Underlying neurobiology and clinical correlates of mania status after subthalamic nucleus deep brain stimulation in Parkinson's Disease : a review of the literature

Deep brain stimulation (DBS) is a novel and effective surgical intervention for refractory Parkinson's disease (PD). The authors review the current literature to identify the clinical correlates associated with subthalamic nucleus (STN) DBS-induced hypomania/mania in PD patients. Ventromedial electrode placement has been most consistently implicated in the induction of STN DBS-induced mania. There is some evidence of symptom amelioration when electrode placement is switched to a more dorsolateral contact. Additional clinical correlates may include unipolar stimulation, higher voltage (>3 V), male sex, and/or early-onset PD. STN DBS-induced psychiatric adverse events emphasize the need for comprehensive psychiatric presurgical evaluation and follow-up in PD patients. Animal studies and prospective clinical research, combined with advanced neuroimaging techniques, are needed to identify clinical correlates and underlying neurobiological mechanisms of STN DBS-induced mania. Such working models would serve to further our understanding of the neurobiological underpinnings of mania and contribute valuable new insight toward development of future DBS mood-stabilization therapies.

Effect of deep brain stimulation on nucleus accumbens dopamine in a preclinicla model of antidepressant treatment-resistance

Background / Purpose: To determine if clinically effective deep brain stimulation (DBS) of neurosurgical targets for treatment-resistant depression regulates transient mesoaccumbens dopamine release in control and antidepressant-resistant animals (rats).

Main conclusion: In control rats, DBS stimulation of either the nucleus accumbens or infralimbic cortex significantly attenuated transient mesoaccumbens dopamine efflux, with nucleus accumbens DBS inducing a greater attenuation than infralimbic DBS. High frequency DBS of both targets induced long-term depression of transient accumbens dopamine release, lasting > 2hr post DBS.

Conversely, in antidepressant-resistant rats, infralimbic DBS significantly potentiated transient mesoaccumbens dopamine efflux during stimulation, but failed to induce long-lasting changes in neurotransmission. This suggests that a key mechanism of DBS for treatment-resistant depression is the regulation of dysfunctional mesoaccumbens dopamine neurotransmission.

Compact stacked planar inverted-F antenna for passive deep brain stimulation implants

A compact meandered three-layer stacked circular planar inverted-F antenna is designed and simulated at the UHF band (902.75 – 927.25 MHz) for passive deep brain stimulation implants. The UHF band is used because it offers small antenna size, and high data rate. The top and middle radiating layers are meandered, and low cost substrate and superstrate materials are used to limit the radius and height of the antenna to 5 mm and 1.64 mm, respectively. A dielectric substrate of FR-4 of εr= 4.7 and δ= 0.018, and a biocompatible superstrate of silicone of er= 3.7 and d= 0.003 with thickness of 0.2 mm are used in the design. The resonance frequency of the proposed antenna is 918 MHz with a bandwidth of 24 MHz at return loss of −10 dB in free space. The antenna parameter such as 3D gain pattern of the designed antenna within a skin-tissue model is evaluated by using the finite element method. The compactness, wide bandwidth, round shape, and stable characteristics in skin make this antenna suitable for DBS. The feasibility of the wireless power transmission to the implant in the human head is also examined.

Multi-layer implantable antenna for closed loop deep brain stimulation system

A multi-layer circular planar inverted-F antenna is designed and simulated at the industrial, scientific, and medical (ISM) band of 915 MHz for closed loop deep brain stimulation implant. The ISM band is considered due to the capabilities of small antenna size, high data rate, and long transmission range. In the proposed four-layer antenna, the top three radiating layers are meandered, and a high permittivity substrate and superstrate materials are used to limit the radius and the height of the antenna to 3.5 mm and 2.2 mm, respectively. The bottom layer works as a ground plate. The Roger RO3210 of εr = 10.2 and δ = 0.003 is used as a dielectric substrate and superstrate. The resonance frequency of the proposed antenna is 915 MHz with a bandwidth of 12 MHz at the return loss of -10 dB in free space. The stacked layered structure reduces the antenna size, and the circular shape makes it easily implantable into the human head. The antenna parameters (e.g. 3D gain pattern), SAR value, and electric field distribution within a six layers spherical head model are evaluated by using the finite element method (FEM). The feasibility of the wireless transmission of power, control and command signal to the implant in the human head is also examined. © 2012 IEEE.

Different current intensities of anodal transcranial direct current stimulation do not differentially modulate motor cortex plasticity

Transcranial direct current stimulation (tDCS) is a noninvasive technique that modulates the excitability of neurons within the motor cortex (M1). Although the aftereffects of anodal tDCS on modulating cortical excitability have been described, there is limited data describing the outcomes of different tDCS intensities on intracortical circuits. To further elucidate the mechanisms underlying the aftereffects of M1 excitability following anodal tDCS, we used transcranial magnetic stimulation (TMS) to examine the effect of different intensities on cortical excitability and short-interval intracortical inhibition (SICI). Using a randomized, counterbalanced, crossover design, with a one-week wash-out period, 14 participants (6 females and 8 males, 22–45 years) were exposed to 10 minutes of anodal tDCS at 0.8, 1.0, and 1.2 mA. TMS was used to measure M1 excitability and SICI of the contralateral wrist extensor muscle at baseline, immediately after and 15 and 30 minutes following cessation of anodal tDCS. Cortical excitability increased, whilst SICI was reduced at all time points following anodal tDCS. Interestingly, there were no differences between the three intensities of anodal tDCS on modulating cortical excitability or SICI. These results suggest that the aftereffect of anodal tDCS on facilitating cortical excitability is due to the modulation of synaptic mechanisms associated with long-term potentiation and is not influenced by different tDCS intensities.

A low power micro deep brain stimulation device for murine preclinical research

Deep brain stimulation has emerged as an effective medical procedure that has therapeutic efficacy in a number of neuropsychiatric disorders. Preclinical research involving laboratory animals is being conducted to study the principles, mechanisms, and therapeutic effects of deep brain stimulation. A bottleneck is, however, the lack of deep brain stimulation devices that enable long term brain stimulation in freely moving laboratory animals. Most of the existing devices employ complex circuitry, and are thus bulky. These devices are usually connected to the electrode that is implanted into the animal brain using long fixed wires. In long term behavioral trials, however, laboratory animals often need to continuously receive brain stimulation for days without interruption, which is difficult with existing technology. This paper presents a low power and lightweight portable microdeep brain stimulation device for laboratory animals. Three different configurations of the device are presented as follows: 1) single piece head mountable; 2) single piece back mountable; and 3) two piece back mountable. The device can be easily carried by the animal during the course of a clinical trial, and that it can produce non-stop stimulation current pulses of desired characteristics for over 12 days on a single battery. It employs passive charge balancing to minimize undesirable effects on the target tissue. The results of bench, in-vitro, and in-vivo tests to evaluate the performance of the device are presented.