Imke Galazky

Successful treatment of chronic resistant alcoholism by deep brain stimulation of nucleus accumbens: first experience with three cases.

1 Depar tment of Psychiatry, Otto-von-Guericke-University of Magdeburg, Magdeburg, Germany 2 Depar tment of Stereotaxy and Functional Neurosurgery, Univ ersity of Cologne, Cologne, Germany 3 Depar tment of Stereotactic Neurosurgery, Otto-von-Guericke-University of Magdeburg, Magdeburg, Germany 4 Depar tment of Neurology, Otto-von-Guericke-University of Magdeburg, Magdeburg, Germany 5 eibni L z Institutor ef NeurobiologyMagde , burGerman g, y Treatment of alcohol dependence remains one of the biggest challenges in psychiatry, since only about half of all patients achieve long-term abstinence by the currently available thera-pies. Dysfunction of the nucleus accumbens, one of the main areas of the brain ’ s reward system, seems to play a central role in addiction and treatment resistance. Following the recent ad-vances of neuromodulation therapy by deep brain stimulation, we designed an o

Counteracting incentive sensitization in severe alcohol dependence using deep brain stimulation of the nucleus accumbens: clinical and basic science aspects.

The ventral striatum/nucleus accumbens (NAcc) has been implicated in the craving for drugs and alcohol which is a major reason for relapse of addicted people. Craving might be induced by drug-related cues. This suggests that disruption of craving-related neural activity in the NAcc may significantly reduce craving in alcohol-dependent patients. Here we report on preliminary clinical and neurophysiological evidence in three male patients who were treated with high frequency deep brain stimulation of the NAcc bilaterally. All three had been alcohol-dependent for many years, unable to abstain from drinking, and had experienced repeated relapses prior to the stimulation. After the operation, craving was greatly reduced and all three patients were able to abstain from drinking for extended periods of time. Immediately after the operation but prior to connection of the stimulation electrodes to the stimulator, local field potentials were obtained from the externalized cables in two patients while they performed cognitive tasks addressing action monitoring and incentive salience of drug-related cues. LFPs in the action monitoring task provided further evidence for a role of the NAcc in goal-directed behaviors. Importantly, alcohol-related cue stimuli in the incentive salience task modulated LFPs even though these cues were presented outside of the attentional focus. This implies that cue-related craving involves the NAcc and is highly automatic.

Deep brain stimulation of the nucleus accumbens for the treatment of addiction

Despite novel medications and other therapeutic strategies, addiction to psychotropic substances remains one of the most serious public health problems worldwide. In this review, beginning with an introduction of deep brain stimulation (DBS), we highlight the importance of the nucleus accumbens (NAc) in the context of the reward circuitry and addictive behavior. We will provide a short historic overview of other neurosurgical approaches to treat addiction and describe the experimental and preclinical data on DBS in addiction. Finally, we call attention to key ethical issues related to using DBS to treat addiction that are important for future research and the design of clinical trials.

Deep brain stimulation of nucleus accumbens region in alcoholism affects reward processing.

The influence of bilateral deep brain stimulation (DBS) of the nucleus nucleus (NAcc) on the processing of reward in a gambling paradigm was investigated using H2[15O]-PET (positron emission tomography) in a 38-year-old man treated for severe alcohol addiction. Behavioral data analysis revealed a less risky, more careful choice behavior under active DBS compared to DBS switched off. PET showed win- and loss-related activations in the paracingulate cortex, temporal poles, precuneus and hippocampus under active DBS, brain areas that have been implicated in action monitoring and behavioral control. Except for the temporal pole these activations were not seen when DBS was deactivated. These findings suggest that DBS of the NAcc may act partially by improving behavioral control.

The whole-brain pattern of magnetic susceptibility perturbations in Parkinson's disease.

Although iron-mediated oxidative stress has been proposed as a potential pathomechanism in Parkinson’s disease, the global distribution of iron accumulation in Parkinson’s disease has not yet been elucidated. This study used a new magnetic resonance imaging contrast, quantitative susceptibility mapping, and state-of-the-art methods to map for the first time the whole-brain landscape of magnetostatic alterations as a surrogate for iron level changes in n = 25 patients with idiopathic Parkinson’s disease versus n = 50 matched controls. In addition to whole-brain analysis, a regional study including sub-segmentation of the substantia nigra into dorsal and ventral regions and qualitative assessment of susceptibility maps in single subjects were also performed. The most remarkable basal ganglia effect was an apparent magnetic susceptibility increase—consistent with iron deposition—in the dorsal substantia nigra, though an effect was also observed in ventral regions. Increased bulk susceptibility, additionally, was detected in rostral pontine areas and in a cortical pattern tightly concordant with known Parkinson’s disease distributions of &agr;-synuclein pathology. In contrast, the normally iron-rich cerebellar dentate nucleus returned a susceptibility reduction suggesting decreased iron content. These results are in agreement with previous post-mortem studies in which iron content was evaluated in specific regions of interest; however, extensive neocortical and cerebellar changes constitute a far more complex pattern of iron dysregulation than was anticipated. Such findings also stand in stark contrast to the lack of statistically significant group change using conventional magnetic resonance imaging methods namely voxel-based morphometry, cortical thickness analysis, subcortical volumetry and tract-based diffusion tensor analysis; confirming the potential of whole-brain quantitative susceptibility mapping as an in vivo biomarker in Parkinson’s disease.

Alien Hand Syndrome: Neural Correlates of Movements without Conscious Will

Background The alien hand syndrome is a striking phenomenon characterized by purposeful and autonomous movements that are not voluntarily initiated. This study aimed to examine neural correlates of this rare neurological disorder in a patient with corticobasal degeneration and alien hand syndrome of the left hand. Methodology/Principal Findings We employed functional magnetic resonance imaging to investigate brain responses associated with unwanted movements in a case study. Results revealed that alien hand movements involved a network of brain activations including the primary motor cortex, premotor cortex, precuneus, and right inferior frontal gyrus. Conscious and voluntary movements of the alien hand elicited a similar network of brain responses but lacked an activation of the inferior frontal gyrus. The results demonstrate that alien and unwanted movements may engage similar brain networks than voluntary movements, but also imply different functional contributions of prefrontal areas. Since the inferior frontal gyrus was uniquely activated during alien movements, the results provide further support for a specific role of this brain region in inhibitory control over involuntary motor responses. Conclusions/Significance We discuss the outcome of this study as providing evidence for a distributed neural network associated with unwanted movements in alien hand syndrome, including brain regions known to be related to movement execution and planning as well as areas that have been linked to inhibition control (inferior frontal gyrus) and experience of agency (precuneus).

Nucleus Accumbens Deep Brain Stimulation for Alcohol Addiction – Safety and Clinical Long-term Results of a Pilot Trial

We report on the long-term clinical outcome (up to 8 years) of 5 patients who received deep brain stimulation (DBS) of the nucleus accumbens to treat their long-lasting and treatment-resistant alcohol addiction. All patients reported a complete absence of craving for alcohol; 2 patients remained abstinent for many years and 3 patients showed a marked reduction of alcohol consumption. No severe or long-standing side effects occurred. Therefore, DBS could be a promising, novel treatment option for severe alcohol addiction, but larger clinical trials are needed to further investigate the efficacy of DBS in addiction.

Attention to somatosensory events is directly linked to the preparation for action.

The present study investigated the neural basis of attention in the somato-sensory system. Subjects directed their attention towards their left or right hand while functional MRI data was collected during tactile stimulation of the fingers. Activations evoked by tactile stimuli when a stimulated hand was attended vs. unattended were contrasted. The tactile stimuli elicited hemodynamic responses in the contralateral primary and secondary somatosensory cortex. No attentional modulations of the BOLD-response could be observed in these regions. However, attention-related modulations were observed at more anterior locations in the ipsi- and contralateral primary motor cortex and in the supplementary motor area. This pattern of results suggests, that attention to somato-sensory events is directly linked to the motor system and the preparation for action. This mechanism appears to be in stark contrast to visual or auditory attention, which primarily serve to separate relevant from irrelevant information.

Waking up the alien hand: rubber hand illusion interacts with alien hand syndrome

It has been shown that combinations of visual, tactile, and proprioceptive manipulations in healthy subjects may elicit illusory feelings of embodiment (the rubber hand illusion and the somatic rubber hand illusion). We report a case of alien hand syndrome in which the alien hand interacted with the somatic rubber hand illusion to provoke a very strong movement of the alien hand. This effect could be reliably replicated at every application of the experimental procedure. Thus, the illusion seemed to wake up the alien hand. The results demonstrate that the alien hand syndrome can be affected by experimentally induced bodily illusions, which are based on the manipulation of touch and proprioceptive information.

Bilateral posterior RION after concomitant radiochemotherapy with temozolomide in a patient with glioblastoma multiforme: a case report

BackgroundRadiation induced optic neuropathy (RION) is a rare but severe consequence of radiation therapy that is associated with adjuvant chemotherapy, specifically therapy with vincristine or nitrosoureas. However, there is very little evidence regarding the occurrence of RION after concomitant radiochemotherapy with temozolomide.Case PresentationThe case of a 63 year old woman with glioblastoma multiforme and concomitant radiochemotherapy with temozolomide is described. Due to a slight depressive episode the patient also took hypericum perforatum. Five months after cessation of fractionated radiation and adjuvant chemotherapy with temozolomide (cumulative dose of 11040 mg) the patient developed bilateral amaurosis due to RION. Tumor regrowth was excluded by magnetic resonance imaging. After the application of gadolinium a pathognomonic contrast enhancement of both prechiasmatic optic nerves could be observed.ConclusionsIn this patient, the occurrence of RION may have been the result of radiosensitization by temozolomide, which could have been strengthened by hypericin. Consequently, physicians should avoid a concomitant application of hypericum perforatum and radiochemotherapy.