The motivation to seek out and consume rewards has evolutionarily been driven by the urge to fulfill physiological needs. However in a modern society dominated more by plenty than scarcity, we tend to think of motivation as fueled by the search for pleasure. Here, we argue that two separate but interconnected subcortical and unconscious processes direct motivation: "wanting" and "liking." These two psychological and neuronal processes and their related brain structures typically work together, but can become dissociated, particularly in cases of addiction. In drug addiction, for example, repeated consumption of addictive drugs sensitizes the mesolimbic dopamine system, the primary component of the "wanting" system, resulting in excessive "wanting" for drugs and their cues. This sensitizing process is long-lasting and occurs independently of the "liking" system, which typically remains unchanged or may develop a blunted pleasure response to the drug. The result is excessive drug-taking despite minimal pleasure and intense cue-triggered craving that may promote relapse long after detoxification. Here, we describe the roles of "liking" and "wanting" in general motivation and review recent evidence for a dissociation of "liking" and "wanting" in drug addiction, known as the incentive sensitization theory (Robinson and Berridge 1993). We also make the case that sensitization of the "wanting" system and the resulting dissociation of "liking" and "wanting" occurs in both gambling disorder and food addiction.

/pdf/roles-of-wanting-and-liking-in-motivating-behavior-gambling-3bv8swscbu.pdf

Roles of "Wanting" and "Liking" in Motivating Behavior: Gambling, Food, and Drug Addictions

Covert video recordings of life-threatening child abuse — lessons for child protection

Rickets and osteomalacia

Heavy use of drugs impacts of the daily activities of individuals in these activities. Several groups of investigators have indeed documented changes in cognitive performance by individuals who have a long history of chronic drug use. In the case of marijuana, a wealth of information suggests that heavy long-term use of the drug may have neurobehavioral consequences in some individuals. In humans, heavy cocaine use is accompanied by neuropathological changes that might serve as substrates for cognitive dysfunctions. Similarly, methamphetamine users suffer from cognitive abnormalities that may be consequent to alterations in structures and functions. Here, we detail the evidence for these neuropsychological consequences. The review suggests that improving the care of our patients will necessarily depend on the better characterization of drug-induced cognitive phenotypes because they might inform the development of better pharmacological and behavioral interventions, with the goal of improving cognitive functions in these subsets of drug users.

/pdf/neuropsychological-consequences-of-chronic-drug-use-4z437jiukx.pdf

Neuropsychological consequences of chronic drug use: Relevance to treatment approaches

Addiction to psychostimulant methamphetamine (METH) remains a major public health problem in the world. Animal models that use METH self-administration incorporate many features of human drug-taking behavior and are very helpful in elucidating mechanisms underlying METH addiction. These models are also helping to decipher the neurobiological substrates of associated neuropsychiatric complications. This review summarizes our work on the influence of METH self-administration on dopamine systems, transcription and immune responses in the brain. We used the rat model of METH self-administration with extended access (15 h/day for eight consecutive days) to investigate the effects of voluntary METH intake on the markers of dopamine system integrity and changes in gene expression observed in the brain at 2 h–1 month after cessation of drug exposure. Extended access to METH self-administration caused changes in the rat brain that are consistent with clinical findings reported in neuroimaging and postmortem studies of human METH addicts. In addition, gene expression studies using striatal tissues from METH self-administering rats revealed increased expression of genes involved in cAMP response element binding protein (CREB) signaling pathway and in the activation of neuroinflammatory response in the brain. These data show an association of METH exposure with activation of neuroplastic and neuroinflammatory cascades in the brain. The neuroplastic changes may be involved in promoting METH addiction. Neuroinflammatory processes in the striatum may underlie cognitive deficits, depression, and parkinsonism reported in METH addicts. Therapeutic approaches that include suppression of neuroinflammation may be beneficial to addicted patients.

/pdf/methamphetamine-addiction-involvement-of-creb-and-3skoxtm0nt.pdf

Methamphetamine addiction: involvement of CREB and neuroinflammatory signaling pathways.

Addictions to licit and illicit drugs are chronic relapsing brain disorders that affect circuits that regulate reward, motivation, memory, and decision-making. Drug-induced pathological changes in these brain regions are associated with characteristic enduring behaviors that continue despite adverse biopsychosocial consequences. Repeated exposure to these substances leads to egocentric behaviors that focus on obtaining the drug by any means and on taking the drug under adverse psychosocial and medical conditions. Addiction also includes craving for the substances and, in some cases, involvement in risky behaviors that can cause death. These patterns of behaviors are associated with specific cognitive disturbances and neuroimaging evidence for brain dysfunctions in a diverse population of drug addicts. Postmortem studies have also revealed significant biochemical and/or structural abnormalities in some addicted individuals. The present review provides a summary of the evidence that has accumulated over the past few years to implicate brain dysfunctions in the varied manifestations of drug addiction. We thus review data on cerebrovascular alterations, brain structural abnormalities, and postmortem studies of patients who abuse cannabis, cocaine, amphetamines, heroin, and “bath salts”. We also discuss potential molecular, biochemical, and cellular bases for the varied clinical presentations of these patients. Elucidation of the biological bases of addiction will help to develop better therapeutic approaches to these patient populations.

/pdf/neuropathology-of-substance-use-disorders-1t2bnjds2z.pdf

Neuropathology of substance use disorders

Expert witnesses are now an accepted part of criminal and civil trials. The use of expert witnesses and the admissibility of their science has developed over the last 250 years, when the concept of allowing an expert witness to give opinion evidence on the facts of other witnesses was allowed by Lord Mansfield in the case of Folkes v. Chadd in 1782. This paper briefly describes how court procedures have changed over the centuries before opinion evidence was admitted and then traces the history of the expert witness in England, USA, and Canada, examining issues of admissibility and duties of the expert from the 18th century to the 21st century. The paper further describes the change in admissibility with US decisions in Frye and Daubert and how they have affected courts in the UK and Canada. Also described are recent decisions in the UK on duties of experts and immunity from suit.

/pdf/a-brief-history-of-the-expert-witness-drsgurvvq7.pdf

A Brief History of the Expert Witness

Cocaine-mediated tissue injury is well established, particularly myocardial ischemia and infarction. Gastrointestinal complications including mesenteric ischemia, ischemic colitis and intestinal perforation occur less frequently. Cocaine-induced visceral arterial thrombosis is a rare finding. We report a case of a 49-year-old chronic cocaine user with superior mesenteric artery (SMA) thrombosis. The patient presented with a 24-h history of abdominal pain, nausea and vomiting. Physical examination documented tachycardia and a soft, non-rigid abdomen with voluntary guarding. Abdominal X-ray did not show any evidence of peritoneal free air or bowel obstruction. Laboratory investigations revealed elevated white blood cells and a high anion gap; a blood gas analysis was not done. Three hours after initial presentation, the patient had a cardiac arrest and died. At autopsy, the jejunum was ischemic, without obvious infarction. The SMA was occluded at its origin by significant atherosclerosis with superimposed thrombus. The myocardium had fibrosis, without acute infarction, and severe triple coronary artery atherosclerosis. Toxicological blood analysis confirmed cocaine use. This report emphasizes the need to consider chronic stimulant drug abuse in accelerated atheroma and thrombosis of visceral arteries.

Sudden death from superior mesenteric artery thrombosis in a cocaine user

Sudden infant death syndrome (SIDS) has been used as a cause of death for over four decades. It has allowed deaths of infants to be registered as natural. Within this group of deaths, a certain number have been recognized to be homicides from inflicted smothering rather than being natural or accidental deaths. Research has been conducted using confidential inquires to determine how frequent homicide is in cases called SIDS. This paper traces the history of quoted rates of homicide. Early work suggested the figure was between 2-10% of all SIDS cases, though other workers have suggested figures as high as 20-40%. With the fall in the rate of infant deaths following the "Back to Sleep" campaigns, these figures have been reevaluated. If the higher figures were correct that 20-40% of SIDS were homicides, the fall in infant deaths would be expected to be less than it has been. Current data suggests a much lower figure than 10% of current cases, with much lower overall rates of infant deaths. As well as 10% of SIDS cases having been stated to be homicides, a related question is whether multiple deaths classified as SIDS are really homicides. The paper discusses the maxim that one death is a tragedy, two is suspicious, and three deaths indicate homicide. The paper also looks at court cases and the approach that has been made in prosecutions of sudden unexpected death in infancy as multiple murder.

/pdf/ten-percent-of-sids-cases-are-murder-or-are-they-dwcez9mtdt.pdf

Ten Percent of SIDS Cases are Murder - or are They?

Fractures are commonly found in cases regarded as child abuse. The most commonly encountered fractures are to the ribs and the metaphyses. This paper examines the specificity of the classical metaphyseal lesion (CML) and rib fractures as hallmarks of child abuse. Recently, vitamin D deficiency (rickets) has been proposed as an alternative cause for the appearances typically described in CML. The literature in this area is examined. Rib fractures have also been highly associated with child abuse, particularly posterior rib fractures. As well as metabolic bone disease, resuscitation has been examined as a cause of rib fractures in young children. The current literature remains strongly supportive of rib fractures and metaphyseal fractures being indicators of child abuse.

/pdf/are-there-hallmarks-of-child-abuse-i-osseous-injuries-mf0i326ykb.pdf

Christopher M. Milroy

Papers

Neuropathology of substance use disorders

A Brief History of the Expert Witness

Sudden death from superior mesenteric artery thrombosis in a cocaine user

Ten Percent of SIDS Cases are Murder - or are They?

Are There Hallmarks of Child Abuse? I. Osseous Injuries: