Marleen Welkenhuysen

An implantable 455-active-electrode 52-channel CMOS neural probe

Several studies have demonstrated that understanding certain brain functions can only be achieved by simultaneously monitoring the electrical activity of many individual neurons in multiple brain areas [1]. Therefore, the main tradeoff in neural probe design is between minimizing the probe dimensions and achieving high spatial resolution using large arrays of small recording sites. Current state-of-the-art solutions are limited in the amount of simultaneous readout channels [2], contain a small number of electrodes [2,3] or use hybrid implementations to increase the number of readout channels [3,4].

Effect of Insertion Speed on Tissue Response and Insertion Mechanics of a Chronically Implanted Silicon-Based Neural Probe

In this study, the effect of insertion speed on long-term tissue response and insertion mechanics was investigated. A dummy silicon parylene-coated probe was used in this context and implanted in the rat brain at 10 μm/s (n = 6) or 100 μm/s ( n = 6) to a depth of 9 mm. The insertion mechanics were assessed by the dimpling distance, and the force at the point of penetration, at the end of the insertion phase, and after a 3-min rest period in the brain. After 6 weeks, the tissue response was evaluated by estimating the amount of gliosis, inflammation, and neuronal cell loss with immunohistochemistry. No difference in dimpling, penetration force, or the force after a 3-min rest period in the brain was observed. However, the force at the end of the insertion phase was significantly higher when inserting the probes at 100 μm/s compared to 10 μm/s. Furthermore, an expected tissue response was seen with an increase of glial and microglial reactivity around the probe. This reaction was similar along the entire length of the probe. However, evidence for a neuronal kill zone was observed only in the most superficial part of the implant. In this region, the lesion size was also greatest. Comparison of the tissue response between insertion speeds showed no differences.

Histological Alterations Induced by Electrode Implantation and Electrical Stimulation in the Human Brain: A Review

Objectives.  Electrical brain stimulation is used as a treatment for patients with intractable chronic pain and movement disorders. However, the implantation of electrodes and electrical stimulation may induce histological changes around the electrode tip. We aimed to review the histological changes in humans that were electrically stimulated in the brain.

A response surface model predicting the in vivo insertion behavior of micromachined neural implants

The mechanical damage caused by the insertion of a foreign body into living tissue is inevitable, especially when a considerable stiffness mismatch is present, as in the case of micromachined neural implants and brain tissue. However, the response surface model based on a central composite experimental design described in this study showed that for particular configurations of the implant tip angle, width, thickness or insertion speed, some of these factors could be safely increased without causing an unwanted significant force or tissue dimpling increase. The model covers chisel tip angles between 10° and 50°, implant widths within the 200-400 µm range and thicknesses between 50 and 150 µm. The insertion speed has been varied from 10 up to 100 µm s(-1) to reach a final insertion depth of 6 mm. Coating the implant with parylene C proved to be beneficial in reducing the friction between the implant and the surrounding tissue. Successfully validated for a particular implant geometry, this model could be used as an insertion behavior prediction tool for the design optimization of future neural implants.

Electrical stimulation in the lateral hypothalamus in rats in the activity-based anorexia model.

OBJECT One quarter of patients with anorexia nervosa have a poor outcome and continue to suffer chronically or die. Electrical brain stimulation may be of therapeutic benefit in some of these patients; however, the brain target for inducing symptom relief is unknown. In this study, the authors evaluated the effects of acute and chronic electrical stimulation in the lateral hypothalamus on food intake, locomotor activity, and survival time in rats in an activity-based anorexia model. METHODS In an acute experiment, the authors electrically stimulated at 100 Hz and 0, 25, 50 and 75% of the maximal stimulation amplitude (that is, the amplitude leading to severe side effects) in the lateral hypothalamus on consecutive days during 4 test sessions in 10 rats and evaluated food intake and locomotor activity. In a chronic experiment, they compared food intake, wheel revolutions, and survival time between 6 rats that underwent electrical stimulation in the lateral hypothalamus (50% of maximal stimulation amplitude) and 8 rats that did not undergo stimulation. RESULTS In the acute experiment, overall electrical stimulation (25, 50, and 75% combined) and stimulation at 75% of the maximal stimulation amplitude significantly decreased the locomotor activity. However, if the authors omitted results of 1 rat, in which the electrode tip was not located in the lateral hypothalamus on one side but rather in the supraoptic chiasm, the remaining results did not yield significance. No other differences were observed. CONCLUSIONS When the findings of the current study are extrapolated to patients with anorexia nervosa, the authors do not expect major effects on symptoms with electrical stimulation at high frequency in the lateral hypothalamus.

Targeting Bed Nucleus of the Stria Terminalis for Severe Obsessive-Compulsive Disorder: More Unexpected Lead Placement in Obsessive-Compulsive Disorder than in Surgery for Movement Disorders

BACKGROUND In preparation for a multicenter study, a protocol was written on how to perform surgical targeting of the bed nucleus of the stria terminalis, based on the lead implantation experience in patients with treatment-refractory obsessive-compulsive disorder (OCD) at the Universitaire Ziekenhuizen Leuven (UZ Leuven). When analyzing the postoperative images, we were struck by the fact that the difference between the postoperative position of the leads and the planned position seemed larger than expected. METHODS The precision of targeting in four patients with severe OCD who received bilateral model 3391 leads (Medtronic) was compared with the precision of targeting in the last seven patients who underwent surgery at UZ Leuven for movement disorders (four with Parkinson disease and three with essential tremor; all received bilateral leads). Because the leads implanted in six of the seven patients with movement disorders were model 3387 leads (Medtronic), targeting precision was also analyzed in four patients with OCD in whom model 3387 leads were implanted in the same target as the other patients with OCD. RESULTS In the patients with OCD, every implanted lead deviated at least 1.3 mm from its intended position in at least one of three directions (lateral, anteroposterior, and depth), whereas in the patients with movement disorders, the maximal deviation of any of all implanted leads was 1.3 mm. The deviations in lead placement were comparable in patients with OCD who received a model 3387 implant and patients who received a model 3391 implant. In the patients with OCD, all leads were implanted more posteriorly than planned. CONCLUSIONS The cause of the posterior deviation could not be determined with certainty. The most likely cause was an increased mechanical resistance of the brain tissue along the trajectory when following the targeting protocol compared with the trajectories classically used for subthalamic nucleus or ventral intermediate nucleus of the thalamus stimulation.

Planar 2D-Array Neural Probe for Deep Brain Stimulation and Recording (DBSR)

Implantable micromachined probes with planar electrode arrays for neural stimulation and recording were designed, fabricated and evaluated. Probes have been realized with distributed electrode sites and different electrode configurations (i.e. size and geometry). These were tested for their ability to selectively record and stimulate cortical brain areas. The probes were stereotactically implanted into the cortical region of the rat brains without breaking and were successfully used to measure neural signals and evoke limb contraction in response to electrical stimulation.

A closed-loop compressive-sensing-based neural recording system

OBJECTIVE This paper describes a low power closed-loop compressive sensing (CS) based neural recording system. This system provides an efficient method to reduce data transmission bandwidth for implantable neural recording devices. By doing so, this technique reduces a majority of system power consumption which is dissipated at data readout interface. The design of the system is scalable and is a viable option for large scale integration of electrodes or recording sites onto a single device. APPROACH The entire system consists of an application-specific integrated circuit (ASIC) with 4 recording readout channels with CS circuits, a real time off-chip CS recovery block and a recovery quality evaluation block that provides a closed feedback to adaptively adjust compression rate. Since CS performance is strongly signal dependent, the ASIC has been tested in vivo and with standard public neural databases. MAIN RESULTS Implemented using efficient digital circuit, this system is able to achieve >10 times data compression on the entire neural spike band (500-6KHz) while consuming only 0.83uW (0.53 V voltage supply) additional digital power per electrode. When only the spikes are desired, the system is able to further compress the detected spikes by around 16 times. Unlike other similar systems, the characteristic spikes and inter-spike data can both be recovered which guarantes a >95% spike classification success rate. The compression circuit occupied 0.11mm(2)/electrode in a 180nm CMOS process. The complete signal processing circuit consumes <16uW/electrode. SIGNIFICANCE Power and area efficiency demonstrated by the system make it an ideal candidate for integration into large recording arrays containing thousands of electrode. Closed-loop recording and reconstruction performance evaluation further improves the robustness of the compression method, thus making the system more practical for long term recording.

The effects of electrical stimulation or an electrolytic lesion in the mediodorsal thalamus of the rat on survival, body weight, food intake and running activity in the activity-based anorexia model

The glucose metabolism in the mediodorsal thalamus (MD) is increased in rats in the activity-based anorexia (ABA) model. In patients, electrical stimulation in hyperactive brain regions reduced symptoms in e.g. major depressive disorder and cluster headache. In two blinded randomised controlled experiments, we therefore examined the effects of high-frequency electrical stimulation and an electrolytic lesion in the MD in a validated rat model for anorexia nervosa. The ABA model was successfully replicated in all our experiments, with a reduction in body weight, food intake, and survival time and an increase in running activity. In a first experiment, we evaluated the effect of electrical stimulation or a curative lesion in the MD on survival, body weight, food intake and locomotor activity in ABA rats. Electrical MD stimulation or an electrolytic MD lesion did not improve the symptoms of rats in the ABA model, compared to control groups. In a second experiment, we investigated the effect of a preventive electrolytic lesion in the MD on rats in the ABA model. Although there was no significant improvement of survival, body weight and food intake, locomotor activity was significantly reduced in the lesion group compared to the control group. Apart from this positive effect on running activity, we found no convincing evidence for the suitability of the MD as a neuromodulation target for anorexia nervosa patients.

Parenthood motives, well-being and disclosure among men from couples ready to start treatment with intrauterine insemination using their own sperm or donor sperm

BACKGROUND As pregnancy and childbirth have long been considered womens issues and male infertility has long been surrounded by taboo, limited research has focused on the experience of infertile men. The purpose of this study was to compare male motives for parenthood, male well-being and disclosure patterns concerning the method of conception among men from couples starting treatment with IUI using their own sperm (autologous sperm recipient, ASR) or donor sperm (donor sperm recipient, DSR). METHODS This prospective study included 46 DSR- and 151 ASR-couples. Self-report questionnaires assessing parenthood motives, well-being and disclosure patterns concerning the method of conception were administered to both men and women prior to treatment. Unpaired T-tests and Fishers exact tests were used to test for significant differences. RESULTS When compared with ASR-men, DSR-men expect more positive effects from parenthood on relationships and feelings of fulfilment, and report less negative effects of infertility on sexuality, but a lower self-image and more guilt. DSR-men plan to disclose the method of conception less frequently and have so far disclosed to a lesser degree than ASR-men. CONCLUSIONS DSR-men feel differently about parenthood and infertility compared with ASR-men, and their higher expectations combined with lower self-esteem need (more) attention during counselling.