Value and efficacy of transcranial direct current stimulation in the rehabilitation of neurocognitive disorders: A critical review since 2000.

open3siNon-invasive brain stimulation techniques, including transcranial direct current stimulation (t-DCS) have been used in the rehabilitation of cognitive function in a spectrum of neurological disorders. The present review outlines methodological communalities and differences of t-DCS procedures in neurocognitive rehabilitation. We consider the efficacy of tDCS for the management of specific cognitive deficits in four main neurological disorders by providing a critical analysis of recent studies that have used t-DCS to improve cognition in patients with Parkinson’s Disease, Alzheimer’s Disease, Hemi-spatial Neglect and Aphasia. The evidence from this innovative approach to cognitive rehabilitation suggests that tDCS can influence cognition. However, the results show a high variability between studies both on the methodological approach adopted and the cognitive functions aspects. The review also focuses both on methodological issues such as technical aspects of the stimulation ( electrodes position and dimension; current intensity; duration of protocol) and on the inclusion of appropriate assessment tools for cognition. A further aspect considered is the best timing to administer tDCS: before, during after cognitive rehabilitation. We conclude that more studies with shared methodology are needed to have a better understanding of the efficacy of tDCS as a new tool for rehabilitation of cognitive disorders in a range of neurological disordersopenCappon, D; Jahanshahi, M; Bisiacchi, PCappon, Davide; Jahanshahi, M; Bisiacchi, Patrizi

Deep Brain Stimulation: A Paradigm Shifting Approach to Treat Parkinson's Disease

Parkinson disease (PD) is a chronic and progressive movement disorder classically characterized by slowed voluntary movements, resting tremor, muscle rigidity, and impaired gait and balance. Medical treatment is highly successful early on, though the majority of people experience significant complications in later stages. In advanced PD, when medications no longer adequately control motor symptoms, deep brain stimulation (DBS) offers a powerful therapeutic alternative. DBS involves the surgical implantation of one or more electrodes into specific areas of the brain, which modulate or disrupt abnormal patterns of neural signaling within the targeted region. Outcomes are often dramatic following DBS, with improvements in motor function and reductions motor complications having been repeatedly demonstrated. Given such robust responses, emerging indications for DBS are being investigated. In parallel with expansions of therapeutic scope, advancements within the areas of neurosurgical technique and the precision of stimulation delivery have recently broadened as well. This review focuses on the revolutionary addition of DBS to the therapeutic armamentarium for PD, and summarizes the technological advancements in the areas of neuroimaging and biomedical engineering intended to improve targeting, programming and overall management

Optimized Targeting in Deep Brain Stimulation for Movement Disorders.

Deep brain stimulation (DBS) is the dominant surgical therapy for medically-refractory Parkinson’s Disease (PD) and Essential Tremor (ET). Despite its success in treating the physical symptoms of many movement disorders, optimal targeting protocols are unknown. The success of the surgery is highly dependent upon proper placement of the electrode in the brain. However, the anatomical targets for PD and ET DBS—the subthalamic nucleus (STN) and ventral intermediate (Vim) nucleus of the thalamus, respectively—are not distinguishable on conventional magnetic resonance imaging. Neurosurgeons typically locate these structures using imprecise atlas-based indirect targeting methods requiring several attempts, increasing the risk of intracranial hemorrhage. The purpose of this work was to optimize targeting in DBS for PD and ET. First, we evaluated the most common indirect STN targeting methods with our validated 3-Tesla MRI protocol optimized for STN visualization. We calculated indirect targets as prescribed by midcommissural point (MCP) -based and red nucleus-based (RN) methods, and compared those coordinates to the position of the STN. We found that RN-based targeting is statistically superior to MCP-based targeting and should be routinely used in the absence of direct STN visualization. In our next study, we investigated the volume of tissue activated (VTA) in thalamic DBS. First, we developed a k-means clustering algorithm that operates on diffusion tensor imaging data to segment the thalamus into its functionally-distinct nuclei. We segmented individual patient thalami and an atlas thalamus in an existing VTA model, and created an individualized VTA model by utilizing each patient’s own anatomy and tissue conductivity. We measured stimulation overlaps with relevant nuclei for clinically efficacious stimulation settings. Our preliminary results indicated that individualized VTA modeling may provide more precise modeling results than existing atlas-based VTA modeling. Next, we investigated the ability of atlas-based and individualized VTA modeling methods to explain common side effects from thalamic DBS. We found that individualized VTA modeling is superior to atlas-based modeling in the prediction of side effects. The results of this work advance the understanding of proper DBS targeting for movement disorders, and our VTA modeling system represents the most individualized approach for ET DBS surgical planning.PHDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111402/1/hlayla_1.pd

Precision non-implantable neuromodulation therapies : a perspective for the depressed brain

Current first-line treatments for major depressive disorder (MDD) include pharmacotherapy and cognitive-behavioral therapy. However, one-third of depressed patients do not achieve remission after multiple medication trials, and psychotherapy can be costly and time-consuming. Although nonimplantable neuromodulation (NIN) techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, and magnetic seizure therapy are gaining momentum for treating MDD, the efficacy of non-convulsive techniques is still modest, whereas use of convulsive modalities is limited by their cognitive side effects. In this context, we propose that NIN techniques could benefit from a precision-oriented approach. In this review, we discuss the challenges and opportunities in implementing such a framework, focusing on enhancing NIN effects via a combination of individualized cognitive interventions, using closed-loop approaches, identifying multimodal biomarkers, using computer electric field modeling to guide targeting and quantify dosage, and using machine learning algorithms to integrate data collected at multiple biological levels and identify clinical responders. Though promising, this framework is currently limited, as previous studies have employed small samples and did not sufficiently explore pathophysiological mechanisms associated with NIN response and side effects. Moreover, cost-effectiveness analyses have not been performed. Nevertheless, further advancements in clinical trials of NIN could shift the field toward a more ‘‘precision-oriented’’ practice

Enhancing Nervous System Recovery through Neurobiologics, Neural Interface Training, and Neurorehabilitation.

After an initial period of recovery, human neurological injury has long been thought to be static. In order to improve quality of life for those suffering from stroke, spinal cord injury, or traumatic brain injury, researchers have been working to restore the nervous system and reduce neurological deficits through a number of mechanisms. For example, neurobiologists have been identifying and manipulating components of the intra- and extracellular milieu to alter the regenerative potential of neurons, neuro-engineers have been producing brain-machine and neural interfaces that circumvent lesions to restore functionality, and neurorehabilitation experts have been developing new ways to revitalize the nervous system even in chronic disease. While each of these areas holds promise, their individual paths to clinical relevance remain difficult. Nonetheless, these methods are now able to synergistically enhance recovery of native motor function to levels which were previously believed to be impossible. Furthermore, such recovery can even persist after training, and for the first time there is evidence of functional axonal regrowth and rewiring in the central nervous system of animal models. To attain this type of regeneration, rehabilitation paradigms that pair cortically-based intent with activation of affected circuits and positive neurofeedback appear to be required-a phenomenon which raises new and far reaching questions about the underlying relationship between conscious action and neural repair. For this reason, we argue that multi-modal therapy will be necessary to facilitate a truly robust recovery, and that the success of investigational microscopic techniques may depend on their integration into macroscopic frameworks that include task-based neurorehabilitation. We further identify critical components of future neural repair strategies and explore the most updated knowledge, progress, and challenges in the fields of cellular neuronal repair, neural interfacing, and neurorehabilitation, all with the goal of better understanding neurological injury and how to improve recovery

Personalized rTMS for Depression: A Review

Personalized treatments are gaining momentum across all fields of medicine. Precision medicine can be applied to neuromodulatory techniques, where focused brain stimulation treatments such as repetitive transcranial magnetic stimulation (rTMS) are used to modulate brain circuits and alleviate clinical symptoms. rTMS is well-tolerated and clinically effective for treatment-resistant depression (TRD) and other neuropsychiatric disorders. However, despite its wide stimulation parameter space (location, angle, pattern, frequency, and intensity can be adjusted), rTMS is currently applied in a one-size-fits-all manner, potentially contributing to its suboptimal clinical response (~50%). In this review, we examine components of rTMS that can be optimized to account for inter-individual variability in neural function and anatomy. We discuss current treatment options for TRD, the neural mechanisms thought to underlie treatment, differences in FDA-cleared devices, targeting strategies, stimulation parameter selection, and adaptive closed-loop rTMS to improve treatment outcomes. We suggest that better understanding of the wide and modifiable parameter space of rTMS will greatly improve clinical outcome

Using a virtual cortical module implementing a neural field model to modulate brain rhythms in Parkinson’s disease

We propose a new method for selective modulation of cortical rhythms based on neural field theory, in which the activity of a cortical area is extensively monitored using a two-dimensional microelectrode array. The example of Parkinson’s disease illustrates the proposed method, in which a neural field model is assumed to accurately describe experimentally recorded activity. In addition, we propose a new closed-loop stimulation signal that is both space- and time- dependent. This method is especially designed to specifically modulate a targeted brain rhythm, without interfering with other rhythms. A new class of neuroprosthetic devices is also proposed, in which the multielectrode array is seen as an artificial neural network interacting with biological tissue. Such a bio-inspired approach may provide a solution to optimize interactions between the stimulation device and the cortex aiming to attenuate or augment specific cortical rhythms. The next step will be to validate this new approach experimentally in patients with Parkinson’s disease