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1.  Human hypocretin and melanin concentrating hormone levels are linked to emotion and social interaction 
Nature communications  2013;4:1547.
The neurochemical changes underlying human emotions and social behavior are largely unknown. Here we report on the changes in the levels of two hypothalamic neuropeptides, hypocretin-1 (Hcrt-1) and melanin concentrating hormone (MCH), measured in the human amygdala. We show that Hcrt-1 levels are maximal during positive emotion, social interaction, and anger, behaviors that induce cataplexy in human narcoleptics. In contrast, MCH levels are minimal during social interaction, but are increased after eating. Both peptides are at minimal levels during periods of postoperative pain despite high levels of arousal. MCH levels increase at sleep onset, consistent with a role in sleep induction, whereas Hcrt-1 levels increase at wake onset, consistent with a role in wake induction. Levels of these two peptides in humans are not simply linked to arousal, but rather to specific emotions and state transitions. Other arousal systems may be similarly emotionally specialized.
PMCID: PMC3595130  PMID: 23462990
2.  Memory Enhancement and Deep-Brain Stimulation of the Entorhinal Area 
The New England journal of medicine  2012;366(6):502-510.
The medial temporal structures, including the hippocampus and the entorhinal cortex, are critical for the ability to transform daily experience into lasting memories. We tested the hypothesis that deep-brain stimulation of the hippocampus or entorhinal cortex alters memory performance.
We implanted intracranial depth electrodes in seven subjects to identify seizure-onset zones for subsequent epilepsy surgery. The subjects completed a spatial learning task during which they learned destinations within virtual environments. During half the learning trials, focal electrical stimulation was given below the threshold that elicits an afterdischarge (i.e., a neuronal discharge that occurs after termination of the stimulus).
Entorhinal stimulation applied while the subjects learned locations of landmarks enhanced their subsequent memory of these locations: the subjects reached these landmarks more quickly and by shorter routes, as compared with locations learned without stimulation. Entorhinal stimulation also resulted in a resetting of the phase of the theta rhythm, as shown on the hippocampal electroencephalogram. Direct hippocampal stimulation was not effective. In this small series, no adverse events associated with the procedure were observed.
Stimulation of the entorhinal region enhanced memory of spatial information when applied during learning. (Funded by the National Institutes of Health and the Dana Foundation.)
PMCID: PMC3447081  PMID: 22316444
3.  Hypothalamic Deep Brain Stimulation Reduces Weight Gain in an Obesity-Animal Model 
PLoS ONE  2012;7(1):e30672.
Prior studies of appetite regulatory networks, primarily in rodents, have established that targeted electrical stimulation of ventromedial hypothalamus (VMH) can alter food intake patterns and metabolic homeostasis. Consideration of this method for weight modulation in humans with severe overeating disorders and morbid obesity can be further advanced by modeling procedures and assessing endpoints that can provide preclinical data on efficacy and safety. In this study we adapted human deep brain stimulation (DBS) stereotactic methods and instrumentation to demonstrate in a large animal model the modulation of weight gain with VMH-DBS. Female Göttingen minipigs were used because of their dietary habits, physiologic characteristics, and brain structures that resemble those of primates. Further, these animals become obese on extra-feeding regimens. DBS electrodes were first bilaterally implanted into the VMH of the animals (n = 8) which were then maintained on a restricted food regimen for 1 mo following the surgery. The daily amount of food was then doubled for the next 2 mo in all animals to produce obesity associated with extra calorie intake, with half of the animals (n = 4) concurrently receiving continuous low frequency (50 Hz) VMH-DBS. Adverse motoric or behavioral effects were not observed subsequent to the surgical procedure or during the DBS period. Throughout this 2 mo DBS period, all animals consumed the doubled amount of daily food. However, the animals that had received VMH-DBS showed a cumulative weight gain (6.1±0.4 kg; mean ± SEM) that was lower than the nonstimulated VMH-DBS animals (9.4±1.3 kg; p<0.05), suggestive of a DBS-associated increase in metabolic rate. These results in a porcine obesity model demonstrate the efficacy and behavioral safety of a low frequency VMH-DBS application as a potential clinical strategy for modulation of body weight.
PMCID: PMC3266267  PMID: 22295102
4.  Diffusion tensor imaging (DTI) and colored fractional anisotropy (FA) mapping of the subthalamic nucleus (STN) and the globus pallidus interna (GPi) 
Acta Neurochirurgica  2010;152(12):2079-2084.
The subthalamic nucleus (STN) and the globus pallidus internus (GPi) are the most common surgical targets for the treatment of Parkinson’s disease. We studied directionally colored fractional anisotropy (FA) and diffusion tensor imaging (DTI) sequences to better target these anatomical regions.
Four patients undergoing stereotactic surgery for movement disorders were studied. Stereotactic targets and fiber tractography were determined on MRIs using the Schaltenbrand–Wahren atlas for definition in the iPlan software. In addition, post-operative imaging was fused to preoperative FA sequences for end-result identification. Axial, sagittal, and coronal images of the FA sequence were studied. DTI parameters used ranged from 2 to 4 mm for voxel size in the x/y/z planes, fiber length was kept constant at 15 mm and FA threshold of 0.25.
Colored FA maps resulted in a key signature in and around the STN and GPi. Regions identified include, but were not limited to: the internal capsule, nigral projections, the thalamic fasciculus, Forel’s fields H1 and H2, zona incerta, suthalamic fasciculus, tegmental tracts, and cerebello-rubro-thalamic tract.
Colored FA maps allow a potential method to identify the STN and GPi accurately. DTI has proven to be a powerful tool that can be used to augment identification of the STN nucleus and GPi used for stereotactic surgery.
PMCID: PMC2991232  PMID: 20890778
Deep brain stimulation; Diffusion tensor imaging; Fiber tractography; Subthalamic nucleus; STN; Globus pallidus; Pars interna
5.  A role of diffusion tensor imaging in movement disorder surgery 
Acta Neurochirurgica  2010;152(12):2089-2095.
The safe and reversible nature of deep brain stimulation (DBS) has allowed movement disorder neurosurgery to become commonplace throughout the world. Fundamental understanding of individual patient’s anatomy is critical for optimizing the effects and side effects of DBS surgery. Three patients undergoing stereotactic surgery for movement disorders, at the institution’s intraoperative magnetic resonance imaging operating suite, were studied with fiber tractography. Stereotactic targets and fiber tractography were determined on preoperative magnetic resonance imagings using the Schaltenbrand–Wahren atlas for definition in the BrainLab iPlan software (BrainLAB Inc., Feldkirchen, Germany). Subthalamic nucleus, globus pallidus interna, and ventral intermediate nucleus targets were studied. Diffusion tensor imaging parameters used ranged from 2 to 8 mm for volume of interest in the x/y/z planes, fiber length was kept constant at 30 mm, and fractional anisotropy threshold varied from 0.20 to 0.45. Diffusion tensor imaging tractography allowed reliable and reproducible visualization and correlation between frontal eye field, premotor, primary motor, and primary sensory cortices via corticospinal tracts and corticopontocerebellar tracts. There is an apparent increase in the number of cortical regions targeted by the fiber tracts as the region of interest is enlarged. This represents a possible mechanism of the increased effects and side effects observed with higher stimulation voltages. Currently available diffusion tensor imaging techniques allow potential methods to characterize the effects and side effects of DBS. This technology has the potential of being a powerful tool to optimize DBS neurosurgery.
PMCID: PMC2991222  PMID: 20652606
Deep brain stimulation; Diffusion tensor imaging; Fiber tractography; STN; GPi; ViM
6.  High-resolution depth electrode localization and imaging in patients with pharmacologically intractable epilepsy 
Journal of neurosurgery  2008;108(4):812-815.
Localization and targeting of depth electrodes in specific regions of the human brain is critical for accurate clinical diagnoses and treatment as well as for neuroscientific electrophysiological research. By using high-resolution magnetic resonance imaging combined with 2D computational unfolding, the authors present a method that improves electrode localization in the medial temporal lobe. This method permits visualization of electrode placements in subregions of the hippocampus and parahippocampal gyrus, allowing for greater specificity in relating electrophysiological and anatomical features in the human medial temporal lobe. Such methods may be extended to therapeutic procedures targeting specific neuronal circuitry in subfields of structures deep in the human brain.
PMCID: PMC2628813  PMID: 18377264
coregistration; depth electrode; electrode localization; epilepsy; hippocampus
7.  Inter-Racial, Gender and Aging Influences in the Length of Anterior Commissure-Posterior Commissure Line 
The length of anterior-posterior commissure (AC-PC) in racial groups, age, gender of patients with deep brain stimulation (DBS) and pallidotomy were investigated.
From January 1996 to December 2003, 211 patients were treated with DBS and pallidotomy. There were 160 (76%) Caucasians, 35 (17%) Hispanics, 12 (5%) Asians and 4 Blacks (2%). There were 88 males and 52 females in DBS-surgery group and 44 males, 27 females in pallidotomy group. Mean age was 58 year-old. There were 19 males and 19 females and mean age was 54.7 years in the control group. Measurements were made on MRI and @Target software.
The average AC-PC distance was 24.89 mm (range 32 to 19), which increased with aging until 75 years old in Caucasian and also increased with aging in Hispanic, but the AC-PC distance peaked at 45 years old in Hispanic. The order of AC-PC distance were 25.2±2 mm in Caucasian, 24.6±2.24 mm in Asian, 24.53 mm in Black, 23.6±1.98 mm in Hispanic. The average AC-PC distance in all groups was 24.22 mm in female who was mean age of 56.35, 25.28 mm in male who was mean age of 60.19 and 24.5±2 mm in control group that was excluded because of the difference of thickness of slice. According to multiple regression analysis, the AC-PC distance was significantly correlated with age, race, and gender.
The AC-PC distance is significantly correlated with age, gender, and race. The atlas of functional stereotaxis would be depended on the variation of indivisual brain that can influenced by aging, gender, and race.
PMCID: PMC2588230  PMID: 19096609
Pallidotomy; Anterior commissure; Posterior commissure

Results 1-7 (7)