Determination of Truth from Deception Using Functional MRI and Cognitive Engrams

D Marks, M Adineh, S Gupta

The Internet Journal of Radiology. 2005 Volume 5 Number 1.

http://ispub.com/IJRA/5/1/9241

Abstract

INTRODUCTION Investigators have attempted for centuries to determine the truthfulness and accuracy of statements (Ford 2006). Methodologies include standard interrogation, with and without use of medication or coercion, polygraph, and brain fingerprinting using brain evoked response potentials (ERP). None of these technologies yields optimal results, for various reasons, and are not entirely suitable for measuring deception.

An association between the ERP and lying on a standard test such as the Guilty Knowledge Test (GKT) suggested that deception may be associated with changes in other measures of brain activity such as regional blood flow (RBF) (Langleben 2002; Mochizuki 2001). Changes in RBF, as Blood Oxygen Level Dependent (BOLD) can be monitored using functional magnetic resonance imaging (fMRI), and have been shown to be measurements of regional brain activity (Ogawa 1990). These areas of brain activation on fMRI have been correlated with active memory encoding (Wegner 1999).
A number of researchers (Slotnick et al, Langlaben et al, Lee et al, Kozel et al) have sought to apply fMRI to discern between truth and deception. In general, test subjects were presented with artificial situations during which they were given the opportunity to tell the truth or give a false response to questions, while undergoing fMRI. The design of presentation of questions were different between research groups. These separate research groups were able to detect truthful or deceptive responses, based upon analysis of activation maps showing where in the brain there was increased neural activity. The areas of activation corresponding to truth or deception differed among groups of researchers, making a universal framework for analysis of interrogation with fMRI difficult to develop.

The purpose of this study was to validate prior work of other investigators, and to develop a paradigm to address interinvestigator variability that needs to be resolved before fMRI can be applied to interrogation in practice. Our methods employ activation area analysis, both for truth and deception, and also use activation map patterns for object recognition. These combination analytical methods should yield a more robust schema for use of fMRI as an interrogation technique. One of the central means of analysis we employ is the concept of the cognitive engram, which we define as the multi-dimensional representation of activation areas in the brain, which we contend represent the actual specific thought process. We have grouped truthful and deceptive responses, and also the recognition of specific faces and objects, into cognitive Engrams. Certainly when an individual thinks of a truthful or a deceptive response, or recognizes a face or an object, that concept transforms into the more generalized concept of truthfulness or deception, or recognition of a specific person. This overall recognition is not simply fragmented into hundreds of isolated activation points, but should be treated as a whole, as a cognitive engram, consisting of a number of widely distributed activation areas representing a single concept.

METHODOLOGY We operated under an IRB-approved protocol, and all volunteers signed an informed consent form. Healthy adult volunteers without exclusions to MRI scanning were explained the study purpose and design, risks and benefits, given a chance to ask questions and then agreed to participate. Continual neuroimaging (fMRI) was performed during viewing of the test stimuli in order to capture structural and functional data. The data was analyzed for the presence of neuroimaging activation that has been shown to correspond to cognition and visual recognition.

Dangers of OTC Herbal Supplements:
Dilated Cardiomyopathy after Ingestion of TRIAC (triiodothyroacetic acid, Tiratricol)

Interferon and Risk for Drug-Seeking Behavior

Donald H. Marks M.D., Ph.D. Department of Medicine, Cooper Green Mercy Hospital
Jesse Milby Ph.D. Department of Psychology, University of Alabama at Birmingham

The Internet Journal of Pain, Symptom Control and Palliative Care ISSN: 1528-8277

Citation: D.H. Marks & J. Milby: Interferon and Risk for Drug-Seeking Behavior. The Internet Journal of Pain, Symptom Control and Palliative Care. 2009 Volume 6 Number 2 Keywords: drug craving, drug seeking behavior, interferon, medication, methadone, cocaine

Abstract
Interferon (IFN), a biological medication used to treat viral hepatitis and certain cancers, has clinically significant potential to cause a wide range of adverse neuropsychiatic effects. The spectrum ranges from agitation, aggression, insomnia and irritability, to suicidal thought and drug-seeking behavior (DSB). Out of a total population of 353 patients infected with hepatitis C virus (HCV), 132 patients at an inner city hepatitis clinic underwent treatment. Those treated were questioned at intake and on a regular basis for the initiation or increase of DSB. In addition, when warranted, patients were tested for the presence of drugs they were not prescribed. Over a four year period, ten patients (4 currently receiving treatment with IFN, 4 with prior treatment, and 2 who never received IFN) reported an increase in DSB. The danger of developing IFN-induced DSB appears to be relatively low (< 3%) in our patient population, and we also observed DSB in HCV patients who were not treated with IFN. To our knowledge, this is the first study of the incidence of DSB associated with IFN treatment for HCV that completely surveyed the HCV-treated population and used urine toxicology to verify illicit drug use.

Introduction
Patients with DSB have an inappropriate focus on obtaining a desired abused drug, i.e. cocaine, opioids, methamphetamine, etc. without concern of other more appropriate issues, such as diagnosis or treatment of their addictive behavior (Vissers, 2002). DSB includes abused drug preoccupation (talk and memories), and the craving and actual search for and use of abused drugs. It may be true that DSB as an observed action may not always be preceded by drug-related thoughts and memories as associated cognitive activity. However, it is likely that in most cases these cognitive activities precede DSB as action. Since DSB and use has the potential for dire consequences to IFN therapy in the treatment of HCV, we have questioned for the self-report of such drug abuse-related cognitive activity in regular office visits. As a general rule, it is reasonable to urge patients to avoid any stimulus to DSB while undergoing treatment for viral hepatitis, because of the potentially harmful effects of non-prescribed and addictive medication on antiviral therapy. Since the principle routes of contraction of infection for HCV include injection drug use (IDU), any increase in DSB caused by a side effect of a therapeutic (such as IFN) could become counter- therapeutic. IDU is known to suppress the immune system in some [for example, HIV] viral infections (Thompson & Salvato, 1998). Even though frequent illicit drug use during treatment of HCV may lead to decreased adherence (Sylvestre & Clements, 2007 ), several researchers (Robaeys & Buntinx, 2005); (Sylvestre, Litwin, Clements, & Gourevitch, 2005); (Sylvestre & Clements, 2007 ); (Grebely et al., 2007 ) have reported that illicit drug use itself may not counter the therapeutic response to IFN. Although the Warnings Section, Neuropsychiatric Subsection of the prescribing information (PI) for pegylated interferon alpha 2 (IFN) mentions that “relapse of drug addiction” may occur in patients, no specific information is given on the frequency of occurrence, the causal relatedness or predisposing or inciting factors. Upon query to the manufacturers, they were not able to supply specific data in these areas. A search of Medline also did not reveal specific published information in this regard. The aim of this observational study was to determine the incidence of DSB in a population being treated for HCV in a inner city community hospital, using standardized and previously validated approaches.

Accutane: Focus on Psychiatric Toxicity and Suicide
Chapter 20
Donald H. Marks, M.D., Ph.D. and Tzarina Middlekoop, Ph.D.

The Internet Journal of Gastroenterology 2007 : Volume 5 Number 2

by Donald H. Marks M.D., Ph.D.

Citation: D. H. Marks : Depression Leading to Suicide As An Adverse Effect of Metoclopramide . The Internet Journal of Gastroenterology. 2007 Volume 5 Number 2
http://ispub.com/IJGE/5/2/10427

Abstract
Metoclopramide (Reglan) is a substituted benzamide derivative with therapeutic utility as a stimulant of upper gastrointestinal motility. Metoclopramide is prescribed widely for diabetic gastric stasis and nausea. Although many of metoclopramide's adverse effects are appreciated by both prescribing physicians and patients, depression can occur, sometimes with devastating results. We describe a case of suicide which was causally related to metoclopramide.

Report of a Case
The patient was a 70 year old Caucasian man who took metoclopramide for the nine months prior to his death from suicide. He had a two year history of documented sliding hiatal hernia with moderate gastroesophageal reflux; an upper GI study showed transient hold up of the barium pill at the level of a hiatal hernia. Medical history included hypertension, hyperlipidemia, bronchiectasis, chronic dysphagia, GERD, hiatal hernia, sick sinus syndrome/atrial fibrillation, and benign prostate hypertrophy. Thyroid panel was normal. The patient's father committed suicide when the patient was 4 years old, and there is little information about this, although the patient's widow thought that there were severe financial pressures involved. The patient did not smoke or use alcohol.

Metoclopramide was prescribed for difficulty swallowing food. Concurrent medications at that point were Zocor, Prenivil, and Protonix. The patient first complained to friends of depression on the third month of treatment with metoclopramide. At the sixth month of metoclopramide treatment, an antidepressant (Zoloft) was prescribed. There was no improvement in his depression. Following the use of Zoloft, three other antidepressant drugs (Prozac, Effexor and Celexa) were tried, also without improvement in his depression. The patient's depression became severe, he lacked motivation to do any physical activity, was increasingly tired, did not desire to interact with others, and slept excessively. According to his wife, the patient had been energetic and optimistic for the 47 years of their marriage prior to the start of metoclopramide. The patient's treating physician stated that his differential diagnoses included Parkinson's vs. Parkinson's with atypical depression pattern vs. early dementia. Thyroid levels were normal. The patient did not exhibit symptoms of akathesia, agitation or flat affect. No cognitive deficits were measured or noted.

Upon referral to a neurologist, it was determined that these symptoms were most likely secondary to metoclopramide use, that the patient was significantly depressed and needed psychiatric follow-up. No mention was given of the danger of suicide or need for protection. A few days later, the patient committed suicide by gunshot to the chest.

Methods
The basis of this case report was a thorough review of the medical records, an interview with the patient's spouse, and a search of the current medical literature using Medline.

Results
Using universally accepted algorithms for the determination of causal relatedness between medication and adverse effects, 1 metoclopramide was determined to be causally related to this suicide. The key bases for this association were: Temporality: Lack of pre-metoclopramide depression or suicidal thoughts, Temporality: Depression and suicide occurred after the start of metoclopramide, Known adverse effect: depression (prescribing info), suicide ideation (peer-reviewed medical literature), Biological Plausibility: Metoclopramide has centrally nervous system actions, and is an antagonist of dopamine, Biological ispub.com/.../depression_leading_to_s... 3/9 5/26/2009 nervous system actions, ISPUB and - Depression is an antagonist Leading to of Suicide... dopamine, Biological Coherence: Does not conflict with what is known, The absence of an alternative explanation.

Discussion
The wide variety of both desired and adverse effects from metoclopramide stem from its ability to act both centrally (nausea) and peripherally (gastric motility), as an antagonist of dopamine, and sensitize gastric smooth muscle to the effects of acetylcholine stimulation. The CNS side effect profile of metoclopramide is broad, and includes drowsiness, extrapyramidal syndrome (dystonias, akathesia), depression, dizziness and insomnia. 2 , 3 , 4

Metoclopramide is similar to two other benzamides - sulpiride and amisulpiride, which are antipsychotics available in England. In fact, metoclopramide itself has clinical antipsychotic efficacy. 5 Antipsychotic treatment has been identified as one of the factors responsible for the increased rate of suicide in schizophrenics, 6 so it follows that any drug with antipsychotic efficacy, and which can cause akathesia (such as metoclopramide) may cause an increased risk of suicide. The current prescribing information for metoclopramide includes a WARNING which states, “Mental depression has occurred in patients with and without prior history of depression. Symptoms have ranged from mild to severe and have included suicidal ideation and suicide. Metoclopramide should be given to patients with a prior history of depression only if the expected benefits outweigh the potential risks.” 2

Clinicians have reported that akathesia can exacerbate psychopathology. 7 It is recognized that akathesia can be linked to both suicide and violence. 9 A link between akathesia and violence, including homicide, following antipsychotic use has also previously been reported. ispub.com/.../depression_leading_to_s... 4/9 8 , 10 , 11 , 12 5/26/2009 ISPUB - Depression Leading to Suicide...

Weddington and Banner identified a patient who developed an organic affective syndrome after administration of metoclopramide. 13 The syndrome was characterized by dysphoria, akathesia, depressed mood with suicidal ideation, insomnia, racing thoughts and labile affect. The symptoms increased within 30 minutes of each dose, and upon discontinuation of metoclopramide, the symptoms gradually resolved (challenge – dechallenge response). Although there have been perhaps eight case reports in the medical literature of depression thought to be causally related to metoclopramide use, to my knowledge this is the first published case of completed suicide caused by metoclopramide.

The DSM-IV defines a Substance-Induced Mood Disorder (SIMD) as having evidence from the history, physical examination or laboratory findings of symptoms developing during, or within a month of substance (in this case, metoclopramide) intoxication or withdrawal, or the medication use is etiologically related, does not occur exclusively during the course of a delirium, the symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning, with Depressive Features: if the predominant mood is depressed. Manic mixed features can also occur. 8

Clearly, from this definition, the patient reported here had experienced a SIMD from metoclopramide toxicity. The patient did not experience a beneficial antidepressive response after treatments with three different antidepressants of the selective serotonin reuptake inhibitor (SSRI) class. This is not completely surprising, in that clinical experience and a number of recent articles point to a disappointing overall beneficial clinical response rate to SSRIs, only slightly greater (57.5%) than for placebo. 14 Increasing the dosage of ispub.com/.../depression_leading_to_s... SSRIs as a means to increase the clinical response often only leads to 5/9 5/26/2009 ISPUB - Depression Leading to Suicide... SSRIs as a means to increase the clinical response often only leads to an increase in adverse effects, and (frequent) switching between SSRIs can lead to its own group of problems (discontinuation syndrome, toxicity).

Fisher and David reported that metoclopramide can interact with SSRI drugs to cause a Serotonin Syndrome. 15 This syndrome results from excessive stimulation of central and peripheral serotonergic receptors, and is characterized by changes in mental status, and motor and autonomic function. SSRI drugs are commonly used antidepressants, which have also been associated with agitation, aggression, and suicide. 2 The two patients reported by Fisher and David were stable on SSRIs before the addition of metoclopramide, 15 whereas in the case reported here, SSRIs were given after depression had arisen from use of metoclopramide. There is no indication that the subject of the current report had developed a Serotonin Syndrome. SSRI medication has clearly been linked with suicidal ideation and suicide. 16 , 17

During the first month of therapy, SSRI antidepressants in patients 66 years of age and older were associated with a nearly fivefold higher risk of completed suicide than other antidepressants. 18 It is possible in this reported case that the addition of SSRI medications may actually have exacerbated the metoclopramide-induced depression and precipitated the suicide. This is why prescribing physicians must be aware of the adverse effect potentials for all medications prescribed for patients, including drug-drug interactions; and must adequately warn their patients and patient families to anticipate problems and what actions to take. In this reported case, depression was caused by metoclopramide, and the appropriate treatment would have been discontinuation of .....

MR Imaging of Drug-Induced Suicidal Ideation

Abstract

Two patients with a history of suicidal ideation (SI) underwent functional MR imaging while undergoing treatment with interferon alpha 2 (IFN) for Hepatitis C virus infection (HCV). Patient #77 had a remote history of SI, but no current SI when treated with IFN. Patient #288 experienced an IFN-heightened SI, although she denied intent, a plan or a means. Visual stimuli were presented during functional MR imaging (fMRI) that were designed to invoke thoughts of suicide and violence. Patient #77 showed activation expected for visual stimulation alone, whereas patient #288 showed heightened activation for some of the visual stimuli with violent emotional content. Functional MR imaging shows promise to screen for a number of medication-induced CNS adverse effects (AE).

Documentation of Acute Neck Pain in a Patient
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