We review the history of efforts to apply central thalamic deep brain stimulation (CT/DBS) to restore consciousness in patients in coma and vegetative state by changing the arousal state. Early experimental and clinical studies and the results of a recent single-subject human study that demonstrated both immediate behavioral facilitation and carry-over effects of CT/DBS are reviewed. We consider possible mechanisms underlying CT/DBS effects on cognitively-mediated behaviors in conscious patients in light of the anatomical connectivity and physiological specializations of the central thalamus. Immediate and carry-over effects of CT/DBS are discussed within the context of possible effects on neuronal plasticity and gene expression. We conclude that CT/DBS be studied as a therapeutic intervention to improve impaired cognitive function in severely brain-injured patients who in addition to demonstrating clinical evidence of consciousness and goal-directed behavior, retain sufficient preservation of large-scale cerebral networks within the anterior forebrain. Although available data provide evidence for proof-ofconcept, very significant challenges for study design and development of CT/DBS for clinical use are identified. OVERVIEWBased on experimental physiology studies in the mid-twentieth century a concept of brainstem and thalamic control of forebrain arousal inspired clinical efforts to apply electrical stimulation to unconscious, severely brain-injured human subjects. Here we first review the history of clinical studies of central thalamic deep brain stimulation (CT/DBS) in patients with disorders of consciousness. The results of earlier clinical studies that examined the potential role of CT/DBS in restoring conscious awareness in patients remaining chronically unconscious in the vegetative state are reviewed as well as a recent singlesubject study of CT/DBS in an awake human subject in the minimally conscious state (MCS). The implications for future study design and rationale for patient selection to test the potential use of CT/DBS are considered in light of the results of these studies. We develop a rationale to support the potential role of CT/DBS to improve impaired cognitive function in some conscious severely brain-injured patients emphasizing the anatomical and physiological specializations of the neurons within the central thalamus. Existing experimental data are reviewed with respect to observed effects of CT/DBS and limitations and future directions are considered.

No abstract

The central thalamus plays an important role in the regulation of arousal and allocation of attentional resources in the performance of even simple tasks. To assess the contribution of central thalamic neurons to short-term adjustments of attentional effort, we analyzed 166 microelectrode recordings obtained from two rhesus monkeys performing a visuomotor simple reaction time task with a variable foreperiod. Multiunit responses showed maintained firing rate elevations during the variable delay period of the task in ∼24% of recording sites. Simultaneously recorded local field potentials demonstrated significant decreases in power at ∼10-20 Hz and increases in power at 30-100 Hz during the delay period when compared against precue baselines. Comparison of the spectral power of local field potentials during the delay period of correct and incorrect trials showed that, during incorrect trials, similar, but reduced, shifts of spectral power occurred within the same frequency bands. Sustained performance of even simple tasks requires regulation of arousal and attention that combine in the concept of "attentional effort". Our findings suggest that central thalamic neurons regulate task performance through brief changes in firing rates and spectral power changes during task-relevant short-term shifts of attentional effort. Increases in attentional effort may be reflected in changes within the central thalamic local populations, where correct task performance associates with more robust maintenance of firing rates during the delay period. Such ongoing fluctuations of central thalamic activity likely reflect a mix of influences, including variations in moment-to-moment levels of motivation, arousal, and availability of cognitive resources.

Age was a key predictor of response to therapy and disease-specific survival in ATA high-risk thyroid cancer patients. Its incorporation as a variable in the ATA risk stratification system would improve its power to predict response to therapy as well as mortality.

Following severe injuries that result in disorders of consciousness, recovery can occur over many months or years post-injury. While post-injury synaptogenesis, axonal sprouting and functional reorganization are known to occur, the network-level processes underlying recovery are poorly understood. Here, we test a network-level functional rerouting hypothesis in recovery of patients with disorders of consciousness following severe brain injury. This hypothesis states that the brain recovers from injury by restoring normal functional connections via alternate structural pathways that circumvent impaired white matter connections. The so-called network diffusion model, which relates an individual's structural and functional connectomes by assuming that functional activation diffuses along structural pathways, is used here to capture this functional rerouting. We jointly examined functional and structural connectomes extracted from MRIs of 12 healthy and 16 brain-injured subjects. Connectome properties were quantified via graph theoretic measures and network diffusion model parameters. While a few graph metrics showed groupwise differences, they did not correlate with patients' level of consciousness as measured by the Coma Recovery Scale — Revised. There was, however, a strong and significant partial Pearson's correlation (accounting for age and years post-injury) between level of consciousness and network diffusion model propagation time (r = 0.76, p < 0.05, corrected), i.e. the time functional activation spends traversing the structural network. We concluded that functional rerouting via alternate (and less efficient) pathways leads to increases in network diffusion model propagation time. Simulations of injury and recovery in healthy connectomes confirmed these results. This work establishes the feasibility for using the network diffusion model to capture network-level mechanisms in recovery of consciousness after severe brain injury.

The growing diversification of the patient population coupled with the increasing demand for cosmetic laser rejuvenation has highlighted the need to develop cutaneous laser systems and establish treatment protocols for patients with a wide range of skin conditions and phototypes. Recent technologic advancements have provided viable treatment options to achieve clinical outcomes that were previously only attainable in patients with lighter skin tones. This review provides an updated discussion of the range of laser treatments available for pigmented skin and sets the stage for further advancements. Pigment-specific laser technology with green, red, or near-infrared light targets a variety of pigmented lesions such as lentigines, ephelides, café-au-lait macules, and melanocytic nevi as well as tattoos and unwanted hair. Short-pulsed alexandrite, ruby, and neodymium:yttrium-aluminum-garnet (Nd:YAG) lasers are used for pigmented lesions and tattoos, whereas their longer pulse-width laser counterparts are used for laser-assisted hair removal. Vascular lesions and hypertrophic scars can be treated with a variety of vascular-specific lasers, but it is the pulsed dye laser (PDL) that has long been the gold standard treatment for these lesions due to its high specificity for hemoglobin and its ability to improve skin surface texture in children and adults. Laser skin resurfacing techniques for photodamaged skin and atrophic scars have been optimized with fractional technology to produce excellent clinical outcomes and minimal complication risks. Radiofrequency and nonablative lasers are also used to provide skin tightening and collagen remodeling with virtually no postoperative recovery.

During a 6-year period that included the initiation of intravitreal melphalan at our institution, the salvage rate of treated Group D eyes was 75% (39/52 eyes). Intravitreal melphalan was utilized for ocular salvage in 42% (22/52 eyes). Systemic chemoreduction combined with intravitreal melphalan for seeding demonstrated a high overall salvage rate for Group D eyes in this cohort.

Deep brain stimulation (DBS) is an established therapy for Parkinson's Disease and is being investigated as a treatment for chronic depression, obsessive compulsive disorder and for facilitating functional recovery of patients in minimally conscious states following brain injury. For all of these applications, quantitative assessments of the behavioral effects of DBS are crucial to determine whether the therapy is effective and, if so, how stimulation parameters can be optimized. Behavioral analyses for DBS are challenging because subject performance is typically assessed from only a small set of discrete measurements made on a discrete rating scale, the time course of DBS effects is unknown, and between-subject differences are often large. We demonstrate how Bayesian statespace methods can be used to characterize the relationship between DBS and behavior comparing our approach with logistic regression in two experiments: the effects of DBS on attention of a macaque monkey performing a reaction-time task, and the effects of DBS on motor behavior of a human patient in a minimally conscious state. The state-space analysis can assess the magnitude of DBS behavioral facilitation (positive or negative) at specific time points and has important implications for developing principled strategies to optimize DBS paradigms.