Mahlon DeLong

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Mahlon DeLong
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Mahlon R. DeLong is an American neurologist and professor at the Medical School of Emory University. His research has advanced the understanding and treatment of Parkinson's disease, dystonia, tremor and other neurological movement disorders.

DeLong attended Stanford University (AB 1962), Harvard Medical School (MD 1966), completed his internship at Boston City Hospital and his residency training at Johns Hopkins Hospital in Baltimore, and subsequently joined the faculty of Johns Hopkins University. Since 1990, he has been a member of the faculty at Emory University, where he has been the William Patterson Timmie Professor of Neurology since 1993. He is a member of the Dana Alliance for Brain Initiative.

In 1968, DeLong began five years of research training in the laboratory of Edward Evarts at the National Institutes of Health in Bethesda, Maryland. In 1971, he and Russell T. Richardson did experiments with monkeys to find out first groups of neurons (nucleus basalis), which are involved in the pathogenesis conditioned learning and they revealed the role played by the neurotransmitter acetylcholine. [1]

At the NIH, DeLong recorded the reactions of single brain cells in a part of the brain called the basal ganglia. At that time, it was known that the basal ganglia were involved in movement, and were the part of the brain most significantly affected in Parkinson’s disease. However, little was known about how the basal ganglia affected movement, or how disease of the basal ganglia caused the movement disorders seen in Parkinson's disease. In meticulous experiments over several years, DeLong measured the firing of specific cells in the basal ganglia of awake monkeys when they performed specific trained movements.

Based on this work, and the work of others, DeLong and his colleagues identified a series of separate circuits that connect the basal ganglia with the cerebral cortex and thalamus. These circuits allow parallel processing of emotions, thoughts, and movement.

In the 1980s, DeLong and his colleagues began to study monkeys with an experimentally-induced disease much like Parkinson’s disease. He discovered that neurons in a part of the basal ganglia called the subthalamic nucleus were firing excessively, and that destroying (ablating) the subthalamic nucleus greatly improved the symptoms.

Shortly thereafter, neurosurgeon Alim-Louis Benabid discovered that the same improvement could be achieved by placing a wire into the subthalamic nucleus, connecting it to a battery and delivering an adjustable high-frequency stimulation to the tip of the wire—a technique called deep brain stimulation. Today, this technique is used to improve symptoms and the quality of life in patients with Parkinson’s disease who are not responding adequately to pharmacologic treatment. Ablation or deep brain stimulation of the subthalamic nucleus has transformed the lives of many people with Parkinson’s disease.

For his work in understanding the circuits connecting the basal ganglia to other parts of the brain, and in applying that knowledge to develop a technique that has eased the suffering of many people with Parkinson’s disease, DeLong was honored in 2014 with the Breakthrough Prize in Life Sciences. [2]

The same accomplishments were recognized by his receipt (with Benabid) of the 2014 Lasker-DeBakey Clinical Medical Research Award. [3]

Related Research Articles

<span class="mw-page-title-main">Putamen</span> Round structure at the base of the forebrain

The putamen is a round structure located at the base of the forebrain (telencephalon). The putamen and caudate nucleus together form the dorsal striatum. It is also one of the structures that compose the basal nuclei. Through various pathways, the putamen is connected to the substantia nigra, the globus pallidus, the claustrum, and the thalamus, in addition to many regions of the cerebral cortex. A primary function of the putamen is to regulate movements at various stages and influence various types of learning. It employs GABA, acetylcholine, and enkephalin to perform its functions. The putamen also plays a role in degenerative neurological disorders, such as Parkinson's disease.

<span class="mw-page-title-main">Substantia nigra</span> Structure in the basal ganglia of the brain

The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. Substantia nigra is Latin for "black substance", reflecting the fact that parts of the substantia nigra appear darker than neighboring areas due to high levels of neuromelanin in dopaminergic neurons. Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta.

<span class="mw-page-title-main">Basal ganglia</span> Group of subcortical nuclei involved in the motor and reward systems

The basal ganglia (BG), or basal nuclei, are a group of subcortical nuclei found in the brains of vertebrates. In humans and some primates, differences exist, primarily in the division of the globus pallidus into external and internal regions, and in the division of the striatum. Positioned at the base of the forebrain and the top of the midbrain, they have strong connections with the cerebral cortex, thalamus, brainstem and other brain areas. The basal ganglia are associated with a variety of functions, including regulating voluntary motor movements, procedural learning, habit formation, conditional learning, eye movements, cognition, and emotion.

<span class="mw-page-title-main">Deep brain stimulation</span> Neurosurgical treatment involving implantation of a brain pacemaker

Deep brain stimulation (DBS) is a neurosurgical procedure involving the placement of a medical device called a neurostimulator, which sends electrical impulses, through implanted electrodes, to specific targets in the brain for the treatment of movement disorders, including Parkinson's disease, essential tremor, dystonia, and other conditions such as obsessive-compulsive disorder (OCD) and epilepsy. While its underlying principles and mechanisms are not fully understood, DBS directly changes brain activity in a controlled manner.

<span class="mw-page-title-main">Subthalamic nucleus</span> Small lens-shaped nucleus in the brain

The subthalamic nucleus (STN) is a small lens-shaped nucleus in the brain where it is, from a functional point of view, part of the basal ganglia system. In terms of anatomy, it is the major part of the subthalamus. As suggested by its name, the subthalamic nucleus is located ventral to the thalamus. It is also dorsal to the substantia nigra and medial to the internal capsule. It was first described by Jules Bernard Luys in 1865, and the term corpus Luysi or Luys' body is still sometimes used.

<span class="mw-page-title-main">Hyperkinesia</span> Excessive movements due to basal ganglia dysfunction

Hyperkinesia refers to an increase in muscular activity that can result in excessive abnormal movements, excessive normal movements, or a combination of both. Hyperkinesia is a state of excessive restlessness which is featured in a large variety of disorders that affect the ability to control motor movement, such as Huntington's disease. It is the opposite of hypokinesia, which refers to decreased bodily movement, as commonly manifested in Parkinson's disease.

Hemiballismus or hemiballism is a basal ganglia syndrome resulting from damage to the subthalamic nucleus in the basal ganglia. Hemiballismus is a rare hyperkinetic movement disorder, that is characterized by violent involuntary limb movements, on one side of the body, and can cause significant disability. Ballismus affects both sides of the body and is much rarer. Symptoms can decrease during sleep.

Hypokinesia is one of the classifications of movement disorders, and refers to decreased bodily movement. Hypokinesia is characterized by a partial or complete loss of muscle movement due to a disruption in the basal ganglia. Hypokinesia is a symptom of Parkinson's disease shown as muscle rigidity and an inability to produce movement. It is also associated with mental health disorders and prolonged inactivity due to illness, amongst other diseases.

The pedunculopontine nucleus (PPN) or pedunculopontine tegmental nucleus is a collection of neurons located in the upper pons in the brainstem. It lies caudal to the substantia nigra and adjacent to the superior cerebellar peduncle. It has two divisions of subnuclei; the pars compacta containing mainly cholinergic neurons, and the pars dissipata containing mainly glutamatergic neurons and some non-cholinergic neurons. The pedunculopontine nucleus is one of the main components of the reticular activating system. It was first described in 1909 by Louis Jacobsohn-Lask, a German neuroanatomist.

<span class="mw-page-title-main">Primate basal ganglia</span>

The basal ganglia form a major brain system in all species of vertebrates, but in primates there are special features that justify a separate consideration. As in other vertebrates, the primate basal ganglia can be divided into striatal, pallidal, nigral, and subthalamic components. In primates, however, there are two pallidal subdivisions called the external globus pallidus (GPe) and internal globus pallidus (GPi). Also in primates, the dorsal striatum is divided by a large tract called the internal capsule into two masses named the caudate nucleus and the putamen—in most other species no such division exists, and only the striatum as a whole is recognized. Beyond this, there is a complex circuitry of connections between the striatum and cortex that is specific to primates. This complexity reflects the difference in functioning of different cortical areas in the primate brain.

The pars compacta (SNpc) is one of two subdivisions of the substantia nigra of the midbrain ; it is situated medial to the pars reticulata. It is formed by dopaminergic neurons. It projects to the striatum and portions of the cerebral cortex. It is functionally involved in fine motor control.

<span class="mw-page-title-main">External globus pallidus</span> Part of the globus pallidus

The external globus pallidus combines with the internal globus pallidus (GPi) to form the globus pallidus, an anatomical subset of the basal ganglia. Globus pallidus means "pale globe" in Latin, indicating its appearance. The external globus pallidus is the segment of the globus pallidus that is relatively further (lateral) from the midline of the brain.

<span class="mw-page-title-main">Internal globus pallidus</span>

The internal globus pallidus and the external globus pallidus (GPe) make up the globus pallidus. The GPi is one of the output nuclei of the basal ganglia. The GABAergic neurons of the GPi send their axons to the ventral anterior nucleus (VA) and the ventral lateral nucleus (VL) in the dorsal thalamus, to the centromedian complex, and to the pedunculopontine complex.

Ablative brain surgery is the surgical ablation by various methods of brain tissue to treat neurological or psychological disorders. The word "Ablation" stems from the Latin word Ablatus meaning "carried away". In most cases, however, ablative brain surgery does not involve removing brain tissue, but rather destroying tissue and leaving it in place. The lesions it causes are irreversible. There are some target nuclei for ablative surgery and deep brain stimulation. Those nuclei are the motor thalamus, the globus pallidus, and the subthalamic nucleus.

<span class="mw-page-title-main">Basal ganglia disease</span> Group of physical problems resulting from basal ganglia dysfunction

Basal ganglia disease is a group of physical problems that occur when the group of nuclei in the brain known as the basal ganglia fail to properly suppress unwanted movements or to properly prime upper motor neuron circuits to initiate motor function. Research indicates that increased output of the basal ganglia inhibits thalamocortical projection neurons. Proper activation or deactivation of these neurons is an integral component for proper movement. If something causes too much basal ganglia output, then the ventral anterior (VA) and ventral lateral (VL) thalamocortical projection neurons become too inhibited, and one cannot initiate voluntary movement. These disorders are known as hypokinetic disorders. However, a disorder leading to abnormally low output of the basal ganglia leads to reduced inhibition, and thus excitation, of the thalamocortical projection neurons which synapse onto the cortex. This situation leads to an inability to suppress unwanted movements. These disorders are known as hyperkinetic disorders.

<span class="mw-page-title-main">Blocq's disease</span> Loss of memory of specialized movements causing the inability to maintain an upright posture

Blocq's disease was first considered by Paul Blocq (1860–1896), who described this phenomenon as the loss of memory of specialized movements causing the inability to maintain an upright posture, despite normal function of the legs in the bed. The patient is able to stand up, but as soon as the feet are on the ground, the patient cannot hold himself upright nor walk; however when lying down, the subject conserved the integrity of muscular force and the precision of movements of the lower limbs. The motivation of this study came when a fellow student Georges Marinesco (1864) and Paul published a case of parkinsonian tremor (1893) due to a tumor located in the substantia nigra.

<span class="mw-page-title-main">Alim Louis Benabid</span>

Alim Louis Benabid is a French-Algerian emeritus professor, neurosurgeon and member of the French Academy of Sciences, who has had a global impact in the development of deep brain stimulation (DBS) for Parkinson's disease and other movement disorders. He became emeritus professor of biophysics at the Joseph Fourier University in Grenoble in September 2007, and chairman of the board of the Edmond J. Safra Biomedical Research Center in 2009 at Clinatec, a multidisciplinary institute he co-founded in Grenoble that applies nanotechnologies to neurosciences.

Clinatec is a biomedical research center based at the Polygone Scientifique in Grenoble. Doctors, biologists and micro- and nanotechnology experts work side by side at the 6,000 m2 facility. Around a hundred researchers and employees work at the center. When it opened at the end of 2011, it was hailed as the first center of its kind in the world. With six hospital rooms, cutting-edge medical imaging equipment and an operating suite, Clinatec was developed by the Research Division of the CEA, Grenoble-Alpes University Hospital (CHU), Inserm and the Université Grenoble Alpes. The primary focus is on cancer, neurodegenerative diseases and disability.

<span class="mw-page-title-main">Mesencephalic locomotor region</span>

The mesencephalic locomotor region (MLR) is a functionally defined area of the midbrain that is associated with the initiation and control of locomotor movements in vertebrate species.

Jerrold Lee Vitek is an American neurologist. He is the Head of the Neurology Department, Director of the Neuromodulation Research Program, and Center Director of the University of Minnesota Udall Center of Excellence for Parkinson's Research. Vitek's clinical interests include movement disorders and evaluation for deep brain stimulation (DBS) and his current research activities focus on Parkinson's disease, dystonia, tremor and deep brain stimulation.

References

  1. z.B. Timeline Behaviourist Approach, Matt Jarvis, Psychology Review, pdf.
  2. Laureates
  3. "The Lasker Foundation - 2014 Awards". www.laskerfoundation.org. Archived from the original on 2014-09-11.