Amytal Research Articles

Effect of Intravenous Sodium Pentobarbital on Pain and Sensory Abnormalities in Patients with Chronic Non-Cancer Pain: Narrative Literature Review, Research Study, and Illustrative Case Reports.

Sodium pentobarbital (SP), a short- to intermediate-acting barbiturate, has limited information in the existing literature. The objectives of this study are to describe (a) the effect of intravenous (IV) SP infusion on pain and sensory abnormalities, and (b) its utility in the diagnosis and management of patients with chronic pain. A narrative review of barbiturate applications for chronic pain was followed by a pragmatic study of 176 consecutive patients admitted to an inpatient pain unit (2004-2009). We collected demographic information upon admission, diagnoses retrieved from chart review, and pain ratings and sensory abnormalities at baseline and after blinded infusion of normal saline (NS) followed by SP. The study group consisted of 83 men and 93 women (mean age 41 ± 11years); the mean NS dose was 7.8 ± 2.3 (range 2-10ml), the SP dose was 223.8 ± 88mg (range 40-420), and the numeric rating scale (NRS) baseline pain score was 6.0 ± 2. The mean reduction in NRS reached both statistical and clinical significance in 150 responders to either NS/SP or SP only. Collectively, we found (a) an extremely high rate of response to IV SP irrespective of the underlying pathology, (b) greater response for pain than for sensory abnormalities (sensory gains or deficits), (c) greater response for sensory gain than for sensory deficit, and (d) greater response for allodynia than for pinprick hyperalgesia. Illustrative case reports are also presented. IV SP infusion is a diagnostic tool that assists in elucidating pain generators and the nature of sensory abnormalities (central vs. peripheral), with effects similar to those of IV sodium amytal. The test cannot be viewed as a tell-all diagnostic modality and must be used in conjunction with clinical judgment, investigations, and psychological reports.

Concordance between Wada, Transcranial Magnetic Stimulation, and Magnetoencephalography for Determining Hemispheric Dominance for Language: A Retrospective Study.

Determination of language hemispheric dominance (HD) in patients undergoing evaluation for epilepsy surgery has traditionally relied on the sodium amobarbital (Wada) test. The emergence of non-invasive methods for determining language laterality has increasingly shown to be a viable alternative. In this study, we assessed the efficacy of transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG), compared to the Wada test, in determining language HD in a sample of 12 patients. TMS-induced speech errors were classified as speech arrest, semantic, or performance errors, and the HD was based on the total number of errors in each hemisphere with equal weighting of all errors (classic) and with a higher weighting of speech arrests and semantic errors (weighted). Using MEG, HD for language was based on the spatial extent of long-latency activity sources localized to receptive language regions. Based on the classic and weighted language laterality index (LI) in 12 patients, TMS was concordant with the Wada in 58.33% and 66.67% of patients, respectively. In eight patients, MEG language mapping was deemed conclusive, with a concordance rate of 75% with the Wada test. Our results indicate that TMS and MEG have moderate and strong agreement, respectively, with the Wada test, suggesting they could be used as non-invasive substitutes.

32 Prediction of Seizure Outcome with Presurgical IAT, MRI, and PET in Patients with Temporal Lobe Epilepsy Undergoing Surgery

Objective:Anterior temporal lobectomy is a common surgical approach for medication-resistant temporal lobe epilepsy (TLE). Prior studies have shown inconsistent findings regarding the utility of presurgical intracarotid sodium amobarbital testing (IAT; also known as Wada test) and neuroimaging in predicting postoperative seizure control. In the present study, we evaluated the predictive utility of IAT, as well as structural magnetic resonance imaging (MRI) and positron emission tomography (PET), on long-term (3-years) seizure outcome following surgery for TLE.Participants and Methods:Patients consisted of 107 adults (mean age=38.6, SD=12.2; mean education=13.3 years, SD=2.0; female=47.7%; White=100%) with TLE (mean epilepsy duration =23.0 years, SD=15.7; left TLE surgery=50.5%). We examined whether demographic, clinical (side of resection, resection type [selective vs. non-selective], hemisphere of language dominance, epilepsy duration), and presurgical studies (normal vs. abnormal MRI, normal vs. abnormal PET, correctly lateralizing vs. incorrectly lateralizing IAT) were associated with absolute (cross-sectional) seizure outcome (i.e., freedom vs. recurrence) with a series of chi-squared and t-tests. Additionally, we determined whether presurgical evaluations predicted time to seizure recurrence (longitudinal outcome) over a three-year period with univariate Cox regression models, and we compared survival curves with Mantel-Cox (log rank) tests.Results:Demographic and clinical variables (including type [selective vs. whole lobectomy] and side of resection) were not associated with seizure outcome. No associations were found among the presurgical variables. Presurgical MRI was not associated with cross-sectional (OR=1.5, p=.557, 95% CI=0.4-5.7) or longitudinal (HR=1.2, p=.641, 95% CI=0.4-3.9) seizure outcome. Normal PET scan (OR= 4.8, p=.045, 95% CI=1.0-24.3) and IAT incorrectly lateralizing to seizure focus (OR=3.9, p=.018, 95% CI=1.2-12.9) were associated with higher odds of seizure recurrence. Furthermore, normal PET scan (HR=3.6, p=.028, 95% CI =1.0-13.5) and incorrectly lateralized IAT (HR= 2.8, p=.012, 95% CI=1.2-7.0) were presurgical predictors of earlier seizure recurrence within three years of TLE surgery. Log rank tests indicated that survival functions were significantly different between patients with normal vs. abnormal PET and incorrectly vs. correctly lateralizing IAT such that these had seizure relapse five and seven months earlier on average (respectively).Conclusions:Presurgical normal PET scan and incorrectly lateralizing IAT were associated with increased risk of post-surgical seizure recurrence and shorter time-to-seizure relapse.

Electron Transport Chain Inhibition to Decrease Injury in Transplanted Donation After Circulatory Death Rat Hearts.

Donation after circulatory death (DCD) donor hearts sustain ischemic damage and are not routinely used for heart transplantation. DCD heart injury, particularly reperfusion injury, is primarily mediated by releasing reactive oxygen species from the damaged mitochondria (complex I of the electron transport chain). Amobarbital (AMO) is a transient inhibitor of complex I and is known to reduce releasing reactive oxygen species generation. We studied the beneficial effects of AMO in transplanted DCD hearts. Sprague-Dawley rats were assigned to 4 groups-DCD or DCD + AMO donors and control beating-heart donors (CBD) or CBD + AMO donors (n = 6-8 each). Anesthetized rats were connected to a ventilator. The right carotid artery was cannulated, heparin and vecuronium were administered. The DCD process started by disconnecting the ventilator. DCD hearts were procured after 25 minutes of in-vivo ischemia, whereas CBD hearts were procured without ischemia. At procurement, all donor hearts received 10 mL of University of Wisconsin cardioplegia solution. The CBD + AMO and DCD + AMO groups received AMO (2 mM) dissolved in cardioplegia. Heterotopic heart transplantation was performed by anastomosing the donor aorta and pulmonary artery to the recipient's abdominal aorta and inferior vena cava. After 14 days, transplanted heart function was measured with a balloon tip catheter placed in the left ventricle. Compared with CBD hearts, DCD hearts had significantly lower developed pressure. AMO treatment significantly improved cardiac function in DCD hearts. Treatment of DCD hearts at the time of reperfusion with AMO resulted in an improvement of transplanted heart function that was comparable with the CBD hearts.

Abstract WMP26: Acute Left Superior Temporal Damage Results In Phonological Errors In Word Comprehension

Right hemisphere deactivation by right carotid injection of sodium amytal (Wada testing) in chronic epilepsy results in few phonological errors in word comprehension. Based on this finding, recent models of language processing indicate that speech sound and spoken word processing is bilateral, so that unilateral stroke should not affect distinguishing phonologically similar words (e.g. boat/note) for word comprehension. We tested the alternative hypothesis that acute left hemisphere stroke in superior temporal gyrus (STG) results in phonological errors in a word-picture verification task, which would support the proposal that the right hemisphere does not support speech sound processing and word comprehension before recovery through reorganization of structure/function relationships. Methods: A series of 218 participants were tested with a word-picture verification test with targets and phonologically similar words and had brain MRI within 4 days of stroke onset. We evaluated associations between any damage to left STG and phonological errors using chi square, and the correlation between degree of damage to STG and number of errors using Spearman Rho. Results: We found a very strong association between infarct in left STG and the production of phonological errors in word comprehension (chi squared= 31.2; p <0.00001). Furthermore, the number of phonological errors was strongly correlated with the degree of infarct in left STG (rho=0.49; p<0.00001). Results indicate that left STG, when acutely damaged, often results in phonological errors in word comprehension. These results indicate that the paucity of such errors in comprehension in studies of chronic left hemisphere stroke or Wada testing is a result of reorganization following chronic left temporal dysfunction. Patients with acute left STG stroke should be tested with sensitive tests for word comprehension deficits, including phonologically similar words, before giving verbal direction on exam or obtaining informed consent for procedures.

Purpose, method, drugs used and health risks of the Narco test

Even in print and electronic media, the murder of a girl in Mehroli, Delhi that took place in May 2022 is being covered as leading news. These days, everyone seems to be talking about the incident. Now that the accused person is in police custody, the judge has granted authorization for the police to conduct a Narco test on him in order to uncover the truth and gather evidence. There are now three contemporary methods for discovering the truth. These include the polygraph test, brain mapping and Narco test. The first two don't need any kind of medication, but the third one does, and they have to inject it into the suspect's body. In the Narco test, psychoactive medications such sodium pentothal, scopolamine, and sodium amytal are injected into the subject in order to cause them to experience hypnosis or become sleepy. Under these circumstances, it is highly assumed that the subject will only speak the truth and nothing else throughout the interrogation. Because of this, the test is also referred to as the truth serum test. Although this test is highly helpful in questioning to solve criminal cases, we cannot ignore the bad consequences of the drugs employed and the negative features of the test on both physical and mental health. The court acknowledged that it was illegal and a violation of the right to privacy. In this article, we discuss the necessity of conducting a Narcoanalysis test, as well as its requirements, the procedure to follow in order to carry it out, the potentially harmful effects of the drugs that are used, as well as the potentially harmful effects of the test itself on one's health and some popular Indian criminal cases that are related to Narco testing.

Abstract 12689: Electron Transport Chain Inhibition to Decrease Reperfusion Injury in Transplanted Donation After Circulatory Death Rat Hearts

Introduction: Intrinsic to the donation after circulatory death (DCD) donation is ischemia and reperfusion injury, primarily mediated through release of reactive oxygen species (ROS) from the damaged mitochondria. Amobarbital (AMO) is a transient, reversible inhibitor of complex I known to decrease ROS generation. We studied whether AMO treatment during reperfusion can improve function in transplanted DCD hearts. Methods: Sprague Dawley rats, were assigned to four heart donor groups- DCD or DCD+AMO and control beating-heart donor (CBD) or CBD+AMO (n=6-8 each). Donor rats were anesthetized using ketamine/xylazine, intubated and connected to a ventilator. The carotid access was used to deliver heparin (1000 U/kg) and vecuronium bromide (4 mg/kg) to paralyze diaphragmatic muscles. The DCD process was initiated by disconnecting the ventilator. Donor hearts were procured following 25 minutes of in-vivo ischemia in the DCD groups, while CBD hearts were procured without terminating the ventilation. At procurement, after clamping the aortic arch, all donor hearts received 10 ml of University of Wisconsin cardioplegia solution delivered through the carotid cannula. The CBD+AMO and DCD+AMO groups received AMO (2 mM), dissolved in the cardioplegia. Heterotopic heart transplantation was performed in recipient rat’s abdomen. After 14 days the transplanted heart function was measured with a balloon tip catheter. Results: Compared to CBD hearts, DCD hearts had significantly lower developed pressure, the rate pressure product (developed pressure times heart rate), and negative dP/dt indicating decreased contractile and impaired diastolic function (Figure). AMO treatment of the DCD hearts resulted in significantly improved cardiac function compared to the untreated DCD hearts. Conclusions: A single treatment with AMO during the heart procurement improves the transplanted DCD heart function which was comparable to the control CBD hearts.

Modulation of Mitochondrial Respiration During Early Reperfusion Reduces Cardiac Injury in Donation After Circulatory Death Hearts.

Donation after circulatory death (DCD) donors are a potential source for heart transplantation. The DCD process has unavoidable ischemia and reperfusion (I/R) injury, primarily mediated through mitochondria, which limits routine utilization of hearts for transplantation. Amobarbital (AMO), a transient inhibitor of the electron transport chain, is known to decrease cardiac injury following ex vivo I/R. We studied whether AMO treatment during reperfusion can decrease injury in DCD hearts. Sprague Dawley rat hearts subjected to 25 minutes of in vivo ischemia (DCD hearts), or control beating donor hearts, were treated with AMO or vehicle for the first 5 minutes of reperfusion, followed by Krebs-Henseleit buffer reperfusion for 55 minutes (for mitochondrial isolation) or 85 minutes (for infarct size determination). Compared with vehicle, AMO treatment led to decreased infarct size (25.2% ± 1.5% vs. 31.5% ± 1.5%; P ≤ 0.05) and troponin I release (4.5 ± 0.05 ng/mL vs. 9.3 ± 0.24 ng/mL, P ≤ 0.05). AMO treatment decreased H 2 O 2 generation with glutamate as complex I substrate in both subsarcolemmal mitochondria (SSM) (37 ± 3.7 pmol·mg -1 ·min -1 vs. 56.9 ± 4.1 pmol·mg -1 ·min -1 ; P ≤ 0.05), and interfibrillar mitochondria (IFM) (31.8 ± 2.8 pmol·mg -1 ·min -1 vs. 46 ± 4.8 pmol·mg -1 ·min -1 ; P ≤ 0.05) and improved calcium retention capacity in SSM (360 ±17.2 nmol/mg vs. 277 ± 13 nmol/mg; P ≤ 0.05), and IFM (483 ± 20 nmol/mg vs. 377± 19 nmol/mg; P ≤ 0.05) compared with vehicle treatment. SSM and IFM retained more cytochrome c with AMO treatment compared with vehicle. In conclusion, brief inhibition of mitochondrial respiration during reperfusion using amobarbital is a promising approach to decrease injury in DCD hearts.

The mitochondrial electron transport chain contributes to calpain 1 activation during ischemia-reperfusion

Activation of calpain1 (CPN1) contributes to mitochondrial dysfunction during cardiac ischemia (ISC) – reperfusion (REP). Blockade of electron transport using amobarbital (AMO) protects mitochondria during ISC-REP, indicating that the electron transport chain (ETC) is a key source of mitochondrial injury. We asked if AMO treatment can decrease CPN1 activation as a potential mechanism of mitochondrial protection during ISC-REP. Buffer-perfused adult rat hearts underwent 25 min global ISC and 30 min REP. AMO (2.5 mM) or vehicle was administered for 1 min before ISC to block electron flow in the ETC. Hearts in the time control group were untreated and buffer perfused without ISC. Hearts were collected at the end of perfusion and used for mitochondrial isolation. ISC-REP increased both the cleavage of spectrin (indicating cytosolic CPN1 activation) in cytosol and the truncation of AIF (apoptosis inducing factor, indicating mitochondrial CPN1 activation) in subsarcolemmal mitochondria compared to time control. Thus, ISC-REP activated both cytosolic and mitochondrial CPN1. AMO treatment prevented the cleavage of spectrin and AIF during ISC-REP, suggesting that the transient blockade of electron transport during ISC decreases CPN1 activation. AMO treatment decreased the activation of PARP [poly(ADP-ribose) polymerase] downstream of AIF that triggers caspase-independent apoptosis. AMO treatment also decreased the release of cytochrome c from mitochondria during ISC-REP that prevented caspase 3 activation. These results support that the damaged ETC activates CPN1 in cytosol and mitochondria during ISC-REP, likely via calcium overload and oxidative stress. Thus, AMO treatment to mitigate mitochondrial-driven cardiac injury can decrease both caspase-dependent and caspase-independent programmed cell death during ISC-REP.

Carrier-Free Deferoxamine Nanoparticles against Iron Overload in Brain

Carrier-Free Deferoxamine Nanoparticles against Iron Overload in Brain

Abstract 13106: Modulation of Mitochondrial Respiration During Early Reperfusion Using Amobarbital Decreases Cardiac Injury in Donation After Circulatory Death Hearts

Introduction: Hearts from donation after circulatory death (DCD) donors are becoming an important source for heart transplantation (HTx). However, DCD hearts undergo ischemia reperfusion injury (IRI) and manifest impaired cardiac function. Blockage of electron transport chain (ETC) with the reversible inhibitor amobarbital (AMO) may mitigate IRI. Since pretreatment is not allowed in the DCD donors, therapeutic interventions at reperfusion are critical to limit injury in DCD hearts. Hypothesis: Transient blockade of ETC using AMO at reperfusion can decrease IRI in the DCD heart. Methods: Sprague Dawley rat hearts were subjected to 25 min. in-vivo ischemia. Hearts were then treated with 2mM AMO or vehicle for the first 5 min. of reperfusion, followed by Krebs-Henseleit buffer perfusion at 37 0 C on a Langendorff setup for 55 or 85 minutes. Infarct size was measured in hearts reperfused for a total of 90 min. Subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM) were isolated from a separate set of hearts reperfused for a total of 60 min. to assess calcium retention capacity (CRC), a measurement of mitochondrial permeability transition pore (MPTP) susceptibility to opening, and H 2 O 2 generation. Control beating donor (CBD) hearts underwent similar evaluation except for the ischemia. Results: AMO treatment caused a significant 19% decrease in infarct size (Figure A) compared to vehicle treated DCD hearts (25±2 vs.31±2 % of the Left Ventricle; mean± SEM, p<0.05). CRC was improved with AMO compared to vehicle treated DCD hearts (360±17 vs. 269±17nmol/mg in SSM; 485±19 vs. 388±26nmol/mg in IFM; p<0.05. Figure B). H 2 O 2 generation was reduced in AMO treated DCD hearts, especially in SSM (37±4 vs.59± 5pmol/mg/min; p<0.05. Figure C). Conclusions: Brief inhibition of mitochondrial respiration with AMO during early reperfusion decreases injury in DCD hearts. AMO is a promising approach to protect myocardium in DCD hearts.

Abstract 14312: Inhibition of the Electron Transport Chain and Inflammasome Pathway Preserve Function in Donor Hearts After Circulatory Death

Introduction: Hearts by donation after circulatory death (DCD) have the potential to increase the number of transplantable hearts. However, the DCD process promotes ischemia and reperfusion injury (IRI). Mitochondrial damage and NLRP3 inflammasome activation contribute to the DCD heart damage. Blockade of electron transport chain (ETC) with the reversible inhibitor amobarbital (AMO) or the NLRP3 inhibitor 16773340 (NLRP3-I) can mitigate IRI. Hypothesis: AMO and/or NLRP3-I given to the DCD hearts at the moment of heterotopic heart transplantation afford lasting protection to the DCD hearts. Methods: We induced the DCD process in anesthetized rats that were intubated and ventilated by paralyzing the animal with vecuronium bromide and removing the ventilatory support. Treatment groups were AMO (1 mM), NLRP3-I, AMO+NLRP3-I, and vehicle (N=8-10/group). The DCD hearts were procured after 25 min of in-body ischemia then flushed with ice-cold cardioplegia solution supplemented or not with the AMO. NLRP3-I was administered orally (100 mg/kg) to the recipient before HTx and once a day. Control beating-heart donors (CBD) were procured without ischemia by giving the cardioplegia. The donor hearts underwent heterotopic transplantation in the abdomen of recipients. After 14 days, the function of the DCD heart was measured using an intraventricular balloon. Results: The developed pressure (DP), the peak -dP/dt, and the rate pressure product (RPP) of DCD hearts were significantly reduced compared to the CBD controls (63±7% vs 99±8%; -851±113 vs -1221±123; 20,729±2,268 vs 11,874±1,987, respectively; all p<0.05). AMO, NLRP3-I, and AMO+NLRP3-I preserved the DCD heart function (all parameters, p<0.03). Double treatment AMO+NLRP3-I trended toward a better improvement without reaching statistical significance over single treatments. Conclusions: Inhibition of ETC with AMO alone or combined with NLRP3 inhibition preserved the function of DCD hearts.

Seizure in Patient with Neurofibromatosis and Amygdala Low-Grade Glioma

A 31-year-old male with history of bipolar disorder, suicidal attempts requiring inpatient hospitalization, and seizures on antiepileptic medications presented with increasing seizure frequency. He was neurologically intact yet had multiple facial, axillary, and inguinal flat pigmented macules (cafe au lait spots) and ophthalmologic examination with iris hamartomas (Lisch nodules) consistent with neurofibromatosis type1. Electroencephalogram was notable for multiple right temporal lobe seizures with anterior temporal interictal epileptiform discharges. Magnetic resonance imaging revealed a T2 hyperintense mass centered in the right amygdala, contiguous with the cystic area. Preoperative intracarotid sodium amobarbital testing showed left-sided language and memory dominance. The patient was operated on for right amygdalohippocampectomy, and initial pathology was consistent with a low-grade neuroepithelial neoplastic process. Further pathologic examination found hypercellular proliferation of predominantly bland, spindled cells with scattered, embedded neurocytic elements with dysplastic appearance, consistent with low-grade glioma. The patient was clinically diagnosed with neurofibromatosis type1.

Intracarotid propofol injection for WADA testing in a paediatric patient–A case report

Surgical management of drug-resistant epilepsy is a well-established method and the lateralization of language and/or memory is essential to avoid resection of the eloquent cortex. The Wada test was developed in the 1960s to determine the lateralization of language and memory by injecting a short-acting anaesthetic drug into the carotid artery, narcotising one single hemisphere and testing the performance of the other isolated hemisphere [1]. Originally, sodium amytal was used, but after its production was stopped in the mid-2000s, it was replaced by methohexital as an alternative drug, which also ceased to be available after 2015.

COVID-19 Catatonia—Would We Even Know?

COVID-19 Catatonia—Would We Even Know?

Narco-Analysis Test

The term narco-analysis is used to define an investigative and psychotherapeutic method that practices psychotropic medicines, mainly barbiturates, to encourage a lethargy in which psychological essentials with strong related affects come to the superficial, where they can be abused by the psychotherapist. This test includes the venous administration of a medicine (such as sodium pentothal, & sodium amytal) that reasons the issue to enter into numerous phases of anesthesia.

Utilization of MEG Among the US Epilepsy Centers: A Survey-Based Appraisal.

The purported underutilization of magnetoencephalography (MEG) among the USA epilepsy centers has never been studied, and any evidence-based understanding of its magnitude is lacking. Two hundred twenty-five National Association of Epilepsy Centers centers (2016) were invited to participate anonymously in a 13-question web-based survey of clinical practice focused on MEG use. On average, centers (N = 70; 61 of which were level 4) reported <6 epileptologists, >7 dedicated epilepsy monitoring unit beds, 206 phase 1 studies, 15 phase 2 studies, 10 direct resections, and 9 indirect resections; 27% owned MEG. On average, 11.2 MEGs per year were ordered for epilepsy localization and 7.6 for any presurgical mapping modalities. Wada test aka the intracarotid sodium amobarbital procedure (ISAP) (43%) and functional MRI (29%) were preferred over MEG (4%) for language mapping. The number of epileptologists and the number of epilepsy monitoring unit beds correlated positively with the most clinical volumes. The centers who own a MEG had surgical volumes significantly higher than those without. The number and complexity of patients as well as the proximity of a MEG were perceived as significant contributors/obstacles to increased MEG use. Only the centers with larger surgical volumes incorporate MEG regularly in presurgical evaluation of patients with drug-resistant epilepsy. A reversal of the pervasive underutilization of epilepsy surgery can benefit from MEG, but this requires a sustained concerted promotion by the epilepsy and MEG communities.

Functional neurology after the Second World War: The beginnings of neurology on screen (III).

Treatment of functional symptoms has a long history, and interventions were often used in soldiers returning from battle. On the 75th anniversary of the end of the Second World War, I review the portrayal of neurology in documentary film. Two documentaries were released in 1946 and 1948 (Let There Be Light and Shades of Gray, respectively), which showed a number of soldiers with functional neurology including paralysis, stuttering, muteness, and amnesia. The films showed successful treatments with hypnosis and sodium amytal by psychoanalytic psychiatrists. These documentaries link neurology with psychiatry and are remarkable examples of functional neurology and its treatment on screen.

Mapping language dominance through the lens of the Wada test.

The sodium amytal test, or Wada test, named after Juhn Wada, has remained a pillar of presurgical planning and is used to identify the laterality of the dominant language and memory areas in the brain. What is perhaps less well known is that the original intent of the test was to abort seizure activity from an affected hemisphere and also to protect that hemisphere from the effects of electroconvulsive treatment. Some 80 years after Paul Broca described the frontal operculum as an essential area of expressive language and well before the age of MRI, Wada used the test to determine language dominance. The test was later adopted to study hemispheric memory dominance but was met with less consistent success because of the vascular anatomy of the mesial temporal structures. With the advent of functional MRI, the use of the Wada test has narrowed to application in select patients. The concept of selectively inhibiting part of the brain to determine its function, however, remains crucial to understanding brain function. In this review, the authors discuss the rise and fall of the Wada test, an important historical example of the innovation of clinicians in neuroscience.

How amytal changed psychopharmacy: off-label uses of sodium amytal (1920-40).

In the early 1930s, American neurologist and psychiatrist William Bleckwenn used sodium amytal to render catatonic patients responsive, so that he could engage in talk therapy. Bleckwenn found a new, 'off-label' use for this anaesthetic and anxiolytic medication in psychiatry and, in doing so, allowed for important discoveries in the diagnosis and treatment of catatonia. Pharmacological textbooks reveal a 'label', while the Index-Catalogue of the Library of the Surgeon-General's Office reveals explorations 'off label' of barbiturates. The 'off-label' use of barbiturates facilitated talk therapy, heralding an important shift in psychopharmacy. Drugs previously only used as chemical restraints became a form of treatment for specific psychiatric diseases. The current strictures against off-label prescribing are overprescriptive and close off innovative new uses.