification performance and could serve as an effective tool for distinguishing IGD patients from HCs.

The hippocampus supports the representation of abstract concepts: Implications for the study of recognition memory.

Words, unlike images, are symbolic representations. The associative details inherent within a word's meaning and the visual imagery it generates, are inextricably connected to the way words are processed and represented. It is well recognised that the hippocampus associatively binds components of a memory to form a lasting representation, and here we show that the hippocampus is especially sensitive to abstract word processing. Using fMRI during recognition, we found that the increased abstractness of words produced increased hippocampal activation regardless of memory outcome. Interestingly, word recollection produced hippocampal activation regardless of word content, while the parahippocampal cortex was sensitive to concreteness of word representations, regardless of memory outcome. We reason that the hippocampus has assumed a critical role in the representation of uncontextualized abstract word meaning, as its information-binding ability allows the retrieval of the semantic and visual associates that, when bound together, generate the abstract concept represented by word symbols. These insights have implications for research on word representation, memory, and hippocampal function, perhaps shedding light on how the human brain has adapted to encode and represent abstract concepts.

The effects of psychotherapy for anhedonia on subcortical brain volumes measured with ultra-high field MRI.

BACKGROUND: Anhedonia is a transdiagnostic symptom often resistant to treatment. The identification of biomarkers sensitive to anhedonia treatment will aid in the evaluation of novel anhedonia interventions. METHODS: This is an exploratory analysis of changes in subcortical brain volumes accompanying psychotherapy in a transdiagnostic anhedonic sample using ultra-high field (7-Tesla) MRI. Outpatients with clinically impairing anhedonia (n = 116) received Behavioral Activation Treatment for Anhedonia, a novel psychotherapy, or Mindfulness-Based Cognitive Therapy (ClinicalTrials.gov Identifiers NCT02874534 and NCT04036136). Subcortical brain volumes were estimated via the MultisegPipeline, and regions of interest were the amygdala, caudate nucleus, hippocampus, pallidum, putamen, and thalamus. Bivariate mixed effects models estimated pre-treatment relations between anhedonia severity and subcortical brain volumes, change over time in subcortical brain volumes, and associations between changes in subcortical brain volumes and changes in anhedonia symptoms. RESULTS: As reported previously (Cernasov et al., 2023), both forms of psychotherapy resulted in equivalent and significant reductions in anhedonia symptoms. Pre-treatment anhedonia severity and subcortical brain volumes were not related. No changes in subcortical brain volumes were observed over the course of treatment. Additionally, no relations were observed between changes in subcortical brain volumes and changes in anhedonia severity over the course of treatment. LIMITATIONS: This trial included a modest sample size and did not have a waitlist-control condition or a non-anhedonic comparison group. CONCLUSIONS: In this exploratory analysis, psychotherapy for anhedonia was not accompanied by changes in subcortical brain volumes, suggesting that subcortical brain volumes may not be a candidate biomarker sensitive to response to psychotherapy.

Control of goal-directed and inflexible actions by dorsal striatal melanocortin systems, in coordination with the central nucleus of the amygdala.

The dorsomedial striatum (DMS) is associated with flexible goal seeking, as opposed to routinized habits. Whether local mechanisms brake this function, for instance when habits may be adaptive, is incompletely understood. We find that a sub-population of dopamine D1 receptor-containing striatal neurons express the melanocortin-4 receptor (MC4R) for α-melanocyte stimulating hormone. These neurons within the DMS are necessary and sufficient for controlling the capacity of mice to flexibly adjust actions based on the likelihood that they will be rewarded. In investigating MC4R function, we found that it suppresses immediate-early gene levels in the DMS and concurrently, flexible goal seeking. MC4R+ neurons receive input from the central nucleus of the amygdala, and behavioral experiments indicate that they are functionally integrated into an amygdalo-striatal circuit that suppresses action flexibility in favor of routine. Publicly available spatial transcriptomics datasets were analyzed for gene transcript correlates of Mc4r expression across the striatal subregions, revealing considerable co-variation in dorsal structures. This insight led to the discovery that the function of MC4R in the dorsolateral striatum complements that in the DMS, in this case suppressing habit-like behavior. Altogether, our findings suggest that striatal MC4R controls the capacity for goal-directed and inflexible actions alike.

Common neural deficits across reward functions in major depression: a meta-analysis of fMRI studies.

Major depressive disorder (MDD) is characterized by deficient reward functions in the brain. However, existing findings on functional alterations during reward anticipation, reward processing, and learning among MDD patients are inconsistent, and it was unclear whether a common reward system implicated in multiple reward functions is altered in MDD. Here we meta-analyzed 18 past studies that compared brain reward functions between adult MDD patients (N = 477, mean age = 26.50 years, female = 59.40%) and healthy controls (N = 506, mean age = 28.11 years, females = 55.58%), and particularly examined group differences across multiple reward functions. Jack-knife sensitivity and subgroup meta-analyses were conducted to test robustness of findings across patient comorbidity, task paradigm, and reward nature. Meta-regression analyses assessed the moderating effect of patient symptom severity and anhedonia scores. We found during reward anticipation, MDD patients showed lower activities in the lateral prefrontal-thalamus circuitry. During reward processing, patients displayed reduced activities in the right striatum and prefrontal cortex, but increased activities in the left temporal cortex. During reward learning, patients showed reduced activity in the lateral prefrontal-thalamic-striatal circuitry and the right parahippocampal-occipital circuitry but higher activities in bilateral cerebellum and the left visual cortex. MDD patients showed decreased activity in the right thalamus during both reward anticipation and learning, and in the right caudate during both reward processing and learning. Larger functional changes in MDD were observed among patients with more severe symptoms and higher anhedonia levels. The thalamic-striatal circuitry functional alterations could be the key neural mechanism underlying MDD patients overarching reward function deficiencies.

Seasonal variation in D2/3 dopamine receptor availability in the human brain.

PURPOSE: Brain functional and physiological plasticity is essential to combat dynamic environmental challenges. The rhythmic dopamine signaling pathway, which regulates emotion, reward and learning, shows seasonal patterns with higher capacity of dopamine synthesis and lower number of dopamine transporters during dark seasons. However, seasonal variation of the dopamine receptor signaling remains to be characterized. METHODS: Based on a historical database of healthy human brain [11C]raclopride PET scans (n = 291, 224 males and 67 females), we investigated the seasonal patterns of D2/3 dopamine receptor signaling. Daylength at the time of scanning was used as a predictor for brain regional non-displaceable binding of the radiotracer, while controlling for age and sex. RESULTS: Daylength was negatively correlated with availability of D2/3 dopamine receptors in the striatum. The largest effect was found in the left caudate, and based on the primary sample, every 4.26 h (i.e., one standard deviation) increase of daylength was associated with a mean 2.8% drop (95% CI -0.042 to -0.014) of the receptor availability. CONCLUSIONS: Seasonally varying D2/3 receptor signaling may also underlie the seasonality of mood, feeding, and motivational processes. Our finding suggests that in future studies of brain dopamine signaling, especially in high-latitude regions, the effect of seasonality should be considered.

Visual training after central retinal loss limits structural white matter degradation: an MRI study.

BACKGROUND: Macular degeneration of the eye is a common cause of blindness and affects 8% of the worldwide human population. In adult cats with bilateral lesions of the central retina, we explored the possibility that motion perception training can limit the associated degradation of the visual system. We evaluated how visual training affects behavioral performance and white matter structure. Recently, we proposed (Kozak et al. in Transl Vis Sci Technol 10:9, 2021) a new motion-acuity test for low vision patients, enabling full visual field functional assessment through simultaneous perception of shape and motion. Here, we integrated this test as the last step of a 10-week motion-perception training. RESULTS: Cats were divided into three groups: retinal-lesioned only and two trained groups, retinal-lesioned trained and control trained. The behavioral data revealed that trained cats with retinal lesions were superior in motion tasks, even when the difficulty relied only on acuity. 7 T-MRI scanning was done before and after lesioning at 5 different timepoints, followed by Fixel-Based and Fractional Anisotropy Analysis. In cats with retinal lesions, training resulted in a more localized and reduced percentage decrease in Fixel-Based Analysis metrics in the dLGN, caudate nucleus and hippocampus compared to untrained cats. In motion-sensitive area V5/PMLS, the significant decreases in fiber density were equally strong in retinal-lesioned untrained and trained cats, up to 40% in both groups. The only cortical area with Fractional Anisotropy values not affected by central retinal loss was area V5/PMLS. In other visual ROIs, the Fractional Anisotropy values increased over time in the untrained retinal lesioned group, whereas they decreased in the retinal lesioned trained group and remained at a similar level as in trained controls. CONCLUSIONS: Overall, our MRI results showed a stabilizing effect of motion training applied soon after central retinal loss induction on white matter structure. We propose that introducing early motion-acuity training for low vision patients, aimed at the intact and active retinal peripheries, may facilitate brain plasticity processes toward better vision.

Significance and Clinical Implications of Morphometric and Morphological Variability in Cadaveric Liver.

Background This study aimed to identify morphological variations, conduct morphometry of the liver, and present its clinical implications. Methodology The study was conducted on 35 preserved cadaveric livers without macroscopic abnormalities. Morphological features such as shape and size were studied and variations such as the absence of lobe, accessory fissures, or accessory lobes were noted in all specimens. Results The caudate lobe was absent in one liver, and the quadrate lobe was absent in six livers. Moreover, seven livers had accessory fissures, and accessory lobes were seen in six livers. The left lobe with a lingular process was seen in three livers, and diaphragmatic grooves were present in seven livers. Conclusions The present research is helpful to radiologists, surgeons, and anatomists as it demonstrates the different morphological variations in the liver.