A stereotaxic atlas of the brain of the cynomolgus monkey (Macaca fascicularis)

Outline drawings of representative frontal sections of the Macaca fascicularis brain are presented in stereotaxic coordinates. The levels extend from the rostral tip of the neostriatum to the posterior end of the deep cerebellar nuclei. The illustrations are based on photographs of unstained frozen sections of three formalin-fixed brains in which stainless steel needles were inserted to mark the horizontal zero and several anteroposterior positions. The sections were not stained in order to prevent shrinkage. Stereotaxic measurements were taken in situ of the highest points on the cortical surface, the position of the central and lunate sulcus, and of certain landmarks at the base of the cranium in a large number of monkeys. These data along with brain dimensions and the weight of animals are displayed in tables to indicate individual variations and to aid investigators in determining the best stereotaxic coordinates for a given structure. It is recommended that the cortical point of entry for an electrode or needle be routinely noted and be compared to the parameters in the atlas to compensate for deviations in the horizontal plane.     

Evidence of cingulate motor representation in humans

A 44-year-old man with a right frontal lobe tumor and intractable seizures underwent subdural grid evaluation before resection. The electrode locations were identified on a three-dimensional surface-reconstructed image of the brain after subdural grid placement. Electrical stimulation of electrodes placed over the right cingulate gyrus revealed evidence of tonic posturing of the left forearm and wrist and tonic extension of the left leg. This finding provides further evidence of a motor area in the cingulate gyrus in humans.     

Moving potential field of frontal midline theta activity during a mental task

The movement of potential field (potential flow) of frontal midline theta activity (Fmθ) was examined by using optical flow detection techniques in image processing in 6 normal subjects. Electroencephalograms (EEGs) over the fronto-central region were recorded from 13 electrodes around F_z. The potential flow of Fmθ was estimated on a frame which consisted of a square grid of 19 × 19 points in which each of the 13 electrodes was positioned with F_z at the center of grid. The peak-to-trough amplitude distribution was rounded or oval with a maximum just anterior to F_z. In each hemisphere, potential field moved medially in a region anterior to F_z, posteriorly near or at the midline and laterally in a region posterior to F_z. In the temporal sequence of potential field, at each point velocity directions tended to change progressively clockwise or counterclockwise. In the whole frame, a rotary movement of potential flow was found with a center at the middle on each side. Our findings suggested that a potential maximum at the midline may be due to overlapping of fields of opposite direction over the frontal scalp, arising from sources of similar orientation in both hemispheres. It can be assumed that Fmθ propagates in a clockwise direction in the left hemisphere and in a counterclockwise direction in the right hemisphere.     

Diurnal Rhythm in Proopiomelanocortin mRNA in the Arcuate Nucleus of the Male Rat

We tested the hypotheses that in the male rat, expression of proopiomelanocortin (POMC) mRNA in cells of the arcuate nucleus displays a diurnal fluctuation and that expression of this rhythm is dependent upon the secretory products of the testis. To accomplish this, we sacrificed groups of testes-intact and castrated adult male rats throughout the day and compared levels of POMC mRNA in individual cells of the arcuate nucleus across time and between groups. Adult male rats were housed on a 12–12 L D cycle with lights on a 0600 h and were divided into groups that were either castrated or left intact. Four days later, pairs from these groups were sacrificed at 0600 h, 1200 h, 1800 h, 2400 h, and again at 0600 h (n = 4 per group at each time point). We used in situ hybridization and a computerized image analysis system to measure cellular levels of POMC mRNA, as reflected by the number of autoradiographic grains over individual cells in the rostral quarter of the arcuate nucleus (counting ～ 30 cells per animal). Using cosinor analysis, we observed that in intact male rats, POMC mRNA levels varied significantly over the 24 h day with a nadir value at 1800 h. In contrast, there was no significant diurnal variation in POMC mRNA levels in castrated animals. POMC mRNA levels were significantly greater in the intact compared with castrated animals at every time point (P<0.01), except at 1800 h, when the groups did not differ significantly from one another. We conclude that adult male rats display at diurnal rhythm in cellular POMC mRNA levels in the arcuate nucleus, and we infer that testosterone or some other secretory product of the testis is a prerequisite for expression of this rhythm.     

Technical considerations regarding accuracy of the MKM navigation system. An experimental study on impact factors.

The purpose of this study was to investigate experimentally, factors determining the navigation accuracy of the MKM navigation system by Zeiss. The MKM consists of an operating microscope mounted to a six-axis motor-driven robot arm and an alpha-workstation. The image-guided surgery device provides navigation information based on calculation of the cartesian coordinates of the robot arm, and coordinates of the focus point assessed by laser assisted measurement. Navigation information (current position, direction and distance to a previously selected target) is optically projected into the microscopic field. Following factors were examined in an experimental setting for their impact on accuracy of the MKM: optical system, mechanical precision of the robot arm, and registration procedure. The robot arm and the optical system of the microscope allow high precision measurements of any focus point (error < 2 mm if the following aspects are considered: the use of auto-focus function instead of manual focusing, positioning of the registration points as a square or a triangle focus point should be selected on a surface that is perpendicular to the optical axis.     

三叉神经体感诱发电位检测的改进

本文对正常80人采用上下唇表面电刺激记录了三叉神经诱发电位。记录电极安放在C_5’/C_6’(10～20系统Cz至外耳孔的中间点),参考电极安放在Fz点,刺激强度为感觉阈的3～4倍。其结果:刺激上唇在C_5’/C_6’点可记录到P_3、N_9、P_(20)、N_(25)、P_(35)、N_(45)各波,刺激下唇时在C_5’/C_6’,可记录到N_3、P_9、N_(13)、P_(20)、N_(25)、P_(35)、N_(45)各波。其记录方法简单,准确,易使被检者接受并在临床应用。     

Lipid alterations following impact spinal cord injury in the rat

A computer-controlled impactor was used to produce a severe spinal cord injury in the rat thoracic spinal cord. Cords were rapidly frozenin situ at 5, 15, 30, and 60 min and 6, 12, and 24 h postinjury. Control cords were noninjured cords from animals having undergone a laminectomy and allowed to recover for 90 min postlaminectomy. The cords were assayed for alterations in lipid metabolism. Specifically, there were rapid increases in prostaglandin F_2α and thromboxane, with a peak increase in thromboxane levels at 30 min. Prostaglandin F_2α levels peaked at 15 min with levels remaining nearly constant for 12 h. There were no detectable changes in phospholipid levels, although diacylglycerol levels and free fatty acid levels were increased. Total free fatty acids were increased at 12 and 24 h postinjury by 2.3- and 3.2-fold over control levels, respectively. Arachidonic acid levels were not significantly elevated at early time points, however, these early time points correspond to elevated eicosanoid synthesis and this may account for the lack of early detectable increases in arachidonic acid. After 6 h postinjury, arachidonic acid levels were 20-fold greater than control levels and remained elevated at 24 h. There were minimal decreases in cholesterol and no decrease in either choline or ethanolamine plasmalogen levels. These results suggest a rapid turnover of arachidonic acid following spinal cord injury with a concomitant increase in vasoconstrictive eicosanoid synthesis. The lack of changes in major membrane constituents suggests the mechanisms may not involve general membrane degradation, but an over-stimulation of phospholipase A₂-linked membrane receptors.     

Validation of CT‐MRI fusion for intraoperative assessment of stereotactic accuracy in DBS surgery

Deep brain stimulation is typically performed with intraoperative microelectrode recording and test stimulation for target confirmation. Recent studies have shown accurate, clinically efficacious results after lead placement without microelectrode recording or test stimulation, using interventional magnetic resonance imaging (MRI) or intraoperative computed tomography (CT; iCT) for verification of accuracy. The latter relies on CT–MRI fusion. To validate CT–MRI fusion in this setting, we compared stereotactic coordinates determined intraoperatively using CT–MRI fusion with those obtained on postoperative MRI. Deep brain stimulation electrodes were implanted with patients under general anesthesia. Direct targeting was performed on preoperative MRI, which was merged with preimplantation iCT images for stereotactic registration and postimplantation iCT images for accuracy confirmation. Magnetic resonance imaging was obtained 6 weeks postoperatively for comparison. Postoperative MRI was obtained for 48 patients, with 94 leads placed over a 1‐year period. Vector error of the targeted contact relative to the initial plan was 1.1 ± 0.7 mm on iCT and 1.6 ± 0.7 mm on postoperative MRI. Variance comparisons (F‐tests) showed that the discrepancy between iCT‐ and postoperative MRI‐determined errors was attributable to measurement error on postoperative MRI, as detected in inter‐rater reliability testing. In multivariate analysis, improved lead placement accuracy was associated with frame‐based stereotaxy with the head of the bed at 0° compared with frameless stereotaxy with the head of the bed at 30° (P = 0.037). Intraoperative CT can be used to determine lead placement accuracy in deep brain stimulation surgery. The discrepancy between coordinates determined intraoperatively by CT–MRI fusion and postoperatively by MRI can be accounted for by inherent measurement error. © 2014 International Parkinson and Movement Disorder Society     

Effect of theta burst stimulation over the human sensorimotor cortex on motor and somatosensory evoked potentials.

OBJECTIVE: To study the after-effect of theta burst stimulation (TBS) over the left sensorimotor cortex on the size of somatosensory as well as motor evoked potentials evoked from both hemispheres in healthy human subjects. METHODS: We used a continuous TBS paradigm for 40 s (600 pulses) in which a burst of 3 transcranial magnetic stimuli at 50 Hz is repeated at 5 Hz [Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron 2005;45:201-6]. Somatosensory evoked potentials (SEPs) following electrical stimulation of right or left median nerve and motor evoked potentials (MEPs) in the right or left first dorsal interosseous (FDI) muscles were recorded before and after TBS over the left motor cortex (M1) or a point 2 cm posterior to left M1. RESULTS: Amplitudes of P25/N33 (parietal components) following right median nerve stimulation were significantly increased for at least 53 min after TBS over the left M1, whereas this component was suppressed for 13 min after TBS over a point 2 cm posterior. MEPs in right as well as left FDI muscles were suppressed with a similar time course after TBS over the left M1. CONCLUSIONS: A single-session of TBS over the sensorimotor cortex can induce a short-lasting change in the size of ipsilateral cortical components of SEPs as well as MEPs evoked from both hemispheres. SIGNIFICANCE: TBS is an interventional tool that can induce rapid reorganization within cortical somatosensory as well as motor networks in humans.     

Patterns of cell proliferation in the retina of the clawed frog during development

Quantitative assays of the spatial pattern of cell production in the developing retina of Xenopus have been made using ³H-thymidine labelling and colcemid blockade of mitosis. Reconstructions were made from serial sections showing the position of every mitotic figure in the retina. After stage 54 the number of mitotic figures decreases at the dorsal margin of the retina and increases at the ventral margin. The ventral:dorsal ratio of mitoses reaches 10:1 by metamorphosis. Density of mitotic figures is maximum at the point of entry of the ophthalmic vessels at the ventral margin. In spite of asymmetrical production of retinal cells the cell density remains constant throughout the retina, probably as a result of displacement of retinal cells dorsally to compensate for the relatively greater proliferation ventrally. It is also proposed that the asymmetrical retinal growth serves to maintain the relationship between each point in visual space and corresponding points in the two retinae as the eyes are displaced dorsally on the head during metamorphosis.     

Stereotactic cortical resection in non-lesional extra-temporal partial epilepsy

The presentation and treatment of a patient with extra-temporal non-lesional partial epilepsy is discussed herein. His clinical semiology was consistent with supplementary motor area seizures; however, MR imaging did not demonstrate a lesion. A region of stable cortical glucose hypermetabolism in the left frontal region was noted with 2-fluoro-2-deoxy-D-glucose (FDG)-PET. This was consistent with the frequent interictal discharges evident over the left fronto-temporal region and the stereotypic high amplitude ictal discharges arising with highest amplitude from the left frontal region. Epileptiform activity evident on an intracranial 64-point subdural recording grid placed over the left dorsolateral frontal cortex confirmed a distribution concordant with FDG-PET findings. The subsequent resection was guided by the PET and EEG findings rather than structural MR imaging, and a limited cortical resection led to an immediate and substantial reduction in seizure frequency.     

The effects of repetitive transcranial magnetic stimulation on depressive symptoms and the P300 event-related potential

Changes in the Hamilton Depression Rating Scale and the P₃₀₀ auditory event-related potential were assessed in 10 patients with depression before and after a treatment course of five daily sessions of 10?Hz repetitive transcranial magnetic stimulation (rTMS) over the left prefrontal cortex. The patients were initially randomly allocated either to an active or a placebo rTMS treatment. All patients received both types of treatment separated by an interval of 4?weeks. The median Hamilton score decreased by 7 points following active rTMS and by 1?point after sham (p=0.075). Active rTMS was associated with a significant increase in the P₃₀₀ amplitude compared with sham (p=0.02). There was no correlation between changes in P₃₀₀ measurements and the Hamilton scores after active treatment. We conclude that five daily sessions of left prefrontal rTMS treatment is not of sufficient duration to make a significant improvement in depressive symptoms.     

Distribution of scalp somatosensory potentials evoked by stimulation of the tibial nerve in man

The scalp distribution of the response to stimulation of the tibial nerve at the medial malleolus was systematically analysed. The somatosensory evoked potential (SEP) was recorded with electrodes placed in a transversal line over the ipsilateral and contralateral postcentral gyri and in a sagittal line over the longitudinal brain fissure. The SEPs recorded over the ipsilateral hemisphere and along the sagittal line were similar to the F response (the response over the foot primary somatosensory region). Over the contralateral hemisphere the waveform of the responses changed obviously from point F to the point C (contralateral hand primary somatosensory region). The C response started with N37, P40 had a longer latency, N50 was not present and the subsequent waves were also considerably different. Mathematical simulation of the responses recorded from the electrodes between points F and C has shown that they represent an electrical algebraic summation of the activity over points F and C. Although the F and C responses may be 2 potentials arising from the opposite sides of a single dipole generator which is located in the medial fissure, it is more probable that the somatosensory evoked potential on tibial nerve stimulation reflects the activity of 2 separate generators.     

A method of basal forebrain anatomical standardization for functional image analysis

Functional as well as structural assessment of the basal forebrain has mostly focused on the dorsal caudate and putamen in axial slices where they are easily outlined or their centers located with stereotaxic methods. The more ventral extent of the basal forebrain, where the irregular form and indistinct boundaries of the nucleus accumbens and substantia innominata are difficult to trace and where the brain's ventral surface may contribute partial volume artifacts to measurement, has been less studied. We present a method based on coronal sections, landmarks placed on clearly visible anchor points, and the computational technique of thin-plate spline warping which allows the alignment of groups of individuals to common coordinates for pixel-by-pixel statistical mapping. The reliability of the landmarks across independent raters yields a median absolute difference of 1.3-1.6 mm. The validity of the method is confirmed by variance maps which reveal significant decreases in variance over spindle and bounding box alignment.     

Noninvasive mapping of human motor cortex

Human motor cortex was stimulated using brief, high-voltage electrical stimulation. Constant-voltage stimuli were delivered through a bipolar surface stimulator with the anode placed at multiple positions on the scalp and the cathode situated 2.5 cm anterior to the anode. Recordings were bilateral from the abductor pollicis brevis, tibialis anterior, and risorius. We averaged the amplitudes of three muscle responses obtained from stimulation of each scalp position and assigned the resultant value to that position. The findings in eight normal volunteers were similar and reproducible. The maximal responses of the right hand were obtained when stimulating over C3, of the left hand when stimulating over C4, of the right and left legs when stimulating over Cz, and of the right side of the mouth when stimulating over T3.     

Longitudinal Behavioral and 6-[F]Fluoro- -DOPA-PET Assessment in MPTP-Hemiparkinsonian Monkeys

Biochemical and behavioral criteria were established to determine the long-term stability of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced unilateral striatal dopamine deficiency in the vervet monkey. At time points over a 12-month period, post-MPTP striatal dopamine synthesis capacity was indexed with 6-[¹⁸F]fluoro- -DOPA (FDOPA)-positron emission tomography. For the MPTP-treated subjects (n = 4), an intrasubject FDOPA influx rate constant (K_i) ratio method of right (lesioned) striatum/left (unlesioned) striatum values was used to assess changes in striatal activity. Striatal FDOPAK_iratios differed less than 5% between studies conducted at 1–2, 5–7, and 9–11 months post-MPTP; these results indicated a stable MPTP-induced striatal lesion over this time period. At the 5–7 and 9–11 month time points, behavioral indices of the MPTP-induced deficits were obtained within a species-typical group setting. For three of the four subjects, persistent decrements in motoric, affiliative, and vigilance behavior were observed while the frequency of aggression toward group members was increased. At the 9–11 month time point, one subject showed a 30% improvement in the social measures, indicative of a partial recovery from the MPTP-induced behavioral decrements although its striatal FDOPAK_iratio remained unchanged. Thus, behavioral and noninvasive biochemical methods can provide complementary indices to assess individual differences in sensitivity to MPTP-induced deficits. Both types of data are required to determine lesion stability and, subsequently, the efficacy of interventions designed to restore normal function in this primate Parkinsonian model.     

Longitudinal Behavioral and 6-[F]Fluoro-l-DOPA-PET Assessment in MPTP-Hemiparkinsonian Monkeys

Biochemical and behavioral criteria were established to determine the long-term stability of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced unilateral striatal dopamine deficiency in the vervet monkey. At time points over a 12-month period, post-MPTP striatal dopamine synthesis capacity was indexed with 6-[¹⁸F]fluoro-l-DOPA (FDOPA)-positron emission tomography. For the MPTP-treated subjects (n = 4), an intrasubject FDOPA influx rate constant (K_i) ratio method of right (lesioned) striatum/left (unlesioned) striatum values was used to assess changes in striatal activity. Striatal FDOPAK_iratios differed less than 5% between studies conducted at 1–2, 5–7, and 9–11 months post-MPTP; these results indicated a stable MPTP-induced striatal lesion over this time period. At the 5–7 and 9–11 month time points, behavioral indices of the MPTP-induced deficits were obtained within a species-typical group setting. For three of the four subjects, persistent decrements in motoric, affiliative, and vigilance behavior were observed while the frequency of aggression toward group members was increased. At the 9–11 month time point, one subject showed a 30% improvement in the social measures, indicative of a partial recovery from the MPTP-induced behavioral decrements although its striatal FDOPAK_iratio remained unchanged. Thus, behavioral and noninvasive biochemical methods can provide complementary indices to assess individual differences in sensitivity to MPTP-induced deficits. Both types of data are required to determine lesion stability and, subsequently, the efficacy of interventions designed to restore normal function in this primate Parkinsonian model.     

Continuous bilateral infusion of GABA in the dorsomedian nucleus of the thalamus elevates the generalized seizure threshold in amygdala-kindled rats

In order to assess the role of continuous intracerebral infusion of GABA over the propagation of generalized seizures from the amygdala, Wistar rats were subjected to a kindling procedure at the left basolateral amygdala. Subsequently, they were implanted with miniosmotic pumps filled with 100 mg/mL of GABA in saline, connected to catheters whose tips were placed bilaterally at both dorsomedian nuclei of the thalamus (DMNT). The threshold intensity to provoke local afterdischarges (ADT) and generalized seizures (GST) were measured before, during and after GABA infusion, as well as seizure intensity and signs of ataxia and sedation.While there was no observed variation on ADT, the median GST was significantly increased during, but not after infusion of GABA (P = 0.047, compared to the preinfusion value). Seizure intensity was not changed. No signs of neurologic side effects were recorded. These data emphasize the role of DMNT in the generalization of seizures originated at the amygdala.     

Lack of hemispheric dominance for consciousness in acute ischaemic stroke

BACKGROUND: Previous reports have suggested left hemispheric dominance for maintaining consciousness, although there is controversy over this claim. OBJECTIVE: To compare early impairment of level of consciousness between patients with right and left hemispheric stroke. METHODS: Data from 564 patients with ischaemic stroke enrolled in the placebo arm of a trial of a putative neuroprotectant were analysed. All patients had major hemispheric stroke with cortical dysfunction, visual field deficit, and limb weakness, with symptom onset within 12 hours of enrolment. Patients were prospectively evaluated on a predefined scale (1-6; 1 = fully awake, higher scores representing greater impairment) to measure level of consciousness at multiple time points over the initial 24 hours after presentation. The National Institutes of Health (NIH) stroke scale score at presentation and infarct volume at 30 days were determined. RESULTS: Some degree of impairment in level of consciousness was observed in 409 of the 564 patients (73%). Median maximum sedation score was 2 for both right and left hemispheric stroke (p = 0.91). Mean sedation score over 24 hours was 1.5 for both right and left stroke (p = 0.75). There was no difference between level of consciousness scores in right and left stroke at any individual time point during the 24 hour monitoring period. No association between side and impairment in level of consciousness was seen after adjustment for stroke severity and infarct volume. CONCLUSIONS: In contrast to previous reports, there was no evidence for hemispheric dominance for consciousness in the setting of a major hemispheric stroke.     

The comparable size and overlapping nature of upper limb distal and proximal muscle representations in the human motor cortex

The purpose of this study was to determine the relative size and location of proximal and distal upper limb muscle representations in the human motor cortex. Motor-evoked potentials (MEPs) evoked by transcranial magnetic stimulation were recorded in the proximal muscle anterior deltoid (AD) and in the distal muscles extensor carpi radialis (ECR) and first dorsal interosseus (1DI). The coil was moved in steps of 1 cm along a grid drawn on a tight-fitting polyester cap placed on the subject's head. At each location, four stimuli were delivered at 1.2 times the active motor threshold (AMT), and MEPs averaged in real-time. The peak-to-peak amplitude of each muscle's mean MEP was measured at each stimulation site. The area of a muscle's representation was measured by a pixel-counting algorithm. The optimal point of each muscle's areal representation, which corresponds to the locus near which the largest MEPs are obtained, was determined by fitting a 3D Lorentzian function to the data points. The optimal point of distal muscles tended to be situated more laterally along the motor strip than that of proximal muscles. However, there was no statistically significant difference between the size of the areal representations and they overlapped considerably. Additionally, in another five subjects, using a small 45-mm coil placed in a hyper-focal orientation, maps were obtained at a stimulus intensity of 1.1-1.15 times the AMT of the muscle with the lowest threshold, usually the 1DI. Even in this very stringent condition, the mapped representations of the AD, ECR and 1DI overlapped, notwithstanding that sharp demarcations between borders were also apparent. These observations demonstrate that stimulus spread alone does not explain the overlap of muscle representations. These results show that commonly used proximal and distal upper-limb muscles, taken individually, are controlled by motor cortical territories of approximately equal size that significantly overlap despite differences in the location of their optimal points.