Deep Brain Stimulation

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Deep Brain Stimulation

Nonablative surgical procedures for treatment of PD involve either unilateral or bilateral implantation of high-frequency stimulation electrodes into deep brain nuclei. Studies detailing neuropsychological outcomes after unilateral globus pallidus (GPi) deep brain stimulation (DBS) have supported the neurobehavioral safety of this technique (113,157), although a few studies have demonstrated minor postoperative declines in verbal fluency (158-160). The majority of studies indicate that even bilateral GPi stimulation is cognitively well tolerated (161-163), although in isolated cases, cognitive declines can occur (152,164).

Neuronal Mechanisms Of Subthalamic Nucleus Deep Brain Stimulation

FIGURE 4 Microelectrode recording of the extracellular action potentials of a globus pallidus internal segment neuron in response to deep brain stimulation in the vicinity of the subthalamic nucleus. This is a 30-second baseline recording followed by 30 seconds of stimulation and then recording for an additional 30 seconds.

Deep Brain Stimulation Of The Globus Pallidus Interna

Kumar et al. (19) reported 22 PD patients who were treated with either unilateral (n 5) or bilateral (n 17) GPi stimulation. Evaluations performed in the medication off stimulation on state at six months reported a 32 improvement in UPDRS motor scores and a 40 improvement in UPDRS activities of daily living (ADL) scores compared to baseline medication off scores. There was also a 68 reduction in dyskinesia. The Deep Brain Stimulation for Parkinson's Disease Study Group (16) reported a multinational, prospective study of bilateral GPi stimulation in PD. Forty-one patients were enrolled and electrodes were implanted in 38 patients. Two patients had cerebral hemorrhages and one patient had intraoperative confusion. In comparison to baseline, there was a significant improvement of 33 in UPDRS motor scores in the medication off stimulation on state. More specifically, tremor was reduced by 59 , rigidity was reduced 31 , bradykinesia was reduced 26 , gait improved by 35 , and postural...

Deep Brain Stimulation Of The Subthalamic Nucleus

Multiple reports have demonstrated the short-term benefits of STN DBS in controlling the cardinal features of PD and reducing dyskinesia and antiparkinsonian medications (16,24-31). One of the largest studies was conducted by the Deep Brain Stimulation for Parkinson's Disease Study Group (16). This was a multicenter study in which 96 PD patients received bilateral STN DBS and 91 completed the Several studies have demonstrated the long-term benefits of STN DBS (23,32-37) (Table 2). Rodriguez-Oroz et al. (23) examined 49 PD patients who received bilateral STN DBS as part of the original Deep Brain Stimulation for Parkinson's Disease Study Group trial (16), three to four years after initial implant. They demonstrated a 43 improvement in UPDRS ADL scores and a 50 improvement in UPDRS motor scores in the medication off stimulation on condition compared to the baseline medication off state. More specifically, there was an 87 improvement in tremor, a 59 improvement in rigidity, a 42...

Effect Of Surgical Treatments For Parkinsons Disease On Speech And Swallowing Deep Brain Stimulation

Many studies of deep brain stimulation (DBS) of the subthalamic nucleus (STN), globus pallidus internus (GPi), and ventral intermediate (Vim) nucleus of the thalamus have reported dysarthria and dysphagia as side effects (88-90). Several studies examined specific aspects of voice, speech, swallowing and related orofacial, and respira-tory-laryngeal functions associated with DBS treatment of PD. Santens et al. (91) found that left-brain stimulation had a profound negative effect on prosody, articulation, and intelligibility not seen with right-brain stimulation. With bilateral stimulation, no differences in speech characteristics were observed on- and off-stimulation. Wang et al. (92) also studied the effects of unilateral STN DBS on respiratory phonatory subsystems of speech production in PD. Speech recordings were made in the medication-off state at baseline and three months post-DBS with stimulation-on and -off, in six right-handed patients. Three patients who received left-brain...

Rapid Eye Movement Behavior Disorder and Restless Legs Syndrome

The treatment of choice for RBD is clonazepam, a benzodiazepine, although the mechanism is unknown and there are no controlled trials (13). Other drugs thought to be helpful for RBD include pramipexole, levodopa, carbamazepine, donepezil, and melatonin (64,89-91). Caution needs to be exercised with the use of clonazepam, as in some cases, RBD may be confused with sleep apnea, which can be worsened by clonazepam. Nighttime dosing with drugs such as selegiline may aggravate RBD. Others have reported a paradoxical worsening of RBD with deep brain stimulation (DBS) of the subthalamic nucleus (STN) (92).

Inferential Context

These kinds of inferential difficulties are not unique to the brain imaging community. Current issues raised in interpreting brain imaging studies seem eerily similar to the debates over electrical brain stimulation in the 1950s. In a famous case, Jose Delgado claimed that he had identified the aggression centers of the brain (also, incidentally, in the caudate nucleus), and by remote-control stimulation of an implanted electrode could make a raging bull as passive as a gentle lamb. Delgado demonstrated his findings by placing himself in a ring with a Spanish bull and using his device to pacify the animal in mid-charge (Valenstein, 1973). The experiment worked the bull stopped - but not likely because he was truly pacified. Valenstein (1973) recounts that the electrodes were placed in motor-control regions of the caudate that forced the bull to turn in one direction (and probably confused the animal as well ).

The Search For A Unified Or Holistic Model Of Human Functioning

Cognitive-affective, attachment patterns, interpersonal configurations, and family structures, have been identified, but their subcomponents or subsystems require further elaboration. Neuroscientists, psychologists, and others are actively pursuing one relevant aspect of unification under the guise of attempting to crack the conundrum of consciousness. The number of volumes devoted to modeling the mind-brain using knowledge gleaned from brain research is staggering. Scientists and theorists are combining this knowledge gleaned from the new tools of neuroscience such as PET scans and combining these findings with insights from developmental psychology, interpersonal theory, and other bodies of knowledge in a creative interdisciplinary and remarkable way. Each author believes that he or she has derived a model that will explain how our brain can give rise to consciousness and the self. These are crucial exercises and useful models, but they don't necessarily carry over directly to the...

Methyl4Phenyl1236Tetrahydropyridine

The administration of MPTP through a number of different dosing regimens has led to the development of several distinct models of parkinsonism in the nonhuman primate. Each model is characterized by unique behavioral and neurochem-ical parameters. As a result, numerous studies addressing a variety of hypotheses have been conducted. These studies consist of new pharmacological treatments, transplantation, mechanisms of motor complications, deep brain stimulation, behavioral recovery, cognitive impairment, and the development of novel neuro-protective and restorative therapies. For example, in some models, there is profound striatal dopamine depletion and denervation with little or no dopaminergic axons or terminals remaining. This model provides an optimal setting to test fetal tissue grafting since the presence of any tyrosine hydroxylase positive axons or sprouting cells would be due to transplanted tissue survival. Other models have less extensive dopamine depletion and only partial...

Electrical Stimulation Of The Spinal Cord And Peripheral Nerves

In additional studies involving neuropathic pain, Harke et al. found that SCS relieved pain in 23 of 28 patients with postherpetic neuralgia and 4 of 4 with acute herpes zoster (24). Katayama et al. found that deep brain stimulation led to pain control in 6 of 10 patients with phantom limb pain, whereas SCS was only efficacious in 6 of 19 patients (25).

Dopamine Agonists And Dopamine Receptors

The dopamine agonists used in the treatment of PD include apomorphine, bromocrip-tine, cabergoline, lisuride, pergolide, pramipexole, ropinirole, and rotigotine. All of these agents activate D2 receptors, whereas pergolide has been shown to be a mild D1 agonist, and pramipexole may have higher affinity for D3 receptors (Table 1). Five subtypes of dopamine agonist receptors have been identified and may be classified into striatal (D1 and D2) receptors or cortical (D3, D4, and D5) receptors. The D3-5 receptors are present in the mesolimbic and mesocortical dopaminergic pathways. The D1-receptor (D1,5) family is associated with activation of adenylate cyclase and dopamine, and dopamine agonists activate the D2-receptor family (D2-4) (6). Postmortem examination of brains of patients with PD revealed upregulation of stri-atal D2 and downregulation of the D1 receptors. It is postulated that these changes lead to alteration of the indirect D2-mediated pathway and disinhibition of the...

Functional Brain Changes in MDD

The subgenual ACC (Brodmann's area 25) is another critical node of the cortico-limbic network that is involved in mood regulation and emotion processing. On the basis of functional imaging results and its pattern of connectivity, this structure was selected as the site for deep brain stimulation of treatment refractory depression (Mayberg et al, 2005 see below). The subgenual ACC is part of the default mode network, i.e., the neural circuit that is engaged during non-task related behavior and is centrally involved in self-awareness, emotion processing, and conscious experience (Mazoyer et al, 2001 Raichle et al, 2001). Accumulating evidence suggests that the subgenual ACC is deactivated during performance of demanding cognitive tasks that require an external focus of attention (Kennedy et al, 2006 Marsh et al, 2006). Such deactivation may be an indicator of the degree to which affective processing is inhibited (Gusnard et al, 2001). Given this evidence, it is not surprising that...

Brain Based Treatments of Depression

Despite the growing knowledge about its biological basis, it is estimated that 10-20 of individuals who suffer from MDD continue to be severely disabled despite adequate trials of psychopharmacologic or psychotherapeutic treatments and or electroconvulsive therapy (Judd et al, 2008). Improved antidepressant treatments are needed. An exciting development is the emerging evidence of the relatively safe and effective methods of brain stimulation in the treatment of depression. A landmark advance in psychiatry occurred in 2005 when it was demonstrated that deep brain stimulation of subgenual ACC was an effective treatment for depression (Mayberg et al, 2005). The decision to stimulate this brain structure was based on a network analysis of functional changes in the brain in depression and a determination of which loci were most important. In the largest study to date, 20 patients with treatment-resistant depression received sub-genual ACC deep brain stimulation and were assessed at...

DBS in the STn of DADepleted PD Patients Corrects Migration

The finding of separable storage and retrieval mnemonic deficits restricted in the temporal domain in PD was followed up by a new set of experiments asking whether distinct neural pathways underlie those deficits. To this end, we applied the same encode-decode design in a series of studies testing PD patients OFF levodopa undergoing deep brain stimulation (DBS) either in the subthalamic nucleus (STn) or the pallidum. The effect of DBS is reversible, and the stimulation parameters (principally site and voltage) can be varied to achieve the optimal therapeutic result (Benabid et al., 1991, 1998). Moreover, the reversibility of DBS means that patients' cognitive performance can be assessed both with (ON) and without (OFF) DBS. This in turn presents the possibility of identifying specific patterns of impairment, including cognitive ones, associated with the stimulated basal ganglia substructures.

Kelly E Lyons and Rajesh Pahwa

Stereotactic surgeries for movement disorders were introduced in the late 1940s (1-3) but were not widely accepted due to significant morbidity, mortality, and limited knowledge of the appropriate target for symptomatic benefit. With advances in pharmacological therapy, particularly the availability of levodopa, these surgeries were rarely performed for Parkinson's disease (PD) until the late 1980s (4). Based on the limitations of drug treatments for PD, and a better understanding of the physiology and circuitry of the basal ganglia there has been a marked increase in the use of surgical treatments for PD. In addition, advances in surgical techniques, neu-roimaging, and improved electrophysiological recordings allow stereotactic procedures to be done more accurately leading to reduced morbidity. Deep brain stimulation (DBS) has largely replaced lesion surgery as the preferred procedure for PD. There are currently three targets for DBS in PD the ventral intermediate (VIM) nucleus of...

Unilateral Subthalamic Nucleotomy

The target lesion in one series included the dorsolateral STN and pallidufugal fibers (Forel's field H2). Postoperative chorea was mild and transient, except in one patient in whom the lesion was confined to the STN only. The chorea in this instance was controlled by the subsequent insertion of a deep brain stimulator in the field H2 fibers and zona incerta. A similar phenomenon was described by comparison of two cases by Chen et al. (108) that is, a subthalamotomy that included the dorsal extranuclear fibers of the zona incerta led to less dyskinesia than a lesion confined to the STN only. Tseng et al. (109) described another patient with a lesion large

Pathophysiology of Psychosis and Risk Factors

Nucleus (STN) deep brain stimulation (DBS) surgery only when the stimulators were turned on (43), leading the authors to hypothesize that this resulted from stimulation of limbic fibers near the STN. Finally, a functional MRI study demonstrated greater activation in the frontal lobe in PD patients with chronic visual hallucinations compared to nonhallucinators (44). The exact contribution of these neurotransmitters and structures to the genesis of psychosis is unclear.

Rc382h36 2007

Parkinson's disease is one of the most common neurodegenerative diseases with a higher prevalence in older adults. It is a slowly progressive condition and has set the standard for research in neurodegeneration throughout the history of medicine. It was the first neurodegenerative disease for which the pathology was discovered, when I. Tretjakov first described the degenerated substantia nigra in 1919. The biochemistry was first described by A. Carlsson, and the transmitter deficit by O. Hornykiewicz. The accidental discovery of the selective neurotoxin (MPTP) for neurones of the substantia nigra in the 1980s has been of a similar importance, as it subsequently became possible to study Parkinson's disease in animal models. All these basic research achievements were the basis for groundbreaking progress in the field of therapy. Parkinson's disease was the first neurodegenerative disease for which transmitter replacement therapy was developed it was the first condition in medical...

Mechanisms

Affective and behavioral changes (e.g., aggression, depression, mania) have also been reported as complications of deep brain stimulation (DBS), especially subthalamic nucleus (STN) DBS (81). Interestingly, depression has been infrequently reported to develop, as a result of thalamic and pallidal DBS (82). In a review of 23 articles reporting on the effect of STN DBS on mood state in PD, nine studies reported a mood elevating or antidepressant effect in 16.7 to 76 of patients, 13 studies reported a depressant effect in 2 to 33.3 of patients, and eight studies reported a mania-inducing effect in 4.2 to 8.1 of patients (83). In one series of 24 consecutive patients undergoing STN DBS, six patients (25 ) experienced significant worsening of mood and three were transiently suicidal despite motor improvement (84). In a series of 137 patients who underwent STN DBS, 16 (12 ) developed depression (85). Mood disturbances induced by STN DBS could be the result of stimulation spreading to...

Brain Blaster

Brain Blaster

Have you ever been envious of people who seem to have no end of clever ideas, who are able to think quickly in any situation, or who seem to have flawless memories? Could it be that they're just born smarter or quicker than the rest of us? Or are there some secrets that they might know that we don't?

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