Effects of Cacao By-Products and a Modest Weight Loss Intervention on the Concentration of Serum Triglycerides in Overweight Subjects: Proof of Concept.

Therapeutic approaches to decrease serum triglyceride (TG) concentrations are not successful mainly due to poor adherence or adverse effects of therapies. In consequence, the search for new low-cost and safer therapeutic alternatives is mandatory. Dark chocolate and cacao have shown promising results improving lipid profiles. Recently, using cacao by-products to reduce elevated cardiometabolic risk markers in an animal model of obesity induced by a high-fat diet and fructose, we showed that TGs, low-density lipoprotein cholesterol, and the TG/high-density lipoprotein (HDL) ratio decreased, suggesting that cacao by-products improved the metabolic function of obese animals. Based on these results, as a proof of concept, a blinded placebo-controlled study was implemented to explore the effects of cacao by-products on anthropometric and biochemical variables in a group of overweight subjects participating in a program composed of reduced-calorie-diet counseling plus a simple aerobic exercise plan. The results showed that counseling induced weight and abdominal circumference reductions in both groups. TGs did not change in the control group; however, TG decreased significantly by 54.9 mg/dL (27.9%) in the experimental group. The TG/HDL cholesterol ratio changed markedly (1.5) in the experimental group. The results reported suggest the use of cacao by-products as an alternative for the treatment of hypertriglyceridemia.

Three consecutive neurotomies in one patient for the treatment of spastic hemiplegia: Spinal, median, and foot toes common flexor.

BACKGROUND: Neurotomies were one of the first procedures performed in the field of functional neurosurgery. Microstimulators and microscopes facilitate the performance of neurotomies to treat focal spasticity. This report shows how three different consecutive neurotomies were performed in one patient with chronic left upper/lower extremity spasticity. CASE DESCRIPTION: A 65-year-old male with intractable epilepsy underwent a right temporal lobectomy for seizure control. Postoperatively, he developed left upper/lower extremity spasticity attributed to a postoperative right internal capsule infarct. The severe spasticity persisted despite the administration of conventional drugs, rehabilitation efforts, and botulinic toxin injections. Three sequential selective neurotomies (e.g., spinal, median, and foot common flexor nerves) were next performed. Postoperatively, the neurotomies resulted in significant symptomatic long-term improvement, 6 years after spinal neurotomy, 7 years after median neurotomy, and 9 years after common flexor neurotomy. Spasticity scores diminished from 4 to 0 points on the Ashworth scale and from 4 to 0 points on the Held-Tardieu scale for each muscular region. CONCLUSION: Multiple regional neurotomies were effective in the management of left-sided postoperative spasticity in a patient who underwent a temporal lobectomy for seizure control with a resultant postoperative right internal capsule infarct.

Electrical stimulation of the inferior thalamic peduncle in the treatment of major depression and obsessive compulsive disorders.

OBJECTIVE: Stimulation of the inferior thalamic peduncle (ITP) is emerging as a promising new therapeutic target in certain psychiatric disorders. The circuitry that includes the nonspecific thalamic system (NSTS), which projects via the ITP to the orbitofrontal cortex (OFC), is involved in the physiopathology of major depression disorder (MDD) and obsessive compulsive disorder (OCD). The safety and efficacy of chronic ITP stimulation in cases of MDD and OCD refractory to medical treatment is presented. MATERIALS AND METHODS: Six patients with OCD and one with MDD were implanted with tetrapolar deep brain stimulation electrodes in the ITP (x = 3.5 mm lateral to the ventricular wall, y = 5 mm behind the anterior commissure, and z = at the intercommissural plane, i.e., anterior commissure-posterior commissure [AC-PC] level). The effect of chronic stimulation at 130 Hz, 450 µs, and 5.0 V on OCD was evaluated before and 3, 6, and 12 months after initiation of electrical stimulation through the Yale-Brown Obsessive Compulsive Scale, Hamilton Depression Rating Scale, and Global Assessment of Function scale. RESULTS: Chronic ITP electrical stimulation in OCD patients decreased the mean Yale-Brown Obsessive Compulsive Scale score to around 51% for the group at the 12-month follow-up, and increased the mean Global Assessment of Function scale score to 68% for a significant improvement (P = 0.026). Three of 6 patients returned to work. The Hamilton Depression Rating Scale score of the only patient with MDD treated to date went from 42 to 6. This condition of the patient, who had been incapacitated for 5 years prior to surgery, has not relapsed for 9 years. Three OCD patients with drug addiction continued to consume drugs in spite of their improvement in OCD. CONCLUSION: Deep brain stimulation in the ITP is safe and may be effective in the treatment of OCD. A multicenter evaluation of the safety and efficacy of ITP in OCD is currently in process.

Bilateral cingulotomy and anterior capsulotomy applied to patients with aggressiveness.

OBJECTIVE: To perform a preliminary study on the effects and safety of bilateral cingulotomy and anterior capsulotomy in patients with aggressive behavior. PATIENTS AND METHODS: Twenty-three psychiatric patients showing aggressive behavior refractory to conventional treatment were initially evaluated. The subjects were clinically selected using the Overt Aggression Scale (OAS) and the Global Assessment of Functioning Scale (GAF). Each case was carefully reviewed by the Ethics Committee of Mexico's General Hospital. Once selection criteria were met, stereotactic lesions were made using radiofrequency on the anterior limb of the internal capsule and supragenual cingulum. Statistical differences were evaluated with a Wilcoxon test at 6 months and at 4 years. RESULTS: Ten patients underwent surgery. Their OAS and GAF scores decreased after the procedure at the 6-month (p < 0.05) and at the 4-year (p = 0.068) follow-up. Four patients showed mild and transitory postsurgical complications (hyperphagia and somnolence). CONCLUSIONS: Bilateral anterior capsulotomy in combination with cingulotomy may reduce aggressive behavior and improve clinical evaluations. Very strict clinical and ethical evaluations were applied prior to considering patients for this treatment.

Coupled obturator neurotomies and lidocaine intrathecal infusion to treat bilateral adductor spasticity and drug-refractory pain.

Spastic diplegia is present in three-fourths of children with cerebral palsy, interfering with gait and frequently accompanied by severe pain. The authors report the case of a 28-year-old woman with history of perinatal hypoxia, who presented with cerebral palsy and severe spastic diplegia (Ashworth Scale Score 4, Tardieu Scale Score 5) and was confined to a wheelchair. She complained of pain in the left hip and knee with mixed neuropathic and somatic components. She consistently rated pain intensity as 10 of 10 on a visual analog scale, and her symptoms were resistant to multiple treatments. The patient underwent selective bilateral adductor myotomies and the implantation of an infusion pump for intrathecal lidocaine application. Postoperative control of pain and spasticity was dramatic (scores of 0 on the Ashworth, Tardieu, and visual analog scales) and persisted throughout a follow-up period of 36 months. This is the first report in the literature of combined selective neurotomies for the treatment of spasticity and chronic lidocaine subarachnoid infusion to treat associated pain. This therapy could represent an alternative to treat spasticity associated with neuropathic and somatic pain.

Effects of Thalamic Reticular Nucleus Electrical Stimulation in Rats in a T-maze Perseverative Behavior Model Induced by 8-OH-DPAT.

Objective. Evaluate the possible decrease of chemically induced perseverative behavior in rats after electrical stimulation at different frequencies in the thalamic reticular nucleus. Material and Methods. A total of 28 male rats were divided in four groups: control, sham, OFF stimulation, and ON stimulation (450 µsec, 1 V, 6 and 120 Hz) that underwent the administration of saline solution and 8-OH-DPAT. The animals were evaluated in a T-maze model in which three choices or more in the same branch are considered as perseverative. Intragroup analysis was done through paired T-student and intergroup analysis through an ANOVA test. Results. The numbers of perseverations mean for the control group were 1.3 before and 1.4 post saline solution injections. Sham group mean of 1.3 pre and 3.4 post 8-OH-DPAT administration; OFF stimulation group 1.1 pre and 3.3 post 8-OH-DPAT administration; and for ON stimulation 1.1 pre and 1.9 post 8-OH-DPAT administration for stimulation at low frequency (6 Hz) and 3.4 at high frequency (120 Hz). Evident intergroup statistical differences were shown (p < 0.01). Conclusions. Electrical stimulation with the low-frequency group was the only group that after manipulation with 8-OH-DPAT showed a decrease in perseverative behavior, even close to baseline.

Effects of bilateral lesions in thalamic reticular nucleus and orbitofrontal cortex in a T-maze perseverative model produced by 8-OH-DPAT in rats.

OBJECTIVE: Stereotaxic lesions of the orbitofrontal-thalamic system, specifically the thalamic reticular nucleus (TRN), could be helpful to prevent perseverative behavior in rats produced by 8-OH-DPAT. METHODS: Fifty rats were conditioned in a T-maze to measure the number of perseverations. Habituation was performed on days 1 and 2, baseline scores were obtained on day 3 and the final test was done on day 4 (chemical induction). Group I only received saline solution injection; group II was only submitted to 8-OH-DPAT; group III received pharmacological treatment with chlorimipramine (CMI) before 8-OH-DPAT administration; group IV and group V were submitted to stereotaxic bilateral lesions, one week before T-maze evaluation, in the TRN and orbitofrontal cortex (OFC), respectively and received 8-OH-DPAT administration. RESULTS: No differences between groups were found at baseline on day 3 (p<0.05). Significant differences were found between days 3 and 4 of evaluation only in group II (p<0.01) and group V (p<0.001). Differences between groups on day 4 were significant (p<0.01). CONCLUSIONS: TRN lesions were as effective as CMI administration to prevent the 8-OH-DPAT action. OFC lesions failed to prevent the perseverative behavior.

A systematic review of the efficacy of globus pallidus stimulation in the treatment of Parkinson's disease.

The aim of this study was to systematically review the data published on deep brain stimulation (DBS) of the globus pallidus internus (GPi) in Parkinson's disease (PD), and to determine its efficacy and optimal stimulation parameters. Only 22 of 4,648 articles fulfilled the inclusion and exclusion criteria of the study. The data were analysed using the Wilcoxon test. For 327 patients who underwent GPi-DBS, the preoperative baseline Unified Parkinson's Disease Rating Scale (UPDRS) score, off-medication, mean was 52.7 (range 26.5-77.2). The postoperative UPDRS score, off-medication/on-stimulation, mean was 33.7 (range 18.7-46.2). The delta mean (the difference in mean UPDRS score between baseline and maximum follow-up) was 19.1 (range -2.2 to 36.5) (p<0.001). When the electrical parameters were compared against the delta UPDRS score, the analysis showed that only frequency was correlated with motor improvement (R(2)=0.42, p<0.05). Thus, GPi-DBS is a highly effective target for neuromodulation in PD. However, we found that significant clinical improvement (>50% delta UPDRS score) in PD is achieved at an amplitude of between 2.0V and 3.5V, a pulse-width between 75 micros and 300 micros and a frequency between 100Hz and 190Hz.

Once-daily extended-release levetiracetam as adjunctive treatment of partial-onset seizures in patients with epilepsy: a double-blind, randomized, placebo-controlled trial.

PURPOSE: Double-blind randomized trial to assess efficacy and tolerability of once-daily extended-release levetiracetam (LEV XR) tablets (2 x 500 mg) as add-on therapy in patients (12-70 years old) with partial-onset seizures (POS) refractory to one to three antiepileptic drugs. METHODS: After an 8-week prospective baseline-period, eligible patients were randomized (1:1) to once-daily LEV XR 1,000 mg/day or placebo for 12 weeks. Evaluations included changes from baseline in POS-frequency/week, responders (>or=50% reduction in POS-frequency/week), seizure-freedom, adverse events, laboratory tests, physical and neurologic examinations, vital signs, body-weight, and 12-lead electrocardiogram. RESULTS: Of 188 patients screened, 158 were randomized (intention-to-treat population): LEV XR (n = 79) or placebo (n = 79). Seventy-one (89.9%) LEV XR and 72 (91.1%) placebo patients completed the trial. Median POS-frequency/week reduction was 46.1% on LEV XR and 33.4% on placebo. Estimated reduction with LEV XR over placebo was 14.4% (p = 0.038). Thirty-four (43%) LEV XR and 23 (29.1%) placebo patients experienced >or=50% reduction in POS-frequency/week. Eight (10.1%) patients receiving LEV XR and one (1.3%) receiving placebo were free of POS during the 12-week treatment period. Forty-one (53.2%) LEV XR and 43 (54.4%) placebo patients reported >or=1 adverse event. Adverse events reported with an incidence >5% and seen more often with LEV XR than with placebo were somnolence, influenza, irritability, nasopharyngitis, dizziness, and nausea. DISCUSSION: Once-daily LEV XR 1,000 mg was effective and well-tolerated as adjunct therapy in patients with POS. Ten percent of patients randomized to LEV XR experienced freedom from POS. These results support the clinical value of this new LEV XR formulation.

[Brain activity associated with a nouns-reading task]. / Activación cerebral asociada a una tarea de lectura de sustantivos.

BACKGROUND: Word reading involves several steps, from the visual perception of each of its constitutent elements to its recognition as an entity with a specific meaning. Various brain structures participate in these processes, depending of the linguistic and cognitive characteristics of the stimulus. Our objective was to characterize brain activity through the use of functional magnetic resonance imaging (FMRI) associated with the process of noun reading. METHODS: Eleven healthy right-handed volunteers participated in a lexical decision task involving 58 written nouns. An equal number of letter sequences were used as control stimuli. Reaction times were also recorded. RESULTS: There was a difference (p < 0.05) in reaction time between nouns and letter sequences in the lexical decision task. FMRI contrasted between conditions revealed significant activations in several areas involved in reading. CONCLUSIONS: The brain activation may reflect the different perceptual demands associated with the initial processing of nouns, as compared to meaningless letter sequences. We attribute the difference between our results and those previously reported to the particular characteristics of the pronunciation rules of written Spanish.

Bilateral electrical stimulation of prelemniscal radiations in the treatment of advanced Parkinson's disease.

OBJECTIVE: Tremor and rigidity have been efficiently controlled by electrical stimulation of contralateral prelemniscal radiations (Raprl) in patients with unilateral Parkinson's disease. The present study determines the effect of bilateral Raprl electrical stimulation in a group of patients with severe bilateral tremor, rigidity, and bradykinesia. METHODS: Five patients with Parkinson's disease (Hoehn and Yahr scale, Stage V) underwent bilateral stereotactic electrode implantation. Postoperative magnetic resonance imaging studies confirmed their position. Bipolar chronic electrical stimulation was performed through contiguous contacts of each electrode, which were selected by means of a screening test that explored multiple combinations. Preoperative and 3-, 6-, 9-, and 12-month postoperative evaluations were performed using international rating scales. Postoperative evaluations were performed with 24 hours off medication-on stimulation. RESULTS: Contralateral tremor and rigidity were significantly decreased by simple insertion of electrodes in Raprl and returned hours to days later. Contacts for chronic stimulation were located in the area between the red and subthalamic nuclei, including Raprl, zona incerta, and substantia Q. Efficient stimulation had at least one contact in Raprl and in four cases, both contacts were only in Raprl. Stimulation parameters were 90 to 130 Hz, 90 to 330 mus, and 1.5 to 3.5 V. Unified Parkinson's Disease Rating Scale (motor, Part III) scores decreased 65% (P < 0.001), with improvements of 90% in tremor (P < 0.001), 94% in rigidity (P < 0.001), 75% in bradykinesia (P < 0.001), 40% in gait, and 35% in postural stability (P < 0.05) at 1 year. CONCLUSION: Raprl electrical stimulation is safe and efficient to treat patients with the Parkinson's disease symptomatic triad. By use of Raprl stereotactic coordinates, electrodes were placed behind the subthalamic nucleus.

Efficacy of motor cortex stimulation in the treatment of neuropathic pain: a randomized double-blind trial.

OBJECT: In this study the authors used a double-blind protocol to assess the efficacy of motor cortex stimulation (MCS) for treating neuropathic pain. METHODS: Eleven patients with unilateral neuropathic pain (visual analog scale [VAS] score 8-10) of different origins and topography were selected for MCS. A 20-contact grid was implanted through a craniotomy centered over the motor cortex contralateral to the painful area. The motor cortex strip was identified using neuroimages, somatosensory evoked potentials, acute electrical stimulation, and corticocortical evoked potentials. Subacute therapeutic stimulation trials allowed the authors to determine the most efficient pair of contacts to use for long-term MCS. The grid was replaced with a 4-contact electrode connected to an internalized stimulator. Bipolar stimulation at a 40-Hz frequency, 90-micro sec pulse width, amplitude 2-7 V, and 1 hour in "ON" and 4 hours in "OFF" mode was used. Pain was evaluated using the VAS, Bourhis, and McGill pain scales applied each month for 1 year. At Day 60 or 90, the stimulators were turned to OFF mode for 30 days in a randomized, double-blind fashion. The statistical tool used was the Wilcoxon test. RESULTS: Three patients did not report improvement in the subacute trial and were excluded from long-term MCS; the remaining patients underwent long-term stimulation. Significant improvement of pain was induced by MCS (p < 0.01); this persisted during the follow-up period. Turning stimulation to OFF mode increased pain significantly (p < 0.05). Improvement at 1 year was >or= 40% (40-86%) in all cases. CONCLUSIONS: Motor cortex stimulation is an efficient treatment for neuropathic pain, according to an evaluation facilitated by a double-blind maneuver. Subacute stimulation trials are recommended to determine the optimum motor cortex area to be stimulated and to identify nonresponders.

Opioid receptor binding in parahippocampus of patients with temporal lobe epilepsy: its association with the antiepileptic effects of subacute electrical stimulation.

Opioid receptor binding was evaluated in parahippocampal cortex (PHC) obtained from patients with intractable mesial temporal lobe epilepsy (MTLE) with and without subacute high frequency electrical stimulation (HFS) in this brain area. Mu, delta and nociceptin receptor binding was determined by autoradiography in PHC of five patients (ESAE group) with MTLE history of 14.8 +/- 2.5 years and seizure frequency of 11 +/- 2.9 per month, two of them (40%) with mesial sclerosis. This group demonstrated antiepileptic effects following subacute HFS (130 Hz, 450 micros, 200-400 microA), applied continuously during 16-20 days in PHC. Values were compared with those obtained from patients with severe MTLE (history of 21.7 +/- 2.8 years and seizure frequency of 28.2 +/- 14 per month) in whom electrical stimulation did not induce antiepileptic effects (ESWAE group, n = 4), patients with MTLE in whom no electrical stimulation was applied (MTLE group, n = 4) and autopsy material acquired from subjects without epilepsy (n = 4 obtained from three subjects). Enhanced 3H-DAMGO (MTLE, 755%; ESAE, 375%; ESWAE, 693%), 3H-DPDPE (MTLE, 242%; ESAE, 80%; ESWAE, 346%) and 3H-nociceptin (MTLE, 424%; ESAE, 217%; ESWAE, 451%) binding was detected in the PHC of all epileptic groups. However, tissue obtained from ESAE group demonstrated lower opioid receptor binding (3H-DAMGO, 44.5%, p < 0.05; 3H-DPDPE, 47%, p < 0.05; 3H-nociceptin, 39.3%, p < 0.5) when compared with MTLE group. The present results indicate that a high effectiveness to the antiepileptic effects induced by HFS is associated with reduced opioid peptide binding.

Neuromodulation of the centromedian thalamic nuclei in the treatment of generalized seizures and the improvement of the quality of life in patients with Lennox-Gastaut syndrome.

PURPOSE: Our aim was to evaluate the efficacy of ESCM (electrical stimulation of the centromedian thalamic nucleus) in treatment of generalized seizures of the Lennox-Gastaut syndrome (LGS) and improvement of patient disability. METHODS: Thirteen patients with LGS were studied. They had severe generalized tonic-clonic seizures (GTC) and atypical absences (AA). All patients had at least a 6-month baseline before bilateral electrode implantation to the centromedian (CM) nuclei of the thalamus to undergo therapeutic ESCM. Once implanted, electrodes were temporally externalized through a retromastoid point for electrophysiologic confirmation of their placement. After target confirmation, stimulation parameters were set. Patients came for follow-up assessment of seizures and neurophysiologic tests every 3 months during an 18-month period of time; AED therapy was not modified. RESULTS: The surgical procedure as well as electrical stimulation was well tolerated by all patients. No side effects occurred with the therapeutic stimulation parameters used, and patients were not aware of device activation. Two patients were explanted because of repeated and multiple skin erosions that could not be controlled by plastic surgery procedures. Overall seizure reduction was 80%. The three patients with poorest outcomes for seizure control did not improve their ability scale score. In contrast, the two patients rendered seizure free are living a normal life at present. The remaining eight patients experienced progressive improvement, from being totally disabled to becoming independent in five cases and partially dependent in two. Patients with adequate electrode placement had a seizure reduction >87%. To consider that an electrode is correctly placed, both stereotactic placement and neurophysiologic responses are taken into account. CONCLUSIONS: ESCM provides a nonlesional, neuromodulatory method with improvement in seizure outcome and in the abilities of patients with severe LGS.

Comparative evaluation of the effects of unilateral lesion versus electrical stimulation of the globus pallidus internus in advanced Parkinson's disease.

OBJECTIVE: To perform a prospective analysis on the effects of unilateral lesion versus unilateral electrical stimulation (ES) of the globus pallidus internus (Gpi) in the treatment of bilateral Parkinson's disease (PD). MATERIALS AND METHODS: We studied 18 patients with stages III-V on the Hoehn and Yahr (H-Y) scale having prominent rigidity, bradykinesia and gait disturbances. Nine patients were treated with lesions and 9 patients with ES. Both groups were evaluated using the New York Parkinson's Disease Scale, the Unified Parkinson's Disease Rating Scale part III, and the H-Y scale and with specific items of tremor, rigidity and bradykinesia independently on each side. Both lesions and electrodes for ES were placed stereotactically in the Gpi as confirmed by postoperative magnetic resonance images. Significance of changes was evaluated with the Wilcoxon test after 3 and 6 months. Significance of intergroup differences was evaluated using the Mann-Whitney U test. RESULTS: Lesions and ES significantly decreased rigidity (p < 0.01) and bradykinesia (p < 0.005) in the contralateral extremities. ES significantly decreased tremor in the contralateral extremities (p < 0.01) and rigidity and bradykinesia ipsilaterally (p < 0.01) at 3 months. There were no significant intergroup differences. The H-Y scale score showed improvement in self-sufficiency. L-DOPA dose was decreased by 31%. CONCLUSIONS: ES was a safer procedure and more efficient in controlling PD symptoms. Unilateral lesions and ES may improve bilateral symptoms to the point of making patients self-sufficient.

Electrocortical and behavioral responses elicited by acute electrical stimulation of inferior thalamic peduncle and nucleus reticularis thalami in a patient with major depression disorder.

OBJECTIVE: Our aim was to study electrocortical and behavioral responses elicited by 6, 60 and 3/s stimulation of the inferior thalamic peduncle (ITP) and nucleus reticularis thalami (Re) in a patient with of major depression disorder resistant to psychotherapy, pharmacotherapy and electroconvulsive therapy and candidate to be treated by electrical stimulation of the ITP. METHODS: In this patient, two multicontact electrodes were implanted bilaterally through frontal coronal parasagittal burr-holes with oblique trajectories aiming ITP and Re. Stimulation was performed through externalized systems. Referential scalp electroencephalographic (EEG) recordings were performed and subjective sensations and clinical symptoms reported by patient and changes in responsiveness in single response tasks during stimulation trials were systematically recorded. RESULTS: Unilateral, low (6/s) and high (60/s) frequency stimulation of either ITP or Re produced identical recruiting-like responses or desynchronization-DC shift changes predominant at frontopolar region, bilaterally. Billateral, high intensity 3/s stimulation or either ITP or Re produced electrocortical responses that consisted in generalized 3/s spike-wave complexes predominant at frontopolar, frontocentral and frontotemporal regions. However, while ITP responses were accompanied by all symptoms described for a spontaneous absence attack, Re responses were behaviorly accompanied only by delayed reaction time. CONCLUSION: These data suggests that in humans as in cats, ITP and Re are both part of a non-specific thalamo-orbitofrontal system normally engaged in cortical synchronization, selective attention and sleep. SIGNIFICANCE: Under abnormal conditions, ITP and RE may play a role in the physiopathology of typical absence attacks and depression disorders.

Neurobiological background for performing surgical intervention in the inferior thalamic peduncle for treatment of major depression disorders.

OBJECTIVE: To present a review of evidence for an inhibitory thalamo-orbitofrontal system related to physiopathology of major depression disorders (MDDs) and to postulate that interfering with hyperactivity of the thalamo-orbitofrontal system by means of chronic high-frequency electrical stimulation of its main fiber connection, the inferior thalamic peduncle (ITP), may result in an improvement in patients with MDD. METHODS: Experimentally, the thalamo-orbitofrontal system has been proposed as part of the nonspecific thalamic system. Under normal conditions, the nonspecific thalamic system induces characteristic electrocortical synchronization in the form of recruiting responses that mimic some sleep stages. It also inhibits input of irrelevant sensory stimuli, thus facilitating the process of selective attention. Permanent disruption of the system, via lesioning or temporary inactivation through cooling of the ITP with cryoprobes, results in a state of hyperkinesia, increased attention, and cortical desynchronization. RESULTS: Surgical lesioning of the medial part of orbitofrontal cortex and white matter overlying area 13, which includes the ITP, may result in significant improvement in MDD. Imaging studies (functional magnetic resonance imaging and positron emission tomography) consistently demonstrate hyperactivity in the orbitofrontal cortex and midline thalamic regions during episodes of MDD. This hyperactivity decreases with efficient control of MDD by medical treatment, indicating that orbitofrontal cortex and midline thalamic overactivity are related to the depressive condition. Conversely, noradrenergic and serotoninergic systems in the frontal lobes have been implicated in the pathophysiology of MDD. Although noradrenergic receptor density in the frontal lobe is consistently increased in depressed patients who commit suicide, 5-hydroxytryptamine reuptake blockers, which are potent antidepressive drugs, decrease hypermetabolism in the orbital frontal cortex in MDD. Therefore, the serotonin hypothesis for depression postulates that norepinephrine and serotonin in the frontal lobes are required to maintain antidepressive responsiveness. Dysregulation of the secretion of both neurotransmitters initiates overactivity of orbitofrontal cortex, resulting in depression. It is possible that surgical interventions in this region, including electrical stimulation of ITP, disrupt adrenergic and serotoninergic dysregulation in patients with MDD. CONCLUSION: Circumscribed lesions or electrical stimulation of the ITP, a discrete target easily identified by electrophysiological studies, may improve MDD. Electrical stimulation may have the advantage of being less invasive and more adjustable to patient needs.