Götz Lütjens

Deep brain stimulation of the entopeduncular nucleus in rats prevents apomorphine-induced deficient sensorimotor gating.

Pharmacologically induced stereotypies and deficient sensorimotor gating, measured as prepulse inhibition (PPI) of the acoustic startle response (ASR), are used as endophenotypes for certain symptoms common to neuropsychiatric disorders, such as schizophrenia and Tourettes syndrome (TS) among others. We here investigated whether high frequency deep brain stimulation (DBS) of the rats entopeduncular nucleus (EPN), the equivalent to the human globus pallidus internus (GPi), would improve PPI-deficits and stereotypies induced by the dopamine receptor agonist apomorphine. Electrodes were stereotactically implanted bilaterally in the EPN of 13 Sprague-Dawley rats. After one week of recovery the rats were stimulated with an amplitude 20% below their individual threshold for side effects (130 Hz, 80 μs pulse width) or sham-stimulated for epochs of five days. At the end of each epoch the effect of ongoing stimulation or sham-stimulation on apomorphine-induced stereotypies (vehicle and 0.5 mg/kg) and deficient PPI (vehicle and 1.0 mg/kg) were tested. In nine rats, in which the full protocol could be applied and in which the electrode position was histologically confirmed in the target, EPN DBS did not affect baseline PPI but counteracted the apomorphine-induced PPI-deficit, while apomorphine-induced stereotypies were not affected by DBS. This work indicates an important role of the EPN in the modulation of apomorphine-induced deficient prepulse inhibition. This model may be useful to further investigate the pathophysiological of deficient sensorimotor gating and mechanisms of action of DBS in certain neuropsychiatric disorders.

Lesions of the entopeduncular nucleus in rats prevent apomorphine-induced deficient sensorimotor gating

Dopamine-induced hyperactivity and deficient sensorimotor gating, measured as prepulse inhibition (PPI) of the acoustic startle response (ASR), are used as animal models for neuropsychiatric disorders such as schizophrenia and Tourettes syndrome. We here investigated whether excitotoxic lesions of the rat entopeduncular nucleus (EPN), the equivalent to the human globus pallidus internus (GPi), would improve apomorphine-induced PPI-deficits and hyperactivity. Additionally, we investigated the effect of EPN lesions on cognition, motivation and motor skills. In male Sprague Dawley rats bilateral EPN lesions were induced by stereotactic injection of ibotenate (4 μg in 0.4 μl phosphate buffered saline, PBS) or sham-lesions by injection of vehicle PBS. After one week, rats were tested for learning and memory (continuous and delayed alternation, T-maze), for motivation (progressive ratio test with breakpoint of 3 min inactivity, Skinner box), and for motor skills (rotating rod). Thereafter, rats were tested for PPI of ASR (startle response system) after subcutaneous injection of apomorphine (1.0mg/kg and vehicle) and for locomotor activity (0.5mg/kg and vehicle). Ibotenate-induced EPN lesions did not affect learning and memory, motivation or motor skills. Basal locomotor activity and PPI was also not affected, but EPN lesions ameliorated apomorphine-induced hyperlocomotion and deficient PPI. This work indicates an important role of the EPN for the modulation of dopamine agonist-induced deficient sensorimotor gating and hyperlocomotion, without affecting normal behavioral function.

The human globus pallidus internus is sensitive to rewards – Evidence from intracerebral recordings

BACKGROUND The globus pallidus internus (GPi) is the final output relay of the basal ganglia for the control of movements but has also been shown to belong to a second pathway projecting to the lateral habenula. This latter pathway is related to reward processing. METHOD This prompted us to record, in eight patients receiving deep brain stimulation of the GPi for the alleviation of various movement disorders, local field potentials (LFP) while these patients performed a lottery task. The task entailed choosing between a higher and a lower number, which changed their color after the patients choice with red (green) signaling a loss (win, in Euro cents) corresponding to the chosen number. RESULTS Surface recordings showed a feedback related negativity from a frontal midline site, while time domain averages in the GPi showed differential modulation depending on the valence of the stimulus with polarity inversion indicating that this reward-modulated activity was indeed generated locally. Furthermore, wavelet decomposition of the LFP showed a reward-related response in the high beta/low gamma range. CONCLUSION We conclude that human GPi is involved in reward processing, possibly in relation to the lateral habenula.

Microvascular decompression of the eighth cranial nerve for unilateral pulsatile tinnitus.

Tinnitus is a common symptom of various underlying diseases. he severity of tinnitus varies from an occasional awareness of oise in one or both ears, to an unbearable sound that markedly nterferes with the patient’s daily activities and sleep, causing onsiderable psychological distress. It may be classified as pulatile (PT) or continuous. PT is puls-synchronous (coinciding with he patient’s heartbeat) and usually suggests a vascular etiolgy ranging from dural arteriovenous fistulae (DAVF), intracranial neurysms, atherosclerotic disease of the craniocervical arteries, ascular tumors of the temporal bone, and cerebello-pontine angle CPA), to conditions associated with high cardiac output (e.g., ypertension, anaemia, and thyrotoxicosis) [1–9]. Based on few reports, vascular compression of the eighth ranial nerve (CN VIII) has been recognised as an additional ause of incapacitating tinnitus [10–25]. However, microvascular ecompression (MVD) of CN VIII solely for relieving tinnitus ielded poor results compared to those achieved for trigeminal euralgia, hemifacial spasm, and glossopharyngeal neuralgia by ecompression of the corresponding cranial nerves. This discrepncy is mainly attributable to the lack of sufficient diagnostic

Transient Global Amnesia Associated with Accidental High-Frequency Stimulation of the Right Hippocampus in Deep Brain Stimulation for Segmental Dystonia

We report on a 66-year-old woman with segmental dystonia treated with chronic bilateral deep brain stimulation of the globus pallidus internus, in whom accidental high-voltage, high-frequency stimulation induced an episode of transient global amnesia (TGA) via an electrode contact which was misplaced in the right hippocampus. A possible mechanism underlying this TGA episode may have been the inhibition of local neuronal activity or fiber activation by high current density via direct electrical stimulation of hippocampal structures. While a unifying etiology of TGA has not been proven so far, our case demonstrates a possible link between focal electrical stimulation of hippocampal structures and the full clinical picture of the syndrome.

Thalamic and basal ganglia regions are involved in attentional processing of behaviorally significant events: evidence from simultaneous depth and scalp EEG

Extensive descriptions exist on cortical responses to change in the acoustic environment. However, the involvement of subcortical regions is not well understood. Here we present simultaneous recordings of cortical and subcortical event-related potentials (ERPs) to different pure tones in patients undergoing surgery for deep brain stimulation (DBS). These patients had externalized electrodes in the subthalamic nucleus (STN), the ventrolateral posterior thalamus (VLp) or the globus pallidus internus (GPi). Subcortical and cortical ERPs were analyzed upon presentation of one frequent non-target stimulus and two infrequent stimuli, either being a target or a distractor stimulus. The results revealed that amplitudes of scalp-recorded P3 and subcortical late attention-modulated responses (AMR) were largest upon presentation of target stimuli compared with distractor stimuli. This suggests that thalamic and basal ganglia regions are sensitive to behaviorally relevant auditory events. Comparison of the subcortical structures showed that responses in VLp have shorter latency than in GPi and STN. Further, the subcortical responses in VLp and STN emerged significantly prior to the cortical P3 response. Our findings point to higher-order cognitive functions already at a subcortical level. Auditory events are categorized as behaviorally relevant in subcortical loops involving basal ganglia and thalamic regions. This label is then distributed to cortical regions by ascending projections.

Akinetic mutism and parkinsonism due to subdural and intraventricular tension pneumocephalus.

Pneumocephalus may occur after intracranial surgery and is most often asymptomatic. It is usually associated with posterior fossa surgery. Here, we present a 56-year-old man who developed akinetic mutism and parkinsonism caused by subdural and intraventricular tension pneumocephalus associated with decompression of a chronic subdural hygroma. As an emergency treatment, air was exchanged with saline via the drainage, which then was removed and a subduro-peritoneal shunt was implanted. The condition described here requires immediate attention and appropriate treatment.

Lesions of the rat entopeduncular nucleus further deteriorate N-methyl-D-aspartate receptor antagonist-induced deficient prepulse inhibition.

Lesions of the rat entopeduncular nucleus (EPN), the equivalent to the human globus pallidus internus (GPi), have been shown to improve deficient prepulse inhibition (PPI) induced by the dopamine agonist apomorphine. We here tested the effect of EPN lesions on the PPI-disruptive effect of the non-competitive NMDA receptor antagonist dizocilpine in rats. Neurotoxic bilateral lesions of the EPN were induced by ibotenic acid (4 μg in 0.4 μl). Rats were tested for PPI and locomotor activity after systemic injection of dizocilpine (vehicle and 0.15 mg/kg). Bilateral EPN lesions further deteriorated the PPI deficit induced by dizocilpine, while locomotion was not affected. This work indicates that the EPN is an important brain region within the neuronal circuit responsible for NMDA receptor antagonist-induced PPI deficits.

Dystonic Hand Associated with Spontaneous Migration of a Retained Bullet

*Correspondence to: Dr. Manolis Polemikos, Department of Neurosurgery, Hannover Medical School, MHH, Carl-Neuberg-Strasse 1, DE-30625 Hannover, Germany; E-mail: polemikos.manolis@mh-hannover.de

Bilateral Pallidal Stimulation Improves Chorea in Antiphospholipid Antibody Syndrome With Oral Anticoagulation

There are only few reports on DBS for chorea, almost all of which are related to Huntington’s disease, neuroacanthocytosis, or cerebral palsy. Chorea may also occur in antiphospholipid antibody syndrome (APLS), which is an adolescent-onset autoimmune disease associated with venous and arterial thromboses as well as miscarriages. Apart from movement disorders, patients with APLS often present with migraine and psychiatric symptoms. Thus far, no experience with DBS has been reported, which may either be owing to its often transient character or to concerns regarding the need for anticoagulation. Here, we report on the (long-term) efficacy and safety of DBS of the posteroventral lateral globus pallidus internus (GPi) in APLS.