Experimental Search for Neutron to Mirror Neutron Oscillations as an Explanation of the Neutron Lifetime Anomaly.

An unexplained >4σ discrepancy persists between "beam" and "bottle" measurements of the neutron lifetime. A new model proposed that conversions of neutrons n into mirror neutrons n^{'}, part of a dark mirror sector, can increase the apparent neutron lifetime by 1% via a small mass splitting Δm between n and n^{'} inside the 4.6 T magnetic field of the National Institute of Standards and Technology Beam Lifetime experiment. A search for neutron conversions in a 6.6 T magnetic field was performed at the Spallation Neutron Source which excludes this explanation for the neutron lifetime discrepancy.

High-Dosage Fosfomycin Results in Adequate Plasma and Target-Site Exposure in Morbidly Obese and Nonobese Nonhyperfiltration Patients.

The objectives of this study were the identification in (morbidly) obese and nonobese patients of (i) the most appropriate body size descriptor for fosfomycin dose adjustments and (ii) adequacy of the currently employed dosing regimens. Plasma and target site (interstitial fluid of subcutaneous adipose tissue) concentrations after fosfomycin administration (8 g) to 30 surgery patients (15 obese/15 nonobese) were obtained from a prospective clinical trial. After characterization of plasma and microdialysis-derived target site pharmacokinetics via population analysis, short-term infusions of fosfomycin 3 to 4 times daily were simulated. The adequacy of therapy was assessed by probability of pharmacokinetic/pharmacodynamic target attainment (PTA) analysis based on the unbound drug-related targets of an %fT>MIC (the fraction of time that unbound fosfomycin concentrations exceed the MIC during 24 h) of 70 and an fAUC0-24h/MIC (the area under the concentration-time curve from 0 to 24 h for the unbound fraction of fosfomycin relative to the MIC) of 40.8 to 83.3. Lean body weight, fat mass, and creatinine clearance calculated via adjusted body weight (ABW) (CLCRCG_ABW) of all patients (body mass index [BMI] = 20.1 to 52.0 kg/m2) explained a considerable proportion of between-patient pharmacokinetic variability (up to 31.0% relative reduction). The steady-state unbound target site/plasma concentration ratio was 26.3% lower in (morbidly) obese than nonobese patients. For infections with fosfomycin-susceptible pathogens (MIC ≤ 16 mg/L), intermittent "high-dosage" intravenous (i.v.) fosfomycin (8 g, three times daily) was sufficient to treat patients with a CLCRCG_ABW of <130 mL/min, irrespective of the pharmacokinetic/pharmacodynamic indices considered. For infections by Pseudomonas aeruginosa with a MIC of 32 mg/L, when the index fAUC0-24h/MIC is applied, fosfomycin might represent a promising treatment option in obese and nonobese patients, especially in combination therapy to complement ß-lactams, in which carbapenem-resistant P. aeruginosa is critical. In conclusion, fosfomycin showed excellent target site penetration in obese and nonobese patients. Dosing should be guided by renal function rather than obesity status. (This study has been registered in the EU Clinical Trials Register under EudraCT no. 2012-004383-22.).

Personalization of pulse arrival time based blood pressure surrogates through single spot check measurements.

OBJECTIVE: We investigate the effect of selective single parameter personalization on the performance of multi-parameter models for pulse arrival time (PAT) based blood pressure (BP) surrogates. METHODS: Our data set stems from 15 surgery patients, and we selected from each patient 5 segments of 30 min length each. We evaluate the root mean squared BP tracking error of the two models with and without single parameter personalization. We further compare the BP tracking performance to a surrogate-free sample-and-hold approach, e.g., as afforded by conventional non-invasive blood pressure (NIBP) oscillometry. RESULTS: Parameter personalization is key to realizing a tracking performance benefit of PAT-based BP surrogates. The highest tracking error reduction of about 3.7 mmHg with respect to a sample-and-hold approach was reached with a personalized model which is linear in the pulse wave velocity domain. It achieves an estimation error of 7.8 mmHg with respect to a continuously measured invasive reference.Clinical Relevance-We give a performance analysis of PAT-based BP surrogates which are personalized to a patient with a single NIBP spot measurement. We show for surgery patients that patient-specific personalization enables continuous beat-to-beat BP monitoring over 30 min intervals with a average root mean squared error of less than 8 mmHg.

Adherence to treatment guidelines in clinical practice for using electroconvulsive therapy in major depressive episode.

BACKGROUND: ECT is the most effective treatment of major depressive episode (MDE) but remains a neglected treatment. The French Society for Biological Psychiatry and Neuropsychopharmacology aimed to determine whether prescribing practice of ECT followed guidelines recommendations. METHODS: This multicenter, retrospective study included adult patients with major depressive disorder (MDD) or bipolar disorder (BD), who have been treated with ECT for MDE. Duration of MDE and number of lines of treatment received before ECT were collected. The reasons for using ECT, specifically first-line indications (suicidality, urgency, presence of catatonic and psychotic features, previous ECT response, patient preference) were recorded. Statistical comparisons between groups used standard statistical tests. RESULTS: Seven hundred and forty-five individuals were included. The mean duration of MDE before ECT was 10.1 months and the mean number of lines of treatment before ECT was 3.4. It was significantly longer for MDD single episode than recurrent MDD and BD. The presence of first-line indications for using ECT was significantly associated to shorter duration of MDE (9.1 vs 13.1 months, p<0.001) and lower number of lines of treatment before ECT (3.3 vs 4.1, p<0.001). LIMITATIONS: This is a retrospective study and not all facilities practicing ECT participated that could limit the extrapolation of the results. CONCLUSION: Compared to guidelines, ECT was not used as first-line strategy in clinical practice. The presence of first-line indications seemed to reduce the delay before ECT initiation. The improvements of knowledge and access of ECT are needed to decrease the gap between guidelines and clinical practice.

Understanding the circuit basis of cognitive functions using mouse models.

Understanding how cognitive functions arise from computations occurring in the brain requires the ability to measure and perturb neural activity while the relevant circuits are engaged for specific cognitive processes. Rapid technical advances have led to the development of new approaches to transiently activate and suppress neuronal activity as well as to record simultaneously from hundreds to thousands of neurons across multiple brain regions during behavior. To realize the full potential of these approaches for understanding cognition, however, it is critical that behavioral conditions and stimuli are effectively designed to engage the relevant brain networks. Here, we highlight recent innovations that enable this combined approach. In particular, we focus on how to design behavioral experiments that leverage the ever-growing arsenal of technologies for controlling and measuring neural activity in order to understand cognitive functions.

Red Blood Cell Omega-3 Fatty Acid Composition and Psychotropic Drug Use in Older Adults: Results from the MAPT Study.

Low docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentration has been associated with the development of some psychiatric disorders. OBJECTIVES: to assess the association between red blood cell (RBC) DHA-EPA concentration and psychotropic drug use in older adults and between the 1-year change in RBC DHA-EPA and psychotropic drug use at 12 months. DESIGN: secondary analysis of multicenter, randomized controlled trial testing multidomain intervention and/or n-3 PUFA supplement on cognitive function (MAPT study). SETTING: France, 2008-2014. PARTICIPANTS: 1680 participants ≥70 years, community-dwelling were included. MEASUREMENTS: Psychotropic drug use was self-reported during medical interviews and assessments. RBC n-3 PUFA concentration was defined by % of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) among total fatty acids. Logistic regressions models controlling for age, sex, education, depression risk and intervention group were used. RESULTS: 1594 participants had baseline DHA-EPA concentration available (mean age=75.5±4.5 years, 65% females). At baseline, participants with DHA-EPA ≤4.82% (lowest quartile) reported higher prevalence of use of overall psychotropic drugs (34.0% vs 24.4%; aOR=1.33, 95%CI=[1.03-1.72]), anxiolytic/hypnotic drugs (25.0% vs 18.2%; aOR=1.42, 95%CI=[1.07-1.89]), and antidepressants (18.3% vs 13.5%; aOR=1.25, 95%CI=[0.93-1.72]) than participants with higher DHA-EPA. Participants who experienced an increase in DHA-EPA from baseline were less likely to use a psychotropic drug at 12 months than participants with no change or a decrease (aOR=0.72, 95%CI=[0.55-0.96]). CONCLUSION: Low RBC DHA-EPA concentration was independently associated with psychotropic drug use. Future studies are needed to assess whether low RBC DHA-EPA is a risk marker for psychotropic drug use in older adults and to better understand underlying pathophysiological mechanisms. Registration number: ClinicalTrials.gov database (NCT00672685).

Combinatorial Targeting of Distributed Forebrain Networks Reverses Noise Hypersensitivity in a Model of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is associated with noise hypersensitivity, the suboptimal extraction of meaningful signals in noisy environments. Because sensory filtering can involve distinct automatic and executive circuit mechanisms, however, developing circuit-specific therapeutic strategies for ASD noise hypersensitivity can be challenging. Here, we find that both of these processes are individually perturbed in one monogenic form of ASD, Ptchd1 deletion. Although Ptchd1 is preferentially expressed in the thalamic reticular nucleus during development, pharmacological rescue of thalamic perturbations in knockout (KO) mice only normalized automatic sensory filtering. By discovering a separate prefrontal perturbation in these animals and adopting a combinatorial pharmacological approach that also rescued its associated goal-directed noise filtering deficit, we achieved full normalization of noise hypersensitivity in this model. Overall, our work highlights the importance of identifying large-scale functional circuit architectures and utilizing them as access points for behavioral disease correction.

[Post-traumatic stress disorder in reaction to psychotic experience: A systematic revue]. / Le Trouble Stress Post-Traumatique secondaire à l'expérience de la psychose : une revue de littérature.

BACKGROUND: The update of the Post-Traumatic Stress Disorder (PTSD) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM5) emphasizes the definition of psychological traumatism as an objective and external event. Nevertheless, the scientific debate about the criteriology of PTSD, its clinical pertinence for application and the role of subjective dimension appears still open. Although the relation between psychotrauma and psychosis has been well examined, in the way of trauma as a risk factor for the development of schizophrenia, the potential traumatism represented by the psychotic experience seems to be less known. OBJECTIVE: This paper aims to provide a state of the art about the PTSD in reaction to psychosis, defined as PTSD post psychosis (PTSD-PP), particularly in epidemiological and psychopathological terms. METHODS: We performed a bibliographic research on Pubmed using the keywords "post-traumatic stress disorder", "psychological trauma", "schizophrenia review", "psychosis", "first episode psychosis"« ¼, "recovery schizophrenia", with a first screening on titles and abstracts. An acute psychotic episode referred to a decompensation of any pathology of the DSM5-schizophrenia spectrum or other psychotic disorders or to a mood disorder with psychotic features. The articles exclusively interested in the traumatic impact of hospitalizations and treatment conditions were excluded. RESULTS: The literature noted that PTSD-PP affected about a quarter to a third of the psychotic patients interrogated during the recovery of an acute psychotic episode. The analytic epidemiology showed that the main validated risk factors for PTSD were also relevant in the development of PTSD-PP, including past traumatic history, childhood trauma and feeling of helplessness during the traumatic event. Criticizing the methodological heterogeneity through studies, the observational approach brought out the lack of clinical pertinence of the DSM5A criteria defining the traumatic event for PTSD. This criteriology failed to consider the subjective dimension of the threat to psychological integrity generated by a psychotrauma. Historical case studies presented a complete post-traumatic symptomatology in reaction to psychosis, suggesting that the supposed psychotic residual symptoms after acute phase could referr to actual traumatic reactions. The PTSD-PP process observed in descriptive research and patients' interviews appeared congruent with the cognitive model of PTSD elaborated by Ehlers and Clark. Indeed, psychotic patients developed negative appraisals about themselves, others and the world because of the occurrence and the content of their psychotic symptoms. Shame, fear of recurrence, intolerance to uncertainty and perception of losing control of one's mind were demonstrated as significantly related to PTSD-PP. A perception of current threat then settled, leading to adaptation strategies, possibly psychotic themselves, to avoid intrusions and others indices about their past psychotic episode. Thus, reliving syndrome, avoidance, emotional numbing could simulate a new psychotic exacerbation to an outer-observer. CONCLUSION: A psychotic experience could be traumatic for patients and lead to complete PTSD. Although it appears as a non-consensual clinical entity, from a likely epistemological slip of the definition of "psychotrauma", the consideration of potential PTSD-PP presents an undoubted clinical relevance. Indeed, it could help practioners to precise the semiological analysis of patients recovering from an acute psychotic episode; to impact the prognosis of psychosis, thinking about impairment on the quality of life and the affective and suicidal comorbidities; and to modify the therapeutic approach in the recovery of schizophrenia. In addition, the literature about psychotic recovery seems particularly related to the concept of "post-traumatic growth" (PTG). The inscription of a psychotic episode in a traumatic frame requires a clinical approach as close as possible to the subjectivity of the patient experience, beyond the evaluation of psychotic symptoms and its remission. The question of trauma-focused therapies applied to PTSD-PP opens the field for future research.

Clinical guidelines for the management of treatment-resistant depression: French recommendations from experts, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental.

BACKGROUND: Clear guidance for successive antidepressant pharmacological treatments for non-responders in major depression is not well established. METHOD: Based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of treatment-resistant depression. The expert guidelines combine scientific evidence and expert clinicians' opinions to produce recommendations for treatment-resistant depression. A written survey comprising 118 questions related to highly-detailed clinical presentations was completed on a risk-benefit scale ranging from 0 to 9 by 36 psychiatrist experts in the field of major depression and its treatments. Key-recommendations are provided by the scientific committee after data analysis and interpretation of the results of the survey. RESULTS: The scope of these guidelines encompasses the assessment of pharmacological resistance and situations at risk of resistance, as well as the pharmacological and psychological strategies in major depression. CONCLUSION: The expert consensus guidelines will contribute to facilitate treatment decisions for clinicians involved in the daily assessment and management of treatment-resistant depression across a number of common and complex clinical situations.

Prefrontal Cortex Regulates Sensory Filtering through a Basal Ganglia-to-Thalamus Pathway.

To make adaptive decisions, organisms must appropriately filter sensory inputs, augmenting relevant signals and suppressing noise. The prefrontal cortex (PFC) partly implements this process by regulating thalamic activity through modality-specific thalamic reticular nucleus (TRN) subnetworks. However, because the PFC does not directly project to sensory TRN subnetworks, the circuitry underlying this process had been unknown. Here, using anatomical tracing, functional manipulations, and optical identification of PFC projection neurons, we find that the PFC regulates sensory thalamic activity through a basal ganglia (BG) pathway. Engagement of this PFC-BG-thalamus pathway enables selection between vision and audition by primarily suppressing the distracting modality. This pathway also enhances sensory discrimination and is used for goal-directed background noise suppression. Overall, our results identify a new pathway for attentional filtering and reveal its multiple roles in sensory processing on the basis of internal goals.

Clinical guidelines for the management of depression with specific comorbid psychiatric conditions French recommendations from experts (the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental).

BACKGROUND: Recommendations for pharmacological treatments of major depression with specific comorbid psychiatric conditions are lacking. METHOD: The French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of depression based on the RAND/UCLA Appropriatneness Method. Recommendations for lines of treatment are provided by the scientific committee after data analysis and interpretation of the results of a survey of 36 psychiatrist experts in the field of major depression and its treatments. RESULTS: The expert guidelines combine scientific evidence and expert clinician's opinion to produce recommendations for major depression with comorbid anxiety disorders, personality disorders or substance use disorders and in geriatric depression. CONCLUSION: These guidelines provide direction addressing common clinical dilemmas that arise in the pharmacologic treatment of major depression with comorbid psychiatric conditions.

Magnetic Field Control of Cycloidal Domains and Electric Polarization in Multiferroic BiFeO_{3}.

The magnetic field induced rearrangement of the cycloidal spin structure in ferroelectric monodomain single crystals of the room-temperature multiferroic BiFeO_{3} is studied using small-angle neutron scattering. The cycloid propagation vectors are observed to rotate when magnetic fields applied perpendicular to the rhombohedral (polar) axis exceed a pinning threshold value of ∼5 T. In light of these experimental results, a phenomenological model is proposed that captures the rearrangement of the cycloidal domains, and we revisit the microscopic origin of the magnetoelectric effect. A new coupling between the magnetic anisotropy and the polarization is proposed that explains the recently discovered magnetoelectric polarization perpendicular to the rhombohedral axis.

Detection rate of fetal distress using contraction-dependent fetal heart rate variability analysis.

OBJECTIVE: Monitoring of the fetal condition during labor is currently performed by cardiotocograpy (CTG). Despite the use of CTG in clinical practice, CTG interpretation suffers from a high inter- and intra-observer variability and a low specificity. In addition to CTG, analysis of fetal heart rate variability (HRV) has been shown to provide information on fetal distress. However, fetal HRV can be strongly influenced by uterine contractions, particularly during the second stage of labor. Therefore, the aim of this study is to examine if distinguishing contractions from rest periods can improve the detection rate of HRV features for fetal distress during the second stage of labor. APPROACH: We used a dataset of 100 recordings, containing 20 cases of fetuses with adverse outcome. The most informative HRV features were selected by a genetic algorithm and classification performance was evaluated using support vector machines. MAIN RESULTS: Classification performance of fetal heart rate segments closest to birth improved from a geometric mean of 70% to 79%. If the classifier was used to indicate fetal distress over time, the geometric mean at 15 minutes before birth improved from 60% to 72%. SIGNIFICANCE: Our results show that combining contraction-dependent HRV features with HRV features calculated over the entire fetal heart rate signal improves the detection rate of fetal distress.

[Work satisfaction and exhaustion among psychiatrists in psychiatric emergency services]. / Facteurs de satisfaction et d'épuisement des psychiatres aux urgences.

BACKGROUND AND AIM: Psychiatric emergency services (PES) have recently occupied a new and growing place in the landscape of mental health services. However, few data are available on the way psychiatrists practice in the PES. Our aim was to survey psychiatrists working in PES, focusing on their job satisfaction and the theoretical models they use in their everyday practice. METHOD: We sent a survey to a sample of 508 psychiatrists working in PES in France. RESULTS: Two hundred and thirty-seven psychiatrists returned the survey, yielding a response rate of 47%. On a 0 to 10 scale, the mean level of job satisfaction was 6.7 (SD: 1.92). Participants reported that facing a variety of clinical situations and playing a key-coordinating role in the mental health system were the two most specific features of emergency psychiatry. The main sources of dissatisfaction were organizational issues and stressful clinical experiences, including violence or hostility. Sixty-three percent (n=150) of participants reported using more than two theoretical models in their practice, while the use of crisis models was reported by almost 40% of them. When assessed for suggestions to improve the PES, the majority of participants indicated that efforts should be focused on organizational factors. CONCLUSION: While emergency psychiatry could appear as an ungrateful practice, the majority of psychiatrists who responded to our survey reported satisfaction with their work and highlighted its unique particularities. Future research and collaborations are needed to identify organizational models of PES and their better integration in mental health networks.

Direct biological effects of fractional ultrapulsed CO2 laser irradiation on keratinocytes and fibroblasts in human organotypic full-thickness 3D skin models.

Molecular effects of various ablative and non-ablative laser treatments on human skin cells-especially primary effects on epidermal keratinocytes and dermal fibroblasts-are not yet fully understood. We present the first study addressing molecular effects of fractional non-sequential ultrapulsed CO2 laser treatment using a 3D skin model that allows standardized investigations of time-dependent molecular changes ex vivo. While histological examination was performed to assess morphological changes, we utilized gene expression profiling using microarray and qRT-PCR analyses to identify molecular effects of laser treatment. Irradiated models exhibited dose-dependent morphological changes resulting in an almost complete recovery of the epidermis 5 days after irradiation. On day 5 after laser injury with a laser fluence of 100 mJ/cm2, gene array analysis identified an upregulation of genes associated with tissue remodeling and wound healing (e.g., COL12A1 and FGF7), genes that are involved in the immune response (e.g., CXCL12 and CCL8) as well as members of the heat shock protein family (e.g., HSPB3). On the other hand, we detected a downregulation of matrix metalloproteinases (e.g., MMP3), differentiation markers (e.g., LOR and S100A7), and the pro-inflammatory cytokine IL1α.Overall, our findings substantiate the understanding of time-dependent molecular changes after CO2 laser treatment. The utilized 3D skin model system proved to be a reliable, accurate, and reproducible tool to explore the effects of various laser settings both on skin morphology and gene expression during wound healing.

Intrathecal Resiniferatoxin Modulates TRPV1 in DRG Neurons and Reduces TNF-Induced Pain-Related Behavior.

Transient receptor potential vanilloid-1 (TRPV1) is a nonselective cation channel, predominantly expressed in sensory neurons. TRPV1 is known to play an important role in the pathogenesis of inflammatory and neuropathic pain states. Previous studies suggest interactions between tumor necrosis factor- (TNF-) alpha and TRPV1, resulting in a modulation of ion channel function and protein expression in sensory neurons. We examined the effect of intrathecal administration of the ultrapotent TRPV1 agonist resiniferatoxin (RTX) on TNF-induced pain-associated behavior of rats using von Frey and hot plate behavioral testing. Intrathecal injection of TNF induces mechanical allodynia (2 and 20 ng/kg) and thermal hyperalgesia (200 ng) 24 h after administration. The additional intrathecal administration of RTX (1.9 µg/kg) alleviates TNF-induced mechanical allodynia and thermal hyperalgesia 24 h after injection. In addition, TNF increases the TRPV1 protein level and number of TRPV1-expressing neurons. Both effects could be abolished by the administration of RTX. These results suggest that the involvement of TRPV1 in TNF-induced pain offers new TRPV1-based experimental therapeutic approaches and demonstrates the analgesic potential of RTX in inflammatory pain diseases.

[French Society for Biological Psychiatry and Neuropsychopharmacology and Fondation FondaMental task force: Formal Consensus for the management of treatment-resistant depression]. / Prise en charge des troubles dépressifs résistants : recommandations françaises formalisées par des experts de l'AFPBN et de la fondation FondaMental.

Major depression represents among the most frequent psychiatric disorders in the general population with an estimated lifetime prevalence of 16-17%. It is characterized by high levels of comorbidities with other psychiatric conditions or somatic diseases as well as a recurrent or chronic course in 50 to 80% of the cases leading to negative repercussions on the daily functioning, with an impaired quality of life, and to severe direct/indirect costs. Large cohort studies have supported that failure of a first-line antidepressant treatment is observed in more than 60% of patients. In this case, several treatment strategies have been proposed by classical evidence-based guidelines from internationally recognized scientific societies, referring primarily on: I) the switch to another antidepressant of the same or different class; II) the combination with another antidepressant of complementary pharmacological profile; III) the addition of a wide range of pharmacological agents intending to potentiate the therapeutic effects of the ongoing antidepressant medication; IV) the association with appropriate psychological therapies; and, V) the use of non-invasive brain stimulation techniques. However, although based on the most recently available data and rigorous methodology, standard guidelines have the significant disadvantage of not covering a large variety of clinical conditions, while currently observed in everyday clinical practice. From these considerations, formalized recommendations by a large panel of French experts in the management of depressed patients have been developed under the shared sponsorship of the French Association of Biological Psychiatry and Neuropsychopharmacology (AFPBN) and the Fondation FondaMental. These French recommendations are presented in this special issue in order to provide relevant information about the treatment choices to make, depending particularly on the clinical response to previous treatment lines or the complexity of clinical situations (clinical features, specific populations, psychiatric comorbidities, etc.). Thus, the present approach will be especially helpful for the clinicians enabling to substantially facilitate and guide their clinical decision when confronted to difficult-to-treat forms of major depression in the daily clinical practice. This will be expected to significantly improve the poor prognosis of the treatment-resistant depression thereby lowering the clinical, functional and costly impact owing directly to the disease.

Thalamic amplification of cortical connectivity sustains attentional control.

Although interactions between the thalamus and cortex are critical for cognitive function, the exact contribution of the thalamus to these interactions remains unclear. Recent studies have shown diverse connectivity patterns across the thalamus, but whether this diversity translates to thalamic functions beyond relaying information to or between cortical regions is unknown. Here we show, by investigating the representation of two rules used to guide attention in the mouse prefrontal cortex (PFC), that the mediodorsal thalamus sustains these representations without relaying categorical information. Specifically, mediodorsal input amplifies local PFC connectivity, enabling rule-specific neural sequences to emerge and thereby maintain rule representations. Consistent with this notion, broadly enhancing PFC excitability diminishes rule specificity and behavioural performance, whereas enhancing mediodorsal excitability improves both. Overall, our results define a previously unknown principle in neuroscience; thalamic control of functional cortical connectivity. This function, which is dissociable from categorical information relay, indicates that the thalamus has a much broader role in cognition than previously thought.