Anatomical location of the spinothalamic tract in the subcortical white matter in the human brain: A diffusion tensor imaging study.

INTRODUCTION: We investigated the anatomical location of the spinothalamic tract and its thalamocortical pathway (STT) in the subcortical white matter in normal subjects, using diffusion tensor tractography (DTT). MATERIALS AND METHODS: The STT was reconstructed using FMRIB software in 40 normal subjects. The most probable locations of the STT were defined as the location on an axial slice of the centrum semiovale (CS), corona radiata (CR), and posterior limb of the internal capsule (PL). RESULTS: The STT was located at an average of 62.66% in the anterior to posterior direction along a horizontal line that passed between the anterior and posterior ends of the brain, and an average of 36.29% lateral from the midline in the CS. In the CR, the STT was located at an average of 79.60% in the anterior to posterior direction along the aforementioned horizontal line, and an average of 36.36% lateral from the midline. In the PL, the STT was located at an average of 83.58% in the anterior to posterior direction along a horizontal line that passed the middle point at the genu of the internal capsule and the posterior endpoint of the putamen, and an average of 69.69% lateral from the midline to the lateral end of the putamen. CONCLUSIONS: We found the precise anatomical location of the STT in the subcortical white matter in the human brain using DTT. We believe that the results of this study will be helpful to clinicians in the neuroscience field.

Somatotopy and Organization of Spinothalamic Tracts in the Human Cervical Spinal Cord.

BACKGROUND: Understanding spinothalamic tract anatomy may improve lesioning and outcomes in patients undergoing percutaneous cordotomy. OBJECTIVE: To investigate somatotopy and anatomical organization of spinothalamic tracts in the human cervical spinal cord. METHODS: Patients with intractable cancer pain undergoing cordotomy underwent preoperative and postoperative quantitative sensory testing for sharp pain and heat pain on day 1 and 7 after cordotomy. Intraoperative sensory stimulation was performed with computed tomography (CT) imaging to confirm the location of the radiofrequency electrode during cordotomy. Postoperative magnetic resonance (MR) imaging was performed to define the location of the lesion. RESULTS: Twelve patients were studied, and intraoperative sensory stimulation combined with CT imaging revealed a somatotopy where fibers from the legs were posterolateral to fibers from the hand. Sharpness detection thresholds were significantly elevated in the area of maximum pain on postoperative day 1 (P = .01). Heat pain thresholds for all areas were not elevated significantly on postoperative day 1, or postoperative day 7. MR imaging confirmed that the cordotomy lesion was in the anterolateral quadrant, and in this location the lesion had a sustained effect on sharp pain but a transient impact on heat pain. CONCLUSION: In the high cervical spinal cord, spinothalamic fibers mediating sharp pain for the arms are located ventromedial to fibers for the legs, and these fibers are spatially distinct from fibers that mediate heat pain.

Microendoscopy-guided percutaneous cordotomy for intractable pain: case series of 24 patients.

OBJECTIVE: The aim of this study was to show that microendoscopic guidance using a double-channel technique could be safely applied during percutaneous cordotomy and provides clear real-time visualization of the spinal cord and surrounding structures during the entire procedure. METHODS: Twenty-four adult patients with intractable cancer pain were treated by microendoscopic-guided percutaneous radiofrequency (RF) cordotomy using the double-channel technique under local anesthesia. A percutaneous lateral puncture was performed initially under fluoroscopy guidance to localize the target. When the subarachnoid space was reached by the guiding cannula, the endoscope was inserted for visualization of the spinal cord and surrounding structures. After target visualization, a second needle was inserted to guide the RF electrode. Cordotomy was performed by a standard RF method. RESULTS: The microendoscopic double-channel approach provided real-time visualization of the target in 91% of the cases. The other 9% of procedures were performed by the single-channel technique. Significant analgesia was achieved in over 90% of the cases. Two patients had transient ataxia that lasted for a few weeks until total recovery. CONCLUSIONS: The use of percutaneous microendoscopic cordotomy with the double-channel technique is useful for specific manipulations of the spinal cord. It provides real-time visualization of the RF probe, thereby adding a degree of safety to the procedure.

Differences of the medial lemniscus and spinothalamic tract according to the cortical termination areas: A diffusion tensor tractography study.

We investigated differences of the medial lemniscus and its thalamocortical pathway (ML), and the spinothalamic tract and its thalamocortical pathway (STT) according to the cortical termination areas. We found that the ML and STT terminated in the motor cortex and the somatosensory cortex. The ML may be closely related to the motor cortex for motor planning and execution, while the STT may be closely related to the cerebral cortex for somatosensory function and motor execution.

Anatomical location of the medial lemniscus and spinothalamic tract at the pons in the human brain: a diffusion tensor tractography study.

Using diffusion tensor tractography, we investigated the anatomical location of medial lemniscus (ML) and spinothalamic tract (STT) at pons. We recruited 47 healthy volunteers. Evaluation of the anatomical location of ML and STT was performed using the highest probabilistic location at the upper, middle, and lower pons. According to findings, MLs were located around the middle to medial one-third, between midline and lateral boundary of pons in the pontine tegmentum and STTs were located posterolaterally to ML.

The location of the major ascending and descending spinal cord tracts in all spinal cord segments in the mouse: actual and extrapolated.

Information on the location of the major spinal cord tracts in the mouse is sparse. We have collected published data on the position of these tracts in the mouse and have used data from other mammals to identify the most likely position of tracts for which there is no mouse data. We have plotted the position of six descending tracts (corticospinal, rubrospinal, medial and lateral vestibulospinal, rostral and caudal reticulospinal) and eight ascending tracts (gracile; cuneate; postsynaptic dorsal columns; dorsolateral, lateral, and anterior spinothalamic; dorsal and ventral spinocerebellar) on diagrams of transverse sections of all mouse spinal cord segments from the first cervical to the third coccygeal segment.

Termination differences in the primary sensorimotor cortex between the medial lemniscus and spinothalamic pathways in the human brain.

The medial lemniscus (ML) and its thalamocortical pathway is responsible for proprioception, in contrast, the spinothalamic tract (ST) and its thalamocortical pathway is the neural tract for pain and body temperature. Therefore, the ML pathway plays a crucial role in skillful movements and may be more linked to motor function than the ST pathway. We investigated the differences in the distribution of the primary motor cortex (M1) and the primary somatosensory cortex (S1) between the ML and ST pathways. Adults (mean age: 40.4 years, range: 21-61 years) were recruited for this study. The seed masks for the ML and ST pathways were given on the color map of the medulla according to the known anatomy and waypoint masks were placed on the ventro-postero-lateral nucleus of the thalamus. The volume of ML pathway did not show any difference between the M1 (10.94) and S1 (13.02) (p>0.05). By contrast, the mean voxel number of the ST pathway in the M1 (18.25) and S1 (27.38) showed significant difference between the M1 and S1 (p<0.05). As for relative voxel number percentage of the M1 compared to the S1, the ML pathway (84%) was significantly higher than ST pathway (67%) (p<0.05). We found that more neural fibers of the ML pathway were terminated in the M1 relative to the S1 compared to the SLP, and this may be linked to the inherent execution of movements of the M1.

Medioventral part of the posterior thalamus in the mouse.

The posterior thalamus (Po) consists of heterogeneous groups of cells, which have not been clearly defined. In the present study, we focused on a part of the Po in the mouse brain, which is located caudally to the ventral posterior nucleus and rostromedially to the medial geniculate nucleus and shows distinct calretinin immunoreactivity. While we found the region had a considerable unity on the cytoarchitectural and histochemical grounds, it did not correspond to any particular nucleus but partially involved three structures in a widely used brain atlas (Franklin and Paxinos, 2008). Therefore, we tentatively designated the region as the medioventral part of the posterior thalamus (PoMV) and examined its anatomical features with immunohistochemistry and retrograde tract-tracing. The PoMV was appreciated as a reticular structure with prominent calretinin immunoreactivity, especially in horizontal sections, and displayed apparent differences in the cytoarchitecture from its surrounding regions. The PoMV had two divisions: the dorsal division (PoMVd), which contained parvalbuminimmunoreactive fibers, and the ventral division (PoMVv), which lacked these fibers. The tract-tracing studies showed that the somata retrogradely labeled from the injections in the insular cortex and some of the extended amygdalar regions were fairly concentrated within the PoMV, especially in the PoMVd. On the other hand, the labeling from the medial hypothalamus injections was found predominantly within the PoMVv. These findings indicate that the PoMV can be regarded as a distinct structure within the Po, and it may play a role in the emotional aspect of somatosensory processing.

Probabilistic somatotopy of the spinothalamic pathway at the ventroposterolateral nucleus of the thalamus in the human brain.

BACKGROUND AND PURPOSE: The STP has been regarded as the most plausible neural tract responsible for pathogenesis of central poststroke pain. The VPL nucleus has been a target for neurosurgical procedures for control of central poststroke pain. However, to our knowledge, no DTI studies have been conducted to investigate the somatotopic location of the STP at the VPL nucleus of the thalamus. In the current study, we attempted to investigate this location in the human brain by using a probabilistic tractography technique of DTI. MATERIALS AND METHODS: DTI was performed at 1.5T by using a Synergy-L SENSE head coil. STPs for both the hand and leg were obtained by selection of fibers passing through 2 regions of interest (the area of the spinothalamic tract in the posterolateral medulla and the postcentral gyrus) for 41 healthy volunteers. Somatotopic mapping was obtained from the highest probabilistic location at the ACPC level. RESULTS: The highest probabilistic locations for the hand and leg were an average of 16.86 and 16.37 mm lateral to the ACPC line and 7.53 and 8.71 mm posterior to the midpoint of the ACPC line, respectively. Somatotopic locations for the hand and leg were different in the anteroposterior direction (P < .05); however, no difference was observed in the mediolateral direction (P > .05). CONCLUSIONS: We found the somatotopic locations for hand and leg of the STP at the VPL nucleus; these somatotopies were arranged in the anteroposterior direction.

Clustering probabilistic tractograms using independent component analysis applied to the thalamus.

The connectivity information contained in diffusion tensor imaging (DTI) has previously been used to parcellate cortical and subcortical regions based on their connectivity profiles. The aim of the current study is to investigate the utility of a novel approach to connectivity based parcellation of the thalamus using probabilistic tractography and independent component analysis (ICA). We use ICA to identify spatially coherent tractograms as well as their underlying seed regions, in a single step. We compare this to seed-based tractography results and to an established and reliable approach to parcellating the thalamus based on the dominant cortical connection from each thalamic voxel (Behrens et al., 2003a,b). The ICA approach identifies thalamo-cortical pathways that correspond to known anatomical connections, as well as parcellating the underlying thalamus in a spatially similar way to the connectivity based parcellation. We believe that the use of such a multivariate method to interpret the complex datasets created by probabilistic tractography may be better suited than other approaches to parcellating brain regions.

Quantitative analysis of spinothalamic tract neurons in adult and developing mouse.

Understanding the development of nociceptive circuits is important for the proper treatment of pain and administration of anesthesia to prenatal, newborn, and infant organisms. The spinothalamic tract (STT) is an integral pathway in the transmission of nociceptive information to the brain, yet the stage of development when axons from cells in the spinal cord reach the thalamus is unknown. Therefore, the retrograde tracer Fluoro-Gold was used to characterize the STT at several stages of development in the mouse, a species in which the STT was previously unexamined. One-week-old, 2-day-old and embryonic-day-18 mice did not differ from adults in the number or distribution of retrogradely labeled STT neurons. Approximately 3,500 neurons were retrogradely labeled from one side of the thalamus in each age group. Eighty percent of the labeled cells were located on the side of the spinal cord contralateral to the injection site. Sixty-three percent of all labeled cells were located within the cervical cord, 18% in thoracic cord, and 19% in the lumbosacral spinal cord. Retrogradely labeled cells significantly increased in diameter over the first postnatal week. Arborizations and boutons within the ventrobasal complex of the thalamus were observed after the anterograde tracer biotinylated dextran amine was injected into the neonatal spinal cord. These data indicate that, whereas neurons of the STT continue to increase in size during the postnatal period, their axons reach the thalamus before birth and possess some of the morphological features required for functionality.

Identification of spinothalamic tract and its related thalamocortical fibers in human brain.

Little is known about the spinothalamic tract (STT) and its related thalamocortical fibers. In the current study, we attempted to identify the STT and related thalamocortical fibers in the human brain, using diffusion tensor tractography (DTT). We recruited 23 healthy volunteers for this study. Diffusion tensor images (DTIs) were scanned using 1.5-T, and the STT and medial lemniscus (ML) were obtained using FMRIB software. Normalized DTI tractography was reconstructed using the Montreal Neurological Institute (MNI) echo-planar imaging (EPI) template supplied with the SPM. The STT began at the posterolateral medulla and ascended to the ventral posterior-lateral (VPL) nucleus of the thalamus, through the pontine tegmentum posterolateral to the ML, and through the mesencephalic tegmentum posterior to the ML. STT-related thalamocortical fibers originated from the VPL nucleus of the thalamus and ascended through the posterior limb of the internal capsule and the posterior portion of the corona radiata, terminating at the primary somatosensory cortex. We identified the STT and its related thalamocortical fibers using DTT. These results would be helpful in the clinical field and also in research on somatosensory function in the human brain.

MR imaging of ventral thalamic nuclei.

BACKGROUND AND PURPOSE: The Vim and VPL are important target regions of the thalamus for DBS. Our aim was to clarify the anatomic locations of the ventral thalamic nuclei, including the Vim and VPL, on MR imaging. MATERIALS AND METHODS: Ten healthy adult volunteers underwent MR imaging by using a 1.5T whole-body scanner. The subjects included 5 men and 5 women, ranging in age from 23 to 38 years, with a mean age of 28 years. The subjects were imaged with STIR sequences (TR/TE/TI = 3200 ms/15 ms/120 ms) and DTI with a single-shot echo-planar imaging technique (TR/TE = 6000 ms/88 ms, b-value = 2000 s/mm(2)). Tractography of the CTC and spinothalamic pathway was used to identify the thalamic nuclei. Tractography of the PT was used as a reference, and the results were superimposed on the STIR image, FA map, and color-coded vector map. RESULTS: The Vim, VPL, and PT were all in close contact at the level through the ventral thalamus. The Vim was bounded laterally by the PT and medially by the IML. The VPL was bounded anteriorly by the Vim, laterally by the internal capsule, and medially by the IML. The posterior boundary of the VPL was defined by a band of low FA that divided the VPL from the pulvinar. CONCLUSIONS: The ventral thalamic nuclei can be identified on MR imaging by using reference structures such as the PT and the IML.

The spinothalamic system targets motor and sensory areas in the cerebral cortex of monkeys.

Classically, the spinothalamic (ST) system has been viewed as the major pathway for transmitting nociceptive and thermoceptive information to the cerebral cortex. There is a long-standing controversy about the cortical targets of this system. We used anterograde transneuronal transport of the H129 strain of herpes simplex virus type 1 in the Cebus monkey to label the cortical areas that receive ST input. We found that the ST system reaches multiple cortical areas located in the contralateral hemisphere. The major targets are granular insular cortex, secondary somatosensory cortex and several cortical areas in the cingulate sulcus. It is noteworthy that comparable cortical regions in humans consistently display activation when subjects are acutely exposed to painful stimuli. We next combined anterograde transneuronal transport of virus with injections of a conventional tracer into the ventral premotor area (PMv). We used the PMv injection to identify the cingulate motor areas on the medial wall of the hemisphere. This combined approach demonstrated that each of the cingulate motor areas receives ST input. Our meta-analysis of imaging studies indicates that the human equivalents of the three cingulate motor areas also correspond to sites of pain-related activation. The cingulate motor areas in the monkey project directly to the primary motor cortex and to the spinal cord. Thus, the substrate exists for the ST system to have an important influence on the cortical control of movement.

A quantitative study of spinothalamic neurons in laminae I, III, and IV in lumbar and cervical segments of the rat spinal cord.

The major ascending outputs from superficial spinal dorsal horn consist of projection neurons in lamina I, together with neurons in laminae III-IV that express the neurokinin 1 receptor (NK1r) and have dendrites that enter the superficial laminae. Some neurons in each of these populations belong to the spinothalamic tract, which conveys nociceptive information via the thalamus to cortical areas involved in pain. A projection from the cervical superficial dorsal horn to the posterior triangular nucleus (PoT) has recently been identified. PoT is at the caudal end of the thalamus and was not included in injection sites in many previous retrograde tracing studies. We have injected various tracers (cholera toxin B subunit, Fluoro-Gold, and fluorescent latex microspheres) into the thalamus to estimate the number of spinothalamic neurons in each of these two populations, and to investigate their projection targets. Most lamina I and lamina III/IV NK1r-immunoreactive spinothalamic neurons in cervical and lumbar segments could be labeled from injections centered on PoT. Our results suggest that there are 90 lamina I spinothalamic neurons per side in C7 and 15 in L4 and that some of those in C7 only project to PoT. We found that 85% of the lamina III/IV NK1r-immunoreactive neurons in C6 and 17% of those in L5 belong to the spinothalamic tract, and these apparently project exclusively to the caudal thalamus, including PoT. Because PoT projects to second somatosensory and insular cortices, our results suggest that these are major targets for information conveyed by both these populations of spinothalamic neurons.

Recommendations for the clinical use of somatosensory-evoked potentials.

The International Federation of Clinical Neurophysiology (IFCN) is in the process of updating its Recommendations for clinical practice published in 1999. These new recommendations dedicated to somatosensory-evoked potentials (SEPs) update the methodological aspects and general clinical applications of standard SEPs, and introduce new sections dedicated to the anatomical-functional organization of the somatosensory system and to special clinical applications, such as intraoperative monitoring, recordings in the intensive care unit, pain-related evoked potentials, and trigeminal and pudendal SEPs. Standard SEPs have gained an established role in the health system, and the special clinical applications we describe here are drawing increasing interest. However, to prove clinically useful each of them requires a dedicated knowledge, both technical and pathophysiological. In this article we give technical advice, report normative values, and discuss clinical applications.

Retrograde analyses of spinothalamic projections in the macaque monkey: input to the ventral lateral nucleus.

The distribution of retrogradely labeled spinothalamic tract (STT) neurons was analyzed in monkeys following variously sized injections of cholera toxin subunit B (CTb) in order to determine whether different STT termination sites receive input from different sets of STT cells. This report focuses on STT input to the ventral lateral nucleus (VL), where prior anterograde tracing studies identified dense or moderately dense STT terminations. Large and very large injections in VL produced large numbers of labeled cells predominantly in laminae V and VII (more than half as many as from massive injections in the entire thalamus). Medium-sized and small injections in VL labeled STT cells almost exclusively in laminae V and VII, in segments consistent with the coarse mediolateral VL topography; few or no cells were labeled in lamina I. All injections labeled the deep cerebellar nuclei (see accompanying article: Evrard and Craig, 2008). Notably, even the most anterior injection in VL that produced dense pallidal labeling still labeled both STT and deep cerebellar cells. These observations indicate that VL receives STT input originating from laminae V and VII neurons that may be coextensive with its cerebellothalamic input. These findings support the role of laminae V and VII STT cells in sensorimotor integration and suggest a significant ongoing influence on both motor and premotor thalamocortical function. Together with the preceding observations of selective STT projections to other thalamic regions, these results provide compelling evidence that the primate STT consists of anatomically and functionally differentiable components.

Asynchrony of the early maturation of white matter bundles in healthy infants: quantitative landmarks revealed noninvasively by diffusion tensor imaging.

Normal cognitive development in infants follows a well-known temporal sequence, which is assumed to be correlated with the structural maturation of underlying functional networks. Postmortem studies and, more recently, structural MR imaging studies have described qualitatively the heterogeneous spatiotemporal progression of white matter myelination. However, in vivo quantification of the maturation phases of fiber bundles is still lacking. We used noninvasive diffusion tensor MR imaging and tractography in twenty-three 1-4-month-old healthy infants to quantify the early maturation of the main cerebral fascicles. A specific maturation model, based on the respective roles of different maturational processes on the diffusion phenomena, was designed to highlight asynchronous maturation across bundles by evaluating the time-course of mean diffusivity and anisotropy changes over the considered developmental period. Using an original approach, a progression of maturation in four relative stages was determined in each tract by estimating the maturation state and speed, from the diffusion indices over the infants group compared with an adults group on one hand, and in each tract compared with the average over bundles on the other hand. Results were coherent with, and extended previous findings in 8 of 11 bundles, showing the anterior limb of the internal capsule and cingulum as the most immature, followed by the optic radiations, arcuate and inferior longitudinal fascicles, then the spinothalamic tract and fornix, and finally the corticospinal tract as the most mature bundle. Thus, this approach provides new quantitative landmarks for further noninvasive research on brain-behavior relationships during normal and abnormal development.

Bilateral high-level percutaneous cervical cordotomy in cancer pain due to lung cancer: a case report.

BACKGROUND: Computed tomography-guided high-level percutaneous cordotomy has been used unilaterally or bilaterally for the treatment of localized intractable pain in malignancies. CASE DESCRIPTION: A 57-year-old man was admitted to the hospital with the complaint of intractable pain involving the left side of the chest, axillary region, and shoulder. He was operated for small cell lung cancer on the left side in December 2003 and received radiotherapy and chemotherapy. His neurological examination was normal. Magnetic resonance imaging of the thorax revealed contrast-enhancing lesions on the left side extending to mediastinum and pleura. His pain was relieved completely after the first cordotomy procedure, and he was discharged from the hospital on the second postoperative day. The patient was readmitted to the hospital with the complaint of severe unilateral chest pain like the initial pain on the right side 4 days after cordotomy. The CT-guided bilateral high-level percutaneous cordotomy was performed with a 15-day interval. CONCLUSION: The CT-guided bilateral high-level percutaneous cordotomy can be used in the treatment of intractable upper trunk pain in patients with cancer without pulmonary dysfunction.

Retrograde analyses of spinothalamic projections in the macaque monkey: input to ventral posterior nuclei.

The distribution of retrogradely labeled spinothalamic tract (STT) neurons was analyzed in monkeys following variously sized injections of cholera toxin subunit B (CTb) in order to determine whether different STT termination sites receive input from different sets of STT cells. This report focuses on STT input to the ventral posterior lateral nucleus (VPL) and the subjacent ventral posterior inferior nucleus (VPI), where prior anterograde tracing studies identified scattered STT terminal bursts and a dense terminal field, respectively. In cases with small or medium-sized injections in VPL, labeled STT cells were located almost entirely in lamina V (in spinal segments consistent with the mediolateral VPL topography); few cells were labeled in lamina I (<8%) and essentially none in lamina VII. Large and very large injections in VPL produced marked increases in labeling in lamina I, associated first with spread into VPI and next into the posterior part of the ventral medial nucleus (VMpo), and abundant labeling in lamina VII, associated with spread into the ventral lateral (VL) nucleus. Small injections restricted to VPI labeled many STT cells in laminae I and V with an anteroposterior topography. These observations indicate that VPL receives STT input almost entirely from lamina V neurons, whereas VPI receives STT input from both laminae I and V cells, with two different topographic organizations. Together with the preceding observation that STT input to VMpo originates almost entirely from lamina I, these findings provide strong evidence that the primate STT consists of anatomically and functionally differentiable components.