UNASSIGNED: Goal-directed fluid therapy (GDFT) has conflicting evidence regarding outcomes in neurosurgical patients. This meta-analysis aimed to compare the effect of GDFT and conventional fluid therapy on various perioperative outcomes in patients undergoing neurosurgical procedures.
UNASSIGNED: A comprehensive literature search was conducted using PubMed, EMBASE, Scopus, ProQuest, Web of Science, EBSCOhost, Cochrane and preprint servers. The search was conducted up until 16 October 2023, following PROSPERO registration. The search strategy included terms related to GDFT, neurosurgery and perioperative outcomes. Only randomised controlled trials involving adult humans and comparing GDFT with standard/liberal/traditional/restricted fluid therapy were included. The studies were evaluated for risk of bias (RoB), and pooled estimates of the outcomes were measured in terms of risk ratio (RR) and mean difference (MD).
UNASSIGNED: No statistically significant difference was observed in neurological outcomes between GDFT and conventional fluid therapy [RR with 95% confidence interval (CI) was 1.10 (0.69, 1.75), two studies, 90 patients, low certainty of evidence using GRADEpro]. GDFT reduced postoperative complications [RR = 0.67 (0.54, 0.82), six studies, 392 participants] and intensive care unit (ICU) and hospital stay [MD (95% CI) were -1.65 (-3.02, -0.28) and -0.94 (-1.47, -0.42), respectively] with high certainty of evidence. The pulmonary complications were significantly lower in the GDFT group [RR (95% CI) = 0.55 (0.38, 0.79), seven studies, 442 patients, high certainty of evidence]. Other outcomes, including total intraoperative fluids administered and blood loss, were comparable in GDFT and conventional therapy groups [MD (95% CI) were -303.87 (-912.56, 304.82) and -14.79 (-49.05, 19.46), respectively].
UNASSIGNED: The perioperative GDFT did not influence the neurological outcome. The postoperative complications and hospital and ICU stay were significantly reduced in the GDFT group.

It is increasingly evident that structural and functional changes in brain regions associated with obsessive-compulsive disorder (OCD) are often related to the development of the disease. However, limited research has been conducted on how the progression of OCD may lead to an imbalance between goal-directed and habit-learning systems. This study employs resting-state functional imaging to examine the relationship between illness duration and abnormal brain function in goal-directed/habitual-learning systems. Demographic, clinical, and multimodal fMRI data were collected from participants. Our findings suggest that, compared to healthy controls, individuals with OCD exhibit abnormal brain functional indicators in both goal-directed and habit-learning brain regions, with a more pronounced reduction observed in the goal-directed regions. Additionally, abnormal brain activity is associated with illness duration, and the abnormalities observed in goal-directed regions are more effective in distinguishing different courses of OCD patients. Patients with different durations of OCD have functional abnormalities in the goal-directed and habitual-learning brain regions. There are differences in the degree of abnormality in different brain regions, and these abnormalities may disrupt the balance between goal-directed and habitual-learning systems, leading to increasing reliance on repetitive behaviors.

A preclinical model of cue exposure therapy, cue extinction, reduces cue-induced cocaine seeking that is goal-directed but not habit-like. Goal-directed and habitual behaviors differentially rely on the dorsomedial striatum (DMS) and dorsolateral striatum (DLS), but the effects of cue extinction on dorsal striatal responses to cue-induced drug seeking are unknown. We used fiber photometry in rats trained to self-administer cocaine paired with an audiovisual cue to examine how dorsal striatal intracellular calcium and extracellular dopamine activity differs between goal-directed and habit-like cue-induced cocaine seeking and how it is impacted by cue extinction. After minimal fixed-ratio training, rats showed enhanced DMS and DLS calcium responses to cue-reinforced compared to unreinforced lever presses. After rats were trained on goal-promoting fixed ratio schedules or habit-promoting second-order schedules of reinforcement, different patterns of dorsal striatal calcium and dopamine responses to cue-reinforced lever presses emerged. Rats trained on habit-promoting second-order schedules showed reduced DMS calcium responses and enhanced DLS dopamine responses to cue-reinforced lever presses. Cue extinction reduced calcium responses during subsequent drug seeking in the DMS, but not in the DLS. Therefore, cue extinction may reduce goal-directed behavior through its effects on the DMS, whereas habit-like behavior and the DLS are unaffected.

BACKGROUND: There is an imbalance between goal-directed and habitual-learning system in patients with obsessive-compulsive disorder (OCD). At present, the relationship between cognitive behavior therapy (CBT) as a first-line therapy and goal-directed and habitual-learning disorder is still unclear. We attempted to discuss the effect of CBT treatment in patients with OCD, using abnormalities in goal-directed and habitual-learning-related brain regions at baseline as predictive factors.
METHODS: A total of 71 subjects, including 35 OCD patients and 36 healthy controls, were recruited. The OCD patients underwent 8 weeks of CBT. These patients were divided into two groups based on treatment response (Nresponders = 18, Nnonresponders = 17). Further subgroup analysis was conducted based on disease duration (Nshort = 17, Nlong = 18) and age of onset (Nearly = 14, Nlate = 21). We collected resting-state ROI-ROI functional connectivity data and apply repeated-measures linear mixed-effects models to investigate the differences of different subgroups.
RESULTS: CBT led to symptom improvement in OCD patients, with varying degrees of effectiveness across subgroups. The orbitofrontal cortex (OFC) and insula, key regions for goal-directed behavior and habitual-learning, respectively, showed significant impacts on CBT efficacy in subgroups with different disease durations and ages of onset.
CONCLUSIONS: The findings suggest that the goal-directed system may influence the efficacy of CBT through goal selection, maintenance, and emotion regulation. Furthermore, we found that disease duration and age of onset may affect treatment outcomes by modulating functional connectivity between goal-directed and habitual-learning brain regions.

Traditionally, dialysis adequacy has been assessed primarily by determining the clearance of a single small solute, urea. Nevertheless, it has become increasingly evident that numerous other factors play a crucial role in the overall well-being, outcomes and quality of life of dialysis patients. Consequently, in recent years, there has been a notable paradigm shift in guidelines and recommendations regarding dialysis adequacy. This shift represents a departure from a narrow focus only on the removal of specific toxins, embracing a more holistic, person-centered approach. This new perspective underscores the critical importance of improving the well-being of individuals undergoing dialysis while simultaneously minimizing the overall treatment burden. It is based on a double focus on both clinical outcomes and a comprehensive patient experience. To achieve this, a person-centered approach must be embraced when devising care strategies for each individual. This requires a close collaboration between the healthcare team and the patient, facilitating an in-depth understanding of the patient\'s unique goals, priorities and preferences while striving for the highest quality of care during treatment. The aim of this publication is to address the existing evidence on this all-encompassing approach to treatment care for patients undergoing peritoneal dialysis and provide a concise overview to promote a deeper understanding of this person-centered approach.

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.

A behavioral strategy crucial to survival is directed navigation to a goal, such as a food or home location. One potential neural substrate for supporting goal-directed navigation is the parahippocampus, which contains neurons that represent an animal\'s position, orientation, and movement through the world, and that change their firing activity to encode behaviorally relevant variables such as reward. However, little prior work on the parahippocampus has considered how neurons encode variables during goal-directed navigation in environments that dynamically change. Here, we recorded single units from rat parahippocampal cortex while subjects performed a goal-directed task. The maze dynamically changed goal-locations via a visual cue on a trial-to-trial basis, requiring subjects to use cue-location associations to receive reward. We observed a mismatch-like signal, with elevated neural activity on incorrect trials, leading to rate-remapping. The strength of this remapping correlated with task performance. Recordings during open-field foraging allowed us to functionally define navigational coding for a subset of the neurons recorded in the maze. This approach revealed that head-direction coding units remapped more than other functional-defined units. Taken together, this work thus raises the possibility that during goal-directed navigation, parahippocampal neurons encode error information reflective of an animal\'s behavioral performance.

Deficits in cognitive flexibility have been characterized in affective, anxiety, and neurodegenerative disorders. This paper reviews data, mainly from studies on animal models, that support the existence of a cortical-striatal brain circuit modulated by dopamine (DA), playing a major role in cognitive/behavioral flexibility. Moreover, we reviewed clinical findings supporting misfunctioning of this circuit in Parkinson\'s disease that could be responsible for some important non-motoric symptoms. The reviewed findings point to a role of catecholaminergic transmission in the medial prefrontal cortex (mpFC) in modulating DA\'s availability in the nucleus accumbens (NAc), as well as a role of NAc DA in modulating the motivational value of natural and conditioned stimuli. The review section is accompanied by a preliminary experiment aimed at testing weather the extinction of a simple Pavlovian association fosters increased DA transmission in the mpFC and inhibition of DA transmission in the NAc.

Hormonal contraceptives are utilized by millions of women worldwide. However, it remains unclear if these powerful endocrine modulators may alter cognitive function. Habit formation involves the progression of instrumental learning as it goes from being a conscious goal-directed process to a cue-driven automatic habitual motor response. Dysregulated goal and/or habit is implicated in numerous psychopathologies, underscoring the relevance of examining the effect of hormonal contraceptives on goal-directed and habitual behavior. This study examined the effect of levonorgestrel (LNG), a widely used progestin-type contraceptive, on the development of habit in intact female rats. Rats were implanted with subcutaneous capsules that slowly released LNG over the course of the experiment or cholesterol-filled capsules. All female rats underwent operant training followed by reward devaluation to test for habit. One group of females was trained at a level that is sub-threshold to habit, while another group of females was trained to a level well over the habit threshold observed in intact females. The results reveal that all sub-threshold trained rats remained goal-directed irrespective of LGN treatment, suggesting LNG is not advancing habit formation in female rats at this level of reinforcement. However, in rats that were overtrained well above the threshold, cholesterol females showed habitual behavior, thus replicating a portion of our original studies. In contrast, LNG-treated habit-trained rats remained goal-directed, indicating that LNG impedes the development and/or expression of habit following this level of supra-threshold to habit training. Thus, LNG may offset habit formation by sustaining attentional or motivational processes during learning in intact female rats. These results may be clinically relevant to women using this type of hormonal contraceptive as well as in other progestin-based hormone therapies.

Most individuals experience their dominant arm as being more dexterous than the non-dominant arm, but the neural mechanisms underlying this asymmetry in motor behaviour are unclear. Using a delayed-reach task, we have recently demonstrated strong goal-directed tuning of stretch reflex gains in the dominant upper limb of human participants. Here, we used an equivalent experimental paradigm to address the neural mechanisms that underlie the preparation for reaching movements with the non-dominant upper limb. There were consistent effects of load, preparatory delay duration and target direction on the long latency stretch reflex. However, by comparing stretch reflex responses in the non-dominant arm with those previously documented in the dominant arm, we demonstrate that goal-directed tuning of short and long latency stretch reflexes is markedly weaker in the non-dominant limb. The results indicate that the motor performance asymmetries across the two upper limbs are partly due to the more sophisticated control of reflexive stiffness in the dominant limb, likely facilitated by the superior goal-directed control of muscle spindle receptors. Our findings therefore suggest that fusimotor control may play a role in determining performance of complex motor behaviours and support existing proposals that the dominant arm is better supplied than the non-dominant arm for executing more complex tasks, such as trajectory control.