Ketamine induces a robust whole-brain connectivity pattern that can be differentially modulated by drugs of different mechanism and clinical profile

Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has been studied in relation to the glutamate hypothesis of schizophrenia and increases dissociation, positive and negative symptom ratings. Ketamine effects brain function through changes in brain activity; these activity patterns can be modulated by pre-treatment of compounds known to attenuate the effects of ketamine on glutamate release. Ketamine also has marked effects on brain connectivity; we predicted that these changes would also be modulated by compounds known to attenuate glutamate release. Here, we perform task-free pharmacological magnetic resonance imaging (phMRI) to investigate the functional connectivity effects of ketamine in the brain and the potential modulation of these effects by pre-treatment of the compounds lamotrigine and risperidone, compounds hypothesised to differentially modulate glutamate release. Connectivity patterns were assessed by combining windowing, graph theory and multivariate Gaussian process classification. We demonstrate that ketamine has a robust effect on the functional connectivity of the human brain compared to saline (87.5 % accuracy). Ketamine produced a shift from a cortically centred, to a subcortically centred pattern of connections. This effect is strongly modulated by pre-treatment with risperidone (81.25 %) but not lamotrigine (43.75 %). Based on the differential effect of these compounds on ketamine response, we suggest the observed connectivity effects are primarily due to NMDAR blockade rather than downstream glutamatergic effects. The connectivity changes contrast with amplitude of response for which no differential effect between pre-treatments was detected, highlighting the necessity of these techniques in forming an informed view of the mechanistic effects of pharmacological compounds in the human brain

Delta-9-tetrahydrocannabinol, neural oscillations above 20 Hz and induced acute psychosis

Rationale: An acute challenge with delta-9-tetrahydrocannabinol (THC) can induce psychotic symptoms including delusions. High electroencephalography (EEG) frequencies, above 20 Hz, have previously been implicated in psychosis and schizophrenia. Objectives: The objective of this study is to determine the effect of intravenous THC compared to placebo on high-frequency EEG. Methods: A double-blind cross-over study design was used. In the resting state, the high-beta to low-gamma magnitude (21–45 Hz) was investigated (n=13 pairs+4 THC only). Also, the event-related synchronisation (ERS) of motor-associated high gamma was studied using a self-paced button press task (n=15). Results: In the resting state, there was a significant condition × frequency interaction (p=0.00017), consisting of a shift towards higher frequencies under THC conditions (reduced high beta [21–27 Hz] and increased low gamma [27–45 Hz]). There was also a condition × frequency × location interaction (p=0.006), such that the reduction in 21–27-Hz magnitude tended to be more prominent in anterior regions, whilst posterior areas tended to show greater 27–45-Hz increases. This effect was correlated with positive symptoms, as assessed on the Positive and Negative Syndrome Scale (PANSS) (r=0.429, p=0.042). In the motor task, there was a main effect of THC to increase 65–130-Hz ERS (p=0.035) over contra-lateral sensorimotor areas, which was driven by increased magnitude in the higher, 85–130-Hz band (p=0.02) and not the 65–85-Hz band. Conclusions: The THC-induced shift to faster gamma oscillations may represent an over-activation of the cortex, possibly related to saliency misattribution in the delusional state

Modulation of functional connectivity following visual adaptation: homeostasis in V1

Abstract: Sensory neurons exhibit remarkable adaptability in acquiring new optimal selectivity to unfamiliar features when a new stimulus becomes prevalent in the environment. In conventionally prepared adult anesthetized cats, we used visual adaptation to change the preferred orientation selectivity in V1 neurons. Cortical circuits are dominated by complex and intricate connections between neurons. Cross-correlation of cellular spike-trains discloses the putative functional connection between two neurons. We sought to investigate changes in these links following a twelve minute uninterrupted application of a specific, usually non-preferred, orientation. We report that visual adaptation, mimicking training, modulates the magnitude of cross-correlograms suggesting that the strength of inter-neuronal relationships is modified. While individual cell-pairs exhibit changes in their response correlation strength, the average correlation of the recorded cell cluster remains unchanged. Hence, visual adaptation induces plastic changes that impact the connectivity between neurons

Treatment and long-term outcome in primary distal renal tubular acidosis

Background Primary distal renal tubular acidosis (dRTA) is a rare disorder, and we aimed to gather data on treatment and long-term outcome.Methods We contacted paediatric and adult nephrologists through European professional organizations. Responding clinicians entered demographic, biochemical, genetic and clinical data in an online form.Results Adequate data were collected on 340 patients (29 countries, female 52%). Mutation testing had been performed on 206 patients (61%); pathogenic mutations were identified in 170 patients (83%). The median (range) presentation age was 0.5 (0-54) years and age at last follow-up was 11.0 (0-70.0) years. Adult height was slightly below average with a mean (SD score) of -0.57 (1.16). There was an increased prevalence of chronic kidney disease (CKD) Stage 2 in children (35%) and adults (82%). Nephrocalcinosis was reported in 88%. Nephrolithiasis was more common with SLC4A1 mutations (42% versus 21%). Thirty-six percent had hearing loss, particularly in ATP6V1B1 (88%). The median (interquartile range) prescribed dose of alkali (mEq/kg/day) was 1.9 (1.2-3.3). Adequate metabolic control (normal plasma bicarbonate and normocalciuria) was achieved in 158 patients (51%), more commonly in countries with higher gross domestic product (67% versus 23%), and was associated with higher height and estimated glomerular filtration rate.Conclusion Long-term follow-up from this large dRTA cohort shows an overall favourable outcome with normal adult height for most and no patient with CKD Stage 5. However, 82% of adult patients have CKD Stages 2-4. Importance of adequate metabolic control was highlighted by better growth and renal function but was achieved in only half of patients.C1 [Lopez-Garcia, Sergio Camilo; Kleta, Robert; Bockenhauer, Detlef] NHS Fdn Trust, Great Ormond St Hosp Children, Dept Paediat Nephrol, London, England.[Lopez-Garcia, Sergio Camilo; Walsh, Stephen B.; Dufek, Stephanie; Iancu, Daniela; Kleta, Robert; Bockenhauer, Detlef] UCL, Ctr Nephrol, London, England.[Walsh, Stephen B.] Bambino Gesu Childrens Hosp IRCCS, Div Nephrol, Rome, Italy.[Fila, Marc] Montpellier Univ Hosp, CHU Arnaud Villeneuve, Pediat Nephrol, Montpellier, France.[Hooman, Nakysa] Iran Univ Med Sci, Ali Asghar Clin Res Dev Ctr, Tehran, Iran.[Zaniew, Marcin] Univ Zielona Gora, Dept Pediat, Zielona Gora, Poland.[Bertholet-Thomas, Aurelia] Ctr Reference Malad Renales Rares, Bron, France.[Colussi, Giacomo] ASST Niguarda, Milan, Italy.[Burgmaier, Kathrin] Univ Hosp Cologne, Dept Pediat, Cologne, Germany.[Levtchenko, Elena] Univ Hosp Leuven, Leuven, Belgium.[Sharma, Jyoti; Singhal, Jyoti] King Edward Mem Hosp, Pune, Maharashtra, India.[Soliman, Neveen A.] Cairo Univ, Dept Pediat, Ctr Pediat Nephrol & Transplantat, Kasr Al Ainy Sch Med, Cairo, Egypt.[Ariceta, Gema] Hosp Univ Vall dHebron, Barcelona, Spain.[Basu, Biswanath] NRS Med Coll, Div Pediat Nephrol, Kolkata, India.[Murer, Luisa] Azienda Osped & Univ Padova, Pediat Nephrol Dialysis & Transplant Unit, Padua, Italy.[Tasic, Velibor] Univ Childrens Hosp, Med Sch, Skopje, Macedonia.[Tsygin, Alexey] Natl Med & Res Ctr Childrens Hlth, Moscow, Russia.[Decramer, Stephane] CHU Toulouse, Serv Nephrol Pediat, Hop Enfants, Ctr Reference Malad Renales Rares Sud Ouest, Toulouse, France.[Gil-Pena, Helena] Hosp Univ Cent Asturias, Oviedo, Spain.[Koster-Kamphuis, Linda] Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands.[La Scola, Claudio] Azienda Osped Univ St Orsola Malpighi, Nephrol & Dialysis Unit, Dept Woman Child & Urol Dis, Bologna, Italy.[Gellermann, Jutta; Thumfart, Julia] Charite Univ Med Berlin, Berlin, Germany.[Konrad, Martin; Koenig, Jens] Univ Childrens Hosp, Munster, Germany.[Lilien, Marc] Univ Med Ctr, Wilhelmina Childrens Hosp, Utrecht, Netherlands.[Francisco, Telma] Ctr Hosp Lisboa Cent, Lisbon, Portugal.[Tramma, Despoina] Aristotle Univ Thessaloniki, Pediat Dept 4, Thessaloniki, Greece.[Trnka, Peter] Lady Cilento Childrens Hosp, Brisbane, Qld, Australia.[Trnka, Peter; Mallett, Andrew] Univ Queensland, Sch Med, Brisbane, Qld, Australia.[Yuksel, Selcuk] Pamukkale Univ, Dept Pediat Nephrol, Sch Med, Denizli, Turkey.[Caruso, Maria Rosa] Azienda Osped Papa Giovani XXIII, Nephrol Unit, Bergamo, Italy.[Chromek, Milan] Lund Univ, Karolinska Inst, Lund, Sweden.[Ekinci, Zelal] Grp Florence Nightingale Hosp, Istanbul, Turkey.[Gambaro, Giovanni] Univ Cattolica Sacro Cuore, Fdn Policlin A Gemelli, Rome, Italy.[Kari, Jameela A.] King Abdulaziz Univ, Pediat Nephrol Ctr Excellence, Fac Med, Jeddah, Saudi Arabia.[Kari, Jameela A.] King Abdulaziz Univ, Pediat Dept, Fac Med, Jeddah, Saudi Arabia.[Taroni, Francesca] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Pediat Nephrol Dialysis & Transplant Unit, Milan, Italy.[Trepiccione, Francesco] Univ Campania L Vanvitelli, Dept Translat Med Sci, Naples, Italy.[Winding, Louise] Lillebaelt Hosp Kolding, Pediat Dept, Kolding, Denmark.[Wuehl, Elke; Schaefer, Franz] Univ Hosp Heidelberg, Div Pediat Nephrol, Ctr Pediat & Adolescent Med, Heidelberg, Germany.[Agbas, Ayse] Haseki Educ & Res Hosp, Istanbul, Turkey.[Belkevich, Anna] Belarusian State Med Univ, Minsk, BELARUS.[Vargas-Poussou, Rosa; Blanchard, Anne] Hop Europeen Georges Pompidou, AP HP, Dept Genet, Paris, France.[Conti, Giovanni] AOU Policlin G Martino, Pediat Nephrol Unit, Messina, Italy.[Boyer, Olivia] Hop Necker Enfants Malad, Paris, France.[Dursun, Ismail; Pinarbasi, Ayse Seda] Erciyes Univ, Dept Pediat Nephrol, Fac Med, Kayseri, Turkey.[Melek, Engin] Cukurova Univ, Adana, Turkey.[Miglinas, Marius] Vilnius Univ, Nephrol Ctr, Santaros Klin, Vilnius, Lithuania.[Novo, Robert] Univ Hosp Lille, Lille, France.[Mallett, Andrew] Royal Brisbane & Womens Hosp, Dept Renal Med, Brisbane, Qld, Australia.[Milosevic, Danko] Univ Hosp Ctr Zagreb, Zagreb, Croatia.[Szczepanska, Maria] SUM Katowice, Dept Pediat, SMDZ Zabrze, Katowice, Poland.[Wente, Sarah] Hannover Med Sch, Dept Pediat Nephrol, Hannover, Germany.[Cheong, Hae Il] Seoul Univ, Dept Pediat, Childrens Hosp, Seoul, South Korea.[Sinha, Rajiv] Inst Child Hlth, Kolkata, India.[Gucev, Zoran] Univ Childrens Hosp, Med Sch, Skopje, Macedonia.[Peco-Antic, Amira] Univ Childrens Hosp, Dept Nephrol, Belgrade, Serbia.[Kaur, Amrit] Royal Manchester Childrens Hosp, Dept Paediat Nephrol, Manchester, Lancs, England.[Paglialunga, Antonino] ASP Ragusa, Modica, Italy.[Servais, Aude] CHU Necker, APHP, Dept Nephrol, Paris, France.[Lutovac, Branko] Inst Childrens Dis, Clin Ctr Montenegro, Podgorica, Montenegro.[Hoorn, Ewout J.] Erasmus MC, Rotterdam, Netherlands.[Shasha-Lavsky, Hadas] Galilee Med Ctr, Nahariyya, Israel.[Harambat, Jerome; Godron-Dubrasquet, Astrid] Bordeaux Univ Hosp, Pediat Nephrol Unit, Bordeaux, France.[Buder, Kathrin] Univ Hosp Carl Gustav Carus Dresden, Pediat Dept, Dresden, Germany.[Allard, Lise] Angers Univ Hosp, Dept Pediat, Angers, France.[Patzer, Ludwig] Childrens Hosp St Elisabeth & St Barbara, Halle, Germany.[Shumikhina, Marina] Filatov Childrens Clin Hosp 13, Moscow, Russia.[Hansen, Matthias] Clementine Childrens Hosp, KfH Ctr Paediat Nephrol, Frankfurt, Germany.[Printza, Nikoleta] Aristotle Univ Thessaloniki, Pediat Dept 1, Thessaloniki, Greece.[Kucuk, Nuran] Kartal Dr Lutfi Kirdar Training & Res Hosp, Istanbul, Turkey.[Beringer, Ortraud] Univ Childrens Hosp, Ulm, Germany.[Bhimma, Rajendra] Cent Hosp, Inkosi Albert Luthuli, Durban, South Africa.[Cerkauskiene, Rimante] Vilnius Univ, Childrens Hosp, Fac Med, Vilnius, Lithuania.[Cerkauskiene, Rimante] Vilnius Univ Hosp, Santaros Klin, Vilnius, Lithuania.[Neuhaus, Thomas J.] Cantonal Hosp Lucerne, Childrens Hosp Lucerne, Luzern, Switzerland.[Stavileci, Valbona] Pediat Clin, Prishtina, Kosovo.[Ulinski, Tim] Armand Trousseau Univ Hosp, APHP, Pediat Nephrol Dept, Paris, France.[Dincel, Nida Temizkan] Hlth Sci Univ, Izmir Dr Behcet Uz Childrens Hosp, Izmir, Turkey.[Mohebbi, Nilufar] Univ Hosp Zurich, Div Nephrol, Zurich, Switzerland

Spectral fingerprints of large-scale neuronal interactions

Cognition results from interactions among functionally specialized but widely distributed brain regions; however, neuroscience has so far largely focused on characterizing the function of individual brain regions and neurons therein. Here we discuss recent studies that have instead investigated the interactions between brain regions during cognitive processes by assessing correlations between neuronal oscillations in different regions of the primate cerebral cortex. These studies have opened a new window onto the large-scale circuit mechanisms underlying sensorimotor decision-making and top-down attention. We propose that frequency-specific neuronal correlations in large-scale cortical networks may be ‘fingerprints’ of canonical neuronal computations underlying cognitive processes