Biomedical subjects
Publications and source records attributed to Ali R Rezai.
Psychosurgery. Psychiatric neurosurgery. Neurosurgery for psychiatric disorders. Whatever the name, each of these refers to the surgical treatment of mental disease. Indeed, as many have pointed out, the most common term, "psychosurgery," is itself a misnomer, because the target of these procedures is not the "mind" or "psyche" but the neural substrates of higher cognitive function.
Intractable OCD and depression cause tremendous suffering in those affected and in their families. The impaired ability to function of those affected imposes a heavy burden on society as a whole. Existing data suggest that lesion procedures offer benefit to a large proportion (ranging from about 35%-70%) of patients with intractable OCD and depression. The literature also suggests that although serious long-term adverse events have occurred, these are relatively infrequent overall. Methodologic limitations of the earlier reports on any of these procedures were described previously in this article. The major academic centers conducting this work have since been obtaining systematic prospective data using modern assessment tools. Nevertheless, even with improved methodologies, more recent studies confront some remaining issues that have been difficult to overcome fully. First, the number of patients who have received any one procedure has been relatively small, constraining statistical power. This limits the ability of researchers to enhance patient selection based on clinical characteristics. This is important, because patients with intractable OCD and depression referred for neurosurgery have high rates of comorbid Axis I diagnoses, personality disorders, and functional impairments, which may have value in predicting response. Other features, such as age of onset, chronicity, and symptom subtypes, may be likewise useful. Another key factor in response may be postoperative management, which has varied most over time but also across patients enrolled in trials. As noted previously, randomized controlled trials of neurosurgical treatment for intractable psychiatric illness have not been reported, although one has been proposed for gamma knife capsulotomy in intractable OCD [23]. The development of deep brain stimulation has also made sham-controlled studies possible and also allows within-patient designs to be considered. Bearing these problems in mind, the literature does provide important guidance on a number of key points, including approaches to referral, patient selection, and the need for long-term prospective follow-up and postoperative management. Nevertheless, important gaps in knowledge remain in all these areas. Research is expected to narrow these gaps in a number of ways, including patient selection, optimizing the procedures themselves, and understanding the mechanisms of therapeutic action. Neuroimaging studies will play a key role in achieving these aims (see the article by Rauch in this issue). So will cross-species translational research on the anatomy and physiology of the pathways implicated in the pathophysiology and response to treatment in these disorders. Future research in psychiatric neurosurgery must proceed cautiously. A recent editorial statement of the OCD-DBS Collaborative Group [26] recommends a minimum set of standards for any multidisciplinary teams contemplating work in this domain. The rationale for those standards is found throughout this issue and is especially developed in the article by Fins. The need for safe and effective therapeutic options for people suffering with these severe illnesses is just as clear. The experience over the last several decades provides grounds for careful optimism that refined lesion procedures or reversible deep brain stimulation may relieve suffering and improve the lives of people with these devastating disorders.
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Deep brain stimulation (DBS) is established as a therapy for movement disorders, and it is an investigational treatment in other neurologic conditions. DBS precisely targets neuroanatomical targets deep within the brain that are proposed to be centrally involved in the pathophysiology of some neuropsychiatric illnesses. DBS is nonablative, offering the advantages of reversibility and adjustability. This might permit therapeutic effectiveness to be enhanced or side effects to be minimized. Preclinical and clinical studies have shown effects of DBS locally, at the stimulation target, and at a distance, via actions on fibers of passage or across synapses. Although its mechanisms of action are not fully elucidated, several effects have been proposed to underlie the therapeutic effects of DBS in movement disorders, and potentially in other conditions as well. The mechanisms of action of DBS are the focus of active investigation in a number of clinical and preclinical laboratories. As in severe movement disorders, DBS may offer a degree of hope for patients with intractable neuropsychiatric illness. It is already clear that research intended to realize this potential will require a very considerable commitment of resources, energy, and time across disciplines including psychiatry, neurosurgery neurology, neuropsychology, bioengineering, and bioethics. These investigations should proceed cautiously.
PURPOSE: To assess magnetic resonance imaging (MRI)-related heating for a neurostimulation system (Activa Tremor Control System, Medtronic, Minneapolis, MN) used for chronic deep brain stimulation (DBS). MATERIALS AND METHODS: Different configurations were evaluated for bilateral neurostimulators (Soletra Model 7426), extensions, and leads to assess worst-case and clinically relevant positioning scenarios. In vitro testing was performed using a 1.5-T/64-MHz MR system and a gel-filled phantom designed to approximate the head and upper torso of a human subject. MRI was conducted using the transmit/receive body and transmit/receive head radio frequency (RF) coils. Various levels of RF energy were applied with the transmit/receive body (whole-body averaged specific absorption rate (SAR); range, 0.98-3.90 W/kg) and transmit/receive head (whole-body averaged SAR; range, 0.07-0.24 W/kg) coils. A fluoroptic thermometry system was used to record temperatures at multiple locations before (1 minute) and during (15 minutes) MRI. RESULTS: Using the body RF coil, the highest temperature changes ranged from 2.5 degrees-25.3 degrees C. Using the head RF coil, the highest temperature changes ranged from 2.3 degrees-7.1 degrees C.Thus, these findings indicated that substantial heating occurs under certain conditions, while others produce relatively minor, physiologically inconsequential temperature increases. CONCLUSION: The temperature increases were dependent on the type of RF coil, level of SAR used, and how the lead wires were positioned. Notably, the use of clinically relevant positioning techniques for the neurostimulation system and low SARs commonly used for imaging the brain generated little heating. Based on this information, MR safety guidelines are provided. These observations are restricted to the tested neurostimulation system.
The effect of subthalamic nucleus (STN) stimulation on cortical electroencephalographic activity was examined in 10 patients with Parkinson's disease and 4 patients with epilepsy. Evoked potentials were created by time-locking electroencephalography to the onset of electrical stimulation delivered through the lead implanted in the STN of patients who had previously undergone deep brain stimulation (DBS) surgery. The effect of different patterns of stimulation on the evoked response, including single- and paired-pulse as well as burst stimulation, was explored. Cortical evoked potentials to single pulses were observed with latencies as short as 1 to 2 msec after a single pulse of stimulation, with activity continuing, in some cases, for up to 400 msec. Paired-pulse experiments revealed refractory periods on the order of 0.5 msec, suggesting that stimulation of axons contributed to the generation of at least some portion of the evoked potential waveform. Evoked potentials were also present in response to 100-msec bursts of stimulation, with some evidence that the potential was initiated within the burst artifact. The potential implications of the types of responses observed as well as potential applications are discussed.
OBJECTIVE: Advances in image-guided stereotactic surgery, microelectrode recording techniques, and stimulation technology have been the driving forces behind a resurgence in the use of functional neurosurgery for the treatment of movement disorders. Despite the dramatic effects of deep brain stimulation (DBS) techniques in ameliorating the symptoms of Parkinson's disease, many critical questions related to the targeting, effects, and mechanisms of action of DBS remain unanswered. In this report, we describe the methods used to localize the subthalamic nucleus (STN) and we present the characteristics of encountered cells. METHODS: Twenty-six patients with idiopathic Parkinson's disease underwent simultaneous, bilateral, microelectrode-refined, DBS electrode implantation into the STN. Direct and indirect magnetic resonance imaging-based anatomic targeting was used. Cellular activity was analyzed for various neurophysiological parameters, including firing rates and interspike intervals. Physiological targeting confirmation was obtained by performing macrostimulation through the final DBS electrode. RESULTS: The average microelectrode recording time for each trajectory was 20 minutes, with a mean of 5.2 trajectories/patient. Typical trajectories passed through the anterior thalamus, zona incerta/fields of Forel, STN, and substantia nigra-pars reticulata. Each structure exhibited a characteristic firing pattern. In particular, recordings from the STN exhibited an increase in background activity and an irregular firing pattern, with a mean rate of 47 Hz. The mean cell density was 5.6 cells/mm, with an average maximal trajectory length of 5.3 mm. Macrostimulation via the DBS electrode yielded mean sensory and motor thresholds of 4.2 and 5.7 V, respectively. CONCLUSION: The principal objectives of microelectrode recording refinement of anatomic targeting are precise identification of the borders of the STN and thus determination of its maximal length. Microelectrode recording also allows identification of the longest and most lateral segment of the STN, which is our preferred target for STN DBS electrode implantation. Macrostimulation via the final DBS electrode is then used primarily to establish the side effect profile for postoperative stimulation. Microelectrode recording is a helpful targeting adjunct that will continue to facilitate our understanding of basal ganglion physiological features.
Persistent cognitive disabilities represent the most troublesome consequences of acquired brain injury. Although these problems are widely recognized, few neuroprosthetic efforts have focused on developing therapeutic strategies aimed at improving general cognitive functions such as sustained attention, intention, working memory or awareness. If possible, effective modulation of these neuropsychologic components might improve recovery of interactive behaviors. The emerging field of neuromodulation holds promise that technologies developed to treat other neurological disorders may be adapted to address the cognitive problems of patients suffering from acquired brain injuries. We here discuss initial efforts at neuromodulation in patients in the persistent vegetative state and aspects of recent studies of the underlying neurobiology of PVS and other severe brain injuries. Innovative strategies for open-loop and closed-loop neuromodulation of impaired cognitive function are outlined. We discuss the possibilities of linking neuromodulation techniques to underlying neuronal mechanisms underpinning cognitive rehabilitation maneuvers. Ethical considerations surrounding the development of these strategies are reviewed.
OBJECT: A substantial number of patients with Parkinson disease (PD) who have undergone unilateral stereotactic pallidotomy ultimately develop symptom progression, becoming potential candidates for further surgical treatment. Bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) has been shown to be effective in the treatment of a subset of patients with refractory PD. Microelectrode recording is performed to help localize the STN and guide final placement of the electrode. Potential alterations in physiological features of the STN after pallidotomy may complicate localization of this structure in this group of patients. METHODS: Bilateral STN DBS surgery guided by microelectrode recording was performed in six patients who had undergone previous unilateral pallidotomies. Physiologically obtained parameters of the STN, including trajectory length, mean firing rate, cell number, and cell density were calculated. These data were compared with those from the side without prior pallidotomy within each patient, as well as with those from our series of 49 subthalamic nuclei explored in 26 patients who had not undergone prior pallidotomy but who underwent bilateral STN stimulator placement. In all patients, analysis of STN cellular activity on the side ipsilateral to the pallidotomy demonstrated a lower mean firing frequency than on the contralateral, intact side. The physiological features on the intact side were not significantly different from those found in our series of patients who had not undergone prior pallidotomy. CONCLUSIONS: Physicians who perform STN surgery in patients with prior pallidotomy should be aware of the electrophysiological differences between the STN that had undergone pallidotomy and the one that had not, to avoid prolonging recording time to search for the typical STN. The implications of these findings for the current models of information processing in the basal ganglia are discussed.
BACKGROUND AND PURPOSE: Recent work has shown a potential for excessive heating of deep brain stimulation electrodes during MR imaging. This in vitro study investigates the relationship between electrode heating and the specific absorption rate (SAR) of several MR images. METHODS: In vitro testing was performed by using a 1.5-T MR imaging system and a head transmit-receive coil, with bilateral deep brain stimulation systems positioned in a gel saline-filled phantom, and temperature monitoring with a fluoroptic thermometry system. Standardized fast spin-echo sequences were performed over a range of high, medium, and low SAR values. Several additional, clinically important MR imaging techniques, including 3D magnetization prepared rapid acquisition gradient-echo imaging, echo-planar imaging, quantitative magnetization transfer imaging, and magnetization transfer-suppressed MR angiography, were also tested by using typical parameters. RESULTS: A significant, highly linear relationship between SAR and electrode heating was found, with the temperature elevation being approximately 0.9 times the local SAR value. Minor temperature elevations, <1 degrees C, were found with the fast spin-echo, magnetization prepared rapid acquisition gradient-echo, and echo-planar clinical imaging sequences. The high dB/dt echo-planar imaging sequence had no significant heating independent of SAR considerations. Sequences with magnetization transfer pulses produced temperature elevations in the 1.0 to 2.0 degrees C range, which was less than theoretically predicted for the relatively high SAR values. CONCLUSION: A potential exists for excessive MR imaging-related heating in patients with deep brain stimulation electrodes; however, the temperature increases are linearly related to SAR values. Clinical imaging sequences that are associated with tolerable temperature elevations in the <or=2.0 degrees C range at the electrode tips can be performed safely within an SAR range <2.4 W/kg local (0.9 W/kg whole body averaged).